Substituted Guanidine Derivative

[0001]The present invention relates to pharmaceutical compositions containing substituted guanidine derivatives and it particularly prevented by VAP-1 inhibitor, for the treatment of alleviation and / or the disease being treated, to pharmaceutical compositions containing substituted guanidine derivatives and it . Background technique

[0002] Type 2 diabetes is a kind of lifestyle-related diseases, the number of patients in recent years has been steadily increasing. Prolonged hyperglycemic state may gradually destroy the microvessels in the body, the eye, can lead to serious damage to various organs, including the kidney. Such severe failures are termed diabetic complications, among them diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, three as a large complications, major challenges onset prevention and suppression of progression of diabetes It has become.

[0003] Preventing onset and suppression of progression of diabetic complications, firstly although glycemic control is fundamental, in recent years, blood VAP-1 in diabetic patients (Vascular Adhesion Protein-1; also referred to as SSAO (Semicarbazide-Sensitive Amine Oxidase) that) the activity is increased, further it was found to be correlated with the amount in the plasma glycated hemoglobin. The enzyme that selectively localize in vascular tissue catalyzes the deamination of methylamine and aminoacetone, respectively, H 2 O 2 in addition to, ammonia, producing formaldehyde or methylglyoxal. Since they have a cytotoxic any, increase in blood VAP-1 activity it has been noted as one cause of onset of inflammatory diseases and diabetic complications (e.g., Non-Patent Documents 1 and 2 reference.).

[0004] This variety of VAP-1 inhibitors have so far been reported. Formula:

Formula 1

a compound represented by having a VAP-1 inhibitory activity, VAP-1 associated disease with various inflammatory diseases and diabetic complications early, especially diabetic nephropathy or diabetic macular edema it is described that are useful in the prevention and / or treatment of (e.g., see Patent Document 1).

[0005] Further, the following formula:

Formula 2

a compound represented by having a VAP-1 inhibitory activity, VAP-1 associated disease with various inflammatory diseases and diabetic complications early, especially diabetic nephropathy or diabetic that are useful in the prevention and / or treatment of macular edema are described (e.g., see Patent Document 2).

[0006] Meanwhile, the VAP-1 expression in the patient's liver with chronic liver disease is increasing, soluble VAP-1 levels and VAP-1 expression in the liver of the patient serum with nonalcoholic fatty liver disease, be elevated compared to that of patients not having the non-alcoholic fatty liver disease, further soluble VAP-1 levels in serum from liver biopsies of patients with non-alcoholic fatty liver disease Toko there is a correlation severity of fibrosis has been reported (e.g., see non-Patent Document 3). Therefore, by VAP-1 inhibitor, in addition to diabetic complications mentioned above, non-alcoholic fatty liver disease, in particular the prevention of non-alcoholic steatohepatitis, relaxation and / or therapy is expected. CITATION Patent Literature

[0007] Patent Document 1: WO 2011/034078 Patent Publication Patent Document 2: WO 2012/124696 Patent Publication Non-Patent Document

[0008] Non-Patent Document 1: Diabetologia (1997) 40: 1243-1250 Non-Patent Document 2: Diabetologia (2002) 45: 1255-1262 Non-Patent Document 3: The Journal of Clinical Investigation ( 2015) 2: 501-520 Summary of the Invention Problems that the Invention is to Solve

[0009] The present invention is prevented by VAP-1 inhibitor, to provide a relief and / or novel compounds useful in the treatment of the disease being treated and pharmaceutical compositions containing them. Means for Solving the Problems

[0010] The present inventors have, VAP-1 inhibitory activity result of extensive research for compounds with a series of substituted guanidine derivatives or salts thereof having an oxime structure in the molecule (= N-O-) is excellent VAP- It has 1 inhibitory activity, preventing the VAP-1 inhibitor, alleviation and / or the disease being treated, found to be particularly useful for the treatment of diabetic nephropathy and non-alcoholic steatohepatitis, and completed the present invention It was.

[0011] The present invention provides the following [1] to [34].

[1] general formula (I): [Chemical Formula 3] {wherein,

R 1 represents a hydrogen atom, protecting group, substituted or unsubstituted C for 1 -C 6 alkyl group, a substituted or unsubstituted C 2 -C 6 alkenyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C for 1 -C 6 alkoxy -C 1 -C 6 alkyl group, -CONR 11 R 12 , substituted or unsubstituted heterocyclyl groups , substituted or unsubstituted heterocyclyl -C 1 -C 6 alkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted C 7 -C 16 aralkyl group; X is, N or C-R 2 be a , where, R

2 is a hydrogen atom, a halogen atom, a substituted or unsubstituted C for 1 -C 6 alkyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C 1 -C 6 alkoxy group or a cyano a group; p and q are, independently of one another, is a natural number of 1 to 3, provided that the sum of p and q is a natural number of 2 to 4; wherein said "substitution" is deuterium atom, halogen atom, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, R 13 O-C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl groups, C 7 -C 16 aralkyl groups, C1 -C 7 acyl group, a cyano group, an oxo group, -CONR 11 R 12 , -OR 13 , -COOR 14 , -NR 15 R 16 and -S (O) n R 17 at least one selected from the group consisting of means being substituted with substituents,, R 11 and R 12 are independently hydrogen atom or a C 1 -C 6 alkyl group, R 13 is a hydrogen atom, C 1 -C 7 an acyl group or a protecting group, R 14 is a hydrogen atom or a C 1 -C 6 alkyl group, R 15 and R 16 are independently hydrogen atom, C 1 -C 6 alkyl groups, C7 -C 16 aralkyl group, C 1 -C 7 acyl group, -COOR 14 or -S (O) n R 17 is, R 17 is C 1 -C 6 alkyl group, and n is 0, 1 or 2 is} compound or a pharmacologically acceptable salt thereof represented by.

