DESCRIPTION CARBOXYLIC ACID DERIVATIVES FIELD OF THE INVENTION [0001] This invention relates to a pharmaceutical, particularly a novel carboxylic acid derivative or a pharmaceutically acceptable salt thereof which is useful as an insulin secretion promoter or a preventive or therapeutic agent for diabetes mellitus. BACKGROUND OF THE INVENTION [0002] Diabetes mellitus is a disease having chronic hyperglycemia as the main symptom, which is developed by the absolute or relative shortage of insulin action. It is roughly divided into insulin-dependent diabetes mellitus (IDDM) and non insulin-dependent diabete: mellitus (NIDDM) based on its clinical characteristics. In the non insulin-dependent diabetes mellitus (NIDDM), reduction of insulin secretion from pancreatic (3 cells is one of the main causes of the onset of the disease, and hyperglycemia after meals by initial stage insulin secretion disorders is particularly observed. [0003] Recently, it was confirmed by large scale clinical tests that correction of hyperglycemia after meals is important for the onset and progress suppression of diabetic complications. In addition, it has been reported that arteriosclerosis is developed during a period of hyperglycemia alone, and that continuation of slight hyperglycemia after meals increases mortality rate caused by cardiovascular diseases and the like. This suggests that even when it is slight, hyperglycemia after meals is an independent risk factor of cardiovascular death. Based on the above findings, necessity of a drug therapy for hyperglycemia after meals has been recognized. [0004] At present, a sulfonylurea (SU) agent is the main current as an insulin secretion promoter, but it is known that this is apt to cause hypoglycemia and induces secondary invalidity due to exhaustion of the pancreas under a long period of time of its administration In addition, though the SU agent is effective in controlling blood glucose level during meals, it is difficult to suppress hyperglycemia after meals. [0005] GPR40 is a G protein-coupled receptor identified as a fatty acid receptor, which is highly expressed in (5 cells of the pancreas, and it has been reported that this is concerned in the insulin secretion action of fatty acids (Non-patent Reference 1). Accordingly, a GPR40 receptor agonist is expected to be effective in correcting hyperglycemia after meals based on its insulin secretion promoting action, and therefore is useful as a preventive or therapeutic agent for insulin-dependent diabetes mellitus (IDDM), non insulin-dependent diabetes mellitus (NIDDM) and their boundary type (abnormal glucose resistance and fasting blood glucose level) slight diabetes mellitus. [0006] In Patent Reference 1, it is reported that the compound shown by formula (A) including a broad range of compounds have a GPR40 receptor regulating action and are useful as an insulin secretion promoting agent and a preventive or therapeutic agent for diabetes mellitus. However, the ring P corresponding to the nitrogen-containing bicyclic ring of this application is limited to aromatic rings. (In the formula, ring P represents an aromatic ring which may have a substituent group, and ring Q an aromatic ring which may further have a substituent group other than X and Y are spacers, and a group capable of releasing a cation.) [0007] In Patent Reference 2, it is reported that the compounds shown by formula (B) have a GPR40 receptor regulating action and are useful as an insulin secretion promoting agent and a preventive or therapeutic agent for diabetes mellitus. However, the ring SI corresponding to the nitrogen-containing bicyclic ring of this application is limited to benzene ring. (See said official gazette for the symbols in the formula.) [0008] In Patent Reference 3, it is reported that the compounds shown by formula (C) have a GPR40 receptor regulating action and are useful as an insulin secretion promoting agent and a preventive or therapeutic agent for diabetes mellitus. However, the ring S1 corresponding to the nitrogen-containing bicyclic ring of this application is limited to benzene ring or pyridine ring. (In the formula, S1 means benzene ring or pyridine ring. See said official gazette for other symbols.) [0009] In Patent Reference 4, it is reported that the compounds shown by formula (D) have a GPR40 receptor regulating action and are useful as an insulin secretion promoting agent and a preventive or therapeutic agent for diabetes mellitus. However, the part corresponding to the nitrogen-containing bicyclic ring of this application is limited to benzene ring. (See said official gazette for the symbols in the formula.) [0010] In Patent Reference 5, it is reported that the compound shown by formula (E) including a broad range of compounds have a GPR40 receptor regulating action and are useful as an insulin secretion promoting agent and a preventive or therapeutic agent for diabetes mellitus. However, there is no illustrative disclosure on the nitrogen-containing bicyclic ring of this application in the ring A which corresponds to the nitrogen-containing bicyclic ring of this application. (See said official gazette for the symbols in the formula.) [0011] In Patent Reference 6, it is reported that the compound shown by formula (F) including a broad range of compounds have a GPR40 receptor regulating action and are useful as an insulin secretion promoting agent and a preventive or therapeutic agent for diabetes mellitus. However, there is no illustrative disclosure on the nitrogen-containing bicyclic ring of this application in the ring B which corresponds to the nitrogen-containing bicyclic ring of this application. (See said official gazette for the symbols in the formula.) [0012] In Patent Reference 7, it is reported that the compound shown by formula (G) including a broad range of compounds have a GPR40 receptor regulating action and are useful as a preventive or therapeutic agent for diabetes mellitus, obesity and the like. However, the Y corresponding to the nitrogen-containing bicyclic ring of this application is limited aryl or heteroaryl. z'VxLQ_Y days at from under cooling to under heating, preferably at from -20°C to 60°C. In this case, the solvent is not particularly limited, but for example, aromatic hydrocarbons, halogen ited hydrocarbons, ethers, N,N-dimethylformamide, dimethyl sulfoxide, ethyl ac state, acetonitrile, pyridine or water or a mixture thereof can be cited. As the coi idensing agent, l-(3-dimemylaminopropyl)-3-ethylcarbodiimide, dicyclohexylcarbodiimide, 1,1'-carbonyldiimidazole, diphenylphosphoric acid azide, phosphorus oxychlori( & and the like can be exemplified, though limited thereto. In some cases, it is desirable f< >r the reaction to use an additive agent (e.g., 1-hydroxybenzotriazole or the like). In view o: effecting smooth advance of the reaction, it is sometimes advantageous to carry out the reaction in the presence of triethylamine, N,N-diisopropylethylamine, N-methylmorpholim; or the like organic base or potassium carbonate, sodium carbonate, potassium hydroxic e or the like inorganic base. In addition, a method in which the carboxylic acid (13) is converted into a reactive derivative and then allowed to react with the amine compound (I-g) can als< > be used. As the reactive derivative of carboxylic acid, an acid halide obtained by reactirj g with phosphorus oxychloride, thionyl chloride or the like halogenation agent, a n lixed acid anhydride obtained by reacting with isobutyl chloroformate or the like, an a utive ester obtained by condensing with 1-hydroxybenzotriazole or the like and the lik; can be exemplified. Reaction of these reactive derivatives with the compound (I- g) can be carried out at from under cooling to under heating, preferably from -20°C to 60°C, inert solvent such as halogenated hydrocarbons, aromatic hydrocarbons, etrjers and the like. [0047] (Production method 10) V, OR4 OR" 0 \^z^ Y \ R* R (I-g) R-SOjLv (14) (R5)n OQ-^ N' Z ' s*° (I-j) RBA0 2 R3 O 22 This production method is a method in which a compound (I-j) of the invention is obtained by allowing the compound (I-g) to react with a compound (14). The reaction is carried out using equivalent amounts of the compound (I-g) and compound (14), or one of them in an excess amount, in a reaction-inert solvent such as halogenated hydrocarbons, aromatic hydrocarbons, ethers and the like, at from under cooling to under heating, preferably from -20°C to 60°C. In view of effecting smooth advance of the reaction, it is sometimes advantageous to carry out the reaction in the presence of triethylamine, N,N-diisopropylethylamine, N-methylmorpholine or the like organic base or potassium carbonate, sodium carbonate, potassium hydroxide or the like inorganic base. [0048] (Production method 11) ^-L^Xiv. rV£ A ^"LV^x4R2 R3 (15) II J-LVV • N 2 V>V-^- S,2 xTIR (1-8) ° «-» ° (Rlc means aryl or aromatic heterocyclic group, and Lv1 a leaving group. The same shall apply hereinafter.) This production method is a method in which a compound (I-k) of the invention is obtained by allowing the compound (I-g) to react with a compound (15). As the Lv1, for example, halogen, trifluoromethane sulfonyloxy and the like can be cited. The reaction is carried out under cooling to under heating, using equivalent amounts of the compound (I-g) and compound (15), or one of them in an excess amount, in a reaction-inert solvent such as aromatic hydrocarbons, ethers and the like in the presence of a palladium catalyst, a phosphine ligand and a base. As the palladium catalyst, palladium acetate or dibenzylidene acetone palladium can for example be used, and as the phosphine ligand, 2,2'-bis(diphenylphosphino)-l,l'-binaphthyl (BINAP), dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine and the like for example, and as the base, cesium carbonate, potassium phosphate and the like for example. 23 [0049] (Production method 12) >& II 0 H XxX3S'>V0R " "r X2\Y3<(X^OR4 o (I-g) tt-*) (Ar means aryl. The same shall apply hereinafter.) This production method is a method in which a compound (I-m) of the invention is obtained by allowing the compound (I-g) to react with a compound (16). The reaction is carried out under cooling to under heating, using equivalent amounts of the compound (I-g) and compound (16), or one of them in an excess amount, in a reaction-inert solvent such as aromatic hydrocarbons, halogenated hydrocarbons, DMF and the like in the presence of copper acetate. [0050] (Production method 13) (R5)n 0^ vv* v3 v^y XRXR3 OH R O O (I-o) (I-n) (In the formula, R means lower alkyl. The same shall apply hereinafter) This production method is a method in which a compound (I-o) of the invention is obtained by hydrolyzing a compound (I-n). The reaction an be carried out by the method described in the aforementioned "Protective Groups in Organic Synthesis". For example, it can be carried out under cooling to under heating, in a reaction-inert solvent such as aromatic hydrocarbons, ethers, halogenated hydrocarbons, alcohols, DMF, DMA, NMP, DMSO, pyridine, water and the like, in the presence of an acid such as sulfuric acid, hydrochloric acid, hydrobromic acid or the like mineral acid, formic acid, acetic acid or the like organic acid or the like; or in the presence of a base such as lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate, ammonia or the like. 24 [0051] In addition, some of the compounds represented by the formula (I) can also be produced from the compounds of the invention obtained in the above manner, by optionally combining alkylation, amidation, oxidation, reduction, hydrolysis and the like steps which can be generally employed by those skilled in the art. [0052] (Production methods of material compounds) The materials to be used in the production of the compounds of the invention can be produced by employing, for example, the methods described in the Production Examples which are described later, conventionally known methods or methods obvious for those skilled in the art, or modified methods thereof. [0053] The compounds of the invention are isolated and purified as free compounds or pharmaceutically acceptable salts, hydrates, solvates or polymorphic substances thereof. Pharmaceutically acceptable salt of the compound (I) of the invention can also be producing by subjecting to a general salt formation reaction. The isolation and purification are carried out by employing extraction, fractional crystallization, various types of fractional chromatography and the like general chemical operations. Various types of isomers can be separated by selecting appropriate material compounds or making use of the difference in the physicochemical properties between isomers. For example, optical isomers can be separated into stereochemically pure isomers by a general optical resolution method (e.g., a fractional crystallization for introducing into optically active diastereomer salts with a base or acid, a chiral column or the like chromatography or the like). In addition, these can also be produced from appropriate optically active material compounds. [0054] Pharmacological activities of the compounds of the invention were confirmed by the test methods shown below. Test method 1: GPR40 agonist activity measurement i) Cloning of human GPR40 In accordance with the following procedure, complete length sequence of GPR40 was obtained by a PCR method using a human genomic DNA (Clontech) as the template. 25 An oligonucleotide consisting of the nucleotide sequence represented by SEQ ID NO:l was used as the forward primer, and an oligonucleotide consisting of the nucleotide sequence represented by SEQ ID NO:2 as the reverse primer. In this connection, a nucleotide sequence containing aXbal recognition sequence is added to the %7 end of each of the aforementioned forward primer and reverse primer. In the PCR, a cycle consisting of 94°C (15 seconds)/55°C (30 seconds)/72°C (1 minute) was repeated 30 times using a Taq DNA polymerase (Ex Taq DNA polymerase; Takara Bio) in the presence of 5% dimethyl sulfoxide (DMSO). As a result, a DNA fragment of about 0.9 kbp was amplified. This DNA fragment was digested withXbal and then inserted into thecal site of a plasmid pEF-BOS-dhfr (Nucleic Acids Research, 18, 5322, 1990) to obtain a plasmid pEF-BOS-dhfr-GPR40. Nucleotide sequence of GPR40 gene in the plasmid pEF-BOS-dhfr-GPR40 was determined by the dideoxy terminator method using a DNA sequencer (ABI 377 DNA Sequencer; Applied Biosystems). Nucleotide sequence of the GPR40 gene was as the nucleotide sequence represented by SEQ ID NO:3. The nucleotide sequence represented by SEQ ID NO:3 was possessed of an open reading frame (ORF) of 903 bases, and the amino acid sequence deduced from this ORF (300 amino acids) was as the amino acid sequence represented by SEQ ID NO:4. ii) Preparation of GPR40 stable expression cell A CHO dhfr cell (a dihydrofolate reductase (dhfr) gene-deficient CHO cell) was used as the cell for expressing GPR40 protein. In addition, the plasmid pEF-BOS-dhfr-GPR40 obtained in the aforementioned i) was used as the expression plasmid for expressing the GPR40 protein. The CHO dhfr cell in 10% fetal calf serum (FCS)-containing aMEM medium was inoculated into a 6 well plate and cultured overnight to a stage of 80 to 90% confluent, and then gene transfer of 2 pig per well of the plasmid pEF-BOS-dhfr-GPR40 was carried out using a transfection reagent (Lipofectamine 2000; Invitrogen). After 24 hours of the culturing since the gene transfer, the cells were diluted and inoculated again. In that case, the aMEM medium containing 10% FCS was changed to aMEM medium which contains 10% FCS but does not contain nucleic acids. After 20 days of culturing, the thus formed colonies of cells were individually recovered and cultured to obtain CHO cells stably expressing GPR40. Cells showing high reactivity for integral ligands oleic acid and linoleic acid were selected from them. 26 iii) GPR40 agonist activity measurement This test was measured by FLIPR (registered trade mark, Molecular Device) using change in the intracellular calcium concentration as the index. The test method is shown below. A human GPR40-expressed CHO cell strain was inoculated in 6 x 103 cells per well portions into a 384 well black plate (Becton-Dickinson). A Calcium-3 assay kit (Molecular Device) was used as the luminescence pigment and dissolved in 10 ml per bottle of HBSS-HEPES buffer (pH 7.4, 1 x HBSS, 20 mM HEPES, Invitrogen). A 35.68 mg portion of probenecid (Sigma) was dissolved in 250 ul of 1 M NaOH and then adjusted by adding 250 ul of HBSS-HEPES buffer. The fluorescence pigment solution was prepared by mixing 16 ml of HBSS-HEPES buffer, 640 ul of the fluorescence pigment and 32 ul of probenecid, per plate. The medium in the plate was discarded, and the fluorescence pigment solution was dispensed in 40 ul per well portions and incubated at room temperature for 2 hours. Each compound to be tested was dissolved in DMSO, diluted with HBSS-HEPES buffer and then dispensed in 10 ul portions into the plate to start the reaction and measure change in the intracellular calcium concentration by FLIPR. EC50 values of the compounds to be tested were calculated from the dose-response curve of fluorescence intensity changes one minute after the measurement. The test results are shown in Table 1. Ex indicates compound numbers of Examples which are described later. 