[2] the general formula (II): [Chemical formula 4] {wherein,

R 1 represents a hydrogen atom, protecting group, substituted or unsubstituted C for 1 -C 6 alkyl group, a substituted or unsubstituted C 2 -C 6 alkenyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C 1 -C 6 alkoxy -C 1 -C 6 Alkyl group, -CONR 11 R 12 , substituted or unsubstituted heterocyclyl groups, substituted or unsubstituted heterocyclyl -C 1 -C 6 alkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted C 7 -C 16 aralkyl group; p and q are, independently of one another, is a natural number of 1 to 3, provided that the sum of p and q is a natural number of 2 to 4; wherein said "substitution", heavy a hydrogen atom, a halogen atom, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, R 13 O-C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl groups, C 7 -C 16 aralkyl groups, C1 -C 7 acyl group, a cyano group, an oxo group, -CONR 11 R 12 , -OR 13 , -COOR 14 , -NR 15 R 16 and -S (O) n R 17 at least one selected from the group consisting of means being substituted with substituents,, R 11 and R 12 are independently hydrogen atom or a C 1 -C 6 alkyl group, R 13 is a hydrogen atom, C 1 -C 7 an acyl group or a protecting group, R 14 is a hydrogen atom or a C 1 -C 6 alkyl group, R 15 and R 16 are independently hydrogen atom, C 1 -C 6 alkyl groups, C7 -C 16 aralkyl group, C 1 -C 7 acyl group, -COOR 14 or -S (O) n R 17 is, R 17 is C 1 -C 6 alkyl group, and n is 0, 1 or 2 is a}

[1] compound or pharmacologically acceptable salt thereof according represented by. [3] R 1 is a hydrogen atom, a substituted or unsubstituted C for 1 -C 6 alkyl group, C 2 -C 6 alkenyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C 1 -C 6 alkoxy -C 1 -C 6 alkyl group or a substituted or unsubstituted heterocyclyl group, wherein said "substituted", a deuterium atom, a halogen atom, -OR

13 and -S (O) n R 17 means that it is substituted with at least one substituent selected from the group consisting of, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group in and, R 17 is C 1 -C 6 salt is an alkyl group, and n, which is 0, 1 or 2, is acceptable compound or a pharmacologically according to [2].

[4] p and q are 1, acceptable salt compound or a pharmacologically according to [3]. [5] R 1 is, C 1 -C 4 alkyl group, or a deuterium atom, at least one is substituted with a substituent a C is selected from the group consisting of fluorine atom and hydroxy group 1 -C 4 alkyl group there, the compound or pharmacologically acceptable salt thereof according to [4]. [6] the general formula (III): [Chemical Formula 5] {wherein, R 1 represents a hydrogen atom, protecting group, substituted or unsubstituted C

1 -C 6 alkyl group, a substituted or unsubstituted C 2 -C 6 alkenyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, -CONR 11 R 12 , substituted or unsubstituted heterocyclyl groups, substituted or unsubstituted heterocyclyl -C 1 -C 6 alkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted C 7 -C 16 aralkyl group; R 2 represents a hydrogen atom, a halogen atom, a substituted or unsubstituted C for 1 -C 6 alkyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C 1 -C6 alkoxy group or a cyano group; p and q are, independently of one another, is a natural number of 1 to 3, the sum of provided that p and q is a natural number of 2 to 4; wherein said "substituted "it is a deuterium atom, a halogen atom, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, R 13 O-C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, a cyano group, an oxo group, -CONR 11 R 12 , -OR 13 , -COOR 14 , -NR 15 R16 and -S (O) n R 17 means that it is substituted with at least one substituent selected from the group consisting of, R 11 and R 12 are independently hydrogen atom or a C 1 - C 6 alkyl group, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 14 is a hydrogen atom or a C 1 -C 6 alkyl group, R 15 and R 16 is , independently, a hydrogen atom, C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, -COOR 14 or -S (O) n R 17 is, R17 is C 1 -C 6 alkyl group, and n is 0, 1 or 2 is} compound or pharmacologically acceptable salt thereof according to [1] represented by. [7] R 1 is a hydrogen atom, a substituted or unsubstituted C for 1 -C 6 alkyl group, C 2 -C is a fluorine atom, compound or pharmacologically acceptable salt thereof according to [8]. [10] p and q are 1, compound or pharmacologically acceptable salt thereof according to [9]. [11] R 1 is, C 1 -C 4 alkyl group, or a deuterium atom, at least one is substituted with a substituent a C is selected from the group consisting of fluorine atom and hydroxy group 1 -C 4 alkyl group there, [10] the compound or a pharmacologically acceptable salt thereof. [12] compound is represented by the following: 2-fluoro-3- {2- [3- (methoxyimino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, ６アルケニル基、置換もしくは非置換のＣ３－Ｃ８シクロアルキル基、置換もしくは非置換のＣ１－Ｃ６アルコキシ－Ｃ１－Ｃ６アルキル基又は置換もしくは非置換のヘテロシクリル基であり、 ここで、前記「置換」は、重水素原子、ハロゲン原子、－ＯＲ１３及び－Ｓ（Ｏ）ｎＲ１７からなる群より選択される少なくとも１個の置換基で置換されていることを意味し、 Ｒ１３は、水素原子、Ｃ１－Ｃ７アシル基又は保護基であり、Ｒ１７は、Ｃ１－Ｃ６アルキル基であり、そしてｎは、０、１又は２である、［６］に記載の化合物又はその薬理上許容される塩。 ［８］ Ｒ２がハロゲン原子である、［７］に記載の化合物又はその薬理上許容される塩。 ［９］ Ｒ２