27 [Table 1] Ex EC50 (uM) 57 0.097 73 0.073 74 0.075 0.019 87 0.082 89 0.62 104 0.42 176 0.091 188 0.036 211 0.93 215 0.32 424 0.13 437 0.73 453 0.025 455 0.36 [0055] Test method 2: Insulin secretion promoting action using MIN6 cell In this test, the insulin secretion promoting action of compounds to be tested was examined using a mouse pancreatic P cell strain, MIN6 cell. The test method is shown below. The MIN6 cell was inoculated onto a 96 well plate to a density of 5 x 104 cells/well (200 ul). As the medium, DMEM medium (25 mM glucose) containing 10% FBS, 55 uM of 2-mercaptoethanol, 100 U/ml of penicillin and 100 ug/ml of streptomycin was used. Two days thereafter, the medium was removed using an aspirator, and the plate was once washed with 200 ul of KRB-HEPES (116 mM NaCl, 4.7 mM KC1,1.2 mM KH2P04,1.2 mM MgS04, 0.25 mM CaCl2,25 mM NaHC03, 0.005% FFA Free BSA, 24 mM HEPES (pH 7.4)) containing 2.8 mM glucose, which had been warmed up to 37°C, and again filled with 200 ul of the same buffer and incubated at 37°C for 1 hour. After removing the aforementioned buffer using an aspirator, this was again washed with the buffer (200 ul), and then a predetermined concentration of each compound to be tested was added to KRB- 28 HEPES containing 2.8 mM or 22.4 mM of glucose, added in 100 ul portions to respective wells and incubated at 37°C for 2 hours. The aforementioned samples were collected and diluted 100 times, and the insulin concentration was determined using an insulin RIA kit (Amersham). The activity value was show by a relative activity value (%) at the time of the addition of 1 uM of each compound, based on the control (DMSO) 100%. The test results are shown in Table 2. As a result, it was confirmed that the compounds of the invention have excellent insulin secretion promoting action. [Table 2] Ex Insulin secretion promoting action (%) _57 167 104 162 [0056] Test method 3: Normal mice single administration oral glucose tolerance test This test examined on the blood glucose suppressive action of compounds to be tested after glucose loading using normal mice. Male ICR mice (6 weeks of age) were reared for 1 week in advance, subjected to overnight fasting and then used as animals to be tested. Each compound to be tested was prepared into a 0.5% methyl cellulose suspension and orally administered at a dose of 10 mg/kg 30 minutes before the glucose (2 g/kg) loading. In the control group, 0.5% methyl cellulose was administered. Blood glucose decreasing ratio (%) at the time of 30 minutes of glucose loading was calculated based on the control group. The test results are shown in Table 3. As a result, it was confirmed that the compounds of the invention have excellent blood glucose decreasing action. [Tab le3] Ex 89 Blood glucose decreasing ratio (%) 21 104 20 188 24 453 24 29 [0057] In addition, it was confirmed on several compounds of the invention that they have excellent pharmacokinetics and are sufficiently separated from the cytochrome P450 (CYP) inhibitory action in which the GPR40 agonist action becomes a cause of drug interaction and the HERG inhibitory action in which the same becomes a cause of Qt prolongation. [0058] From the results of the aforementioned respective tests, it was confirmed that the compounds of the invention have excellent GPR40 agonist action. Based on this, these are useful as an insulin secretion promoter and a preventive or therapeutic agent for diabetes mellitus (insulin-dependent diabetes mellitus (IDDM), non insulin-dependent diabetes mellitus (NIDDM) and their boundary type (abnormal glucose resistance and fasting blood glucose level) slight diabetes mellitus) and the like diseases. [0059] The pharmaceutical preparation which comprises one or two or more of the compounds (I) of the invention or salts thereof as the active ingredient can be prepared by generally used methods using medicinal carriers, fillers and the like which are generally used in said field. The administration may be either oral administration by tablets, pills, capsules, granules, powders, solutions and the like, or parenteral administration by intraarticular, intravenous, intramuscular and the like injections, suppositories, eye drops, eye ointments, solutions for percutaneous use, ointments, patches for percutaneous use transmucosal solutions, transmucosal patches, inhalations and the like. [0060] As the solid composition for oral administration by the invention, tablets, powders, granules and the like are used. In such a solid composition, one or two more active substances are mixed with at least one inert filler such as lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinyl pyrrolidone and/or aluminum magnesium silicate or the like. In accordance with the usual way, the composition may contain inert additives such as magnesium stearate and the like lubricants, carboxymethylstarch sodium and the like disintegrators, stabilizes and solubilizing agents. As occasion demands, the tablets or pills may be coated with a sugar coating or a gastric or enteric coating. As the liquid composition for oral administration, pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs and the like are included, which contain 30 generally used inert diluents such as purified water or ethanol. In addition to the inert diluents, said liquid composition may contain solubilizing agents, moistening agents, suspending agents and the like auxiliary agents, sweeteners, correctives, aromatics and antiseptics. As the injections for parenteral administration, sterile aqueous or non-aqueous solutions, suspensions and emulsions are included. As the aqueous solvent, for example, distilled water for injection and physiological saline are included. Examples of the non-aqueous solvent include propylene glycol, polyethylene glycol, olive oil or the like plant oil, ethanol or the like alcohols, polysorbate 80 (the name in Pharmacopeia) and the like. Such a composition may further contain tonicity agents, antiseptics, moistening agents, emulsifying agents, dispersing agents, stabilizing agents and solubilizing agents. These are sterilized by, for example, filtration through a bacteria retaining filter, formulation of bactericides or irradiation. In addition, these can also be used by producing a sterile solid compositions and dissolving or suspending them in sterile water or a sterile solvent for injection prior to use. [0061] As the external preparations, ointments, plasters, creams, jellies, cataplasmas, sprays, lotions, eye drops, eye ointments and the like are included. These contain generally used ointment base, lotion base, aqueous or non-aqueous solutions, suspensions, emulsions and the like. For example, polyethylene glycol, propylene glycol, white petrolatum, white beeswax, polyoxyethylene hydrogenated castor oil, glycerol monostearate, stearyl alcohol, cetyl alcohol, lauromacrogol, sorbitan sesquioleate and the like can be cited as the ointment or lotion base. Inhalations, transnasal preparations and the like transmucosal preparations are used in a solid, liquid or semisolid form and can be produced in accordance with conventionally known methods. For example, a conventionally known filler, as well as a pH adjusting agent, an antiseptic, a surfactant, a lubricant, a stabilizer, a thickener and the like, may be optionally added. An appropriate device for inhalation or blowing can be used for the administration. For example, using a measured administration inhalation device or the like conventionally known device or a sprayer, a compound can be administered alone or as a powder of a formulated mixture, or as a solution or suspension by a combination with a medicinally acceptable carrier. The dry powder inhaler or the like may be for single or multiple administration use, and a dry powder or a powder-containing capsule can be used. 31 Alternatively, it may be a pressurized aerosol spray or the like form which uses chlorofluproalkane, hydrofluoroalkane or carbon dioxide or the like suitable gas. [0062] In the case of oral administration, daily dose is generally from about 0.001 to 100 mg/kg body weight, preferably from 0.1 to 30 mg/kg, more preferably from 0.1 to 10 mg/kg, and this is administered once or dividing into 2 to 4 times. When intravenously administered, it is suitable that the daily dose is from about 0.0001 to 10 mg/kg body weight, and this is administered once a day or dividing it into two or more times. In addition, as a transmucosal preparation, a daily dose of from about 0.001 to 100 mg/kg body weight is administered once a day or dividing it into two or more times. The dose is optionally decided in response to individual cases, taking symptom, age, sex and the like into consideration. [0063] The compounds of the invention can be used concomitantly with various therapeutic or preventive agents for diseases in which the aforementioned compounds of the invention are considered to be effective. Said concomitant use may be effected by simultaneous administration or by administering individually continuously or at a desired interval of time. The simultaneous administration preparations may be a combination drug or separately prepared. EXAMPLES [0064] The following describes production methods of the compounds (I) of the invention further in detail based on examples. The compounds of the invention are not limited to the compounds described in the following examples. Also, production methods of the material compounds are shown in production examples. [0065] Production Example 1 Under ice-cooling, sodium hydride (about 40% mineral oil was added, 7.0 g) was added to a THF (120 ml) solution of ethyl diethylphosphonoacetate (38 ml) and stirred under ice-cooling for 30 minutes. A THF (200 ml) solution of 2-fluoro-4-methylbenzaldehyde (20 g) was added dropwise under ice-cooling to the reaction mixture and stirred under ice-cooling for 1 hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous 32 solution and then dried with anhydrous magnesium sulfate. The desiccant was removed, the solvent was evaporated under a reduced pressure, and then the residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl (2E)-3-(2-fluoro-4- methylphenyl)acrylate (30 g) as a colorless oil. [0066] Production Example 2 A mixture of ethyl (2E)-3-(2-fluoro-4-methylphenyl)acrylate (30 g), N-bromosuccinimide (31 g), 2,2'-azobisisobutyronitrile (1.2 g) and carbon tetrachloride (360 ml) was stirred for 10 hours under heating reflux. After separating the insoluble matter by filtration, the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), ethyl (2E)-3-[4-(bromomethyl)-2-fluorophenyl]acrylate (42 g) was obtained as a colorless solid. [0067] Production Example 3 N-Bromosuccinimide (30.76 g) and 2,2'-azoisobutyronitrile (645 mg) were added to a carbon tetrachloride (500 ml) solution of ethyl (2E)-3-(2-fluoro-4-methylphenyl)acrylate (16.36 g), and stirred for 21 hours under heating reflux. The reaction mixture was concentrated under a reduced pressure, ethyl acetate was added to the residue, followed by washing with water, saturated sodium thiosulfate aqueous solution, water and saturated sodium chloride aqueous solution in that order and subsequent drying with anhydrous magnesium sulfate. After removing the desiccant, the solvent was evaporated under a reduced pressure, the thus obtained yellow oil (24.91 g) was dissolved in acetone (581 ml) and water (119 ml) followed by the addition of silver nitrate (34.69 g), and the reaction mixture was stirred under shade at room temperature for 15 hours. The precipitate was removed by filtration, and ethyl acetate was added to the thus obtained filtrate. The organic layer was washed with saturated sodium bicarbonate aqueous solution, water and saturated sodium chloride aqueous solution in that order and dried with anhydrous magnesium sulfate. After removing the desiccant, the solvent was evaporated under a reduced pressure and the thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl (2E)-3-[2-fluoro-4-(hydroxymethyl)phenyl]acrylate (4.70g) as a yellow oil. 33 [0068] Production Example 4 In an atmosphere of nitrogen and under cooling on an ice-methanol bath, nickel(II) chloride hexahydrate (1.06 g) was added to an ethanol (40 ml) and THF (40 ml) solution of ethyl (2E)-3-[2-fluoro-4-(hydroxymethyl)phenyl]acrylate (4.00g), followed by the addition of sodium borohydride (1.35 g) in small portions. The reaction mixture was stirred under ice-cooling for 1.5 hours and then warmed up to room temperature and stirred as such for 1.5 hours. Under ice-cooling, 10% citric acid aqueous solution (100 ml) was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated sodium chloride aqueous solution in that order and dried with anhydrous magnesium sulfate. By removing the desiccant and then evaporating the solvent under a reduced pressure, ethyl 3-[2-fluoro-4-(hydroxymethyl)phenyl]propanoate (3.81 g) was obtained as a pale yellow oil. [0069] Production Example 5 l,l,l-Triacetoxy-l,l-dihydro-l,2-benzoiodoxol-3(lH)-one (6.50 g) was added to a dichloromethane (35 ml) solution of ethyl 3-[2-fluoro-4-(hydroxymethyl)phenyl]propanoate (1.73 g) and stirred at room temperature for 1 hour. The reaction mixture was poured into saturated sodium bicarbonate aqueous solution (100 ml) and extracted with chloroform. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. After removal of the desiccant, the solvent was evaporated under a reduced pressure, and the thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-(2-fluoro-4-(formylphenyl)propanoate (1.41 g) as a pale yellow oil. [0070] Production Example 6 Under ice-cooling, thionyl chloride (0.75 ml) was added to a methanol (26 ml) solution of rel-(lR,2R)-2-(4-aminophenyl)cyclopropanecarboxylic acid (1.30 g) and stirred at room temperature for 3 hours. After evaporation of the solvent under a reduced pressure, methanol and subsequent saturated sodium bicarbonate aqueous solution were added to the residue, and the solvent was evaporated under a reduced pressure. The residue was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. By drying the residue 34 under a reduced pressure, methyl rel-(lR,2R)-2-(4-aminophenyl)cyclopropanecarboxylate (1.25 g) was obtained as a pale brown oil. [0071] Production Example 7 Under ice-cooling, 2-nitrobenzenesulfonyl chloride (2.46 g) was added to a pyridine (15 ml) solution of methyl rel-(lR,2R)-2-(4-aminophenyl)cyclopropanecarboxylate (1.93 g) and stirred at room temperature for 12 hours. After evaporating the solvent under a reduced pressure, water and ethyl acetate were added to the residue, and the insoluble matter was separated by filtration. After separation of layers of the filtrate, the organic layer was washed with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution in that order, and dried with anhydrous magnesium sulfate. The desiccant was removed, the solvent was evaporated under a reduced pressure, and then the residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain methyl rel-(lR,2R)-2-(4-{[(2-nitrophenyl)sulfonyl]amino}phenyl)cyclopropanecarboxylate (3.30 g) as a pale yellow oil. [0072] Production Example 8 Di-t-butyl dicarbonate (10.4 g) was added to a dioxane (26 ml) solution of ethyl 3-(4-amino-2-fiuorophenyl)propanoate (10.0 g) and stirred at 90°C for 20 hours. This reaction mixture was spontaneously cooled down to room temperature, and the solvent was evaporated under a reduced pressure. Ethyl acetate was added to the residue, followed by washing with saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueous solution. The organic layer was dried with anhydrous magnesium sulfate, and then the desiccant was removed and the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), ethyl 3-{4-[(tert-butoxycarbonyl)amino]2-fluorophenyl}propanoate (14.9 g) was obtained as a colorless oil. [0073] Production Example 9 A mixture of l,2,3,4-tetrahydroquinolin-5-ylmethanol (5.29 g)di-tert-butyl dicarbonate (10.6 g) and dioxane (50 ml) was stirred at 80°C for 12 hours. The solvent was evaporated under a reduced pressure, and then the residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain tert-butyl 5-(hydroxymethyl)-3,4-dihydroquinoline-l(2H)carboxylate (7.64 g) as a pale yellow oil. 35 [0074] Production Example 10 Under ice-cooling, sodium borohydride (3.2 g) was added to an ethanol (160 ml) solution of tert-butyl 8-formyl-3,4-dihydroquinoline-l(2H)-carboxylate and stirred under ice-cooling for 40 minutes. Water was added to the reaction mixture, the solvent was evaporated under a reduced pressure, and then the residue was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography, tert-butyl 8-(hydroxymethyl)-3,4-dihydroquinoline-l(2H)-carboxylate (10 g) was obtained as a colorless oil. [0075] Production Example 11 In an atmosphere of hydrogen, 10% palladium-activated carbon (4.50 g) was added to a methanol (325 ml) and THF (325 ml) solution of methyl 4-[(lE)-3-ethoxy-3-oxoprop-l-en-l-yl]-3-nitrobenzoate (11.4 g) and stirred at room temperature for 20 hours. The insoluble matter was separated by filtration, and 1 M hydrochloric acid (190 ml) was added to the filtrate and stirred at room temperature for 5 hours. The solvent was evaporated under a reduced pressure, and the thus formed solid was collected by filtration to obtain methyl 2-oxo-l,2,3,4-tetrahydroquinoline-7-carboxylate (34.8 g) as a pale green solid. [00761 Production Example 12 A mixture of methyl 2-oxo-l,2,3,4-tetrahydroquinoline-7-carboxylate (500 mg), iodobenzene (0.42 ml), copper(I) iodide (44 mg), 1,10-phenanthroline (44 mg), 40% potassium fluoride-alumina (1.77 g) and toluene (15 ml) was heated under reflux for 1 day. Iodobenzene (0.41 ml) and copper(I) iodide (44 mg) were added to the reaction mixture and further stirred under heating reflux for 2 days. The reaction mixture was cooled down to room temperature, the insoluble matter was separated by filtration, and the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (chloroform-methanol), methyl 2-oxo-1 -phenyl-1,2,3,4-tetrahydroquinoline-7-carboxylate (150 mg) was obtained as a pale yellow solid. 36 [0077] Production Example 13 To a THF (5 ml) and methanol (1 ml) solution of methyl 2-oxo-l-phenyl-1,2,3,4-tetrahydroquinoline-7-carboxylate (530 mg), 1 M sodium hydroxide aqueous solution (5.7 ml) was added and stirred at room temperature for 1 week. After evaporation of the solvent under a reduced pressure, 1 M hydrochloric acid was added to the residue to adjust to pH 3 to 4, and the thus formed solid was collected by filtration. By drying under a reduced pressure, 2-oxo-l-phenyl-1,2,3,4-tetrahydroquinoline-7-carboxylic acid (385 mg) was obtained as a white solid. [0078] Production Example 14 Under ice-cooling, isobutyl chloroformate (0.21 ml) was added dropwise to a THF (5 ml) mixture of 2-oxo-l-phenyl-1,2,3,4-tetrahydroquinoline-7-carboxylic acid (385 mg) and 4-methylmorpholine (0.19 ml) and stirred at the same temperature for 30 minutes, followed by the addition of sodium borohydride (82 mg) and methanol (1 ml). Water was added to the reaction mixture, followed by extraction with chloroform. After drying the organic layer with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (chloroform-methanol) to obtain 7-(hydroxymethyl)-l-phenyl-3,4-dihydroquinolin-2(lH)-one (306 mg) was obtained as a white solid. [0079] Production Example 15 A mixture of 7-dimethoxymethyl-1,2,3,4-tetrahydro-l,8-naphthyridine (500 mg), bromobenzene (0.55 ml), tris(dibenzylideneacetone)dipalladium (44 mg), dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (46 mg), potassium phosphate (2.04 g) and dimethoxyethane (10 ml) was stirred at 90°C for 12 hours. The reaction mixture was spontaneously cooled to room temperature and extracted with ethyl acetate by adding water. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. By removing the desiccant and evaporating the solvent under a reduced pressure, 7-(dimethoxymethyl)-l-phenyl-1,2,3,4-tetrahydro-l,8-naphthyridine (1.14 g) was obtained as a black oil. 37 [0080] Production Example 16 3 M Hydrochloric acid (20 ml) was added to a THF (10 ml) solution of 7-(dimethoxymethyl)-l-phenyl-1,2,3,4-tetrahydro-l,8-naphthyridine (1.14 g) and stirred at room temperature for 2 hours. 3 M Sodium hydroxide aqueous solution (20 ml) was added, extracted with ethyl acetate, and the organic layer was dried with anhydrous magnesium sulfate. Under ice-cooling, sodium borohydride (76 mg) was added to a methanol (10 ml) solution of the residue and stirred for 10 minutes. Water was added to the reaction mixture, and extracted with ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), (8-phenyl-5,6,7,8-tetrahydro-l,8-naphthyridin-2-yl)methanol (556 mg) was obtained as a pale yellow oil. [0081] Production Example 17 Concentrated sulfuric acid (32.0 ml) was added to a mixture of 3-amino-2-methylbenzoic acid (25.0 g), glycerol (49.9 g), boric acid (7.5 g) and nitrobenzene (13.6 g) and stirred at 160°C for 12 hours. This reaction mixture was spontaneously cooled to room temperature and allowed to stand still for 1 day by adding water (110 ml) and sodium hydroxide (59.5 g). This reaction mixture was subjected to decantation, and the supernatant alone was transferred. Acetic acid (37.9 ml) was added to the thus obtained supernatant. The thus formed solid was washed with water and then dried under a reduced pressure. Methanol (250 ml) and concentrated sulfuric acid (9.1 ml) were added to the thus obtained black solid, and 2 days of stirring was carried out under heating reflux. After spontaneous cooling of the reaction mixture to room temperature, sodium bicarbonate (35.9 g) was added in small portions, and the solvent was evaporated under a reduced pressure. Ethyl acetate was added to the residue, the insoluble matter was separated by filtration, and the filtrate was washed with saturated sodium chloride aqueous solution. After drying the organic layer with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), methyl 8-methylquinoline-7-carboxylate (10.6 g) was obtained as a pale yellow solid. 38 [0082] Production Example 18 Under cooling on an ice-methanol bath, sodium borohydride (1.50 g) was added in small portions to a methanol (80 ml) solution of methyl 8-methylquinoline-7-carboxylate (8.00 g) and nickel (II) chloride hexahydrate (2.84 g) and stirred for 1 hour. Saturated ammonium chloride aqueous solution was added to the reaction solution and the solvent was evaporated under a reduced pressure. Water and ethyl acetate were added to the residue, the insoluble matter was removed by celite filtration and the filtrate was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried with anhydrous magnesium sulfate. By removing the descant and evaporating the solvent under a reduced pressure, methyl 8-methyl-1,2,3,4-tetrahydroquinoline-7-carboxylate was obtained as a pale yellow oil. [0083] Production Example 19 A mixture of methyl l,2,3,4-tetrahydroquinoline-7-carboxylate (3.28 g), triphenylbismuthin (11.3 g), copper(II) acetate (3.12 g) and dichloroethane (30 ml) was stirred at 80°C for 12 hours. The insoluble matter was removed by celite filtration and then the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), methyl 1-phenyl-1,2,3,4-tetrahydroquinoline-7-carboxylate (4.36 g) was obtained as a pale yellow oil. [0084] Production Example 20 Sodium triacetoxyborohydride (4.3 g) was added at room temperature to a mixture of l,2,3,4-tetrahydroquinolin-8-ol (1.0 g), 2-methylpropanal (1.2 ml) and dichloroethane (10 ml) and stirred at room temperature for 6 hours. Water added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed, the solvent was evaporated under a reduced pressure, and then the residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain l-isobutyl-l,2,3,4-tetrahydroquinolin-8-ol (1.4 g) as a brown oil. [0085] Production Example 21 N,N-diisopropylethylamine (2.0 ml) and benzyl bromide (1.00 ml) were added to a DMF (20 ml) solution of 6-nitro-3,4-dihydro-2H-l,4-benzoxazine (1.00 g), and the reaction 39 mixture was stirred at 60°C for 2 days. The reaction mixture was spontaneously cooled to room temperature, followed by the addition of water (80 ml) and subsequent extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. After removing he desiccant, the solvent was evaporated under a reduced pressure, and the thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain 4-benzyl-6-nitro-3,4-dihydro-2H-l,4-benzoxazine (1.49 g) as an orange solid. [0086] Production Example 22 Reduced iron (1.51 g) and ammonium chloride (290 mg) were added to an ethanol (24 ml) and water (6 ml) solution of 4-benzyl-6-nitro-3,4-dihydro-2H-l,4-benzoxazine (1.46 g), and the reaction mixture was stirred for 2 hours under heating reflux. The reaction mixture was spontaneously cooled to room temperature and filtered over celite. By washing with ethanol, the thus obtained filtrate was concentrated under a reduced pressure. Chloroform and saturated sodium bicarbonate aqueous solution were added to the residue, followed by extraction with chloroform. The organic layer was dried with anhydrous magnesium sulfate, and after removing he desiccant, the solvent was evaporated under a reduced pressure. By purifying the thus obtained residue by a silica gel column chromatography (chloroform-methanol), 4-benzyl-3,4-dihydro-2H-l ,4-benzoxazine-6-amine (1.19 g) was obtained as a light brown solid. [0087] Production Example 23 Under an atmosphere of nitrogen, a THF (5.6 ml) solution of methyl 8-methyl-l-propyl-l,2,3,4-tetrahydroquinoline-7-carboxylate was added dropwise at 0°C to a THF (30 ml) suspension of lithium aluminum hydride (410 mg) and stirred for 30 minutes. By adding water (1.67 ml) and 15% sodium hydroxide aqueous solution (0.40 ml), 1 hour of stirring was carried out at room temperature. After removing the insoluble matter by filtration, the filtrate was concentrated under a reduced pressure to obtain (8-methyl-l-propyl-l,2,3,4-tetrahydroquinolin-7-yl)methanol (1.52 g) as a colorless oil. [0088] Production Example 24 A mixture of (l-phenyl-l,2,3,4-tetrahydroquinolin-7-yl)methanol (2.0 g), manganese dioxide (3.6 g) and chloroform (40 ml) was stirred at 60°C for 12 hours. After removing the insoluble matter by celite filtration, the solvent was evaporated under a 40 reduced pressure. By purifying the residue by a silica gel column chromatography (hexane- ethyl acetate), 1-phenyl-1,2,3,4-tetrahydroquinoline-7-carbaldehyde (1.6 g) was obtained as a yellow oil. [0089] Production Example 25 Under ice-cooling, sodium hydride (about 40% mineral oil was added, 1.2 g) was added to a mixture of ethyl (2E)-3-[4-(bromomethyl)-2-fluorophenyl]acrylate (8.0 g), 8-quinolinol (4.2 g) and DMF (150 ml) and stirred under ice-cooling for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. After removing the desiccant, the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), ethyl (2E)-3-{2-fluoro-4-[(quinolin-8-yloxy)methyl]phenyl}acrylate (0.32 g) was obtained as a yellow solid. [0090] Production Example 26 Under ice-cooling, sodium hydride (about 40% of mineral oil was added, 0.19 g) was added to a mixture of 7-(bromomethyl)quinoline hydrochloride (0.45 g), ethyl 3-(2-fluoro-4-hydroxyphenyl)propanoate (0.55 g) and DMF (5 ml) and stirred under ice-cooling for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), ethyl 3-[2-fluoro-4-(quinolin-7-ylmethoxy) phenyl]propanoate (0.32 g) was obtained as a colorless solid. [0091] Production Example 27 10% palladium-activated carbon (80mg) was added to a methanol (10 ml) and THF (5 ml) solution of methyl (6-{[(l-benzyl-l,2,3,4-tetrahydroquinolin-8-yl)methyI]amino}-l-benzofuran-3-yl)acetate (659 mg) and stirred at room temperature for 8 hours in an atmosphere of hydrogen. The catalyst was removed by celite filtration and the filtrate was concentrated under a reduced pressure. By purifying the thus obtained residue by a silica gel column chromatography (hexane-ethyl acetate), methyl (6-amino-2,3-dihydro-l-benzofuran-3-yl)acetate (389 mg) was obtained as a pale pink oil. 41 [0092] Production Example 28 Under ice-cooling, 4 M hydrogen chloride dioxane solution (6.0 ml) was added to a THF (1.5 ml) solution of ethyl (2E)-3-(4-{[tert-butoxycarbonyl)(l-propyl-l,2,3,4-tetrahydroquinolin-8-yl)amino]methyl}-2-fluorophenyl)acrylate (1.23 g) and stirred under ice-cooling for 12 hours. After evaporation of the solvent under a reduced pressure, saturated sodium bicarbonate aqueous solution was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. By drying the residue under a reduced pressure, ethyl (2E)-3-(4-{[(l-propyl-l,2,3,4-tetrahydroquinolin-8-yl)amino]methyl}-2-fluorophenyl)acrylate (0.98 g) was obtained as a yellow oil. [0093] Production Example 29 Under ice-cooling, sodium cyanoborohydride (1.54 g) was added to an acetic acid (65 ml) solution of methyl rel-(lR,2R)-2-(4-{[(2-nitrophenyl)sulfonyl](quinolin-8-ylmethyl)arnino}phenyl)cyclopropanecarboxylate (4.24 g) and stirred at room temperature for 1 hour. The reaction mixture was neutralized by adding saturated sodium bicarbonate aqueous solution and sodium carbonate, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated sodium chloride aqueous solution in that order and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), methyl rel-(lR,2R)-2-(4-{[(2-nitrophenyl)sulfonyl](l,2,3,4-tetrahydroquinolin-8- ylmethyl)amino}phenyl)cyclopropanecarboxylate (3.41 g) was obtained as a pale yellow amorphous solid. [0094] Production Example 30 Under ice-cooling, trifluoroacetic anhydride (0.31 ml) was added to a dichloromethane (10 ml) solution of tert-butyl rel-8-[({4-[(lR,2R)-2-(methoxycarbonyl)cyclopropyl]phenyl} amino)methyl]-3,4-dihydroquinoline-1 (2H)-carboxylate (800 mg) and stirred under ice-cooling for 2 hours. Saturated sodium bicarbonate aqueous solution was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous 42 solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. By drying the residue under a reduced pressure, tert-butyl rel-8-{[{4-[(lR,2R)-2- (methoxycarbonyl)cyclopropyl]phenyl}(trifluoroacetyl)amino]methyl}-3,4- dihydroquinoline-l(2H)-carboxylate (940 mg) was obtained as a pale yellow oil. [0095] Production Example 31 A mixture of ethyl 3-{4-[(tert-butoxycarbonyl)(l,2,3,4-tetrahydroquinolin-7-ylmethyl)amino]-2-fluorophenyl}propanoate (670 mg), 1 -bromo-2-methylbenzene (0.35 ml), tris(dibenzylideneacetone)dipalladium (26.9 mg), dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (28.0 mg), potassium phosphate (1.25 g) and dimethoxyethane (6.7 ml) was stirred for 2 days under heating reflux. The reaction mixture was spontaneously cooled to room temperature and extracted with ethyl acetate by adding water. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed, the solvent was. evaporated under a reduced pressure, and the residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-{4-[(tert-butoxycarbonyl){[l-(2-methylphenyl)-(l,2,3,4-tetrahydroquinolin-7-ylmethyl)amino]-2-fluorophenyl}propanoate (527 mg) as a yellow oil. [0096] Production Example 32 Under ice-cooling, sodium borohydride (67 mg) was added to a mixture of ethyl 3-[2-fluoro-4-([(2-nitrophenyl)sulfonyl] {[ 1 -(2-oxo-2-phenylethyl)-1,2,3,4-tetrahydroquinolin-5-yl]methyl}amino)phenyI]propanoate (1.17 g), ethanol (12 ml) and THF (6 ml) and stirred under ice-cooling for 5 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-[2-fluoro-4-({[l-(2-hydroxy-2-phenylethyl)-l,2,3,4-tetrahydroquinolin-5-yl]methyl}[(2-nitrophenyl)sulfonyl]amino)phenyl]propanoate (1.15 g) as a colorless oil. 43 [0097] Production Example 33 Under ice-cooling, mercaptoacetic acid (0.36 ml) and lithium hydroxide monohydrate (430 mg) were added to a DMF (20 ml) solution of methyl (6-{[(l-benzyl-1,2,3,4-tetrahydroquinolin-8-yl)methyl] [(2-nitrophenyl)sulfonyl]amino} -1 -benzofuran-3 -yl)acetate (1.56 g), warmed up to room temperature and stirred for 3 hours. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. After removing the desiccant, the solvent was evaporated under a reduced pressure and the thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain methyl (6-{[(l-benzyl-l,2,3,4-tetrahydroquinolin-8-yl)methyl]amino}-l-benzofuran-3-yl)acetate (670 mg) as a pale yellow syrup. [0098] Production Example 34 1 M Tetrabutylammonium fluoride THF solution (1.18 ml) was added to a THF (4.7 ' ml) solution of ethyl 3-{4-[(tert-butoxycarbonyl){[l-(2-{[tert-butyl(dimethyl)silyl]oxy} ethyl)-1,2,3,4-tetrahydroquinoIin-7-yl]methyl} amino]-2-fluorophenyl}propanoate (291 mg) and stirred at room temperature for 1 day. The solvent was evaporated under a reduced pressure and saturated ammonium chloride aqueous solution was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. After removing the desiccant, the solvent was evaporated under a reduced pressure and the thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-{4-[(tert-butoxycarbonyl){[l-(2-hydroxyethyl)-l,2,3,4-tetrahydroquinolin-7-yI]methyl}amino]-2-fluorophenyl}propanoate (234 mg) as colorless oil. [0099] Production Example 35 l,l'-(Azodicarbonyl)dipiperidine (390 mg) was added under ice-cooling to a mixture of ethyl 3-[2-fluoro-4-({ [1 -(2-hydroxyethyl)-l ,2,3,4-tetrahydroquinolin-5-yl]methyl}[(2-nitrophenyl)sulfonyl]amino)phenyl]propanoate (600 mg), 2-fluorophenol (230 mg), tributylphosphine (0.38 ml) and THF (6 ml) and stirred at room temperature for 3 days. After separation of the insoluble matter by filtration, the solvent was evaporated under a 44 reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), ethyl 3-[2-fluoro-4-{({l-[2-(2-fluorophenoxy)ethyl]-l,2,3,4-tetrahydroquinolin-5-yl}methyl)[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate(610 mg) was obtained as a yellow oil. [0100] Production Example 36 4 M Hydrogen chloride dioxane solution (13 ml) was added to a dioxane (2 ml) solution of ethyl 3-{4-[{[l-(2-tert-butoxy-2-oxoethyl)-8-methyl-l,2,3,4-tetrahydroquinolin-7-yl]methyl}(trifluoroacetyl)amino]-2-fluorophenyl}propanoate (1.50 g) and stirred at room temperature for 6 hours. The solvent was evaporated under a reduced pressure and pH was adjusted to 7 by adding water and saturated sodium bicarbonate aqueous solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed, the solvent was evaporated under a reduced pressure and the residue was purified by a silica gel column chromatography (chloroform-methanol) to obtain [7-({[4-(3-ethoxy-3-oxopropyl)-3-fluorophenyl](trifluoroacetyl)amino}methyl)-8-methyl-3,4-dihydroquinolin-l(2H)-yl]acetic acid (1.40 g) as a yellow oil. [0101] Production Example 37 To a DMF (5 ml) solution of [7-({[4-(3-ethoxy-3-oxopropyl)-3-fluorophenyl](trifluoroacetyl)amino}methyl)-8-methyl-3,4-dihydroquinolin-l(2H)-yl]acetate (429 mg), morpholine (0.17 mi), 1-hydroxybenzotriazole monohydrate (138 mg) and N,N-diisopropylethylamine 0.34 ml), l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (376 mg) was added and stirred at room temperature for 3 days. Water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure to obtain ethyl 3-[2-fluoro-4-[{[8-methyl-1 -(2-morpholin-4-yl-2-oxoethyl)-1,2,3,4-tetrahydroquinolin-7-yl]methyl}(trifluoroacetyl)amino]phenyl}propanoate (356 mg) as a yellow oil. [0102] Production Example 38 Methanesulfonyl chloride (0.24 ml) was added dropwise to a mixture of ethyl 3-[2-fluoro-4-[ {[ 1 -(2-hydroxyethyl)-8-methyl-1,2,3,4-tetrahydroquinolin-7- 45 yl]methyl}(trifluoroacetyl)amino]phenyl}propanoate (1.20 g), triethylamine (0.45 ml) and ethyl acetate (15 ml) and stirred at room temperature for 3 hours. The insoluble matter was separated by filtration and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-(2-fluoro-4- {[(8-methyl-1 - {2-[(methylsulfonyl)oxy]ethyl} -1,2,3,4-tetrahydroquinoIin-7-yI)methyl](trifluoroacetyI)amino}phenyl)propanoate (1.13 g) as a colorless oil. [0103] Production Example 39 Piperidine (0.48 ml) was added to a DMF (10 ml) solution of ethyl 3-(2-fluoro-4-{[(8-methyl-1 - {2-[(methylsulfonyl)oxy]ethyl} -1,2,3,4-tetrahydroquinolin-7-yl)methyl](trifluoroacetyl)amino}phenyl)propanoate (574 mg) and potassium iodide (162 mg) and stirred at 70°C for 1 day. Water was added thereto, followed by extraction with ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (chloroform-methanol) to obtain ethyl 3- {2-fluoro-4-[ {[8-methyl-1 -(2-piperidin-1 -ylethyl)-1,2,3,4-tetrahydroquinolin-7-yl]methyl}(trifluoroacetyl)amino]phenyl}propanoate (515 mg) as a colorless oil. [0104] Production Example 40 While stirring, concentrated sulfuric acid (30 ml) was added to a mixture of 3-amino-4-chlorobenzoic acid (25.25 g), sodium 3-nitrobenzenesulfonate (37.0 g) and boric acid (9.20 g). Thereafter, glycerol (37 ml) was added thereto, and temperature of the mixture was gradually increased to around 155°C while mixing with a glass rod. Thereafter, by attaching a condenser, the reaction mixture was stirred at 160°C for 3 hours and then spontaneously cooled to room temperature. Under ice-cooling, water (200 ml) was added to the reaction mixture, sodium hydroxide (ca. 50 g) was added in small portions thereto, followed by 30 minutes of stirring as such. Next, acetic acid (50 ml) and water (100 ml) were added thereto under ice-cooling, and the thus formed solid was collected by filtration and washed with water (approximately 100 ml). Methanol (200 ml) and toluene (200 ml) were added to the thus obtained paste-like solid, followed by concentration under a reduced pressure (the same operation was repeated twice). By drying the thus obtained residue under a reduced pressure, a dark brown solid (42.78 g) was obtained. Under ice-cooling, concentrated sulfuric acid (30 ml) was slowly added to a methanol (500 ml) 46 suspension of the thus obtained dark brown solid, and the reaction mixture was stirred for 19 hours under heating reflux and then spontaneously cooled to room temperature. The reaction mixture was concentrated under a reduced pressure, and saturated sodium bicarbonate aqueous solution (700 ml) and chloroform (200 ml) were added in small portions to the thus obtained residue under ice-cooling. Sodium bicarbonate (20 g) was further added in small portions, followed by 10 minutes of stirring under ice-cooling. The mixture was filtered through celite, the insoluble matter was removed and then the filtrate was extracted with chloroform. By purifying the thus obtained residue by a silica gel column chromatography (hexane-ethyl acetate), methyl 8-chloroquinoline-5-carboxylate (22.97 g) was obtained as a pale yellow solid. [0105] Production Example 41 A mixture of (2-bromoethoxy)benzene (25.00 g), ethyl 1,2,3,4-tetrahydroquinoline-5-carboxylate (6.24 g), diisopropylethylamine (43 ml), potassium iodide (10.00 g) and DMF (60 ml) was stirred at 120°C for 21 hours. The reaction mixture was concentrated under a reduced pressure and water was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed, the solvent was evaporated under a reduced pressure, and the thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 1 -(2-phenoxyethyl)-l,2,3,4-tetrahydroquinoline-5-carboxylate (9.67 g) as a pale yellow oil. [0106] Production Example 42 A DMSO (15 ml) solution of sulfur trioxide-pyridine complex (2.57 g) was added dropwise at room temperature to a mixture of [l-(2-phenoxyethyl)-l,2,3,4-tetrahydroquinolin-5-yl]methanol (9.67 g) and DMSO (15 ml) and stirred for 10 minutes. Water (120 ml) was added to the reaction mixture, followed by extraction with diethyl ether. The organic layer was washed with water and saturated sodium chloride aqueous solution in that order and then dried with anhydrous magnesium sulfate. The desiccant was removed and then the solvent was evaporated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain l-(2-phenoxyethyl)-l,2,3,4-tetrahydroquinoline-5-carbaldehyde (1.44 g) as a yellow oil. 47 [0107] Production Example 43 (2-Bromoethoxy)benzene (2.60 g), N,N-diisopropylethylamine (4.5 ml) and potassium iodide (850 mg) were added to a DMF (20 ml) solution of methyl 8-methyl-l,2,3,4-tetrahydroquinoline-5-carboxylate (1.05 g) and the reaction mixture was stirred at 120°C for 16 hours and then spontaneously cooled to room temperature. (2-Bromoethoxy)benzene (7.80 g), N,N-diisopropylethylamine (14 ml) and potassium iodide (850 mg) were added to the reaction mixture and the reaction mixture was again stirred at 130°C for 23 hours and then spontaneously cooled to room temperature. (2-Bromoethoxy)benzene (3.90 g), N,N-diisopropylethylamine (7 ml) and potassium iodide (850 mg) were added to the reaction mixture and the reaction mixture was again stirred at 150°C for 5 hours and then spontaneously cooled to room temperature. Water (100 ml) was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain a/yellow solid (1.75 g). Lithium aluminum hydride (200 mg) was added under ice-cooling to a THF (30 ml) solution of the thus obtained yellow solid, warmed up to room temperature and then stirred for 1.5 hours. Under ice-cooling, water (1.0 ml) was slowly added dropwise to the reaction mixture and stirred for 5 minutes. After adding anhydrous sodium sulfate to the reaction mixture, celite filtration was carried out, followed by washing with THF. The filtrate was concentrated under a reduced pressure and the thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain [8-methyl-l-(2-phenoxyethyl)l,2,3,4-tetrahydroquinolin-5-yl]methanol (1.48 g) as a pale yellow syrup. [0108] Production Example 44 3 M Hydrochloric acid (5 ml) was added to a THF (3 ml) solution of 7-(dimethoxymethyl)-l-propyl-l,2,3,4-tetrahydro-l,8-naphthyridine (207 mg) and stirred at room temperature for 1.5 hours. 