3- {2- [3- (ethoxyimino) azetidin-1-yl] pyrimidin-5-yl} -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(methoxy -d 3 ) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(2-fluoroethoxy) imino] azetidin- yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 3- (2- {3 - [(2,2-difluoro-ethoxy) imino] azetidin-1-yl} pyrimidin-5-yl) -2-fluoro benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(2,2,2-trifluoroethoxy) imino] azetidin- Yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(3-fluoro-propoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamate Mimi Doyle carbamate, 2-fluoro-3- {2- [3 - ({4 - [(tetrahydropyran-2-yl) oxy] butoxy} imino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamate Mimi Doyle carbamate, 2-fluoro-3- (2- {3 - [(2-methoxyethoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, [({1- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] Zechijin-3-ylidene} amino) oxy] methyl pivalate, 1 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] -3- methoxypropan-2-yl acetate, 4 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene } amino) oxy] butane-1,2-diyl diacetate, 2 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl ] azetidin-3-ylidene} amino) oxy] ethyl acetate, 2 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) Oki ] Methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] ethyl propionate, 2 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy ] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] ethyl butyrate, 2 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy ] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] ethyl benzoate, 2-fluoro-3- {5-fluoro-6- [3- (methoxyimino) azetidine 1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- (5-full Oro-6- {3 - [(methoxy -d 3) Imino] azetidin-l-yl} pyridin-3-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- {6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {6- [3- (methoxyimino) azetidin-1-yl] -5-methyl-3-yl} benzyl carbamimidoyl carbamate, 3- {5 - cyano-6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} -2-fluorobenzyl carbamimidoyl carbamate, 3- {5-chloro-6- [3- (methoxyimino ) azetidin-1-yl] pyridin-3-yl} -2-fluorobenzyl carbamimidoyl carbamate, 3- {5- (difluoromethyl ) -6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} -2-fluorobenzyl carbamimidoyl carbamate, 3- {5-cyclopropyl-6- [3- (methoxy imino) azetidin-1-yl] pyridin-3-yl} -2-fluorobenzyl carbamimidoyl carbamate, 3- {5-ethyl-6- [3- (methoxyimino) azetidin-1-yl] pyridine -3 - yl} -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- {6- [3- (methoxyimino) azetidin-l-yl] -5- (methoxymethyl) pyridin-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {5-methoxy-6- [3- (methoxyimino) azetidin-l-yl] pyridinium Down-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [4- (methoxyimino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 3- {2- [4- (ethoxyimino) piperidine -1 - yl] pyrimidin-5-yl} -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [4- (isopropoxycarbonyl alkoximinoalkyl amino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [4- (propoxyimino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 3- (2- {4- [ (allyloxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carba-mer DOO, 2-fluoro-3- {2- [4 - ({2 - [(tetrahydropyran-2-yl) oxy] ethoxy} imino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl-carba Mart, 2-fluoro-3- (2- {4 - [(2-methoxyethoxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2 - [({1- [ 5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] piperidin-4-ylidene} amino) oxy] ethyl acetate, (E / Z) -2- fluoro-3- {2- [3- (methoxyimino) pyrrolidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [3- (hydroxyimino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(2 - hydroxyethoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(3-hydroxypropoxy) imino] azetidin- yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(4-hydroxy-butoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamate Mimi Doyle carbamate, 2-fluoro-3- [2- (3 - {[2- (2-hydroxyethoxy) ethoxy] imino} Zechijin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[3-fluoro-2- (hydroxymethyl) propoxy] imino} azetidine -1 - yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(4-hydroxy-3-methoxy-butoxy) imino] azetidin-1-yl} pyrimidine -5 - yl) benzyl carbamimidoyl carbamate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidine -3 - ylidene} amino) oxy] -2- (hydroxymethyl) propyl acetate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] -2- (hydroxymethyl) propyl propionate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] -2- (hydroxymethyl) propyl butyrate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl ] azetidin-3-ylidene} amino) oxy] -2- (hydroxymethyl) propyl isobutyrate, 3 - [({1- [5 (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] -2- (hydroxymethyl) propyl pivalate, 3- [ ({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] -2- (hydroxymethyl ) propyl hexanoate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino ) oxy] -2- (hydroxymethyl) propyl benzoate, 2-fluoro-3- {5- (2-hydroxy Propan-2-yl) -6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(2-hydroxyethoxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- { 4 - [(3-hydroxypropoxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(4-hydroxy-butoxy) imino ] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(3-hydroxy-2,2-dimethyl propoxy) imino] piperidine -1 - yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(3-hydroxy 3-methylbutoxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(2-hydroxypropoxy) imino] piperidine - 1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(3-hydroxy-2-methyl-propoxy) imino] piperidin-1-yl} pyrimidine - 5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[3-hydroxy-2- (hydroxymethyl) propoxy] imino} azetidin-1-yl) pyrimidin-5-yl ] benzyl carbamimidoyl carbamate, 3- (2- {3 - [(2,3-dihydroxy-propoxy) imino] Zechijin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 3- (2- {3 - [(3,4-dihydroxy-butoxy) imino] azetidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 3- (6- {3- [(3,4-dihydroxy-butoxy) imino] azetidin-l-yl} -5-fluoro-3-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- {5-fluoro -6 - [3 - {[3-hydroxy-2- (hydroxymethyl) propoxy] imino} azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[3-hydroxy-2- (hydroxymethyl) propoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl Karubami Mi Doyle carbamate, 2-fluoro-3- [2- (4 - {[3-hydroxy-2- (hydroxymethyl) -2-methyl propoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- (2- {4 - [(2,3-dihydroxy-propoxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2- fluoro-3- [2- (3 - {[3-hydroxy-2- (methoxymethyl) propoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro -3 - (2- {3 - [(3-hydroxy-2-methoxypropoxy) imino] azetidin-1-yl} pyrimidine-5-y Le) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(2-fluoro-3-hydroxy-propoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (5-fluoro-6- {3 - [(2-fluoro-3-hydroxy-propoxy) imino] azetidin-l-yl} pyridin-3-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2 - {3 - [(2-hydroxy-3-methoxypropoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [4- (hydroxymethyl imino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {5- Ruoro-6- [3- (hydroxyimino) azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, tert-butyl 2 - [({l- [5- (3 - {[(carba Mimi Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] acetate, 2 - [({l- [5- (3 - {[(Karubamimi Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] acetic acid, 3- [2- (3 - {[(dimethylcarbamoyl) oxy] imino} azetidine 1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate 2-fluoro-3- [2- (3 - {[2- (methylamino) -2-oxo-ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- ( 2- {3 - [(3-amino-3-oxopropoxy) imino] azetidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[3- (methylamino) -3-oxopropoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, ethyl 4 - [({l- [5- ( 3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy Butanoate, 4 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] butane acid, 2-fluoro-3- [2- (3 - {[4- (methylamino) -4-oxobutoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3 - [2- (3 - {[2- (dimethylamino) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- {2- [3- ({2- [benzyl (methyl) amino] ethoxy} imino) azetidin-1-yl] pyrimidin-5-yl} -2-fluorobenzyl Karubamimido Rukarubamato, 3- [2- (3 - {[3-acetamido-2- (hydroxymethyl) propoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- [ 2- (3 - {[3- (dimethylamino) -2- (hydroxymethyl) propoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- ( 2- {3 - [(3-acetamido-2-methoxy propoxy) imino] azetidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[2- (piperidin-1-yl) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl Ca Luba Mimi Doyle carbamate, 2-fluoro-3- (2- {3 - [(2-morpholinoethoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 3- [2 - (3 - {[2- (azetidin-1-yl) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- [2- (3- {[2- (3,3-difluoro-1-yl) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[2- (3-fluoro-1-yl) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl Carbamimidoyl carbamate 2-fluoro-3- [2- (3 - {[2- (3-Methoxy-1-yl) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[(4-methyl-morpholin-2-yl) methoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- [ 2- (3 - {[(4-acetyl-2-yl) methoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[(5-oxo tetrahydrofuran-2-yl) methoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl Cal Ba Mimi Doyle carbamate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino ) oxy] cyclobutyl acetate, 2-fluoro-3- (2- {3 - [(3-hydroxy-cyclo-butoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 3- ( 2- {3 - [(benzyloxy) imino] azetidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[( 4-methoxybenzyl) oxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carba-mer , 2-fluoro-3- [2- (3 - {[(1-methyl-3-yl) oxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- [2- (3 - {[(1-acetyl-3-yl) oxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- [2 - (3 - {[(1-benzyl-3-yl) oxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [3 - ({[1- (2,2,2-trifluoroethyl) azetidin-3-yl] oxy} imino) azetidin-1-yl] pyrimidin-5-yl} Ben Le carbamimidoyl carbamate, 2-fluoro-3- {2- [3 - ({[l- (methylsulfonyl) azetidin-3-yl] oxy} imino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 3- [2- (3 - {[(1-ethyl-3-yl) oxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carba Mimi Doyle carbamate, methyl 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino ) oxy] azetidine-1-carboxylate, 2-fluoro-3- (2- {3 - [(oxetan-3-yloxy) imino] azetidine Down-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2- {3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] azetidin-1-yl} ethyl acetate, 2-fluoro-3- {2- [3 - ({[1- (2-hydroxyethyl) azetidin-3-yl] oxy} imino) azetidin-1-yl] pyrimidine - 5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [3 - ({[1- (2-methoxyethyl) azetidin-3-yl] oxy} imino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [3 - ({[1- (2-fluoroethyl) azetidin-3-yl] Carboxymethyl} imino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, ethyl 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} - 2-fluorophenyl) pyrimidin-2-yl] piperidin-4-ylidene} amino) oxy] propanoate, 3- (2- {4 - [(3-amino-3-oxopropoxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[3- (methylamino) -3-oxopropoxy] imino} piperidin-1-yl ) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, ethyl 4 - [({l- [5- (3 - {[(Karubamimido Carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] piperidin-4-ylidene} amino) oxy] butanoate, 4 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] piperidin-4-ylidene} amino) oxy] butanoic acid, 3- [2- (4 - {[3- (dimethylamino) -3-oxopropoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- ( 2- {4 - [(2-acetamide ethoxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4- { [2-(N-methylacetamide) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2 - fluoro -3- [2- (4 - {[ 2- (N- methyl sulfonamide) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro - 3- [2- (4 - {[2- (methylsulfonamido) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- [2- (4 - {[ 2- (dimethylamino) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate 2-fluoro-3- [2- (4 - {[2- (methyl amino) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate 3- (2- {4 - [(2- Minoetokishi) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 3- (2- {4 - [(2-cyano-ethoxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 3- (2- {4 - [( 3-cyano-propoxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[2- (methylsulfonyl) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[3- (methylsulfonyl) propoxy] imino} piperidine -1 - yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[(1-methyl -1H Pyrazol-3-yl) methoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- [2-(4 - {[(1H-pyrazol-3-yl) methoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [4 - ({[1- (tetrahydropyran-2-yl) -1H- pyrazol-4-yl] methoxy} imino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 3- [2-(4 - {[(1H-pyrazol-4-yl ) methoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[(1-methyl -1H- pyrazol-4-yl) methoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- [2- (4 - {[ 2- (1H- pyrazol-1-yl) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2- fluoro-3- (2- {4 - [(pyridin-4-ylmethoxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 3- [2- (4 - {[2 - (2,5-dioxo-1-yl) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluoro-benzyl carbamate ear de dolphins Rubamato, 2-fluoro-3- [2- (4 - {[2- (2-oxopyrrolidin-1-yl) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate , 2-fluoro-3- [2- (4 - {[2- (2-oxo-oxazolidine-3-yl) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[2- (3-oxomorpholino) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro -3 - {2- [4- (phenoxyimine amino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(pyrimidin-5-yloxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, or 2-fluoro-3- (2 - {4 - [(pyrimidin-2-yloxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate is, acceptable salt compound or a pharmacologically according to [1] .