3 M Sodium hydroxide aqueous solution (5 ml) was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The thus obtained residue was dissolved in methanol (10 ml) and sodium 48 borohydride (16 mg) was added thereto under ice-cooling, followed by 10 minutes of stirring. Water (20 ml) was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain (8-propyl-5,6,7,8-tetrahydro-l,8-naphthyridin-2-yl)methanol (144 mg) as a yellow oil. [0109] Production Example 45 Benzoyl chloride (2.5 ml) was added under ice-cooling to a pyridine (30 ml) solution of tert-butyl 7-(hydroxymethyl)-8-methyl-3,4-dihydroquinoline-1 (2H)-carboxylate and stirred at room temperature for 12 hours. After 10 minutes of stirring by adding water, the solvent was evaporated under a reduced pressure. Water was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with 1 M hydrochloric acid, saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed, the solvent was evaporated under a reduced pressure and then the thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain tert-butyl 7-[(benzoyloxy)memyl]-8-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (3.95 g) as a pale yellow oil. [0110] Production Example 46 Toluene (13.2 ml) was added to (8-methyl-l,2,3,4-tetrahydroquinolin-7-yl)methyl benzoate (880 mg), l-bromo-2-methylbenzene (0.57 ml), palladium(II) acetate (35 mg), tri-tert-butylphosphine (0.94 ml) and sodium tert-butoxide (460 mg). This mixture was allowed to undergo the reaction at 150°C for 18 hours in a sealed tube using a microwave reactor (Biotage). The reaction mixture was spontaneously cooled down to room temperature, the insoluble matter was separated by filtration and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain (8-methyl-l-(2-methylphenyl)-l,2,3,4-tetrahydroquinolin-7-•yl)methyl benzoate (658 mg) as a pale yellow oil. 49 [0111] Production Example 47 1 M Sodium hydroxide aqueous solution (3.5 ml) was added to a methanol (6.4 ml) and THF (6.4 ml) solution of (8-methyl-l -(2-methylphenyl)-1,2,3,4-tetrahydroquinolin-7-yl)methyl benzoate (640 mg) and stirred at room temperature for 4 hours. The solvent was evaporated under a reduced pressure and then the residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain [8-methyl-l-(2-methylphenyl)-1,2,3,4-tetrahydroquinoIin-7-yl)methanoI (364 mg) as a white solid. [0112] Production Example 48 Potassium carbonate (718 mg) and 3-hydroxy-3-methylbutyl 4-methylbenzenesulfonate (1.16 g) were added to a DMF (7 ml) solution of methyl l-(4-hydroxyphenyl)-8-methyl-l,2,3,4-tetrahydroquinoline-7-carboxylate (700 mg), and the reaction mixture was stirred at 70°C for 24 hours and then spontaneously cooled down to room temperature. Water (30 ml) was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. By purifying the thus obtained residue by a silica gel column chromatography (hexane-ethyl acetate), methyl l-[4-(3-hydroxy-3-methylbutoxy)phenyl]-8-methyl-l,2,3,4-tetrahydroquinoline-7-carboxylate (935 mg) was obtained as a colorless oil. [0113] Production Example 49 Under ice-cooling, m-chloroperbenzoic acid (650 mg) was added to a chloroform (15 ml) solution of ethyl 3-{2-fluoro-4-[{[4-(2-phenoxyethyl)-3,4-dihydro-2H-l,4-benzothiazin-8-yl]methyl}(trifluoroacetyl)amino]phenyl}propanoate (472 mg), warmed up to room temperature and then stirred for 1.5 hours. 10% Sodium hydrogen sulfite aqueous solution (40 ml) was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with saturated sodium bicarbonate aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. By purifying the thus obtained residue by a silica gel column chromatography (chloroform-methanol), ethyl 3-{4-[{[l,l-dioxido-4-(2-phenoxyethyl)-3,4-dihydro-2H-l,4-benzothiazin-8-yl]methyl}(trifluoroacetyl)amino]-2-fluorophenyl}propanoate (364 mg) was obtained as a pale yellow amorphous solid. 50 [0114] The compounds of Production Examples 50 to 197 shown in the tables which are described later were produced in the same manner as in the methods of Production Examples 1 to 49. Structures, production methods and physicocherhical data of the production example compounds are shown in Tables 4 to 31. [0115] Example 1 Under ice-cooling, 1 M sodium hydroxide aqueous solution (1.21 ml) was added to a mixture of ethyl 3-(2-fluoro-4-{[l-(2-phenylethyl)-l,2,3,4-tetrahydroquinolin-7-yl]methoxy}phenyl)propanoate (186 mg), methanol (3 ml) and THF (3 ml) and stirred at room temperature for 1 hour. 10% Citric acid aqueous solution was added to the reaction solution to adjust to pH 5 to 6, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate aqueous solution and then dried with anhydrous magnesium sulfate. After removing the desiccant and evaporating the solvent under a reduced pressure, the residue was purified by a silica gel column chromatography (hexane-ethyl acetate), 1 M sodium hydroxide aqueous solution (0.26 ml) was added to a methanol (3 ml) and THF (3 ml) solution of the thus obtained colorless oil (119 mg) and the solvent was evaporated under a reduced pressure. The residue was crystallized by adding 2-propanol-diisopropyl ether to the residue, collected by filtration and then dried by heating under a reduced pressure to obtain sodium 3-(2-fluoro-4-{[l-(2-phenylethyl)-l,2,3,4-tetrahydroquinolin-7-yl]methoxy}phenyl)propanoate (95 mg) as pale yellow crystals. [0116] Example 2 1 M Sodium hydroxide aqueous solution (5 ml) was added to a methanol (3 ml) and THF (10 ml) solution of ethyl 3-{2-fluoro-4-[{[l-(4-hydroxybutyl)-8-methyl-l,2,3,4-tetrahydroquinolin-7-yl]methyl}(trifluoroacetyl)amino}propanoate (430 mg) and stirred at room temperature for 12 hours. After dropwise addition of 1 M hydrochloric acid (5 ml) and subsequent extraction with chloroform, the organic layer was dried with anhydrous magnesium sulfate. After removing the desiccant and evaporating the solvent under a reduced pressure, 4 M hydrogen chloride dioxane solution (1 ml) was added to a THF (10 ml) solution of the thus obtained yellow oil (411 mg) and the solvent was evaporated under a reduced pressure. After adding THF-diisopropyl ether to the residue, the thus formed solid was collected by filtration and dried by heating under a reduced pressure to obtain 3-[2- 51 fluoro-4-({[l-(4-hydroxybutyl)-8-methyl-l,2,3,4-tetrahydroquinolin-7-yl]methyl}amino)-phenyl]propanoic acid dihydrochloride (404 mg) as a white solid. [0117] Example 3 Under ice-cooling, lithium hydroxide monohydrate (184 mg) was added to a mixture of ethyl 3-[2-fluoro-4-([(2-phenylethyl)sulfonyl] {[1 -(2-phenylethyl)-l ,2,3,4-tetrahydroquinolin-8-yl]methyl}amino)phenyl]propanoate (707 mg), mercaptoacetic acid (0.152 ml) and DMF (10 ml) and, after rising the temperature to room temperature, stirred for 2 hours. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate), and 1 M sodium hydroxide aqueous solution (2.27 ml) was added under ice-cooling to a mixture of the thus obtained oil (349 mg), methanol (3 ml) and THF (3 ml) and stirred at room temperature for 5 hours. After evaporating the solvent under a reduced pressure, 10% citric acid aqueous solution was added to the residue to adjust to pH 5 to 6, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. After removing the desiccant and evaporating the solvent under a reduced pressure, 1 M sodium hydroxide aqueous solution (0.74 ml) was added to the residue and the solvent was evaporated under a reduced pressure. The residue was crystallized by adding ethanol to the residue, and the thus formed crystals were dissolved by heating and then spontaneously cooled to room temperature and recrystallized. By drying with heating under a reduced pressure after collection by filtration, sodium 3-[2-fluoro-4-({[l-(2-phenylethyl)-l ,2,3,4-tetrahydroquinolin-8-yl]methyl}amino)phenyl]propanoate (122 mg) was obtained as colorless crystals. [0118] Example 4 Benzyl bromide (0.53 ml) was added to a mixture of ethyl 3-(2-fluoro-4-{[(8-methyl-l,2,3,4-tetrahydroquinolin-7-yl)methyl](trifluoroacetyl)amino}phenyl)propanoate (1.00 g), diisopropylethylamine (1.12 ml) and DMF (10 ml) and stirred at 70°C for 12 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated 52 sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. After removing the desiccant and evaporating the solvent under a reduced pressure, the residue was purified by a silica gel column chromatography (hexane-ethyl acetate), and 1 M sodium hydroxide aqueous solution (5 ml) was added to a methanol (5 ml) and THF (10 ml) mixture of the thus obtained yellow oil (1.09 g), and stirred at room temperature for 12 hours. After adding 1 M hydrochloric acid (5 ml) dropwise and subsequent extraction with chloroform, the organic layer was dried with anhydrous magnesium sulfate. After removing the desiccant and evaporating the solvent under a reduced pressure, 4 M hydrogen chloride dioxane solution (1 ml) was added to a THF (10 ml) solution of the thus obtained yellow oil (1.07 g), and the solvent was evaporated under a reduced pressure. After adding THF to the residue, the thus formed solid was collected by filtration and dried by heating under a reduced pressure to obtain 3-(4-{[(l-benzyl-8-methyl-l,2,3,4-tetrahydroquinolin-7-yl)methyl]amino}-2-fluorophenyl)propanoic acid dihydrochloride (823 mg) as a white solid. [0119] Example 5 l,l'-(Azodicarbonyl)dipiperidine (741 mg) was added at room temperature to a mixture of ethyl 3 - {2-fluoro-4-[ {[ 1 -(2-hydroxyethyl)-8-methyl-1,2,3,4-tetrahydroquinolin-7-yl]methyl}(trifluoroacetyl)amino]phenyl}propanoate (1.00 g), 2-chlorophenol (504 mg), tributylphosphine (0.73 ml) and THF (10 ml) and stirred at room temperature for 2 days. After separating the insoluble matter by filtration, the solvent was evaporated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate), and 1 M sodium hydroxide aqueous solution (5.0 ml) was added under ice-cooling to a mixture of the thus obtained pale yellow oil (741 mg), methanol (5 ml) and THF (5 ml) and stirred at room temperature for 12 hours. 1 M Hydrochloric acid (5 ml) was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. After removing the desiccant and evaporating the solvent under a reduced pressure, the thus obtained residue was dissolved in THF, followed by the addition of 4 M hydrogen chloride dioxane solution (1 ml) and then diethyl ether, the thus formed solid was collected by filtration. By drying with heating under a reduced pressure, 3-{4-[({l-[2-(2-chlorophenoxy)ethyl]-8-methyl-l,2,3,4-tetrahydroquinolin-7-yl}methyl)amino]-2-fluorophenyl}propanoic acid dihydrochloride (587 mg) was obtained as a pale yellow solid. 53 [0120] Example 6 Toluene (8 ml) was added to a mixture of ethyl 3-(2-fluoro-4-{[(8-methyl-l,2,3,4-tetrahydroquinolin-7-yl)methyl](trifluoroacetyl)amino}phenyl)propanoate (500 mg), 1-bromo-4-fluorobenzene (0.15 ml), tris(dibenzylideneacetone)dipalladium (49 mg), dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (51 mg) and potassium phosphate (910 mg). This mixture was allowed to undergo the reaction at 170°C for 60 minutes in a sealed tube using a microwave reactor (Biotage). The reaction mixture was spontaneously cooled down to room temperature, the insoluble matter was separated by filtration and the filtrate was evaporated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate), and 1 M sodium hydroxide aqueous solution (3.0 ml) was added to a THF (3 ml)-ethanol (3 ml) solution of the thus obtained pale yellow syrup (241 mg) and the reaction mixture was stirred at room temperature for 15 hours. 1 M Hydrochloric acid (3.0 ml) and water (10 ml) were added to the reaction mixture, followed by extraction with chloroform. After drying the organic layer with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure. The thus obtained residue was dissolved in THF and 4M hydrogen chloride dioxane solution was added thereto, followed by concentration under a reduced pressure. The thus obtained residue was solidified with diethyl ether, collected by filtration and then dried with heating under a reduced pressure to obtain 3-[2-fiuoro-4-({[ 1 -(4-fluorophenyl)-8-methyl-1,2,3,4-tetrahydroquinolin-7- ylJmethyl}amino)phenylJpropanoic acid hydrochloride (172 mg) as a pale yellow solid. [0121] Example 7 Acetic anhydride (0.06 ml) was added to a pyridine (2 ml) solution of isopropyl {6-[(l,2,3,4-tetrahydroquinolin-8-ylmethyl)(trifluoroacetyl)amino]2,3-dihydro-l-benzofuran-3-yl} acetate, and the reaction mixture was stirred at room temperature for 2 days. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried with anhydrous magnesium sulfate, and then the desiccant was removed and the solvent was evaporated under a reduced pressure to obtain a pale yellow syrup (229 mg). The thus obtained pale yellow syrup (229 mg) was dissolved in THF (2 ml)-ethanol (2 ml), 1 M sodium hydroxide aqueous solution (3.0 ml) was added thereto and the reaction mixture was stirred at room temperature for 2 days. To the reaction mixture 54 were added 1 M hydrochloric acid (3.0 ml) and water (20 ml), followed by extraction with chloroform. After drying the organic layer with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol), and 1 M sodium hydroxide aqueous solution (0.39 ml) was added to a THF (5 ml)-methanol (5 ml) solution of the thus obtained pale yellow syrup (145 mg), followed by concentration under a reduced pressure. The thus obtained residue was crystallized with 2-propanol-diethyl ether, collected by filtration and then dried with heating under a reduced pressure to obtain sodium (6-{[(l-acetyl-l,2,3,4-tetrahydroquinolin-8-yl)methyl]amino}2,3-dihydro-l-benzofuran-3-yl)acetate (104 mg) as slightly yellow crystals. [0122] Example 8 Under ice-cooling, sodium borohydride (70 mg) was added to a THF (5 ml)-ethanol (5 ml) solution of ethyl 3-{2-fluoro-4-[{[8-methyl-l-(2-oxo-2-phenylethyl)-l,2,3,4-tetrahydroquinolin-7-yl]methyl}(trifluoroacetyl)amino]phenyl}propanoate, and the reaction mixture was warmed up to room temperature and stirred for 2 hours. Under ice-cooling, 1 M hydrochloric acid (10 ml) was added to the reaction mixture and stirred for 5 minutes. Thereafter, saturated sodium bicarbonate aqueous solution (20 ml) was added thereto, followed by extraction with chloroform. After drying the organic layer with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure to obtain a yellowish brown syrup (501 mg). 1 M Sodium hydroxide aqueous solution (3.0 ml) was added to a THF (5 ml)-elhanol (5 ml) solution of the thus obtained yellowish brown syrup (501 mg) and the reaction mixture was stirred at room temperature for 3 hours. 1 M Hydrochloric acid (3.0 ml) and water (20 ml) were added to the reaction mixture, followed by extraction with chloroform. After drying the organic layer with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure. The thus obtained residue was dissolved in THF (15 ml) and 4 M hydrogen chloride dioxane solution (2 ml) was added thereto, followed by concentration under a reduced pressure. Diethyl ether (20 ml) was added to the thus obtained residue and the resulting solid was collected by filtration, washed with diethyl ether and then dried with heating under a reduced pressure to obtain 3-[2-fluoro-4-({[l-(2-hydroxy-2-phenylethyl)-8-methyl-1,2,3,4-tetrahydroquinolin-7-yl]methyl}amino)phenyl]propanoic acid dihydrochloride (437 mg). 55 [0123] Example 9 DMF (15 ml) was added to ethyl 3-(2-fluoro-4-{[(8-methyl-l,2,3,4-tetrahydroquinolin-7-yl)methyl](trifluoroacetyl)amino}phenyl)propanoate (1.00 g), 4-(2-chloroethyl)morpholine hydrochloride (1.99 g), potassium phosphate (4.55 g) and potassium iodide (711 mg). This mixture was allowed to undergo the reaction at 175°C for 60 minutes in a sealed tube using a microwave reactor (Biotage). Water was added to the reaction mixture, followed by extraction with ethyl acetate. After washing the organic layer with saturated sodium chloride aqueous solution, the organic layer was dried anhydrous magnesium sulfate. The desiccant was removed, the solvent was evaporated under a reduced pressure and then the residue was purified by a silica gel column chromatography (hexane-ethyl acetate), and 1 M sodium hydroxide aqueous solution (5 ml) was added to a methanol (5 ml) and THF (10 ml) mixture of the thus obtained yellow oil (220 mg) and stirred at room temperature for 12 hours. After dropwise addition of 1 M hydrochloric acid (5 ml) and subsequent extraction with chloroform, the organic layer was dried with anhydrous magnesium sulfate. The desiccant was removed, the solvent was evaporated under a reduced pressure and then 4 M hydrogen chloride dioxane solution (1 ml) was added to a THF (10 ml) solution of the thus obtained yellow oil (170 mg) and the solvent was evaporated under a reduced pressure. THF-diisopropyl ether was added to the thus formed solid was collected by filtration and then dried with heating under a reduced pressure to obtain 3-[2-fluoro-4-({[8-methyl-l-(2-morpholin-4-ylethyl)-l,2,3,4-tetrahydroquinoiin-7-yljmethyl)amino)phenyi]propanoic acid irihydrochloride (183 mg) as a white solid. [0124] Example 10 Sodium triacetoxyborohydride (490 mg) was added at room temperature to a mixture of methyl rel-(lR,2R)-2-{4-[(l,2,3,4-tetrahydroquinolin-8-ylmethyl)(trifluoroacetyl)amino]phenyl} cyclopropanecarboxylate (333 mg), phenylacetaldehyde (0.30 ml), acetic acid (2 drops) and dichloromethane (3 ml) and stirred at room temperature for 6 hours. Phenylacetaldehyde (0.30 ml) was added to the reaction mixture and further stirred at room temperature for 12 hours. After cooling the reaction mixture with ice, methanol (1.0 ml) and sodium borohydride (87 mg) were added thereto and stirred under ice-cooling for 3 hours to consume excess amount of phenylacetaldehyde. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed 56 by extraction with ethyl acetate. After washing the organic layer with saturated sodium chloride aqueous solution, the organic layer was dried anhydrous magnesium sulfate. The desiccant was removed, the solvent was evaporated under a reduced pressure and then the residue was purified by a silica gel column chromatography (hexane-ethyl acetate), and 1 M sodium hydroxide aqueous solution (4.7 ml) was added under ice-cooling to a mixture of the thus obtained colorless oil (506 mg), methanol (5 ml) and THF (5 ml) and stirred at room temperature for 3 hours. The solvent was evaporated under a reduced pressure and then 10% citric acid aqueous solution was added to the residue to adjust to pH 5 to 6. After extraction with ethyl acetate and subsequent washing of the organic layer with saturated sodium chloride aqueous solution, the organic layer was dried anhydrous magnesium sulfate. The desiccant was removed, the solvent was evaporated under a reduced pressure and then the residue was purified by a silica gel column chromatography (hexane-ethyl acetate), and the thus obtained oil was purified by a fractional HPLC (Kanto Kagaku, Mightysil RP-18 GP (20 x 250 mm, 5 um)) to obtain an oil. The thus obtained oil was dissolved in acetonitrile, and the solid formed by adding water was collected by filtration and then dried with heating under a reduced pressure to obtain rel-(lR,2R)-2-[4-({[l-(2-phenylethyl)-l,2,3,4-tetrahydroquinolin-8-yl]methyl}amino)phenyl]cyclopropanecarboxylic acid (35 mg) as a pale yellow solid. [0125] Example 11 Titanium(IV) isopropoxide (0.91 ml) was added to a dichloromethane (8 ml) solution of 4-benzyl-3,4-dihydro-2H-l,4-benzoxazine-6-amine (370 ml) and ethyl 3-(2-fluoro-4-formylphenyl)propanoate (356 mg) and stirred at room temperature for 15 hours. Ethanol (8 ml) was added under ice cooling to the reaction mixture, followed by the addition of sodium borohydride (90 mg), and stirred as such for 1 hour. Under ice-cooling, 1 M hydrochloric acid (10 ml) was added dropwise to the reaction mixture and stirred at room temperature for 1 hour. The liquid property was adjusted to pH 9 to 10 with saturated sodium bicarbonate aqueous solution, and the precipitate was removed by celite filtration. The filtrate was extracted with chloroform, the organic layer was dried with anhydrous magnesium sulfate, and then the desiccant was removed and the solvent was evaporated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain a yellow syrup (371 mg). 1 M Sodium hydroxide aqueous solution (4.0 ml) was added to a THF (6 ml)-ethanol (6 ml) solution of the thus obtained yellow syrup (371 mg) and stirred at room temperature for 12 hours. The 57 reaction mixture was mixed with 1 M hydrochloric acid (4.0 ml) and water (20 ml) and extracted with chloroform. After drying the organic layer with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol), and the thus obtained light yellow amorphous solid (344 mg) was dissolved in THF (5 ml)-ethanol (5 ml) and, after adding 1 M sodium hydroxide aqueous solution (0.80 ml), concentrated under a reduced pressure. By solidifying the thus obtained residue with water-2-propanol-diethyl ether, sodium 3-(4-{[(4-benzyl-3,4-dihydro-2H-l,4-bensoxazin-6-yl)amino]methyl}2-fluorophenyl)propanoate (316 mg) was obtained as a light yellow solid. [0126] Example 12 Cyclopropanecarbonyl chloride (0.06 ml) was added to a pyridine (2 ml) solution of isopropyl {6-[(l,2,3,4-tetrahydroquinolin-8-ylmethyl)(trifluoroacetyl)amino]-2,3-dihydro-l-benzofuran-3-yl} acetate (200 mg), and the reaction mixture was stirred at room temperature for 2 days. Saturated sodium bicarbonate aqueous solution (20 ml) was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried with anhydrous magnesium sulfate, and then the desiccant was removed and the solvent was evaporated under a reduced pressure to obtain a light yellow syrup (241 mg). The thus obtained light yellow syrup (241 mg) was dissolved in THF (2 ml)-ethanol (2 ml), 1 M sodium hydroxide aqueous solution (3.0 ml) was added thereto, and the reaction mixture was stirred at room temperature for 2 days. The reaction mixture was mixed with 1 M hydrochloric acid (3.0 ml) and water (20 ml) and extracted with chloroform. After drying the organic layer with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol), and the thus obtained light yellow amorphous solid (171 mg) was dissolved in THF (5 ml)-methanol (5 ml) and, after adding 1 M sodium hydroxide aqueous solution (0.42 ml), concentrated under a reduced pressure. The thus obtained residue was crystallized from 2-propanol-diethyl ether, collected by filtration and then dried with heating under a reduced pressure to obtain sodium [6-({ [1 -(cyclopropylcarbonyl)-l,2,3,4-tetrahydroquinolin-8-yl]methyl}amino)-2,3-dihydro-l-benzofuran-3-yl]acetate (158 mg) as light yellow crystals. 58 [0127] Example 13 Benzenesulfonyl chloride (0.09 ml) was added to a pyridine (2 ml) solution of isopropyl {6-[(l ,2,3,4-tetrahydroquinolin-8-ylmethyl)(trifluoroacetyl)amino]-2,3-dihydro-1 -benzofuran-3-yl}acetate (200 mg), and the reaction mixture was stirred at room temperature for 2 days. Saturated sodium bicarbonate aqueous solution (20 ml) was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried with anhydrous magnesium sulfate, and then the desiccant was removed and the solvent was evaporated under a reduced pressure to obtain a light yellow syrup (243 mg). The thus obtained light yellow syrup (243 mg) was dissolved in THF (2 ml)-ethanol (2 ml), 1 M sodium hydroxide aqueous solution (3.0 ml) was added thereto, and the reaction mixture was stirred at room temperature for 2 days. The reaction mixture was mixed with 1 M hydrochloric acid (3.0 ml) and water (20 ml) and extracted with chloroform. After drying the organic layer with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure. The thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol), and the thus obtained light yellow amorphous solid (193 mg) was dissolved in THF (5 ml)- methanol (5 ml) and, after adding 1 M sodium hydroxide aqueous solution (0.41 ml), concentrated under a reduced pressure. The thus obtained residue was solidified with 2-propanol-diethyl ether, collected by filtration and then dried with heating under a reduced pressure to obtain sodium [6-({[l-(phenylsulfonyl)-i ,2,3,4-tetrahydroquinoiin-8-yl]melhy 1}amino)-2,3-dihydro-1 -benzofuran-3-yl]acetate (165 mg) as a light yellow solid. [0128] Example 14 Under ice-cooling, sodium triacetoxyborohydride (440 mg) was added to a mixture of ethyl 3-[2-fluoro-4-((l ,2,3,4-tetrahydroquinolin-8-ylmethoxy)phenyl)propanoate (250 mg), phenylacetaldehyde (840 mg), acetic acid (2 drops) and dichloroethane (5 ml) and stirred at room temperature for 5 hours. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate), and 1 M sodium hydroxide aqueous solution was added at room 59 temperature to a methanol (3 ml) solution of the thus obtained oil (310 mg) and stirred at room temperature for 3 hours. The reaction solution was adjusted to pH 5 to 6 by adding 10% citric acid aqueous solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain a colorless oil (96 mg). 1 M Sodium hydroxide aqueous solution (0.22 ml) was added to an ethanol solution (2 ml) of the thus obtained colorless oil, and the solvent was evaporated under a reduced pressure. Diethyl ether was added to the residue, and the thus formed solid was collected by filtration and dried with heating under a reduced pressure to obtain sodium 3-(2-fluoro-4-{[l-(2-phenylethyl)-l,2,3,4-tetrahydroquinolin-8-yl]methoxy}phenyl)propanoate (66 mg) as a light yellow amorphous solid. [0129] Example 15 Ethyl 3-{4-[(l,2,3,4-tetrahydroquinolin-8-yloxy)methyl]phenyl}propanoate (14 mg) was dissolved in a dichloroethane-acetic acid mixed solution (1 ml, 9:1 (v/v)), added to N-(4-formylphenyl)acetamide (13 ml) and stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (25 mg) was added to the solution and stirred at room temperature for 3 days. Thereafter, the solvent was evaporated under a reduced pressure and an extraction operation was carried out by adding saturated sodium bicarbonate aqueous solution and chloroform. The organic layer was concentrated, and the residue was dissolved in ethanol (1 ml) and stirred at 60°C for 18 hours by adding 1 M sodium hydroxide aqueous solution (0.16 ml). After spontaneous cooling, 1 M hydrochloric acid (0.16 ml) was added thereto and stirred at room temperature for 10 minutes, followed by concentration. By purifying the residue by a fractional HPLC (Waters, SunFire Prep C18OBD (19 x 100 mm, 5 urn)), 3-[4-({[l-(4-acetamidobenzyl)-l,2,3,4-tetrahydroquinolin-8-yl]oxy}methyl)phenyl]propanoic acid (2.8 mg) was obtained. [0130] Example 16 2-Chlorobenzoic acid (13 mg) was dissolved in dichloroethane (0.5 ml), mixed with oxalyl chloride (9 ul) and DMF-dichloroethane mixed solution (5 ul, 1:1 (v/v)) and stirred at room temperature for 30 minutes. Thereafter, ethyl 3-[4-(2,3-dihydro-lH-indol-7-ylmethoxy)-2-fluorophenyl]propanoate (14 mg) was dissolved in dichloroethane (0.3 ml) 60 and added thereto together with triethylamine (0.025 ml) and stirred at 40°C for 18 hours. After spontaneous cooling to room temperature, an extraction operation was carried out by adding saturated sodium bicarbonate aqueous solution and chloroform to the solution. The organic layer was concentrated, and the residue was dissolved in ethanol (1 ml), mixed with 1 M sodium hydroxide aqueous solution (0.2 ml) and stirred at room temperature for 3 hours and then at 45°C for 18 hours. After spontaneous cooling, 1 M hydrochloric acid (0.2 ml) was added thereto and stirred at room temperature for 10 minutes, followed by concentration. By purifying the residue by a fractional HPLC (Waters, SunFire Prep C,8OBD (19 x 100 mm, 5 urn)), 3-(4-{[l-(2-chlorobenzoyl)-2,3-dihydro-lH-indol-7-yl]methoxy}-2-fluorophenyl)propanoic acid (8.8 mg) was obtained. [0131] Example 17 Ethyl 3-{4-[(l,2,3,4-tetrahydroquinolin-8-yloxy)methyl]phenyl}propanoate (14 mg) was dissolved in DMF (0.5 ml) and added to l-(bromomethyl)-2-fluorobenzene (23 mg), further added to N,N-diisopropylethylamine (0.042 ml) and stirred at 60°C for 18 hours. After spontaneous cooling, an extraction operation was carried out by adding saturated sodium bicarbonate aqueous solution and chloroform to the solution. The organic layer was concentrated, and the residue was dissolved in ethanol (1 ml), mixed with 1 M sodium hydroxide aqueous solution (0.2 ml) and stirred at 50°C for 18 hours. After spontaneous cooling, 1 M hydrochloric acid (0.2 ml) was added thereto and stirred at room temperature for 10 minutes, followed by concentration. By purifying the residue by a fractional HPLC (Waters, Sunf ire Prep QgOBD (19 x 100 mm, 5 urn)), 3-[4-({[l-(2-fIuorobeuzyl)-l,2,3,4-tetrahydroquinolin-8-yl]oxy}methyl)phenyl]propanoic acid (10.9 mg) was obtained. [0132] Example 18 Ethyl 3-[4-(2,3-dihydro-lH-indol-7-ylmethoxy)-2-fluorophenyl]propanoate (14 mg) was dissolved in pyridine (0.5 ml), added to 3-methylbenzenesulfonyl chloride (15 mg) and stirred at room temperature for 4 days. Thereafter, an extraction operation was carried out by adding saturated sodium bicarbonate aqueous solution and chloroform to the solution. The organic layer was concentrated, and the residue was dissolved in ethanol (1 ml), mixed with 1 M sodium hydroxide aqueous solution (0.2 ml) and stirred at 50°C for 18 hours. After spontaneous cooling, 1 M hydrochloric acid (0.2 ml) was added thereto and stirred at room temperature for 10 minutes, followed by concentration. By purifying the residue by a fractional HPLC (Waters, SunFire Prep CigOBD (19 x 100 mm, 5 urn)), 3-[2-fluoro-4-({l- 61 [(3-methylphenyl)sulfonyl]-2,3-dihydro-lH-indol-7-yl}methoxyphenyl)propanoic acid (8.4 mg) was obtained. [0133] Example 19 l,l'-(Azodicarbonyl)dipiperidine (0.43 g) was added under ice-cooling to a mixture of l-(2-phenylethyl)-l,2,3,4-tetrahydroquinolin-8-ol (0.44 g), ethyl 3-[2-fluoro-4-(hydroxymethyl)phenyl]propanoate (0.30 g), tributylphosphine (0.43 ml) and THF (3.0 ml) and stirred at room temperature for 2 days. After separation of the insoluble matter by filtration, the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), ethyl 3-[2-fluoro-4-({[l-(2-phenylethyl)-l,2,3,4-tetrahydroquinolin-8-yl]oxy}methyl)phenyl]propanoate (0.16 g) was obtained as a colorless oil. [0134] Example 20 l,r-(Azodicarbonyl)dipiperidine (0.43 g) was added under ice-cooling to a mixture of tert-butyl 5-(hydroxymethyl)-3,4-dihydroquinoline-l(2H)-carboxylate (0.930 g), ethyl 3-(2-fluoro-4-hydroxyphenyl) propanoate (1.12 g), tributylphosphine (1.31 ml) and THF (9.0 ml) and stirred at room temperature for 12 hours. After separation of the insoluble matter by filtration, the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), tert-butyl 5-{[4-(3-ethoxy-3-oxopropyl)-3-fluorophenoxy]methyl}-3,4-dihydroquinoline-l(2H)-carboxylate (1.08 g) was obtained as a colorless oil. [0135] Example 21 Acetic acid (0.14 ml) was added to a dichloroethane (5 ml) solution of tert-butyl 7-formyl-8-methyl-3,4-dihydroquinoline-l(2H)-carboxylate (480 mg) and ethyl 3-(4-amino-2-fluorophenyl)propanoate (368 mg) and stirred at room temperature for 5 hours. Sodium triacetoxyborohydride (480 mg) was added to the reaction mixture and stirred at room temperature for 30 minutes. By adding ethyl acetate, washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueous solution. After drying the organic layer with anhydrous magnesium sulfate, the desiccant was removed and the solvent was evaporated under a reduced pressure. By purifying the residue by a silica gel column chromatography (hexane-ethyl acetate), tert-butyl 7-({[4-(3-ethoxy-3-oxopropyl)-3- 62 fluorophenyI]amino}methyl)-8-methyl-3,4-dihydroquinoline-l(2H)-carboxylate(740mg) was obtained as a colorless oil. [0136] Example 22 Titanium(IV) isopropoxide (2.50 ml) was added to a dichloroethane (25 ml) solution of methyl (6-amino-2,3-dihydro-l-benzofuran-3-yl)acetate (1.468 g) and tert-butyl 8-formyl-3,4-dihydroquinoline-l(2H)-carboxylate (1.85 g) and stirred at room temperature for 5 hours. Sodium triacetoxyborohydride (480 mg) was added to the reaction mixture, and the reaction mixture was stirred at room temperature for 3 days. Under ice-cooling, ethanol (25 ml) was added to the reaction mixture and then sodium borohydride (270 mg) was added thereto, and stirred as such for 1 hour. Under ice-cooling, 10% citric acid aqueous solution (20 ml) was added to the reaction mixture and, after warming up to room temperature, stirred for 15 minutes. Thereafter, the liquid property was adjusted to pH 9 to 10 by adding saturated sodium bicarbonate aqueous solution and the precipitate was removed by celite filtration. The filtrate was extracted with ethyl acetate and the organic layer was dried with anhydrous magnesium sulfate. After removing the desiccant, the solvent was evaporated under a reduced pressure and the thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain isopropyl [6-({[l-(tert-butoxycarbonyl)-l,2,3,4-tetrahydroquinolin-8-yl]methyl}amino)-2,3-dihydro-l-benzofuran-3-yl]acetate as a colorless amorphous solid. [0137] Example 23 Sodium triacetoxyborohydride (1.20 g) and acetic acid (0.19 ml) were added at room temperature to a mixture of ethyl 3-(2-fluoro-4-{[(l-propyl-l,2,3,4-tetrahydroquinolin-8-yl)amino]methyl}phenyl)propanoate (0.45 g), 37% formaldehyde aqueous solution (0.91 g) and dichloroethane (4.5 ml) and stirred at room temperature for 1 hour. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-(2-fluoro-4-{[methyl(l-propyl-l,2,3,4-tetrahydroquinolin-8-yl)amino]methyl}phenyl)propanoate (0.38 g) as a colorless oil. 63 [0138] Example 24 Under ice-cooling on an ice-methanol bath, sodium borohydride (0.41 g) was added to a mixture of methyl (2E)-3-{4-[(quinolin-8-yloxy)methyl]phenyl}acrylate (1.16 g), nickel(II) hexahydrate (0.26 g) and methanol (20 ml) and stirred under ice-cooling for 1.5 hours. 10% Citric acid aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain methyl 3-{4-[(l,2,3,4-tetrahydroquinolin-8-yloxy)methyl]phenyl}propanoate (0.82 g) as a colorless oil. [0139] Example 25 Under ice-cooling on an ice-methanol bath, sodium borohydride (210 mg) was added to a mixture of ethyl 3-[2-fluoro-4-(quinolin-7-ylmethoxy)phenyl]propanoate (320 mg), nickel(II) hexahydrate (65 mg) and methanol (5 ml) and stirred under ice-cooling for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-[2-fluoro-4-(l,2,3,4-tetrahydroquinoiin-7-ylmethoxy) phenyl]propanoate (170 mg) as a colorless oil. [0140] Example 26 Under ice-cooling on an ice-methanol bath, sodium borohydride (110 mg) was added to a mixture of ethyl (2E)-3-(2-fluoro-4-{[(l-propyl-l,2,3,4-tetrahydroquinolin-8-yl)amino]methyl}phenyl)acrylate (980 mg), nickel(II) hexahydrate (180 mg), methanol (10 ml) and THF (10 ml) and stirred under ice-cooling for 5 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column'chromatography (hexane-ethyl acetate) to obtain ethyl 3-(2-fluoro-4-{[(l-propyl-l,2,3,4-tetrahydroquinolin-8-yl)arnino]methyl}phenyl)propanoate (900 mg) as a colorless oil. 64 [0141] Example 27 Under ice-cooling, 4 M hydrogen chloride dioxane solution (15 ml) was added to a THF (15 ml) solution of tert-butyl 8-{[4-(3-ethoxy-3-oxopropyl)-3-fluorophenoxy]methyl}-3,4-dihydroquinolin-l(2H)-yl]carboxylate (3.2 g) and stirred at room temperature for 4 hours. The solvent was evaporated under a reduced pressure and then saturated sodium bicarbonate aqueous solution was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-[2-fluoro-4-(l,2,3,4-tetrahydroquinolin-8-ylmethoxy)phenyl]propanoate (1.8 g) as a colorless oil. [0142] Example 28 Under ice-cooling, sodium triacetoxyborohydride (1.6 g) was added to a mixture of methyl 3-{4-[(l,2,3,4-tetrahydroquinolin-8-yloxy)methyl]phenyl}propanoate (0.82 g), benzaldehyde (0.38 ml), acetic acid (0.43 ml) and dichloroethane (10 ml) and stirred at room temperature for 9 hours. Benzaldehyde (0.38 ml) and sodium triacetoxyborohydride (0.80 g) were added to the reaction mixture and stirred at room temperature for 12 hours. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated sodium chloride aqueous solution in thai order and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain methyl 3-(4-{[(l-benzyl-l,2,3,4-tetrahydroquinolin-8-yl)oxy]methyl}phenyl)propanoate (0.82 g) as a colorless amorphous solid. [0143] Example 29 4 M Hydrogen chloride dioxane solution (15 ml) was added at room temperature to ethyl 3-(4-{(tert-butoxycarbonyl)[(l -methyl-1,2,3,4-tetrahydroquinolin-7-yl)methyl]amino} -2-fluorophenyl)propanoate (648 mg) and stirred for 30 minutes. The solvent was evaporated under a reduced pressure and saturated sodium bicarbonate aqueous solution was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium 65 sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure to obtain ethyl 3-(2-fluoro-4-{[(l-methyl-l,2,3,4-tetrahydroquinolin-7-yl)methyl]amino}phenyl)propanoate (496 mg) as a brown oil. [0144] Example 30 A mixture of ethyl 3-{2-fluoro-4-[(l,2,3,4-tetrahydroquinolin-8-yioxy)methyi]phenyi}propanoate (400 mg), i-(bromomethyi)-4-methoxybenzene (680 mg), N,N-diisopropylethylamine (0.58 ml) and DMF (4 ml) was stirred at 80°C for 12 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-[2-fluoro-4-({[l-(4-methoxybenzyl)-l,2,3,4-tetrahydroquinolin-8-yl]oxy}methyl)phenyl]propanoate (240 mg) as a colorless oil. [0145] Example 31 Benzoyl chloride (0.13 ml) was added at room temperature to a pyridine (2 ml) solution of ethyl 3-[2-fluoro-4-(l,2,3,4-tetrahydroquinolin-8-ylmethoxy)phenyl]propanoate (200 mg) and stirred at room temperature for 3 hours. After evaporation of the solvent under a reduced pressure, 10% citric acid aqueous solution was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-{4-[(l-benzoyl-l,2,3,4-tetrahydroquinolin-8-yl)methoxy]-2-fluorophenyl}propanoate (220 mg) as a light yellow oil. [0146] Example 32 Benzenesulfonyl chloride (0.14 ml) was added at room temperature to a pyridine (2 ml) solution of ethyl 3-[2-fiuoro-4-(l,2,3,4-tetrahydroquinolin-8-ylmethoxy)phenyl}propanoate (200 mg) and stirred at room temperature for 12 hours. After evaporation of the solvent under a reduced pressure, 10% citric acid aqueous solution was added to the residue, followed by extraction with ethyl acetate. The organic layer was 66 washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-(2-fluoro-4-{[l-(phenylsulfonyl)-l,2,3,4-tetrahydroquinolin-8-yl]methoxy}phenyl]propanoate (230 mg) as a colorless oil. [0147] Example 33 Acetic anhydride (0.254 ml) was added at room temperature to a pyridine (5 ml) solution of ethyl 3-(2-fluoro-4- {[(1 -propyl-1,2,3,4-tetrahydroquinolin-8-yl)amino]methyl}phenyl)propanoate (450 mg) and stirred at room temperature for 3 days. 10% Citric acid aqueous solution was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution in that order and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-(4-{[acetyl(l-propyl-l,2,3,4-tetrahydroquinolin-8-yl)amino]methyl}-2-fluorophenyl)propanoate (430 mg) as a colorless oil. [0148] Example 34 A mixture of ethyl 3-[2-fluoro-4-(l,2,3,4-tetrahydroquinolin-8-ylmethoxy)phenyl]propanoate (380 mg), triphenylbismulhine (520 mg), copper(II) acetate (140 mg) and dichloroethane (3 ml) was stirred at 100°C for 12 hours. After removing the insoluble matter by celite filtration, the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-{2-fluoro-4-[(l-phenyl-l,2,3,4-tetrahydroquinolin-8-yl)methyl]phenyl}propanoate (120 mg) as a light yellow oil. [0149] Example 35 In an atmosphere of hydrogen, a mixture of ethyl 3-[2-fluoro-4-({[l-(2-methoxy-2-phenylvinyl)-l ,2,3,4-tetrahydroquinolin-5-yl]methyl}amino)phenyl]propanoate (200 mg), 10% palladium-activated carbon (44 mg), ethanol (1.5 ml) and THF (1.5 ml) was stirred at room temperature for 6 hours. After removing the insoluble matter by celite filtration, the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-[2-fluoro-4-({[l-(2- 67 methoxy-2-phenylethyl)-1,2,3,4-tetrahydroquinolin-5-yl]methyl} amino)phenyl]propanoate (130 mg) as a light yellow oil. [0150] Example 36 1 M Sodium hydroxide aqueous solution (9.0 ml) was added to a THF (10 ml) and ethanol (10 ml) solution of diethyl methyl[4-({[l-(2-phenylethyl)-l,2,3,4-tetrahydroquinoiin-5-yi]methyl}amino)benzyi]malonate (955 mg) and stirred at room temperature for 15 hours. 1 M Hydrochloric acid (9.0 ml) and water (30 ml) were added to the reaction mixture, followed by extraction with chloroform, and the organic layer was dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure The thus obtained residue was dissolved in THF (10 ml) and ethanol (10 ml), mixed with 5 M sodium hydroxide aqueous solution (5.0 ml), stirred at 70°C for 8 hours and then spontaneously cooled to room temperature. 1 M Hydrochloric acid (25 ml) and water (30 ml) were added to the reaction mixture, followed by extraction with chloroform, and the organic layer was dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure The thus obtained residue was dissolved in dioxane (20 ml) and stirred at 120°C for 2 hours. The reaction mixture was stirred at 130°C for 17 hours and then spontaneously cooled to room temperature. The reaction mixture was concentrated under a reduced pressure, and the thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol) to obtain a brown solid (454 mg). The thus obtained brown solid was dissolved in THF (10 ml) and ethanol (10 ml) and 1 M sodium hydroxide aqueous solution (1.02 ml) was added thereto, followed by concentration under a reduced pressure. Diethyl ether (15 ml) was added to the thus obtained residue and stirred for 1 hour. The solid was collected by filtration, washed with diethyl ether and then dried at 60°C under a reduced pressure to obtain sodium 2-methyl-3-[4-({[l-(2-phenoxyethyl)-l,2,3,4-tetrahydroquinolin-5-yl]methyl}amino)phenyl]propanoate (400 mg) as a light brown solid. [0151] Example 37 3 M Hydrochloric acid (5 ml) was added to a THF (10 ml) solution of 7-(dimethoxymethyl)-l-(4-fluorophenyl)-l,2,3,4-tetrahydro-l,8-naphthyridine (665 mg) and stirred at room temperature for 2 hours. 3 M Sodium hydroxide aqueous solution (5 ml) was added to the reaction mixture, followed by extraction with ethyl acetate, and the organic layer was dried with anhydrous magnesium sulfate. The desiccant was removed and the 68 solvent was evaporated under a reduced pressure The thus obtained residue was dissolved in dichloroethane (10 ml), mixed with ethyl 3-(4-amino-2-fluorophenyI)propanoate (465 mg), acetic acid (0.18 ml) and sodium triacetoxyborohydride (606 mg) and stirred at room temperature for 30 minutes. Saturated sodium bicarbonate aqueous solution (30 ml) was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-[2-fluoro-4-({[8-(4-fluorophenyl)-5,6,7,8-tetrahydro-l,8-naphthyridin-2-yl]methyl}amino)phenyl]propanoate (735 mg) as a yellow solid. [0152] Example 38 Tributylphosphine (3.10 ml) and 1,1 '-(azodicarbonyl)dipiperidine (3.13 g) were added to a THF (20 ml) solution of [8-methyl-l-(2-phenoxyethyl)-1,2,3,4-tetrahydroquinolin-5-yl]methanol (1.48 g) and ethyl 3-(2-fluoro-4-{[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (2.17 g), and the reaction mixture was stirred at room temperature for 2 days. The precipitate was separated by filtration and washed with THF, and the filtrate was mixed with silica gel (10 g) and concentrated under a reduced pressure. By purifying the thus obtained carrier by a basic silica gel (Fuji Silysia Chemical) column chromatography (hexane-ethyl acetate), a yellow syrup (4.79 g) was obtained. Under ice-cooling, mercaptoacetic acid (1.05 ml) and lithium hydroxide monohydrate (1.25 rr\ Ivor** IAAPA to o F>M"F ex^ xviW onlii+irm of tVip tVmc; obtained v*llow SVTUT3 and after warming up to room temperature, stirred for 2 hours. Saturated sodium bicarbonate aqueous solution (50 ml) and water (50 ml) were added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure By purifying the thus obtained residue by a basic silica gel (Fuji Silysia Chemical) column chromatography (hexane-ethyl acetate), a light yellow syrup (2.24 g) was obtained. By further purifying the thus obtained light yellow syrup by an ODS column chromatography (acetonitrile-water), ethyl 3-[2-fluoro-4-({[8-methyl-l-(2-phenoxyethyl)-l,2,3,4-tetrahydroquinolin-5-yl]methyl}amino)phenyl]propanoate (1.32 g) was obtained as a colorless solid. 69 [0153] Example 39 Tributylphosphine (0.45 ml) and l,l'-(azodicarbonyl)dipiperidine (3.13 460 mg) were added to a THF (20 ml) solution of [l-(2-phenoxyethyl)-l,2,3,4-tetrahydroquinolin-5-yl]methanol (400 mg) and ethyl 3-(2-fluoro-4-hydroxyphenyl)propanoate (450 mg), and the reaction mixture was stirred at room temperature for 12 hours. The precipitate was separated by filtration and then the solvent was evaporated under a reduced pressure. By purifying the thus obtained residue by a silica gel column chromatography (hexane-ethyl acetate), a white solid (393 mg) was obtained. 1 M Sodium hydroxide aqueous solution (3.0 ml) was added to a mixture of the thus obtained white solid, ethanol (5 ml) and THF (5 ml) and stirred at room temperature for 20 hours. 1 M Hydrochloric acid (3.0 ml) was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. 1 M Sodium hydroxide aqueous solution (0.823 ml) was added to a THF (5 ml) solution of the thus obtained residue and the solvent was evaporated under a reduced pressure. Diethyl ether was added to the thus obtained residue and the thus formed solid A was collected by filtration. By drying with heating under a reduced pressure, sodium 3-(2-fluoro-4- {[ 1 -(2-phenoxyethyl)-1,2,3,4-tetrahydroquinolin-5 -yl]methoxy }phenyl)propanoate (328 mg) was obtained as a white solid. [0154] Example 40 Under ice-cooling, lithium hydroxide monohydrate (150 mg) was added to a mixture of ethyl 3-[2-fluoro-4-([(2-nitrophenyl)sulfonyl] {[ I -(3-phenylpropyl)-1,2,3,4-tetrahydroquinolin-5-yl]methyl}amino)phenyl]propanoate (591 mg), mercaptoacetic acid (0.13 ml) and DMF (6 ml) and, after warming up to room temperature, stirred for 2 hours. Saturated sodium bicarbonate aqueous solution was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueous solution and then dried with anhydrous magnesium sulfate. The desiccant was removed and the solvent was evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain ethyl 3-[2-fluoro-4-({[l-(3-phenylpropyl)-l,2,3,4-tetrahydroquinolin-5-yl]methyl}amino)phenyl]propanoate (401 mg) as a light yellow oil. 70 [0155] In the same manner as in the methods of Examples 1 to 40, the Example compounds 41 to 478 shown in the following tables were produced using respectively corresponding materials. Structures and production methods of respective Example compounds are shown in Tables 32 to 109, and physicochemical data thereof in Tables 110 to 133. [0156] Also, structures of other compounds of the invention are shown in Tables 134 to 136. These can be easily synthesized using the aforementioned production methods, the methods described in Examples and the methods obvious to those skilled in the art, or modified methods thereof. [0157] In addition, the following abbreviations are used in the following tables. PEx: production example, Ex: Example, No: compound number, EI: m/z value of EI-MS ((M)+ unless otherwise noted), CI: m/z value of CI-MS ((M+H)+ unless otherwise noted), ESI+: m/z value of ESI-MS (anion) ((M-H)" unless otherwise noted), FAB+: m/z value of FAB-MS (cation) ((M+H)+ unless otherwise noted), FAB-: m/z value of FAB-MS (anion) ((M-H)" unless otherwise noted), NMRl: 5 (ppm) of lH NMR in DMSO-d6, NMR2: 5 (ppm) of 'H NMR in CDC13, NMR3: 5 (ppm) of 'H NMR in CD3OH, PSyn: production method (The number means that the production example compound was produced using a corresponding material in the same manner as in the production example compound having the number as a production example number. The case of having E before the number means that the production example compound was produced using a corresponding material in the same manner as in the Example compound having the number as an Example number.), Syn: production method (The number means that the Example compound was produced using a corresponding material in the same manner as in the Example compound having the number as an Example number. The case of having P before the number means that the Example compound was produced using a corresponding material in the same manner as in the production example compoimd having the number as a production example number.), Me: methyl, Et: ethyl, iPr: isopropyl, Boc: tert-butoxycarbonyl, Ns: 2-nitrobenzenesulfonyl. Also, the HC1 in the structural formulae represents hydrochloride, and the number before HC1 represents molar ratio. For example, 2HC1 represents dihydrochloride.) Also, ="< represents double bond of E or Z. 71 [0158] [Tab le4] i PEx PSyn Structure Data 1 1 MeY^Y'F EL208 50 1 Me02Cv^/N02 ^^^C02Et FAB+:280 2 2 Br"OC ^^^C02Et EL289 3 3 HO^|pYF ^^^C02Et FAB+:225 4 4 HcTNpYF EI:226 5 5 ^^^C02Et ESI+225 6 6 EI:191 7 7 H Us>.C02Me FAB+:377 8 8 H ^^-^C02Et ESI+:312 9 9 Boc 00 OH FAB+:264 72 [0159] [Tab e5] i i rr^i 10 10 FAB+264 r^ r i ■i r1U Vv Boc I OH 11 11 H Me02C^_N^O FAB+:206 9 12 12 T ESI+:282 9 13 13 H02C^^N^O ESI+268 fT^i 14 14 V *o ESI+254 IAJ r^Y^ 15 15 J\ OMe 0 ESI+:285 73 [0160] [Table 6] 16 | i 16 6 ESI+241 17 17 VY"C02Me Me ESI+202 18 18 ^V^C02Me H Me ESI+:206 19 19 ^N^^C02Me 6 FAB+:268 52 19 ^N^fX02Me 6m ESI+:282 20 20 Me.J OH Me EL2Q5 53 20 o92 ESI+-254 54 20 9? M ^ 0H Me ESI+:178 ._ 74 [0161] [Table 7] i I rv*\ 55 20 Me—J 0H EI:205 rt^ 56 20 FAB+.291 OT\ 57 20 KjKj Me ESI+:310 fV\ 21 21 Sr^S<02 ESI+271 Ct^\ 58 21 fy1 HKBOO FAB+:339 ^^ Z.1 1 k IL "N' ^ ~C02Me Me^^ Me f°Y^ 22 22 EL240 CY^ 23 23 ^NAjA^OH Me-^J Me ESI+220 75 [0162] [Table 8] 60 23 KXj Me ESI+282 01 23 6*" T—>riT i ^^ /« 62 23 6 FAB+:240 24 24 on 6 Et237 63 24 Boc Me EL275 25 25 ^N ^^^C02Et FAB+.352 64 25 FAB+:320 65 25 ^^^C02Et ESI+352 76 [0163] [Table 9] 66 1 25 k/N Boc kA^C02Et Me FAB+:497 67 25 ^N Boo ^^CO;Et 6 FAB+:545 26 26 ^^C02Et FAB+:354 68 26 XXJf FAB+:518 69 26 f^l NS k^N ILA ^ OU2bl FAB+:538 70 26 ^~C02Me FAB+:350 71 26 ^C02Me ESI+:532 77 [0164] [Table 10] 72 26 f^f^\ B°C SA^sprF ^^C02Et ESI+.-453 73 E20 Boc..A^ A .NL x^ .F N T v T "^T O kA^C02Et FAB+:641 (M)+ 74 E20 kNV^NTYF S Me ^-^C02Et Me ESI+:598 75 E20 ^O Me U^~c02Et ESI+:660 76 E20 yyUyyF X Me ^^Co2Et ESI+:632 77 E20 Boo Me ^^c02Et FAB+:655 78 E20 ESI+.-632 79 E20 Boo ^A~Co2Et ESI-:642 78 [0165] [Table 11] 80 E20 A ^^C02Et ESI+-.619 27 27 ^C02Me H:207 28 28 Me FAB+:397 81 28 6 FAB+:445 82 28 ^ ^ ^C02Et ESI+:353 83 E23 f^Y^l Me ^^^C02Et ESI+:367 84 E25 ^^^C02Et ESI+:457 79 [0166] [Table 12] 29 29 r^l Ns ESI-:520 85 29 CNH U^C02Et FAB+:541 (M>f 86 29 f^l NS ^C02Me ESI+:536 30 30 [^ °YCF:J ^Boc ^^C02Et FAB+:533 87 30 ^s 0YCF3 uC02iPr ESI+.-577 88 30 ^ ^ CK CF. Boc Me ^^Co2Et . FAB+:567 89 E27 n^rCF3 CNH UxTxc02Me ESI+:433 80 [0167] [Table 13] 90 E27 ^ °YCF3 ^C02iPr ESI+477 91 E27 f^\ Ns HN^V^^NYf] [(M- rT^ 164 23 o. *N' k> ,0H ESI+284 OH>f] [(M- OMe 165 15 OMe CI:302 166 15 OMe OMe EI:320 92 [0179] [Table 25] 167 15 N y OMe EL318 168 15 J 6 N y OMe CI:318 169 15 N N il V Br I ^\/OMe N y OMe CL364366 170 15 k JL ^L^OMe N N y A 0Me F EI:338 93 [0180] [Table 26] NMR2:0.90(3H,a =74Hz),1.60(2H,t qrI=7.3,7.4Hz),1.9 CCi (X2PitU=5-6,6.4H 171 21 \Xn\0Me Me-^J OMe Hz),3.37(2H,tJ=5. 6Hz)3.40(6H^)3. 57(2H,tJ=7.3Hz),5 .12(1H^),6.61(1H, dU=7.3Hz),7.08(l H,dJ=7.3Hz) 44 44 ESI+207 fY^i 172 18 ^N-^f^C02Me H Me ESI+206 rr^\ 173 23 Me ESI+:178 174 9 «. N 1 Boc T Me ^ .OH FAB+:278 ^YS r^i 45 45 V ^^ k.o i^ FAB+:382 i i ii Boc Me 0 94 [0181] [Table 27] 175 28 H Me 0 ESI+282 46 46 Me. en n n A* ° ESI+:372 47 47 ESI+:268 176 46 ^N>Y^02Me 6" 14 Me J Me>L .i> Me^Si MP Me ESI+:412 177 46 0 "6 CI Me ESI+283 178 41 ^N^f^C02Me /^O^J Me ESI+:326 95 [0182] [Table 28] 179 34 \^f^C02Me VI 1 ESI+:298 48 48 ^N""Y*^C02Me 6"* Me Me ESI+:384 180 23 Me Me V 9 Me \/0H ESI+:356 181 24 Me Me ESI+:354 96 [0183] [Table 29] N 182 23 ». Me M6>k . Me^ Si Me Me Me .OH FAB+:383 [(M>f] OH 183 23 N Me ESI+255 OH 184 23 O^ J Me ESI+298 185 E20 C02ht ESI+:646 186 E20 Me Me N Me Ns i X02Et ESI+:762 Me Si Me Me 97 [0184] [Table 30] H N' 187 33 Me *C02Et ESI+:577 *, Me Me. I Me^Si Me Me 188 E20 N ^N' Ns i ESI+:585 Me ^C02Et Ns i 189 E20 N N' Me C02Et ESI+:633 N 190 30 k Y N O^ XF0 ESI+:591 49 49 CX 'N f^\ °TCF3 6 C02Et ESI+:623 191 41 C02Et ESI+:675 98 [0185] [Table 31] H Ck XF„ 192 193 E21 30 Boc, C r^^ 'N' ^ UV C02Et M C02Et Me l C02Et ESI+:545 FAB+:553 r<^ ^Y^' 3 194 36 HN' N. ^ ^F C02Et FAB+:453 r .N. ^ .F 195 41 HO. N Cv XF, C02Et ESI+:497 196 35 .CF, F3C~^ ^N >v OyCF3 N *CO„Et ESI+:683 197 35 Cv .CF, C02Et ESI+:547 99 [0186] [Table 32] Ex Structure i^ii 41 AjP^cy^F l^NH KJ^- ^C02Na P^°YV 14 CJ ^C02Na f T n HT 42 ^N JD K^K^ ^C02Na 6 r*^ 43 PvP-°^rvF 6 ^C02Na A^°rvF 44 0 vC02Na 100 [0187] [Table 33] °TCC 45 C02Na O 46 C02Na ^Me ^^ .N 47 O C02Na O 48 ,Nk Boc IX. CQ2Na |\j v v -yr vcv C02Na 49 N °XX C02Na 101 [0188] [Table 34] 10 V ,*CO,H H .*COzNa 50 4*C02Na Me 51 C02Na 52 (X ^1 ^N Me ^C02Na 54 C02Na \J 102 [0189] [Table 35] H 55 i: U ) L „.CO,Na V 56 XX H f ^NH k^ ^^^C02Na H rF 3 °\ TO ^^C02Na 57 ^^\ ,/^v^ H rF ^N^ -~Me^ ^^C02Na XX JVN /F 58 ) ^^C02Na A (V -°YN /F 59 F ) u x^^C02Na o- -F 103 [0190] [Table 36] j^N 60 D ^^^C02Na ^\ X^o v^ 61 UL i x^V 6 ^C02Na 62 ^Boc L ^C02Na 63 30 ^-C02Na (1^1 H 7 rV^% Yi Uy> 1! Me ^C02Na 13 3$ 6 ^C02Na 104 [0191] [Table 37] N^O 12 <^ o C02Na 64 o C02Na 65 °YVF C02Na 66 O^Me N -N Y° Me C02H 67 NT ^ H o C02Na O 68 Me C02Na %, 69 ^N Me^J C02Na 105 [0192] [Table 38] 70 VOUlyYF 71 A] ^-^^C02Na 72 Me0^ k^^C02Na 73 Ffi^ ^A^C02Na 74 75 ^^"C02Na 76 Me k^-^C02Na 77 106 [0193] [Table 39] 78 ^NXJ^NyYF F3C^ ^-^C02Na 79 Me^/\ ^Jl^O^/^/F ^^ ^^^C02H HCI 80 ■V ^ ^^C02H HCI 81 A A k^ ^^^C02H HCI 82 HCI 83 HN-^V^°YVF kj ^k^^C02H HCI 84 ^N^-k^NY^/F Me^° k^k^-C02Na 107 [0194] [Table 40] ^ 85 Me ^N C02Na H 86 N ^C02Na 87 Me. C02H 2HCI 88 C02H 2HCI 89 2HCI C02H 90 C02H 2HCI 91 2HCI C02H 108 [0195] [Table 41] 92 ^NAJ^NY^VF O^Me UC^0" 0.5 Ca2+ ° 93 r^V^i Me ^—^C02Na 94 ^NAA/NYYF 0.5 Ca2+ 0 95 0.5 Ca2+ 0 96 97 S^JU^YYF k-J ~ 2+ o ^^ 0.5 Ca 98 ^NXJv/Oy^.OMe J\ ^^^C02Na 109 [0196] [Table 42] 99 ^N>^k-0YVMe C02Na C02Na 100 k N' .0 H 101 ^N '^ ^C02Na 102 N NL^Me C02Na N 103 ^^ 2HCI ^C02H O^/^ 104 C02H 2HCI ,N 105 0 ^i ^N HCI C02H 110 [0197] [Table 43] Me. J Me K^> 106 C02Na 107 r^>, N' Me H C02Na 108 OH 2HCI C02H 109 C02Na 110 O^N C02Na 111 N "N 2HCI C02H H 112 N' C02Na ill [0198] [Table 44] ^s ^ 113 MeO C02Na 114 MeO IN H C02Na 115 OMe C02Na 116 C02H 117 C02Na Me 11 C02Na N' 118 N' C02Na Me 112 [0199] [Table 45] f^l rr °^r /wF 119 \^V/ ^C02Na n 120 Me Me ^C02Na n 121 Me ^C02Na d rr °^ /wF 122 Me v^V^ ^C02Na Hi 123 rY <0 k^-N_,Me H Me ^C02Na f\ 124 Me /wF ^C02Na 113 [0200] [Table 46] 125 C02Na ^CF„ O 126 C02Na O 127 Me C02Na O 128 C02Na 129 T u HO C02H 130 114 [0201] [Table 47] XX F 131 p yu^^ f Me ^ ^C02H f^ ^Y^°">^ /F 132 k^yo kJ V/ ^C02Na A /f^o^ rF 133 Me c ^C02H A rx"°">^ii rF 134 k^yo kJ OMe o ^C02Na if) rVW^, ^F u:> k>yo k^ Me^"Me ^C02Na JPI rV^o^v^ rF 136 k^yo k/ Me C ^C02H 115 [0202] [Table 48] J^S rr"o'~y*r> rF 137 k/N^O I^J- k/ ^C02Na A fYoY rF 138 ic ^C02H [P*l 139 Me c ^C02Na if^l 140 6 c ^C02Na fT^i 141 Me c ^C02Na \T*\ 142 s Me \^ ""C02Na 116 [0203] [Table 49] 143 Me^ ^^C02Na 144 145 kN^^^O^Y:VF 146 ^N> ^^C02H i^Ji 2HCI 147 ^-N^ ^-^C02H CN 2HCI 148 WNJ 2HCI 117 [0204] [Table 50] 0 149 C02Na CF„ O 150 OMe C02Na ONa 151 152 r^N OJ 153 2HCI C02H 118 [0205] [Table 51] 154 l^N Me kA^c02H 6 HC, 155 t^ 0 156 OF L J y. >JL ^ o — ^-^ —^ (.11 Ma VN^^I NCI 157 158 O ^^^C02Na 159 C\ H 160 'xT^Mx^. 119 [0206] [Table 52] ^ 161 C02Na 162 O. /^. IN CI H C02Na C^Y^O^/^ 163 C02Na o^^ ~^r 164 CI C02Na 165 N C02H 166 MeO ^N-^Y^ Me HCI ^C02H 167 Me 2HCI C02H H N' 168 N Me C02H 3HCI 120 [0207] [Table 53] 169 CJVL-N^-YF F3C^J Me \^^^co H 2HCI 2 170 ^N>Y^NwF MeY^ Me ^-^CO2H Me 2HCI 171 MeO^J Me \^^^C0 H 2HCI 172 UQJ Me k^k^Co2H 2HCI 173 m^J Me kA^-Co2H 2HCI 174 ,, A.. Me ^^-^CO H Me Me uu2n 2HCI 175 J Me ^A^rn H v 2HCI 121 [0208] [Table 54] 176 n jTl W P 2HCI 177 u u U^C02H 2HCI 178 III H 2HCI 179 0 f^i H HCI 180 OMe O M^C02H HCI 181 ^M^-°Y^1 F F kJJ HCI 182 C|A/J Me ^A^Co2H 2HCI 122 [0209] [Table 55] 183 clTl Cf\ H ^j- ^J Me kA^™ 2HCI 184 A FA> ^J Me k^^Co2H 2HCI 185 FT\ ^NXrA^^YYF KJ- ^J Me kA^CoH 2HCI 186 n L9?^Y F3C^ ^J Me ^^^C02H 2HCI 187 FJCy\ Q?^ VrF ki k^J Me ^A^C02H 2HCI 188 a CN3yljyYF ^A ^ Me kA^co H OMe 2HCI 189 r MeO"^ 2HCI 123 [0210] [Table 56] 190 MeO N k Me 2HCI C02H C02H C02H 191 C02H 192 193 194 195 124 [0211] [Table 57] 196 CF3 kN>vk-NYY A^O^J Me [U1^-C02H K^ 2HCI 197 F3C Y^Y0^ Me ^v^co H Kj 2HCI 198 C*f°^ Me ^^CO,H ffiXJ 2HCI 199 VO Me KA^C0H 2HCI 200 VN-^ Me ^-^C02H 0 2HCI 201 OMe ^N'V^^YYF X.O^J Me kA^Co2H il^J 2HCI 202 MeOyyO^ Me ^^^co H \^ 2HCI 125 [0212] [Table 58] 203 fW°^ Me ^^C02H Me0AJ 2HCI 204 OCF3 ^N\0NYVF A^O Me 0^^co2H Kj? 2HCI 205 kN^y^NY^Y F3COx^wO^ Me ^^^C02H ^^ 2HCI 206 [fV0^ Me ^-^C02H F3CO^^ 2HCI 207 \A \^^^C02H 2HCI 208 HCI 6 A Me ^-^CO2H kJJ HCI F 126 [0213] [Table 59] 209 AA H kN^A^NY^rF A Me A^co H FA^ HCI 210 lN\AH^F A Me A^co H Ljl HCI OMe 211 A ^ A^^CQM LJI HCI CF3 212 ^N-V^AYF A Me AA-co H F,C^ HCI •J 213 ^N^V^^YYF X Me kA^-C0 H JL J HCI 214 X Me UN^C02H A. J HC| 127 [0214] [Table 60] 215 Me N Me H HCI C02H H 216 K Me F ^^ F HCI C02H H Me HCI 217 C02H H Me 218 F y F F HCI C02H H Me 219 CI C02Na H 220 Me'^O HCI C02H 128 [0215] [Table 61] MeO C02H 221 222 i, . j ~'NYVF Me^cO Me ^^^C0 H 2HCI 223 MeO C02H 2HCI 224 C02H Me^T 225 Me O N Me H 2HCI C02H 129 [0216] [Table 62] C02H 226 227 L NT Me n 2HCI C02H 2HCI C02H HO. Me 2HCI C02H C02H 228 Me Me N' 229 MeO Me 2HCI C02H 230 130 [0217] [Table 63] N N 231 Me 3HCI C02H 232 Me Me^N Me 3HCI H C02H C02H 233 C02H 234 235 ^^-^COoH 236 237 131 [0218] [Table 64] 238 VY^SfTF Me^J Me lvA^co H OH 2HCI 239 MelekJNY^NTXF Me^V ^^-^CO.H OH 2HCI 240 Me Me^N^j^NYYF MpLJ Me kA^Co2H 0 2HCI 241 /V Me ^-^CO2H ^ 2HCI 242 k^ ^^^C02H 243 k^N ^^—C02H 0=S=0 6 132 [0219] [Table 65] [f^1 r^0^ ^1 LN B ^k ^C02H 15 6 i HN^Me T 0 iPl rVo-| ^ kA. ^ >A ^C02H 244 (1^1 M°^ ^ 245 CF3 ^A ^C02H n rr °^f "^1 kA 1 vA. ^C02H 246 I [0220] [Table 66] 247 6 248 ^-"y.O ^^C02H O 249 o^VrF Nyo ^^^CO2H Me 250 0 251 134 [0221] [Table 67] 252 O 253 o H2N-S O O C02H O 254 0 C02H N N. Me C02H 255 256 ^^ 135 [0222] [Table 68] [f^l A^<\ rvF 257 ) Me UC ^C02H if*i rA°i ^yF y° NjA^- ^C02H 258 fy Me if^l X^Co ^rF H*° >A/ ^C02H 259 IN" \, o A rA°^ fTF 260 6 UX/ "^C02H 136 [0223] [Table 69] .0 CI 16 C02H r^ MeO 261 -N O .0 C02H HO 262 '-cc. C02H 263 F3C. \—-n \^^^CO~H %J 264 137 [0225] [Table 71] r^ M-°-T -"WF 270 cT CI ^—^C02H r^i r ^ 17 CO2H 298 ^ C02H 299 C02H OCF, 145 [0232] [Table 78] 300 301 OMe 302 F Aci V F 304 146 [0233] [Table 79] C02H 305 ^^N 306 C02H C02H 307 308 C02H 309 147 [0234] [Table 80] O 310 s=o >" F C02H C02H 311 C02H 312 18 W P s=o /Ck C02H C02H 313 148 [0235] [Table 81] C02H 314 C02H 315 OMe 316 CI -N £0 ^A^Co2H 317 C02H 318 Me -N g0 M^-Co2H 149 [0236] [Table 82] O 319 C02H -°v^vF MeO / 320 O 321 CI CT C02H O 322 C09H C02H 323 150 [0237] [Table 83] C02H 324 325 J. ^C02H r9 Me C02H 326 327 s=o C02H 151 [0238] [Table 84] C*) /Xo, ]TTF 328 V-N P s=o xS 0 H ^A-^C02H A f^O --wF 19 ^-^C02Et ^1 329 Me Me ^^^C02Et n 330 671 Me ^^^C02Et n fY °^ ^YF 331 kA 1 Me ^-^C02Et XX 332 L^N^Me I Me ^^C02Et 152 [0239] [Table 85] XC 20 Boc. C02Et 333 T Boc n ^ ,F C02Et CX/^/F 334 Boc C02Et O C02Et 335 N ^^\ ^Me C02Et 338 ^N Xky C02Et 153 [0240] [Table 86] 21 Boc Me C02Et ,N 22 Boc u C02iPr 339 Boc C02Me N^/N^ 340 N C02Et 341 ^N h^Me C02Et N Me 23 C02Et *Me N KL Me 342 C02Et 154 [0241] [Table 87] 24 343 n k/NH U^Co2Et 344 m ^-^C02Et 25 l\^^C02Et 345 sA^NY^fF kA^cc>2Et 26 Me 346 6 155 [0242] [Table 88] f^i 347 ^C02Me 27 ry^o /wF k/NH I ^^-^CO^t 348 I y H L^NH ll ^^^C02Me A 349 M-°^ /wF V-NH I! ^^^C02Et f^l 350 HN-V^0- ccF ^^^C02Et f^l rYo-Y ^ 28 6 ^^C02Me n rr °^i /wF 351 TO ^k-^CO.Et 156 [0243] [Table 89] n r\V T^TF 352 A k^V^C02Et Mo- iTTF 353 k/N Me kA^^C02Et r^ii 354 A^o- TV ^N-Me k^v-—C02Et fs rY°" YTF 355 CF3 kk^Co2Et n r^f^o^ fYF 356 0 ^^^—C02Et n rrV YYF 357 HO—-0 ^^^C02Et 157 [0245] [Table 91] 364 F ) ^^-^C02Et 365 X^O^P 6 366 X^O^P k^. ^k^C02E, Me 367 OS^HJU^, 368 Me ^^^C02Et 369 370 F3O 0 ^^^C02Et 159 [0246] [Table 92] ^ 394 C02Et Me N 395 Me ^N GO-Et °wF N^>0 K*K^ 31 C02Et , .F 404 ciCF, ^C02Et f~\ 32 6 ^C02Et (*^ii 405 COTCC 6 srn Pt if^i 406 CflTOC Me ^C02Et [f^i 407 Me "C02Et 165 [0252] [Table 98] 408 M)YYF ^Ks=o ^>—C02Et Me 33 Me^*^^C02Et 409 Af^N^Me XJX' 34 410 A ^-^C02Et 411 166 [0253] [Table 99] °€C 412 C02Et s^>i r^ 35 Y N OMe' H C02Et 413 CI Me C02Na 414 N N C02Na 415 N N C02Na 416 N N' CI 1 ,Na 167 [0254] [Table 100] 417 Cfl H CIJ6 ^ 418 Yfl H kNANA^NYVF fK ^Y^C02Na F\^F F 419 SrV^yYF V Br 420 Meyk Me l-^^^C02Na 421 S^V^^YYF X Me kA^Co2Na Me Me 168 [0255] [Table 101] Me 422 ONa C02Na 423 Me N^V H .N C02Na 424 CX Me C02Na 425 C02Na o^^ 426 C02Na N 427 0^/ S=0 o C02Na r^N H N 428 ,Na 169 [0256] [Table 102] 429 ^^/O^J Me •°I ^-^C02Na II 430 fr°^rp ^-o^ n v KJ KJ ^^-^COjNa ^x 39 ff^Y°^"N^V^ -°> [TTF u u ^^^C02Na r^ii 431 r^V^^N^T^ ^ PTMe u u ^^^C02Na r^l 432 ^YQ^^NA^ ^o^ /^OMe u u ^^^C02Na | H ^"OMe ^ ^^^COjNa 446 OMe r^ H 447 fr^°^^Nx^Y^NV::YF 448 kAF kJ k^^C02Na 449 (^N^.NXJLNY^F o kJ kk^C02Na 450 kj kA^Co2Na 451 ^^OMe ^ ^^-^C02Na 172 [0259] [Table 105] ■^ 452 CI XX C02Na C02Na 453 454 C02Na °s^A 455 ,C02Na 456 V ,C02Na H 37 NT N C02Et 457 173 [0260] [Table 106] m H ^ A A ^NL /\ ^F N N^ i TV 458 <> ^^^C02Et CT\ H k >k A .. ,N^ /\ ^F VN N V^^V/Sv" 459 1 1 i oX) ^^-^C02Et ' rn H | ^^Y^f 460 6 Br ^^^C02Et ^^ l_l L X Jk ^N^ ^^ ^F i YT 461 i F ^^-^C02Et rn H 462 kN^N^ ^N^^F Me^ k^-^C02Et PA H SrVL x/NYVF 463 i ' Me^ ^-v Me | I kJ ^^-"^(X^Et [0261] [Table 107] Me 464 HO ^ Me Me n C02Et C02Et 465 C02Et 466 467 Me C02Et ^^ 38 MeTi 468 175 [0262] [Table 108] 469 I H ^\^C02Et 470 oVc1 H ^^^C02Et 471 ^°T^i FF 472 Q°^U ^^N^C02Et 473 IPY°^^N'S^ ^V^CCLEt 1 2 Me 474 0°^9 ^N Y^l Me Me ^"S^C02Et 475 IA .C02Et 176 [0263] [Table 109] 476 a°'^6x H s_A. ,X02Et V 477 1^1 H Boc.N/^J^N^ 0 ^C02Et 40 IPY^^N "y^ H 478 H -"I ^^^C02Et 177 [0264] [Table 110] Ex Syn Data 41 1 FAB+:330 14 14 FAB+:434 42 1 NMRl:li5-2.(XX2H^n)^.05(2H,tTJ=7.8Hz)2.64(2H,U=7.8Hz)^.68-2.93(2H^i)327- 355(lH^)3.6942(XlH^n),4.37-522(2Hm),626-6.76(2Iim),6.93-7.72(9Iim) FAB+:434 43 14 >MRl:lJ6-13(KlHjn)a384.54(lH^)a.82-1.97(lH^n)^.05(2H,y=8.0Hz)^25- 2.40(lHin)2.64{2H,M=8.0Hz)3.29-3.57(iiim)3.95- 4.17(lH,m),5.19(lH,cU=13.0Hz),532(lH,cy=13.0Hz),6.56- 6.66(2H^)J.05(lH,cU^.8HzyT7(lH,U^.9Hz)J26(lH,tJ=7.6Hz)J45(lH,cy=7.1H z),7.54-7.59(4Hm)7.69-7.76(lH^n) ESI-:468 44 1 NMRl:lJ3-1.86(2H^)2.03(2H,U=8.0Hz)2.62(2H,U^.0Hz)2.8()(2H,y^.6Hz)2.90- 3.02(2Hm),4.10(2Hs)^.03(2Hs),6.49- 6.6(K2H^)^93(lH,y=7.5HzX7.03(lH,cU=7.1Hz),7.08(lH,y=9.0Hz),721- 729(2H^n),734(2H5y=7.4Hz),7.43(2H,dTJ=7.4Hz) FAB+:420 45 14 FAB+:426 46 1 FAB+372 47 1 FAB-.-404 48 1 FAB-:428 1 1 NMRl:1.73-1.89(2H^i)2.04(2H,y=8.0Flz)2.58- 2.69(4H^)275(2H,y=7.6Hz)3.19(2H,U^.7Hz)343(2H,y=7.7Hz),4.98(2Iis),6.53(l H,cU=7.5Hz),6.64-6.80(3H^i),6.86(lH,cy=7.5Hz),7.16(lH,y=8.8Hz),7.19- 725(3Hm),725-732(2tim) FAB+:434 49 1 FAB+:420 10 NMRl:1.16-125(2Fim),126-135(lP^),137-1.66(lHm),1.73-1.9(K2H^)221(ddcy=42,6.4,9.8Hz)2.70-3.04(6H^n)3.12-322(2H^)A17(2H^)^7(2H,cU=7.8Hz),6J8^.97(4FMn),7.10-732(6Iirn) FAB+:427 50 1 FAB+322 51 1 FAB+365 52 1 FAB+:420 53 1 FAB+358 54 1 NMRl:Z05(2H,y=«.0Hz)2.64(2H,y=8.0Hz)2.95(2H,tJ=8.7Hz)329- 3.42(2Hm),4.43(2Hs),4.90(2Iis),6J8-6.69(3Iim),7.01- 7.09(2H^n),7.13(lHtyJ=8.8Hz),720-7.34(5Iim) ESI+:406 178 [0265] [Table 111] 55 1 FAB-:411 56 1 FAB+:329 3 3 NMRl:173-1.86(2Hm)2.03(2H,tJ=81Hz)2i6(2H,a^.lHz)^76(2H,tJ==6.6Hz)^.88- 3.02(4H^i),3.11-321(2Iim),4.12(2H,(y=5.6Hz),6.14- 630(3tim),6.82(lH,trf=7.4Hz),6.86-6.94(2H^i),7.10-726(6H^i) FAB+:419 57 1 NMRl :0.85(3H,y=73Hz,),l .60-1.82(4fim)2.01 (2^=8. lHz)2.54(2H,tTI=8. lHz)2-63-2.80(4Iim)3.00-3.1 l(2Iim),4.1 l(2H4^7Hz),6.13-£26(3Jim),677-6.92(3Iim)7.12(lH,MRl:lJ9-1.88(2H^)J^2.05(2H^)233-2.47(2Iirii)2.48-2.57(2H^n)2.58- 2.66(2H^)3.18-326(2H^)342-3i2(2H^n),4.09(2H,cy=6.4HzX6.15-632(3H^i),6.47- 6.55(2HUri),6.79-6.92(2Iim) ESI+:425 79 1 >MRl:0.9(K3H,a=74Hz),li2-1.69(2H^)4.84-2.1(K2H^n)2.48(2H,tJ-7.5Hz)2.68- 2.82(4Hjn)3.18-338(4H^i),4.99(2fis),6.68-7.02(4P^),7.03- 7.15(lH^n),721(lH,t,J=8.8Hz) FAB+372 80 1 FAB+:420 81 1 NMR1.-1.77- 1.91(2H^)2.48(2Hy=7.5Hz)2.68(2Hy^4Hz)2.77(2Hy=7.6Hz)2.83(2H,y=7.7H2 )323(2H,y=53Hz)3.49(2H,tyJ=7.8Hz),4.96(2Jis),6.66- 6.83(3Iim),6.86(lH,ddJ=25,12.2Hz),7.15-724(2IimX725-735(4Iim) FAB+:434 82 1 ESI+:406 83 1 ESI+330 84 1 ESI-:405 85 1 iNTvlRl :0.83(3H,tf=73Hz), i 34-i 31(2^ 2.67(4H^)3.08-3a6(2H^n)3.17-325(2H^nX4-06(2H,bis),6.13-633(3H^n),638- 6.46(lHm),6.48-6.55(lIim),6.73-6.80(lH^iX6.84-6.93(lH^n) ESI+371 86 1 NMRl:l,84-1.95(2H^)J.96-2.07(2H^)2.47-239(2H^)2.66-278(2Iirn)3.51- 3.60(2H^p.95-4.02(2H^X6.08-622(3H^X6.62^.67(lH^iX6.68-6.72(lIimX6.85- 6.91(lH^iX6.94-7.05(2IimX7.08-7.15(2IiinX7-22-730(2H^n) ESI+:405 180 [0267] [Table 113] 87 1 NMRl:0.91(3H,tJ=7.4HzX1.56-1.72(21im),1.92- 2.08(21itn)^.42(2H,trF=7.7Hz)^.67(2H,trJ=7.7Hz)2.72-2.81(2H^i)3.21- 3.43(41im),4.14{2Iis),632-6.48(2H^n),6.77-7.27(4Iim) ESI+371 88 1 NMRl:1.9l- 2.04(2Hm)^.44(2H,U=7.7Hz)^7()(2H,y=7.7Hz)^J5(2HU=63Hz)3.34(2H,U=5.5Hz ),4J5(2H^),4il(2H^),639^76(4H^),6.9(XlHtJ=7.7Hz)7.04(lH,U=8.7Hz),720- ESI+:419 89 1 NMRl:1.84-1.98(2H^)^3)2H,U=7.6Hz)2.63-2.77(4H^n)^.88(2H,U=7.6Hz)3.19- 337(2H^i)3.52(2H,trJ=7.8Hz),4.15(2Iis),637-6.59(2H^n),6.66-6.97(2Iim),6.98- 7.13(2Hm),7.17-735(5Iim) ESI+.-433 90 1 NMR1:1.90- 2.01(2H^)^3(2H,U=7.6Hz)^.68(2H,y=7.6Hzpj8(2H,tJ==6.5Hz)3.56(2H,U=5.6Hz ),4.15(2Iis),636- 65(X2H^)^^7(lH,dJ=7.7Hz)A72(iadJ=7.7Hz)A85(lH,y=7.7Hz),6.99(lH,tTJ:=8.6H z),7.07(lH,trJ=73Hz),7.15-7.22(2H^i),735(2H,y=7.9Hz) ESI+.-405 91 1 ESI+329 92 1 ESI+371 93 1 ESI+343 94 1 ESI+385 95 1 NMRl:1.69-1.87(2H^)^.04-220(2H^)^.44-2Jl(4H^)3.14-3.53(9Iim)3.96- 4J2(2H^)AH^34(3H^),639^.47(lH^n),6.51-6.59(lH^n),6.72-6.83(lHm),6.84- 6.98(llim) ESI+387 96 1 ESI-371 97 1 >MR1:1,84-2.02(5H^)2.07-227(2H^ 3.54(2H^)3.81-3.92(2H^)3.84-5.9(KlH^p.9^ 6.95(2HmX7.08-732(4Hm) ESI+.419 98 1 ESI+:418 99 1 FAB+:402 100 1 NMRl:1.89-2.06(4H^i)2.58- 2.69C2H^)2.77(2H,U=^.4Hz)3.57(2H,U=5.7Hz),4.87(2Iis),6.53(2Hni),6.64- 674(2HM7-02(lHAJ=7/7Hz)JX)9(lH^^ z) FAB+.-424 181 [0268] [Table 114] 101 1 NMR1:1.84- 1.97(2H^)2.04(2H,U=7.8Hz)2i3(2H,trI=7.8Hz)2.72(2H,y=6.3Hz)3.54(2H,U=5.6Hz )A16(2H,dJ^.9Hz),627(lHcy^.6Hz),6i2(lH,tTl=6.0H2),6.63(lH,cU=7.7Hz),6.69(lH 46.94(lH,dJ=7.7Hz)7.02(lH,tJ=73Hz)7.13(2H,dJ=7.8Hz)J.19(lH,cldrI=22,8.5Hz),7. 27(2H,trI=7.8Hz),7.71(lH,dJ=2.2Hz) ESI+:388 102 1 FAB+:402 1UJ i ESI+:447 104 1 NMRl:1.84-1.95(2H4n)2-43(2H,y=7.6Hz)2.62- 276(4H^n)3.39(2H,tyJ==5.3Hz)3.69(2H5y-=5.5Hz),4.13(2Iis),4.16(2H,tyJ==5.6Hz),6.45- 6.60(2Iim),6.67(lH,dJ=7.3Hz),6.74(lH,dJ=82Hz),6.89- 6.96(3H^n),6.99(lPi,U=7.9Hz),7.04{lH,trr=8.7Hz),7.23-7.32(2Jim) ESI+:449 105 1 ^Mll:lJ6-1.89(2H^)2.4()-2.48(2H^l)2.59-2.74(4Hm)3.05-3.18(2I^m)3.18-331(4H^)337-351(2H^)3.6M.12(6Hm),422(2H,htsJ),6.52-6.58(2Iim),6.67-678(2H^),6.81^.86(2H^)A96-7.01(2Hm),7.04-7.13(2H^n),11.4(brs,lH) ESI+:442 106 1 NMRl:0.89(3Hy=74Hz)a.57-177(4Iim),l,97-2.08(2Iim)2.17(3Its)2.51- 274{6H^)2.95-3.05(2H^)A034.11(2H^),5.93^.01(lH^n),6.19-6.34(2Hm),672- 6.85(2Hm),6.87-6.96(l}im) ESI+:385 107 1 >MRl:1.85-1.96(2H^)2.12-221(21im)232(3Hs)2.65-275(2Iim)2.80-2.9(X2H^)2.98-3J4(4H^)323-332(2H^n),4.16426(2H^n),6.07-6.15(lIim),635-6.48(2H^),6.89^.99(2H^)7.(^7.1()(lH^)730-737(lHm)738-7.49(4H^i) ESI+:447 108 1 >MRl:1.684.9(X2H^)243(2H,y=7.6H^ 3.47(3Iim),4.1 l(2H^),4.86(lH,tyJ-63Hz),6.40- 6i2(2H5m),6.65(lH,drJ=73Hz),6.72(lH,cy=8.1Hz),6.96-7.05(2Hm),723- 729(lHjn)730-7.42(4H^i) ESI+:449 109 1 NMRl:173(2H,ttJ^4A6Hzy.82(3H^)2.02(2H,trr=7.9Hz)2.57(2H,trr-7.9Hz)271(2 HU^.6Hz)3.66(2H,y^4Hz)A07(2H,bis)A03(lH,bis),6.18-635(2Hrri),6.07-676(2H^)A78^.86(lP!^),6.88^.96(lH^)56.96-7.()6(2H^)JJ3-723(2Jiin) ESI+:419 182 [0269] [Table 115] 110 1 NMRl:1.97-2.05(2Rm)T2.47-2.59(2H^i)2.64-2.73(2Hm)>2.95-3.03(2H^)3-99(2H,d^4Hz),6.04^J8(3H^),6.19^24(lHm),6.81-6.89(lIim),6.91-6.99(lPim),7.13-724(3Hm),737-7.51 (3H, m) ESI+:419 111 1 NMR12.05(2HtU^i,6.0Hz)2.44^^ )3.81(2H,trJ=5.5Hz)3.904.83(5Iim),625-6.35(2Iim),6.81-6.89(lH)m),6.95-7.04(lH^n)!7.42-7.51(3Iim),7.51-7.60(2H;m),7.75-7.84(lHm) ESI+:406 112 1 NMRl:1.96-2.07(2H^)2472.61(2H^)3.62-3.69(2H^)3.954.04(2H^n),4.14- 422(2H^)A08^25(3H4n)A68^73(lH^n),6.75-6.80(lIim),6.85-6.93(21im),7.05- 7.07(lH^n),7.11-7.17(2H^n),725-732(2Iim) ESI-:405 113 1 NMR1:1.78- 1.88(2H^)2.03(2H,U=8.1Hz)2-57(2Iiy^.lHz)2.66(2H,tgf=63Hz)2.72(2H,tyJ=7.7Hz )3-18(2H,tJ^4Hz)3.4(X2H,y=7.7Hz)3.72(3H^)A03(2H,cy=53Hz),5.93(lH,tTJ=53H z),626(lHddJ-2J43.1}fe)A31(lHddJ=2.132Hz)A54(lHdJ=73Ife),6.6(XlHcU=8. 2Hz)A82^.89(2H^),6.92(lH,trJ=8.7Hz),6.95(lH,U=7.8Hz),7.12-725(2Hm) ESI+:463 114 1 NMR1:1.79-1.89(2H^i)2.00- 2T(X2H^)2i8(2H,y^.lHz)2.66(2H,y-6.4Hz)2.76(2H,tTJ=7.6Hz)3.19(2H,trr==5.6Hz )3-45(2H,U=7.6Hz)3J4(3H^),4.03(2H,dJ^4Hz)^.94(lH,trr=5.4Hz),627(lH,cHJ=2.1, 132Hz)A31(lH,ddJ=2.1,83Hz)A54(lH,dJ=74Hz),6.62(lH,dJ=82Hz),6.77(lH,ddJ=2 3J.7Hz)A81^.87(2Hm),6.92(lH,U=8.7HzX6.96(lH,tJ=7.8Hz),721(lH,trr==8.0Hz) ESI+:463 115 1 NMRl:1.80-1.90(2H^n),1.97- 2.07(2H^)2-57(2H,y==8.0Hz)2.66(2H,U==63Hz)2.78(2H,y=7.7Hz)3.22(2H,tyJ==5.4Hz )337(2H,y=7.7Hzp.84(3P^)A03(2H^),627(lH,ddTJ=22,13.1Hz),632(l]H,ddrJ=22,8. 3Hz),6.53(lH,dJ=73Hz)A71(lH,dJ=82Hz),6.84-7.01(4Iim),7.13-725(2H^n) FAB+:463 116 1 miRl:1.63-177(2Il4ri)2.44-2.56(2I]4n)2.70(21I,U=6.4IIz)2-74- 2.87(4H^)A12(2H^)3.04(2H^)A65(lHcy=7.7Hz)A79(lH,tyJ=7.7Hz),6.86(lH,dJ=7.7 Hz),7.14(2H,drI=«.lHz),7.16-721(3HmX724-733(4Iim) FAB+:402 183 [0270] [Table 116] 117 1 NMll:0.87(3HU-73Hzy49-1.69(2H^)J.69-1.84(2H^i)2.01-2.16(2}im)2.59- 2.77(6Iim)2.93- 3.02(2H^),426(2H^),627(lH,dJ=8.0Hz)A31(lH;cU=7.5HzX6.69(lH,trJ==7.7Hz)56.98- 7.10(2Hm),724{lH,trf=8.1Hz) ESI+:371 11 11 NMRl:2.02-2.17(21im)2.63-2.78(2Iim)325-3.33(2H^n)3.97- 4.11(4H^),434(2H^)^i7(lH,U^2Hz),5J6(lH,ddTJ=2.4,8.4Hz)^.98(lH,(y=2.4Hz),6. 4{X0.H5dJ^4Hz),6.93(lH^),6.94^.99(lH^)7Ji()-736(6Hm) ESI+:421 118 11 ESI+373 119 1 FAB+:434 . 120 1 FAB+386 121 1 ESI+358 122 1 FAB+386 123 1 ESI+372 124 1 NMRl:0.67(3H,y=7.4Hz),138-1.52(2Iim),1.63-1.75(2H^i)2.07- 2.18(2Iim)2.66(2H,U=6.4Hz)2.76(2H,U:-8.0Hz)2.84- 3.03(4H^X4-98(2H^),6.58(lHdJ=7.7HzX6.68(lH,U=7.7Hz)A77(lH,drJ=7.7Hz),7.11- 721(2Ftm),730(lH,trJ=7.8Hz) FAB+372 125 1 FAB+:426 126 1 FAB+384 127 1 FAB+344 128 1 FAB+:420 129 1 FAB+:480 130 1 ESI+330 131 1 FAB+372 132 1 FAB+398 133 1 FAB+386 134 1 FAB+:402 135 1 FAB+:400 136 1 FAB+.414 137 1 NMRl:1.63476(lH^)^.05-225(3H^)2.68-2.84(4Ftm)3.19-3.50(lIim),4.03-423(lH^)A47(lHdJ=12.7Hz),4.79(lH,dU=12.7Hz),6.65(lH,dJ=7.8Hz),6.73-6.85(2H^X6.88(lH,cy=7.8HzX7.03(lH,g=7.8Hz)J14-728(5H^i),732-7.40(lH^n) FAB+:434 138 1 FAB+:502 139 1 FAB+:408 140 1 ESI-:468 184 [0271] [Table 117] 141 1 FAB-.-420 142 1 FAB+.-436 143 1 ESI+:372 144 1 ESI+:434 145 1 ESI+:420 146 1 ESI+:421 147 1 ESI+.-421 148 1 j. ESI+:421 149 1 FAB+:488 150 1 FAB+:450 151 1 FAB+385 152 1 FAB+.-413 153 1 NMRl:1.84-229(2Ftm)^.47-2.57(2Hm)^.73-2.93(4Iim)3.11- 333(2H^),439(2H^),4.43-5.02(2H,bs),6.56^.71(2Iim),7.06-734(4H^n),737- 7.49(3Hm),7.57-7.69(2tim) ESI+:419 154 1 FAB+:433 155 1 FAB-:459 156 1 ESI+:501 157 1 ESI+:501 158 1 ESI+:501 159 1 ESI+:467 160 1 ESI+:467 161 1 NMRl:1.814.92(2H^)J.98-2.()9(2H^i)^.53-2.61(2H^i)2.63-2.71(2H^i)3.24- 347(2H^)3.64(2H,y^.7Hz)A03(2PidJ=^.4Hz),4.10(2H,tJ=5.7Hz)^.93(lH,U=5.4Hz ),625(lH^=2JJ3.1Hz)A30(lH,ddJ=2J,83Hz),6.54(lIi(y=7.4Hz),6.61(lH,clTI==82 Hz),6.87-6.97(4H^n),7.05-7.14(2Iim) ESI+:467 162 1 ESI+:483 163 1 NMRl:1.80-1.92(2Hm)4.97-2.08(2H^ri)2.53-2.61(2Hm)^.67(2H,U=63Hz)330- 3.4(X2H^)3.65(2H,U^.6HzX4.03(2HdJ^3Ife)A16(2H,y=^.6Hz)^.93(lH,trJ=53Hz ),625(lHddJ=2A13.1Hz),63(XlH,ddJ=2A83Hz),6i4MR.l:027-0i5(2H^)A6(M).77(2Iim),126-1.41(lIim),1.87-233(2H^)2.42(2H,tJ-8.0Hz)2.53(3Iis)2.68(2H,t,=8.0Hz)2.85-2.96(2H^i)321-3i(X3H^)3.814.01(lH^),4.15431(2H^n),6.00-7.54(8Iim),11.9-123(lH,bis) ESI+ : 397 176 3 ESI+:479 177 3 ESI+:479 178 3 ESI+-.479 179 3 ESI+371 180 1 NMRl:1.64-1.87(2Hm)2.42(2H,U=7.6Hz)2.59-2.73(4Iim)2.99- 3.08(lH^n)3.14(3H^)324- 337(2H^)33(KlH,ckU=7.8,15.0Hz),4.08(2Iis),4.47(lH,ddJ==4.8,7.8Hz),6.37- 6.49(2Hm),6.54^.65(2Iim),6.91-7.03(2Ftm),728-7.43(5H^n) ESI+.463 181 1 NMR1:1.87- 1.99(2H^)2J7(2H,tJ^.4Hz)332(2H,tJ=173Hz)3i7(2H,a=n.4Hz),4.86(2fis),6.67- 674(2H^),6.84(2H,dJ^.7Hz)J.02(lH,cU=7iHz)J.08(lH,U=73Hz)J.13(2H,cU=8.7 Hz),7.17(2H,cy=7.6Hz)>733(2H,U=7.6Hz) ESI+.-424 182 4 >MRl:1.85-222(2H^)2.34-2.54(7H^)2.66(2H,a=7.6Hz)277-2.94(2H^n)3.09- 3.64(4H^)A18(2H^),626^42(2H^),6.96(lHy^-6Hz),6.98-722(2H^n),727- 739(3Hm),7.42-7.47(lIim) ESI+:481 183 4 ESI+:481 186 [0273] [Table 119] 184 4 m^l:1.83-223(2H^)rI41(2HU=7.6Hz)^44-2.53(5}imy.66(2H,trJ=7.6Hz)^.79-2.97(2Hm)3.1 l-3.92(4Iim),421(2Iis),627- 645(2H^n),6.97(lH,trJ=8.6Hz)J.08(2H,dy=2.2,8.6Hz),7.13-729(3H^n),7.32- 7.42(llim) ESI+:465 185 4 ESI+:465 186 4 mdRl:1.84-2J9(2H^)229-2i5(7H^n)2.66(2H,y=7.7Hz)2.75-2.96(2Iim)3.09- 372(4Rm)A18(2H,s).623-6.43(2Rm\6.95riRU=8.7Hz\6.98-727r2Hm\7.49- 7.78(4Hm) ESI+:515 187 4 ESI+:515 188 4 NMRl:1.84-225(2H^)2.4(X2H,U=7.7I^)2432.53(5H^n)2.65(2H,trJ=7.7Hz)2.77-2.97(2Hm)3.01-3.55(4H^n)3.82(3H^),420(2Hs),623- 642(2H^)^9(XlH,U=74Hz)A95(lH,y=8.7Hz)J.(XXlH,cU==8.1Hz),7.03-7.32(4Itm) ESI+.-477 189 4 NMRl:1.81-227(2H^)2-4(K2H,a=7.7Ife)2.432.52(5H^n)2.66(2H,trr=7.7Hz)2.77-2.95(2H4n)3.06-3.55(4Iim)3.75(3Iis),420(2H^),626-6.42(2Iim),6.78-6.85(lH^),6.86^.93(2H^),6.95(lH,trr==8.7Hz)57.01-721(2H^i),724(lIitTJ=7.8Hz) ESI+.-477 190 4 NMRl:1.82-229(2H^)2.4(K2H,y=7.6Hz)2.432.53(5Hjn)2.66(2fitrr=7.6Hz)2.77- 2.97(2Iim)3.01-3.56(4Iim)3.73(3H^),420(2H^),624- 6.42(2H^),6.89(2HdJ^.6Hz),6.95(lH,trr=8.6Hz),7.00-731(4Hm) ESI+:477 5 5 NMRl:1.91-223(2H^n)2-42(2H,trJ=7.6Hz)2.45-2.53(5Iim)2.68(2H,y=7.6Hz)2.81-2.97(2H^)334-3.91(2H^)^22(2H^)A45^.68(2H^),630^.54(2Itm),6.93-7.1()(3H^)7.12-728(2H^)J35(lH,dU==1.5,7.8Hz),7.47(lH,ddTJ=1.5,7.9Hz) ESI+:497 191 5 ESI+:497 192 5 ESI+:497 193 5 ^1Rl:1.89-22()(2H^)236-2.54{7H,m)2.68(2HtJ=7.6Hz)379-2.95(2Hrm)330- 3.87(2IimX421(2Iis),4.424.61(2H^n),631-6.53(2H^n),6.92-733(7fim) ESI+.481 194 5 ESI+:481 195 5 ESI+:481 196 5 ESI+:531 197 5 ESI+:531 187 [0274] [Table 120] 198 5 ESI+:531 199 5 NMR1:1.80- 1.91(2H^)^.16(3Hs)^43(2H,y=7.6Hz)^69(2H,trJ=7.6Hz)^.77(2H,trJ=6.6Hz)3.14-325(2H4n)33()-3.44(2H4n),4.18(2P^),4.57(2H,trJ=6.6Hz),627(lH,a=2.1Hz),6.41-653(2H^),6.93(lHdJ=7.9Hz),6.97-7.07(2H^n),7.51(lH,dJ=2.1Hz),7.83(lH,cU=2.1Hz) ESI+:437 200 5 >Mll:2.01-2.14(2H^)^37-247(5Pl^)^.68(2HU=7.6Hz)^.87(2H,y=^.6Hz)3.47- 3.57(2Hm)3.62-3.72(2Iiin),422(2}is),4.72(2H,a^52Hz),6.37- 6.48(2Hm),6.92(lH,drJ=8.3Hz),7.00(lH,tJ=«.7Hz),7.03- 7.