[13] 2-fluoro-3- {2- [3- (methoxyimino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, or a pharmacologically acceptable salt thereof.

[14] 3- {2- [3- (ethoxyimino) azetidin-1-yl] pyrimidin-5-yl} -2-fluorobenzyl carbamimidoyl carbamate, or a pharmacologically acceptable salt thereof.

[15] 2-fluoro-3 - (2- {3 [(methoxy -d 3 is) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, or a pharmacologically acceptable salt.

[16] 2-fluoro-3 - is (2- {3 [(2-fluoroethoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, or a pharmacologically acceptable salt.

[17] 2-fluoro-3- {5-fluoro-6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, or a pharmacologically acceptable salt thereof .

[18] 2-fluoro-3- (5-fluoro-6- {3 - [(methoxy -d 3 ) imino] azetidin-l-yl} pyridin-3-yl) benzyl carbamimidoyl carbamate, or a pharmacologically tolerated salt that.

[19] 3- (6- {3 - [(3,4-dihydroxy-butoxy) imino] azetidin-l-yl} -5-fluoro-3-yl) -2-fluorobenzyl carbamimidoyl carbamate, or a pharmacologically acceptable salt thereof.

[20] 2-fluoro-3- {5-fluoro-6- [3 - {[3-hydroxy-2- (hydroxymethyl) propoxy] imino} azetidin-1-yl] pyridin-3-yl} benzyl Karubamimi Doyle carbamate, or a pharmaceutically acceptable salt thereof.