()9(2H^)J21(lH,dJ=7.9Hz)J79(lH,ddcU=2.0,7.1,8.8Hz),8.21(lH,ddJ=1.7^.0Hz) ESI+:464 201 5 NMRl:1.88-2.19(2H^p35-2.54(7H^)^.67(2HU=7.6Hz)^79-2.94(2H^n)328-3.72(2H^)379(3H^),42(K2H^),432449(2H^),629-6.44(2Iim),6.87-728(7Iirn) ESI+:493 202 5 NMRl:1.88-2J8(2H^)235-2.54(7H^)2.67(2H,U=7.7Hz)2.79-2.95(2Iim)328- 3.70(2Hm)3.75(3Iis),420(2Iis),4334.51(2HmX631-6.46(2Iim),6.53- 6.63(3Pim),6.93-728(4Hm) ESI+:493 203 5 NMRl:1.89-2.18(2H^)235-2i5(7H^n)2.67(2H,g=7.6Hz)2.79-2.93(2H^i)332- 3.68(2H^)3Jl(3H^),42(X2H^),4294.44(2H^)A3()^45(2H^)A84-728(7H^i) ESI+:493 204 5 ESI+:547 205 5 ESI+:547 206 5 ESI+-.547 207 3 NMR1:1.93- 2.05(2H^)242(2Hy=7.6Hz)2.67(2HU=7.6Hz)2.79(2H,U==6.5Hz)3.93(2H,trr==6.1Hz ),425(2H^),633-6.48(2Iim),6.98(lH,y=8.7Hz),7.09- 722(3H^n),728(lH,ddrJ=2.1,6.8Hz),738(lH,cy=8.9Hz),7.93- 8.03(lH^n),821(lH,dcU=1.4^.9Hz) ESI+:406 208 3 NMR1:1.82-1.98(2H^)242(2H,U=7.6Hz)2.67(2HU=7.6Hz)2J3(2H,y^.6Hz)3J0(2H,a=6.0Hz ),420(2H^),4.94(2H^),631(2IimX6-73- 6.88(2HUn),6.93(lH,y=73Hz),6.98(lH,trJ=8.6Hz),7.09-7.17(2H^i),722- 730(2IimX737-752(lIim) FAB+:463 188 [0275] [Table 121] 6 209 210 6 NMR1:1.65-1 •76(2Iim),1.78(3Ils)2.43(2H,trJ=7.8Hz)2.63-2.80(41im)3.55- 3.68(2H^n),4.15(21is)!6.35-6.56(2Hjn),6.65-6.77(2H^n),6.94-7.10(5Itm) ESI+:437 6 NMRl:1.71-1.82(2Iim),1.85(3fis)2.45(2H,U=7.9Hz)2.62-2.80(4Iim)3.58- 374{2H^n),424(2H,s),6.346.53(2Iim),6.54-6.74(3Hm),6.97-724(4Iim) ESI+:437 6 NMR1:1.59- 1.72(2I-V-i),lJ6(3I^ 3.59(2H^n)3.69(3H^)3.744.60(4H^n),629- 6.48(2H^n),6.67(2H,dJ=8.9Hz)56.78(2H,cU=8.9Hz),6.91-7.06(3H^i) ESI+:449 211 6 ESI+:487 212 6 ESI+:487 213 6 ESI+:453 214 6 NMRl:1.73-1.83(2H^n),1.84(3Iis)2.42(2H,tyJ=7.7Hz)2.62-2.73(4H^i)3.64- 3.8(X2H^)A16(2H^)A31^47(2H^),6.92(lH,cy=7.9Hz),6.99(lH,tyI=8.7Hz),7.02- 7.17(3Hm),721(lH,dJ=7.8Hz),735(lH,a=8.0Hz) ESI+:444 215 6 NMRl:1.65-177(2H^)J.8(X3H^)220(3H^)2.44(2H,trf=7.7Hz)2.65-2.77(4Iim)3.59- 3.67(2H^),42(K2H^)A43(lH,dJ^.0Hz),6.5O^.62(3Iim),6.64(lJiy=7.5Hz),6.95- 7.13(4Hm) ESI+:433 216 6 NMR1:1.76- 1.87(2H^),1.91(3H^)2.45(2HU=7.7Hz)2.66(2H,tJ=6.8Hz)2.72(2H,trr=7.6Hz)3.59- 3J8(2Hm)5426(2fis),6.10-6.41(2Hm),6.5()-6.72(3Iim),7.00- 7.13(2I^mX7.18(lH,dJ=7.8Hz) ESI+:455 217 6 NMRl:1.69-1.8(X2H^i),1.84(3Iis)2.44(2H,tyJ=7.6Hz)2.64-2.76(4H^n)3.58- 3.69(2H^),42(X2H,s),636^47(lH^),6.48-6.64(2H^i),6.68-6.80(lH^n),6.99- 7.14(3Iim),7.14-725(l}im) ESI+:455 218 6 NMRl:1.72-1.85(2H^n),1.90(3H^)2.43(2H,tJ=7.7Hz)2.63-2.75(4H^n)3.58- 373(2H^X421(2H^)A4O-6.6(K4H^),6.98-7.08(2H^n),7.13(lH,(y=7.8Hz) ESI+:473 189 [0276] [Table 122] 219 6 NMRl:1.69-1.80(2Rm),1.83(3RsX1.96-2.07(2Rm);2.48-2.62(2Rrn)^.65-2.73(2Rm),3.61-3.70(2Rm),4.054.12(2Rm),5.98-6.06(lRm),6.20-633(2Rm),6.70(2Ii(y=8.9Hz)J6.87-7.()6(3Rm)57.2()(2H,(y=8.9Rz) ESI-:451 220 7 ESI+:385 221 7 ESI+:415 8 8 ESI+:463 222 4 >^v!Pvl:1.17(3RU=7.0Kz),1.88-224(2K^)^38-248(5H^)2.67(2H,U-7.6Hz)^.84-2.94(2Rm)324-3.98(8H^n),423(2H^),632-6.47(2H^i),6.94-7.03(lRrn),7.06-7.14(lRm),721-734(lRm) ESI+ : 415 223 4 NMll:1.85-232(7H^)2,42(2H,y-7.7Hz)2.67(2H,y=7.7Hz)2.84-2.96(2Rm)3.13-3.82(9H^),424(2Rs),630^.46(2H^)A93-7.03(lIim),7.07-7.18(lHm),723-735(lRm),11.9-123(lRm) ESI+ : 415 224 4 NMRl:1234.44{2H^)a.5()-1.67(lH^)4.84-2.54(7Rm)2.67(2RtrJ=7.6Hz)2.78-3J8(10Rin)3.81-3.94(2Hm),422(2Rs),629-6.44(2Rm),6.93-7.02(lRm),7.05-7.16(lRm),721-733(lRjn),l 1.4-11.9(lRm) ESI+ : 441 225 4 NMRl:1.44(9H^)a.674J8(2R^)2.13(3Rs)236-2.44<2H^)2.61-2.72(4Rm)2.99-3.()6(2H^)349(2H^)A07(2Rdrr=5.0Hz),6.06(lRy=5.0Hz),624-635(2Rm),6.75-6.83(2Rm),6.89-6.98(lRm),12.0-12.1(lRm) ESI+ : 457 4 4 >MRl:1.82-2.19(2Rm)232-247(5Rna)2.69(2RtTJ=7.6H2)2.81-2.98(2Rm)3.08-338(2H^),4214.64(4H^)J553-671(5H^n),6.94-731(3Hm),737-7.49(3Rm)J3()-7.61(2Rm) ESI+ : 433 226 4 NMR1:1.73-1.86(2HjTi)2.14(3Rs)2.43f2RU=7.7Hz)2.69(2RtJ=7.7Hz)2.80(2RU=6.7Hz)2.99- 3.07(2H^)A18(2H^),4.46(2H^)M2^.53(2H^),d90-6.95(lRni),6.97-7.06(2H^X7.95-8.()(XlH^),8.19^25(lH^)3.56-8.62(lR^i),8.85-8.90(lRm) ESI+ : 434 227 4 NMR1:1.72- 1.85(2H^)2J8(3H^)239(2HU=7.6Hz)2.69(2RU=7.6Hz)2.79(2H,y=6.7Hz)2.92-3.(XK2H^)AH(2Rs)A13(2H^)A46-6i6(2R^i),6.89-6.94(lRin),6.96-7.07(2H^)^.l()-8.16(lH^)58.69-8J5(lH^X8.88-8.93(lH^),8.96-9.00(lH^i) ESI+ : 434 190 [0277] [Table 123] 9 9 >MRl:lJ6-1.88(2H^)228(3H^)2.44(2H,U=7.4Hzp.62-2.84(4Hm),3.01-3.54(10H^)3754.(XX4Iim),4.14-426(2Iim),5.75-7.56(9Hm),l 1.5-11.9(lfim) ESI+ : 456 2 2 MyiRl:1414i7(2H^)4J9-231(8Hm)242(2H,y=7.6Hzp.67(2H,U=7.6Hz)2.85-2.96(2H^),3.11-3.81(6H^),423(2H^),6.32-6.45(2Iim),6.94-7.04833-8.40(lHm) ESI+ : 482 235 4 NMRl:1.86-231(4H^)235-2.46(5Hjn)2.61-2.74(4Hjii)2.82-2.95(6Pim),4.10-6.03(5Hm),629-6.44(2Hm),6.93-7.02(lHm),7.07-7.14(111,111),7.17-737(6H^i),l 1.7-12.6(llim) ESI+ : 461 236 2 ESI+ : 470 191 [0278] [Table 124] 237 2 NMRl:1.66-179(2H^)2J4(3Rs)2.4()(2IiU=7.6Hz)^.61-2.75(4H^i)^97-3.07(2H^i)3.13-3.65(4H^i),4.07(2H,dJ==3.8Hz),6.07(lH,tJ=3.8Hz),6.23-6.36(2H^n),6.74-6.85(21im)56.88-6.98(lRm),11.7-12.8(2Iim) ESI+:401 238 8 ESI+.-401 239 8 ESI+.-444 240 4 ESI+:441 241 4 ESI+:411 242 15 ESI+ : 479 243 15 ESI+ : 557 15 15 ESI+ : 459 244 15 ESI+ : 468 245 15 ESI+ : 470 246 15 ESI+ : 479 247 15 ESI+:480 248 16 ESI+-.448 (M+Na) 249 16 ESI+:394 (M+Na) 250 16 ESI+ : 455 251 16 ESI+:457 M+Na) 252 16 ESI+-.457 (M+Na) 253 16 ESI+:487 (M+Na) 254 16 ESI+:456,478 (M+Na) 255 16 ESI+:464 M+Na) 256 16 ESI+:498 (M+Na) 257 16 ESI+:436 (M+Na) 258 16 ESI+.-499 (M+Na) 259 16 ESI+ : 490 260 16 ESI+-.442 (M+Na) 16 16 ESI+:476 (M+Na) 261 16 ESI+:472 (M+Na) 262 16 ESI+:458 (M+Na) 263 16 ESI+:510 (M+Na) 264 16 ESI+:456 (M+Na) 265 16 ESI+:485 (M+Na) 266 16 ESI+:472 (M+Na) 267 16 ESI+:458 (M+Na) 268 16 ESI+:456 (M+Na) 269 16 ESI+:526 (M+Na) 270 16 ESI+:476 M+Na) 192 [0279] [Table 125] 271 16 ESI+ : 499 (M+Na) 272 16 ESI+:485 (M+Na) 273 16 ESI+.-526 (M+Na) 274 16 ESI+:472 (M+Na) 275 16 ESI+: 553,575 (M+Na) 276 16 ESI+: 519,541 (M+Na) Til 16 ESI+:486 (M+Na) 278 16 ESI+:470 OVI+Na) 279 16 ESI+:524 flVl+Na) 280 16 ESI+:499 (M+Na) 281 16 ESI+:470 (M+Na) 282 16 ESI+ : 470 (M+Na) 283 16 ESI+: 490,512 (M+Na) 284 16 ESI+:471 (M+Na) 285 16 ESI+:539 (M+Na) 286 17 ESI+ : 427 287 17 ESI+ : 427 288 17 ESI+ : 427 289 17 ESI+ : 470 290 17 ESI+ : 470 291 17 ESI+ : 470 292 17 ESI+ : 436 293 17 ESI+ : 436 294 17 ESI+ : 436 295 17 ESI+ : 416 296 17 ESI+ : 416 297 17 ESI+ : 432 17 17 ESI+ : 420 298 17 ESI+ : 420 299 17 ESI+:486 300 17 ESI+ : 486 301 17 ESI+ : 500 302 17 ESI+ : 454 303 17 ESI+:448 304 17 ESI+ : 478 305 17 ESI+ : 433 306 17 ESI+ : 403 307 18 ESI+:478 (M+Na) 308 18 ESI+:512 (M+Na) 309 18 ESI+:492 (M+Na) 193 [0280] [Table 126] 310 18 ESI+:496 (M+Na) 311 18 ESI+.-546 (MrNa) 312 18 ESI+:512 (M-Na) 18 18 ESI+:492 (M--Na) 313 18 ESI+:546 (M-Na) 314 18 ESI+:496 (M-Na) 315 18 ESI+:508 (M-Na) 316 18 ESI+:512 (M-Na) 317 18 ESI+:546 (MH-Na) 318 18 ESI+:492 (MWa) 319 18 ESI+.-496 (MWa) 320 18 ESI+:508 (M-iNa) 321 18 ESI+:526 OvBNa) 322 18 ESI+:528 (M+Na) 323 18 ESI+: 549,571 M+Na) 324 18 ESI+:528 (M+Na) 325 18 ESI+:549 (M+Na) 326 18 ESI+.-522 (M+Nfa) 327 18 ESI+:518 (M+Na) 328 18 ESI+:534 (M+Na) 19 19 ESI+:462 329 19 ESI+:414 330 19 ESI+386 331 19 ESI+:414 332 19 ESI+:400 20 20 FAB+:458 333 20 FAB+:458 334 20 FAB+-.444 335 20 ESI+:452 336 20 ESI+.-430 337 20 ESI+:446 338 20 ESI+:452 21 21 ESI+:471 22 22 ESI+:481 339 22 ESI+-.437 340 22 FAB+:416 341 22 FAB+:430 23 23 FAB+:413 342 23 ESI+:461 24 24 FAB+-.326 194 [0281] [Table 127] 343 24 ESI+.-358 344 24 ESI+.-358 25 25 ESI+.-358 345 25 ESI+:371 26 26 ESI+:399 346 26 FAB+:447 347 P29 ESI+:354 27 27 FAB+358 348 27 FAB+:336(M)+ 349 27 FAB+-.344 350 27 FAB+:358 28 28 FAB+:416 351 28 ESI+:462 352 28 ESI+:412 353 28 ESI+:400 354 28 FAB+:372 355 28 FAB+:454 356 28 FAB+:448 357 28 FAB+:508 358 28 FAB+:449 359 28 FAB+:449 360 28 ESI+:449 361 28 FAB+.-516 362 28 FAB+:448 363 28 FAB+:386 364 28 FAB+:470 365 28 ESI+:448 366 28 FAB+:400 367 28 ESI+:462 368 28 ESI+:372 369 28 ESI+:400 370 28 ESI+:454 371 28 ESI+:400 372 28 ESI+:462 373 28 ESI+:400 374 28 ESI+:448 375 28 ESI+:462 29 29 ESI+:371 376 29 ESI+:453 377 29 ESI+:461 195 [0282] [Table 128] 378 29 ESI+:357 - 379 29 ESI+:447 380 29 ESI+-.399 381 29 ESI+:415 382 29 ESI+:401 383 29 ESI+.-433 384 29 ESI+:435 OQ ESI+:399 386 29 ESI+:447 387 29 ESI+:470 30 30 ESI+:478 388 30 FAB+:434 389 30 FAB+-.398 390 30 ESI+:444 391 30 ESI+:448 392 30 ESI+:448 393 30 ESI+:416 394 30 ESI+:448 395 30 ESI+:413 31 31 ESI+:462 396 31 ESI+:400 397 31 FAB+:400 398 31 FAB+:426 399 31 FAB+:414 400 31 FAB+:430 401 31 FAB+:428 402 31 FAB+:442 403 31 FAB+:462 404 31 "32 " FAB+:530 FAB+:498 - 32 405 32 FAB+:498 406 32 FAB+:436 407 32 FAB+:450 408 32 ESI+:464 33 33 FAB+:441 409 33 ESI+.-489 34 34 FAB+:434 410 34 ESI+:434 411 34 FAB+:420 412 34 FAB+.-434 196 [0283] [Table 129] 35 35 ESI+:491 413 2 NMR1:1.69-1.80(2Hm), 1.83(3Rs), 1.96-2.07(2Iim)2.48-2.62(2H^n)2.65-2.73(2Hm)3.61-3.70(2H^n),4.054.12(2Km),5.98-6.06(lH^n),620-6.33(2Hm),6.70(2H,dJ=8.9Hz),6.87-7.06(3Iim),720(2H,cU=8.9Hz) ESI-:451 414 NMRl:1.94-2.07(4H^)2.53-2.6(X2H^)274-2.81(2H^i)3.67-3.74(2Hm)3.90-3.97(2H^),5.99-6.()4(lH^)A13-623(2H^),6i8(lH,dJ=74Hz),6.87^.94(lH^n),7.11-7.19(2Rm);725(lRdJ=7.4Hz).7.31-7.38(2Rm) ESI+:424 ' , 415 NMRl:1.92-2.09(4Iim)2.53-2.61(2Iim)2.73-2.81(2Iim)3.68-3J5(2P^)3.98(2H,drr^.4HzX6.08(lPI,y==5.4Hz),6.15-626(2H5m),6.61-6.68(lH^)^86^.95(lH^n),7.13-720(lH)m),724-7.40(2H^),7.41-7.51(lHm) ESI+:442 416 NMRl:1.91-2.08(4Iim)2.53-2.61(2Hm)2.72-2.81(2Hm)3.69-3.76(2H^i)3.97(2H,(y=5.8HzX6.07(lH,U=5.8Hz),6.14- 625(2H^)A64(lH,dJ=74Hz)A87-6.94(lH^)J28(lH,cU=7.4Hz),7.32-7.39(4H^n) ESI+:440 417 NMRl:1.91-2.08(4HJm)2.54-2.61(2Iim)2.73-2.80(2H5m)3.71-3.77(2Iim)3.98(2H,drJ=5.7Hz),6.05(lH,a=6.7Hz),6.15-627(2H^i),6.64-6.69(lH^)A88-6.95(lH^),7.10-7.15(lH^n),728-736(3Hm),7.43-7.47(lHm) ESI+:440 418 NMRl:1.90-2.09(4H^)2.522.63(2H^)2.692.82(2Iim)3.67-3.77(2Hm)3.97- 4.()9(2H^)A08-629(3H^)A68-675(lHm),6.85^.95(lIim),726-7.41(3Hm) ESI+:460 419 NMRl:1.874.96(2H^)a.972.()6(2H^)2i22.61(2H^n)2.73-2.80(2Hm)3.92-4.(XK2H^)Al(M.18(2H^),62(>^32(3H^)A83-6.88(lH^n),6.89-6.97(lHUn),7.40-7.47(mm),7.65-7.71(lIim),7.77-7.84(lHm),837-8.41(lHm) ESI+: 485,487 420 NMR3:1.6()-1.69(4H^)179-1.93(lH^)231-239(2Jim)2.44(3H^)2.71- 279(2H^)2,82-2.95(2H^)333-3.44{2H,m)3.98-412(2H^a6.15-6.22(lH3mX625- 631(lHm),6.41-6-48(ltim)6.89-7.00(5H^n),7.19-726(lHni) ESI+:433 421 ESI+:521 197 [0284] [Table 130] 422 1 NMR1:1.66-174C2Km),l .84<3Hs),l .99-2.08(2Iim)2.53-2.61 (2IimU65- 274(2H^)3il-3i8(2H^),4.004.07(2H^),5.92-5.98(lH^i)^.99-6.05(2Iim),6.09- 6.16(lH^n),621-632(2H^i),678-6.85(lH^i),6.88-6.96(3Iim) ESI+:435 423 1 ESI+:372 424 1 ESI-:461 425 1 ESI-.-481 1 ESI-:465 427 2 ESI-:497 428 1 ESI+-.462 429 1 FAB+:464 430 1 ESI+:468 39 39 ESI+:450 431 39 ESI+:446 432 39 ESI+:462 433 39 ESI+.-468 434 11 FAB+:431 435 11 ESI+:445 436 11 ESI+.461 437 11 FAB+:432 438 11 FAB+:446 439 1 ESI+:445 36 36 ESI+.-445 440 11 NMRl:lJ6-2.00(2Iim)2.68(2H,U=8.0Hz)328- 342(2Hjn)3.65(2H,y^.7Hz)3.93(2H^)3.99(2H,dJ^.4Hz),4.12(2H,U^.7Hz)^.30(l H,y^.6Hz)A46(2H,dJ=8.8HzX6i2-6.66(4H^)A86-6.98(4H^)J22-732(2H^n) ESI+:433 441 21 NMR1:176-1.96(2H^)2.67(2EU^.4Hz)325(2Ils)3.65(2HtJ=6.7Hz),4.04r2H,dJ=63HzX4.12(2 HU^.71^),5.9(XlH,y^.4HzX6.49(2^^ Hz),6.85-6.97(4H^n),7.06(2H,(U=8.5Hz),722-732(2Iim) ESI+:449 442 1 ESI+:477 443 1 ESI+:507 444 5 ESI+:509 445 5 ESI+:509 198 [0285] [Table 131] 446 5 Mv4Rl:1.80-1.93(2H^yj4(2HU=8.0Hz)2.59(2H,y==8.0Hz)^.66(2H,a==6.3Hz)3.34- 341(2H^)3.63(2HtJ^.8Hz)376(3Iis),4.03(lH,cy=52Hz),4.07(2H,tJ=5.8Hz)^.96(l H,U^2Hz)A26(lH,dd7J=22,132Hz),631(lH,ckU=22,8.3Hz),6.53(lH,drJ-7.4Hz),6.60 (lH,(y=8.7Hz),6.61-6.67(lIim),6.85^.96(4H^i) ESI+.-497 447 5 MvlRl:lJ84.93(2H^)2.1(X2H,U=8.0Hz)2i9(2H,U=8.0Hz)2.67(2H,trr=62Hz)333- 339(2H^)3.66(2H,trr=^.5Hz),4.03(2H,dJ=5.1Hz),4.19(2H,tJ=5.5Hz)^.95(lH,y=5.1Hz X6260H^^1.9,13.1HzX631(lH#UN1.9,83Hz^ Hz)A85-7.02(3H^)JJ8(lHdy^A94Hz),727(lH,dddU=3.0,8.8,11.7Hz) ESI+:485 448 5 M^l:1.81-1.93(2H^y.012J5(2H^)2.54-2.61(2Hjrn)2.63-2.72(2H^n)327- 342(2H^)3.68(2H,y^.5Hz)A03(2H,dg[==5.2Hz),4.22(2H,U=5.5Hz),5.95(lH,trF=52Hz ),625(lH,dJ=132Hz),63()(lH,dU^.5Hz),6.54(lH,dJ=74Hz),6.61(lH,dU=8iHz)A74(l H,ty=3.1,8.5Hz),6.87- 6.96(2Iim),7.1 l(lH,dd4J=3.1,7.1,10.1Hz),724(lH,ddcy=5.4,9.1,l 1.1Hz) ESI+:485 449 5 MV1Rl:lJ94.91(2H^)2.04-2.15(2H^)2i52.62(2H^n)2.63-2.71(2HUn)329- 337(2H^)3-64(2H,y^.0Hz)A02(2H,cy^JHz)A41(2Ha^.OIfe)^.94(lH,trJ==5.1Hz ),626(lH,cy=13.1Hz)5631(lH,dJ^3Hz)A53(lH,cy=74Hz)J6.67(lH5cy=83Hz),6.80(l H,dJ^4Hz),6.88-7.(XX3H^n),7.66-7.73(lIirn),8.15(lH,dcy=1.7,5.0Hz) ESI+:450 450 2 NMRl:171-1.83(2H^y.982J()(2H^)2J3-2.59(2Iim)2.60-2.66(2Hm)3.00- 3.08(2H^p74(2Hy^.0Hz)A(^2Hdrf=53Hz)34.49(2H5y-6.OHz)^.95(lH,y=53Hz ),623(lH,ddJ=22,13.2Hz),629(lH,ddJ=22,83Hz),642(lH,cy=83Hz),6.55(lH,cy=73 Hz),6.84-6.95(2H^n),7.56(lIts) ESI+:559 451 5 NMRl:1.81-1.92(2H^)2.022Jl(2H^)2.54-2.62(2H^)2-63-2.72(2Iim)333- 338(2H^np.59(2H,y==5.9Hz)3.77(3H^),4.03(2H,dyJ=53Hz),4.11(2H,y=5.9Hz)^.95(l H,y^3Ife)A25(lH,cldJ=2.1432Hz),63(KlH,cldJ=2.133Hz)A48^36(2H^),6.79- 6.95(4Hm)57.04(m;dtyT=6358-5H7) ESI+.-497 199 [0286] [Table 132] 452 5 NMR.l:1.80-1.92(2Hm)2m-112(2HjTi)2.54-2.61(2Iim)2,62-2.69(2H^n)3.15-322(2Hm)323-329(2Rm)3.43- 349(2H^)A03(2HdJ^2Hz)^.95(lH,tJ^2Hz),625(lH,ddJ=2.0,13.1Hz),6.30(lH,cld rJ=2.0,8.3Hz),6.45(lH,dTI=82Hz),6.55(lH,cy=7.4Hz),6.86^.95(2H^i),722-729(lHm),7.3 l-736(2}im),7.40-7.46(lHm) FAB-:497 453 1 MvlRl:lJ7-1.87(2Hm),1.93(3iis),1.99-2.08(2}im)2.53-2.68(4Iim),3.82- 4.08(2H,m)54.15(2H5d;J^4Hz)56.08(lHtJ^4Hz);6.18-^36(3Hni)j6.68- 6J6(lH^),6.9O^.98(lH^)J.03(lH,cirJ=7.8Hz),7.()9(lH,dJ=7.8Hz),7.41- 7.49(llim),8.17-823 ESI+:420 454 2 >MRl:1.69-1.81(2H^)241(2H,U=7.6Hz)2.62(2Ha^-4Hz)2.67(2H,tJ=7.6Hz)2.96- 3.03(2Hm)3.62(2H,tTJ^62Hz),4.05(2Iis),427(2H,y^62Hz),622(lH,lyI=2.0Hz),632- 6.42(2Hm),6.49(lH,dJ=82Hz),6.55(lH,cU=7.4Hz),6.88- 7.00(2Hm),7.48(lH,drl=2.0Hz),7.68(lH,(y=2.0Hz) ESI-:421 455 1 NMRl:0.6(K).68(lIim),0.98-1.06(lH^i),122-130(lltm),1.80- 1.92(3Iim)2.67(2H,tyI=63Hz)332- 342(2H4n)3.65(2Hy^.7Hz),4.02(2H,dJ^3Hz),4.12(2H,y=5.7Hz)^.61(lPl,trr==5.5Hz )A45(2HdJ=84Hz),634{lHdJ=74Hz)A60(lH,dTJ=82Hz),6.71(2H,cy-8.4Hz),6.87- 6.95(4H^n),723-730(2Iim) ESI+:443 456 1 NMRl:0.75-0.84(lH^i),1.05-1.12(lJim),1.50-1.59(lIim),1.79- 1.92(3Iim)2.68(2H,U=63Hz)328- 3.34(2H^)3.65(2Ha^-7Hz),4.01(2H,drl-53Hz),4.12(2H,trJ==5.7Hz)^.49(lH,a=5-5Hz )^37(2Hd^4Hz),6.56(lH in the following SEQUENCE LISTING. Illustratively, the nucleotide sequence represented by the sequence of SEQ ID NO:l of the SEQUENCE LISTING is a nucleotide sequence of an artificially synthesized primer. Also, the nucleotide sequence represented by the sequence of SEQ ID NO:2 of the SEQUENCE LISTING is a nucleotide sequence of an artificially synthesized primer. 204 1. A carboxylic acid derivative represented by the following formula (I) or a pharmaceutically acceptable salt thereof (symbols in the formula represent the following meanings; R : -H, lower alkyl, halogeno-lower alkyl, cycloalkyl, aryl, heterocyclic group, lower alkylene-RA, -C(0)RB, -C02RB or -S(0)PRB, with the proviso that the lower alkylene, aryl and heterocyclic group in R1 may be respectively substituted, RA: cycloalkyl, aryl, heterocyclic group, -S(0)pR°, -S(0)p-aryl, -S(0)p-heterocyclic group, -C(0)R°, -C(0)-aryl, -C(0)-heterocyclic group, -C02R°, -OR0, -O-aryl, -O-heterocyclic group, -N(R°)2, -N(R°)-aryl, -N(R°)-heterocyclic group, -CO(R°)(aryl)2, -C(0)N(R°)- cycloalkyl or -C(O)N(R0)-aryl, with the proviso that the aryl and heterocyclic group in RA may be respectively substituted, RB: lower alkyl, halogeno-lower alkyl, cycloalkyl, aryl, heterocyclic group, lower alkylene- cycloalkyl, lower alkylene-aryl, lower alkylene-heterocyclic group, lower alkylene-OR°, lower alkylene-O-aryl or lower alkylene-S(0)2NH2, with the proviso that the aryl and heterocyclic group in RB may be respectively substituted, R°: -H or lower alkyl, n and p: the same or different from each other and each represents 0,1 or 2, J: -C(R6)(R7)-, -O- or -S-, R2, R3, R6 and R7: the same or different from one another and each represents -H, halogen, lower alkyl, -OR0 or aryl, with the proviso that R2 and R3, R3 and R6 and R6 and R7 may together form a lower alkylene, R4: -H or lower alkyl, X: single bond, -CH2-, -(CH2)2-, -0-, -S-, -S(O)- or -S(0)2-, Y: -CH2- or -C(O)-, 205 Z: C(-*), C(R ), N or N(O), with the proviso that the * in Z means binding to L, X and X : the same or different from each other and each represents C(R9), N or N(O), X and X : the same or different from each other and each represents C(R10), N or N(O), R : lower alkyl, halogen, halogeno-lower alkyl, -OR0 or -O-halogeno-lower alkyl, R , R and R : the same or different from one another and each represents -H, lower alkyl, halogen, halogeno-lower alkyl, -OR0 or -O-halogeno-lower alkyl, with the proviso that R6 and R!0 may together form a lower aikyiene, -O-iower aikyiene or lower alkylene-O-, L: -O-lower aikyiene, lower alkylene-O-, -N(RH)-lower aikyiene, lower alkylene-N(Rn)-, -O-lower alkylene-O-, -N(Rn)-lower alkyIene-N(Rn)-, -O-lower alkylene-N(Rn)- or -N(Rn)-lower alkylene-O-, and R11: -H, lower alkyl or -C(0)R°). 2. The compound described in claim 1, wherein J is -C(R6)(R7)-. 3. The compound described in claim 2, wherein X and Y are -CH2-. 4. The compound described in claim 3, wherein L is *-CH2-NH- or *-CH2-0-(wherein * means binding to the nitrogen-containing bicyclic ring group to which R is bonded). 5 The compound described in claim 4, wherein Z is CH, C(!ower alkyl), C(-*) (wherein * means binding to L) or N. 6. The compound described in claim 5, wherein n is 0; or n is 1 and R is halogen or lower alkyl. 7. The compound described in claim 6, wherein X1 and X2 are the same or different from each other and each is CH or N, and X3 and X4 are the same or different from each other and each is CH or C(halogen). ") "X ft 7 8. The compound described in claim 7, wherein R , R , R and R is H. 9. The compound described in claim 8, wherein R is -H. 10. The compound described in claim 9, wherein R1 is lower alkyl, halogeno-lower alkyl, aryl, heterocyclic group, lower alkylene-OR°, lower alkylene-aryl, lower alkylene-heterocyclic group or lower alkylene-O-aryl (however, the aryl and heterocyclic group in R1 may be respectively substituted by a group selected from halogen, -CN, lower alkyl, halogeno-lower alkyl, -OR0 and -O-halogeno-lower alkyl). 11. A compound described in claim 1, which is selected from the group consisting of 3-[2-fluoro-4-({[l-(2-phenylethyl)-l,2,3,4-tetrahydroquinolin-5-yl]methyl}amino)phenyl]propanoicacid, 3-[2-fluoro-4-({ [1 -(2-phenoxyethyl)-1,2,3,4-tetrahydroquinolin-5-yljmethyl} amino)phenyl]propanoic acid, 3-(2-fluoro-4- {[(8-methyl-1 -propyl-1,2,3,4-tetrahydroquinolin-7-yl)methyl]amino}phenyl)propanoicacid, 3-[2-fluoro-4-({ [8-methyl-1 -(2-phenylethyl)-l ,2,3,4-tetrahydroquinolin-7-yljmethyl} amino)phenyl]propanoic acid, 3 -(2-fluoro-4- {[(8-methyl-1 -phenyl-1,2,3,4-tetrahydroquinolin-7-yl)methyl] amino} phenyl)propanoic acid, 3-(2-fluoro-4-{[(8-phenyl-5,6,7,8-tetrahydro-l,8-naphthyridin-2- yl)methyl]amino}phenyl)propanoicacid, 3-{2-fluoro-4-[({l-[2-(4-methoxyphenyl)ethyl]-l,2,3,4-tetrahydroquinolin-5- yi} ineihyl)amino]phenyi} propanoic acid, 3-{2-fluoro-4-[({l-[2-(4-fluorophenoxy)ethyl]-l,2,3,4-tetrahydroquinolin-5- yl}methyl)amino]phenyl}pTopanoicacid, 3-{4-[({l-[2-(3-chlorophenoxy)ethyl]-l,2,3,4-tetrahydroquinolin-5- yl}methyl)amino]-2-fluorophenyl}propanoicacid, 3-[2-fluoro-4-({[l-(3-fluorophenyl)-8-methyl-l,2,3,4-tetrahydroquinolm-7- yllmethyl}amino)phenyl]propanoicacid, 3-{2-flu0ro-4-({[8-methyl-lK3-methylPhenyl)-l,2,3,4-tetrahydroqumohn-7- yl]methyl}amino)phenyl}propanoic acid, and 3-[4-({[l-(3,4-difluor0phenyl)-8-methyl-l,2,3,4-tetrahydroqmnohn-7- yl]methyl}amino)-2-fluorophenyl]propanoicacid, or a pharmaceutical^ acceptable salt thereof. ( 12. A pharmaceutical composition, which comprises a compound described in claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. 13. The pharmaceutical composition described in claim 12, which is a GPR40 agonist. 14. The pharmaceutical composition described in claim 12, which is an insulin secretion promoter.. 15. The pharmaceutical composition described in claim 12, which is an agent for preventing and/or treating diabetes mellitus. 16. Use of the compound described in claim 1 or a pharmaceutically acceptable salt thereof, for producing a GPR40 agonist, an insulin secretion promoter or a preventive and/or therapeutic agent for diabetes mellitus. 17. A method for preventing and/or treating diabetes mellitus, which comprises administering an effective amount of the compound described in claim 1 or a salt thereof to a patient.