[21] 2-fluoro-3- (2- {3 - [(2-fluoro-3-hydroxy-propoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, or a pharmacologically salt to be above acceptable.

[22] 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] cyclobutyl acetate or a pharmaceutically acceptable salt thereof.

[23] is allowed - ({[(3-hydroxy-cyclo-butoxy) imino] azetidin-l-yl 3} pyrimidin-5-yl 2-) benzyl carbamimidoyl carbamate or a pharmacologically 2-fluoro-3- salt.

[24] 2-fluoro-3- {2- [3 - ({[l- (methylsulfonyl) azetidin-3-yl] oxy} imino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate or a pharmacologically acceptable salt thereof.

[25] is allowed - ({[(oxetan-3-yloxy) imino] azetidin-l-yl 3} pyrimidin-5-yl 2-) benzyl carbamimidoyl carbamate or a pharmacologically 2-fluoro-3- salt.

[26] Salts pharmacologically acceptable salt is a salt of an organic acid, which is pharmacologically acceptable compound according to any one of [1] to [25].

[27] the pharmacologically acceptable salt is a salt of a dicarboxylic acid, pharmacologically acceptable salts of a compound according to any one of claims [1] to [25].

[28] [1] to [27] the compound or a pharmacologically acceptable salt thereof according to any one of, containing an additive acceptable at least one pharmacologically, pharmaceutical compositions.

[29] prevented by VAP-1 inhibitor, for the treatment of alleviation and / or the disease being treated, the pharmaceutical composition according to [28].

[30] the disease is diabetic nephropathy, the pharmaceutical composition according to [29].

[31] the disease is non-alcoholic steatohepatitis, the pharmaceutical composition according to [29].

[32] prevented by VAP-1

[33] Prevented by VAP-1 inhibitor, for the manufacture of a medicament for the treatment of alleviation and / or the disease being treated, [1] to a compound or use of a pharmacologically acceptable salt thereof according to any one of [27] .

[34] A therapeutically effective amount of a compound or a pharmacologically acceptable salt thereof according to any one of [1] to [27], comprising administering to a patient in need thereof, preventing the VAP-1 inhibitor the method treatment of diseases which are alleviated and / or treatment. Effect of the invention

[0012] Compound or a pharmacologically acceptable salt thereof represented by the general formula (I) of the present invention has a high VAP-1 inhibitory activity and excellent pharmacokinetic properties, preventing the VAP-1 inhibitor, alleviating and / or disease being treated, typically, non-alcoholic fatty liver disease, such as nonalcoholic steatohepatitis; atopic dermatitis, inflammatory diseases such as psoriasis; diabetic neuropathy, diabetic retinopathy (particularly, useful in the treatment of metabolic disorders such as obesity; heart diseases such as myocardial infarction; vascular disease atherosclerosis and the like; diabetic macular edema), diabetic complications such as diabetic nephropathy. DESCRIPTION OF THE INVENTION

[0013] The means of terms used in the specification and claims, is described below. Unless stated otherwise, terms used in the specification and claims have the following meanings.

[0014] Numerical range expressed by using "to" in the specification are indicative of the range including the respective minimum and maximum values ​​of the numerical values ​​described before and after "to".

[0015] In the present invention, compounds of general formula (I) includes its isotope isomer. That is, in the compounds of formula (I), all or part of each atom may be replaced by the corresponding isotopes atoms. The isotopic atom refers to an atom having a different mass number and mass number found in nature. Examples of such isotopes atom, hydrogen atom ( 2 H, 3 H), carbon atoms ( 13 C, 14 C), nitrogen atom ( 15 N), oxygen atom ( 17 O, 18 include O) and the like It is. In particular, a deuterium atom ( 2 H) may be referred to as "D". In such a case, in the compound of formula (I), all of the hydrogen atoms of a particular location which is denoted by D is replaced by deuterium atom, a different molecular weight than the molecular weight calculated from the mass number found in nature.

[0016] The "halogen atom" or "halo", alone or in combination with other groups, means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

[0017] "C 1 -C 6 includes alkyl groups", alone or in combination with other groups, having 1-6 carbon atoms, straight-chain or branched-chain saturated aliphatic hydrocarbon monovalent It refers to the group. C 1 -C 6 Examples of alkyl groups include methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group (including various isomers). C 1 -C 6 Preferred embodiments of the alkyl groups, C 1 -C 4 alkyl group, e.g., methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec- butyl group, with tert- butyl is there.

[0018] "C 1 -C 6 The alkoxy group", alone or in combination with other groups, group -O-R 4 (wherein, R 4 is the C 1 -C 6 is an alkyl group) means a to. C 1 -C 6 Examples of the alkoxy group include a methoxy group, an ethoxy group, a propoxy group, butyloxy group, pentyloxy group, hexyl group (including various isomers). C 1 -C 6 a preferred embodiment of the alkoxy groups, C 1 -C 4 alkoxy group include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, butyloxy group, isobutyl group, sec- butyloxy, tert - is a butyloxy group.

[0019] "C 1 -C 6 alkoxy -C 1 -C 6 includes alkyl groups", the C 1 -C 6 C above substituted with an alkoxy group 1 -C 6 means an alkyl group. C 1 -C 6 alkoxy -C 1 -C 6 Examples of alkyl groups, methoxymethyl group, ethoxymethyl group, propoxymethyl group, butyl oxymethyl group, pentyloxymethyl group, hexyloxy group, a methoxyethyl group, ethoxyethyl ethyl group, propoxyethyl group, butyl oxy ethyl group, pentyloxy ethyl group, hexyloxyethyl group, methoxypropyl group, ethoxypropyl group, propoxypropyl group, etc. butoxybutyl (including various isomers). C 1 -C 6 alkoxy -C 1 -C 6 Preferred embodiments of the alkyl groups, C 1 -C 4 alkoxy -C 1 -C 4An alkyl group, e.g., methoxymethyl group, ethoxymethyl group, 2-methoxyethyl group, a 2-ethoxyethyl group, 3-methoxypropyl group, 2-methoxypropyl, 3-methoxybutyl group or the like.

[0020] "Halo C 1 -C 6 alkyl group" means linear, identical or replaced with a different halogen atoms as mentioned above the above C 1 -C 6 means an alkyl group. Halo C 1 -C 6 Examples of the alkyl group, fluoromethyl group, chloromethyl group, bromomethyl group, difluoromethyl group, dichloromethyl group, dibromomethyl group, trifluoromethyl group, trichloromethyl group, tribromomethyl group, 2 - fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2-difluoroethyl group, 2,2-dichloroethyl group, 2,2-dibromo ethyl group, 2,2,2-trifluoroethyl group, 2,2,2-trichloroethyl group, 2,2,2-bromoethyl group, pentafluoroethyl group, pentachloroethyl group, pentabromoethyl group, 3-fluoropropyl group, 3-chloropropyl group, 3- bromopropyl group, a straight-chain or branched halo C and 2,3-difluoro-propyl 1 -C 6 include alkyl groups .

[0021] "C 3 -C 8 Cycloalkyl group" has 3 to 8 carbon atoms, refers to a monovalent group of cyclic saturated aliphatic hydrocarbon. C 3 -C 8 Examples of cycloalkyl groups include cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group and the like. C 3 -C 8 a preferred embodiment of the cycloalkyl group, C 3 -C 6 cycloalkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group or cyclohexyl group.

[0022] "C 2 -C 6 includes alkenyl group" having 2 to 6 carbon atoms, containing at least one double bond, straight-chain or branched aliphatic unsaturated hydrocarbon monovalent It refers to the group. C 2 -C 6 Examples of alkenyl groups include vinyl, allyl, isopropenyl, 1-butenyl, 2-butenyl, 1,3-butadienyl, 2-pentenyl and the like. C 2 -C 6 preferred embodiment of the alkenyl groups, C 2 -C 4 alkenyl group, for example, vinyl, allyl, isopropenyl, 1-butenyl, 2-butenyl, 1,3-butadienyl and the like.

[0023] The "aryl group", having 6-10 carbon atoms, means a monovalent radical of an aromatic hydrocarbon. Examples of aryl groups are phenyl, 1-naphthyl, 2-naphthyl and the like.

[0024] "C 7 -C 16 and aralkyl group", the C substituted by the above aryl group 1 -C 6 means an alkyl group. C 7 -C 16 Examples of aralkyl groups are benzyl, 1-phenylethyl, 2-phenylethyl group, a 1-naphthylmethyl group and the like.

[0025] The "heterocyclyl group", the nitrogen atom, is independently selected from the group consisting of an oxygen atom and a sulfur atom, containing from 1 to 4 heteroatoms, a 4 to 7 membered, saturated, partially unsaturated or unsaturated It means a monocyclic heterocyclic monovalent group or the monocyclic heterocyclic ring is a benzene or cyclohexane fused bicyclic heterocycle monovalent group. Examples of such heterocyclyl groups include azetidinyl group, pyrrolidinyl group, pyrrolinyl group, a pyrrolyl group, a piperidyl group, a pyridyl group, azepanyl group, azepinyl group, imidazolidinyl group, imidazolinyl group, imidazolyl group, pyrazolidinyl group, pyrazolinyl group, pyrazolyl group, piperazinyl group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, triazolyl group, tetrazolyl group, oxetanyl group, tetrahydrofuryl group, a furyl group, pyranyl group, tetrahydropyranyl group, a thienyl group, a thiazolyl group, isothiazolyl group, oxazolidinyl group, oxazolinyl, oxazolyl, isooxazolidinyl group, isoxazolinyl group, isoxazolyl group, monocyclic heterocyclic groups such as morpholinyl group, or indolyl, Benzofura, , Benzothiophene, quinoline, isoquinoline, tetrahydroquinoline, groups of bicyclic heterocycles such as tetrahydroisoquinoline.

[0026] "Heterocyclyl -C 1 -C 6 includes alkyl groups", the substituted C above heterocyclyl group 1 -C 6 means an alkyl group. Heterocyclyl -C 1 -C 6 Examples of alkyl groups include 2- (piperidin-1-yl) ethyl group, 2-morpholinoethyl group, 2- (azetidin-1-yl) ethyl group, morpholin-2-ylmethyl, ( tetrahydrofuran-2-yl) methyl group, 1H-pyrazol-3-ylmethyl group, 1H-pyrazol-4-ylmethyl group, 2-(1H-pyrazol-1-yl) ethyl group, pyridin-4-ylmethyl group, pyridin - 3-ylmethyl group, pyridin-2-ylmethyl group, 2- (pyrrolidin-1-yl) ethyl group, 2- (oxazolidin-3-yl) ethyl group, 2- (3-oxomorpholino) ethyl group, 2- ( etc. 1H- tetrazol-5-yl) ethyl group.

[0027] 「Ｃ１－Ｃ７アシル基」とは、基－ＣＯ－Ｒ５（ここで、Ｒ５は、水素原子、上記Ｃ１－Ｃ６アルキル基又はフェニル基である）を意味する。Ｃ１－Ｃ７アシル基の例として、ホルミル基、アセチル基、プロピオニル基、ブチリル基、イソブチリル基、バレリル基、イソバレリル基、ピバロイル基、ヘキサノイル基、ベンゾイル基等が挙げられる。

[0028] "Protecting group" means a protecting group for hydroxy group, one of ordinary skill in the art, well known in the art, for example Protective Groups in Organic Synthesis, 4th edition, TW Greene, PGM Wuts al., John Wiley & Sons Inc. (2006 year ) arbitrarily be selected from among the hydroxy-protecting group described in such. The protecting group of such hydroxy groups, C 1 -C 7 acyl group (e.g., formyl group, acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a valeryl group, an isovaleryl group, a pivaloyl group, a hexanoyl group, a benzoyl group ) acyl type protecting groups such as, methoxymethyl, 1-ethoxyethyl group, a methylthiomethyl group, benzyloxymethyl group, acetal-type protective groups such as tetrahydropyranyl group; tri (C 1 -C 4 alkyl) silyl group ( For example, a trimethylsilyl group, triethylsilyl group, triisopropylsilyl group, dimethylisopropylsilyl group, tert- butyldimethylsilyl group), (C 1 -C 4 alkyl) diarylsilyl groups (e.g., tert- butyldiphenylsilyl group, diphenylmethyl silyl group), triaryl Lil group (e.g., a triphenylsilyl group), a silyl based protective group such as tribenzylsilylamino; benzyl, p- methoxybenzyl, a benzyl-based protecting group such as triphenylmethyl and the like. A preferred embodiment of the protecting group, C 1 -C 7 acyl group, tetrahydropyranyl group, tri (C 1-C 4 alkyl) silyl group, a benzyl group, p- methoxybenzyl group, a triphenylmethyl group and the like.

[0029] In the case the compound represented by the general formula (I) contains a 1,2- or 1,3-diol structure, protecting groups, protected by two hydroxy groups to form a 5- or 6-membered cyclic compound , it may be a cyclic acetal. Examples of cyclic acetals, methylene acetal, ethylidene acetal, acetonide, benzylidene acetal, p- methoxybenzylidene acetal, and the like. R 1 is, two -OR 13 substituted with groups, if containing 1,2- or 1,3-diol structure, a preferred embodiment of the protecting group is acetonide.

[0030] In the present invention, the term "substituted or unsubstituted", the group is unsubstituted or substituted by a given substituent group, for example, a deuterium atom, a halogen atom, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, R 13 O-C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, a cyano group, an oxo group, -CONR 11 R 12 , -OR 13 , -COOR 14 , -NR 15 R 16 and -S (O) n R17 (wherein, R 11 and R 12 are independently hydrogen atom or a C 1 -C 6 alkyl radical, R 13 represents a hydrogen atom, C 1 -C 7 acyl group or a protecting radical, R 14 is a hydrogen atom or a C 1 -C 6 alkyl group, R 15 and R 16 are independently hydrogen atom, C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, -COOR 14 or -S (O) n R 17 is, R 17 is, C 1 -C 6An alkyl group, and n means that it is substituted with at least one substituent selected from the group consisting of 0, 1 or 2).

[0031] In the present invention, "substituted or unsubstituted C for 1 -C 6 preferred embodiment of the alkyl group", (unsubstituted) C 1 -C 6 or an alkyl group, or a deuterium atom, a halogen atom, C 1 - C 7 acyl group, a cyano group, an oxo group, -CONR 11 R 12 , -OR 13 , -COOR 14 , -NR 15 R 16 and -S (O) n R 17 (wherein, R 11 and R 12 are, independently hydrogen atom or a C 1 -C 6 alkyl group, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 14 is a hydrogen atom or a C 1 -C 6An alkyl group, R 15 and R 16 are independently hydrogen atom, C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, -COOR 14 or -S ( O) n R 17 is, R 17 is C 1 -C 6 alkyl group, and n is substituted with at least one substituent selected from the group consisting of 0, 1 or 2) and which C 1 -C 6 alkyl group. "Substituted or unsubstituted C for 1 -C 6 and more preferred embodiments of the alkyl group", (unsubstituted) C 1 -C 6 or an alkyl group, or a deuterium atom, a halogen atom, a cyano group, -CONR 11 R 12 , -OR 13, -COOR 14 , -NR 15 R 16 and -S (O) n R 17 C is substituted with at least one substituent selected from the group consisting of 1 -C 6 alkyl group. "Substituted or unsubstituted C for 1 -C 6 further preferred embodiment of the alkyl group", (unsubstituted) C 1 -C 6 or an alkyl group, or a deuterium atom, a halogen atom, -OR 13 and -S (O) n R 17 C is substituted with at least one substituent selected from the group consisting of 1 -C 6 alkyl group. "Substituted or unsubstituted C for 1 -C 6 particularly preferred embodiment of the alkyl group", (unsubstituted) C 1 -C 6 from the group consisting of either an alkyl group or a deuterium atom, a fluorine atom and a hydroxyl group C substituted with at least one substituent selected 1-C 6 alkyl group.

[0032] In the present invention, "substituted or unsubstituted C 2 -C 6 preferred embodiment of the alkenyl group", (unsubstituted) C 2 -C 6 or an alkenyl group, or a deuterium atom, a halogen atom, -OR 13 and -S (O) n R 17 (wherein, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 17 is C 1 -C 6 alkyl group, and n is , C is substituted with at least one substituent selected from the group consisting of 0, 1 or 2) 2 -C 6 alkenyl group. "Substituted or unsubstituted C 2 -C 6 and more preferred embodiment of the alkenyl group", (unsubstituted) C 2 -C 6 alkenyl group.

[0033] In the present invention, "substituted or unsubstituted C for 3 -C 8 a preferred embodiment of the cycloalkyl group", (unsubstituted) C 3 -C 8 or a cycloalkyl group, or a deuterium atom, a halogen atom, - oR 13 and -S (O) n R 17 (wherein, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 17 is C 1 -C 6 alkyl group, and n is, C is substituted with at least one substituent selected from the group consisting of 0, 1 or 2) 3 -C 8 cycloalkyl group. "Substituted or unsubstituted C for 3 -C 8 more preferred embodiment of the cycloalkyl group", (unsubstituted) C 3 -C 8 cycloalkyl group, or at least one -OR 13 C is substituted with 3 -C8 is a cycloalkyl group.

[0034] In the present invention, "substituted or unsubstituted C for 1 -C 6 alkoxy -C 1 -C 6 Preferred embodiments of the alkyl group", (unsubstituted) C 1 -C 6 alkoxy -C 1 -C 6 alkyl group or some or deuterium atom, a halogen atom, -OR 13 , -NR 15 R 16 and -S (O) n R 17 (wherein, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group in and, R 15 and R 16 are independently hydrogen atom, C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, -COOR14 or -S (O) n R 17 is, R 17 is C 1 -C 6 alkyl group, and n is at least one selected from the group consisting of 0, 1 or 2) C is substituted with a substituent 1 -C 6 alkoxy -C 1 -C 6 alkyl group. "Substituted or unsubstituted C for 1 -C 6 alkoxy -C 1 -C 6 and more preferred embodiments of the alkyl group", (unsubstituted) C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, or -OR 13 and -NR 15 R 16 C is substituted with at least one substituent selected from the group consisting of 1 -C 6 alkoxy -C 1-C 6 alkyl group.

[0035] In the present invention, "substituted or unsubstituted heterocyclyl group" and "substituted or unsubstituted heterocyclyl -C 1 -C 6 Preferred embodiments of the alkyl group", (unsubstituted) heterocyclyl and heterocyclyl -C 1 -C 6 or an alkyl group, or a heterocyclyl moiety is a deuterium atom, a halogen atom, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkoxy -C 1 -C 6 alkyl radical, R 13 O-C 1 -C 6 alkyl group, halo -C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, an oxo group, -COOR 14 and -S (O) nR 17 (wherein, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 14 is a hydrogen atom or a C 1 -C 6 alkyl group, R 17 is C 1 - C 6 alkyl group, and n is at least one heterocyclyl group substituted by a substituent and heterocyclyl -C selected from the group consisting of 0, 1 or 2) 1 -C 6 alkyl group is there. "Substituted or unsubstituted heterocyclyl group" and "substituted or unsubstituted heterocyclyl -C 1 -C 6 and more preferred embodiments of the alkyl group", (unsubstituted) heterocyclyl and heterocyclyl -C 1 -C 6 alkyl group or some, or heterocyclyl moiety is a halogen atom and -S (O) n R 17 at least one heterocyclyl group and the heterocyclyl -C substituted with substituents selected from the group consisting of 1 -C6 is an alkyl group.

[0036] In the present invention, a preferred embodiment of the "substituted or unsubstituted aryl group" is either (unsubstituted) aryl group, or a deuterium atom, a halogen atom, -OR 13 and -S (O) n R 17 ( here, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 17 is C 1 -C 6 alkyl group, and n is 0, 1 or 2) at least one aryl group substituted with a substituent selected from the group consisting of. A more preferred embodiment of the "substituted or unsubstituted aryl group" is an (unsubstituted) aryl group.

[0037] General formula (I) compounds represented by the present invention, (if present) a stereoisomer thereof. Stereoisomers means isomers that differ in the arrangement of their atoms in space, diastereomers, optical isomers enantiomers such or geometrical isomers, and the like. For example, when a compound represented by the general formula (I) of the present invention have one or more chiral centers, the compounds represented by the general formula (I) of the present invention, optically pure enantiomers, racemic mixtures of enantiomers etc., optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates, can be present in the form of a mixture of racemic diastereomers. Further, when the compound represented by the general formula (I) of the present invention, geometrical isomers based on C = C, double bond such as C = N is represented by the general formula (I) of the present invention compounds, geometrical isomers in pure E isomer or Z isomer, can be present in the form of mixtures of geometric isomers of E-form and Z-form.

[0038] The pharmaceutically acceptable salts of the compounds represented by the general formula (I) of the present invention, for example, hydrochloride, hydrobromide, hydroiodide, nitrate, inorganic, such as sulfate or phosphate salt; or acetate, trifluoroacetate, benzoate, oxalate, malonate, succinate, maleate, fumarate, tartrate, citrate, methanesulfonate, ethanesulfonate salt, trifluoromethanesulfonate, benzenesulfonate, p- toluenesulfonate, organic acid salts such as glutamate or aspartate salts. A preferred embodiment of the organic acid salt, oxalate, malonate, succinate, maleate, fumarate, a salt of a dicarboxylic acid such as tartaric acid salt.

[0039] The pharmaceutically acceptable salts of the compounds represented by the general formula (I) of the present invention, other such as sodium salts, potassium salts, calcium salts or magnesium salts of metal salts: ammonium inorganic salts such as salt: or organic amine salts such as triethylamine salt or guanidine salt.

[0040] Compound or pharmacologically acceptable salt thereof represented by the general formula (I) of the present invention includes a solvate pharmacologically acceptable. A preferred embodiment of the solvate is a hydrate. Note hydrate may be one produced as a result of the general formula (I) compound or hygroscopicity of a pharmacologically acceptable salt thereof represented by the present invention.

[0041] When the compound or a pharmacologically acceptable salt thereof represented by the general formula (I) of the present invention is crystalline, it may show crystal polymorphism. Crystalline polymorph, crystal structure mean different things in the same material. Each crystal or a mixture thereof in any proportion are encompassed by the present invention.

[0042] Will be described in detail embodiments of the present invention are described below. The present invention relates to compounds of the general formula (I): [Chemical Formula 6] {wherein,

R 1 represents a hydrogen atom, protecting group, substituted or unsubstituted C for 1 -C 6 alkyl group, a substituted or unsubstituted C 2 -C 6 alkenyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C for 1 -C 6 alkoxy -C 1 -C 6 alkyl group, -CONR 11 R 12 , substituted or unsubstituted heterocyclyl group, a substituted or unsubstituted heterocyclyl -C 1 -C 6 alkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted C 7 -C 16 aralkyl group; X is, N or C-R 2 in Yes, here, R 2

Represents a hydrogen atom, a halogen atom, a substituted or unsubstituted C for 1 -C 6 alkyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C for 1 -C 6 alkoxy group or a cyano group in it; p and q are, independently of one another, is a natural number of 1 to 3, provided that the sum of p and q is a natural number of 2 to 4; wherein the "substituted", a deuterium atom , halogen atom, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, R 13 O-C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1-C 7 acyl group, a cyano group, an oxo group, -CONR 11 R 12 , -OR 13 , -COOR 14 , -NR 15 R 16 and -S (O) n R 17 , at least one selected from the group consisting of the means that have been substituted with a substituent, R 11 and R 12 are independently hydrogen atom or a C 1 -C 6 alkyl group, R 13 is a hydrogen atom, C 1 -C 7 acyl a group or a protecting group, R 14 is a hydrogen atom or a C 1 -C 6 alkyl group, R 15 and R 16 are independently hydrogen atom, C 1 -C 6 alkyl group, C 7-C 16 aralkyl group, C 1 -C 7 acyl group, -COOR 14 or -S (O) n R 17 is, R 17 is C 1 -C 6 alkyl group, and n is 0, 1 or 2 a} compound or to a pharmaceutically acceptable salt thereof.

[0043] In certain embodiments, the present invention is, p and q are 1, compound or to a pharmacologically acceptable salt thereof represented by the general formula (I) of the present invention.

[0044] In certain embodiments, the present invention, p is 1, q is 2 (a or p is 2, q is 1), the compound or a general formula (I) of the present invention It relates pharmacologically acceptable salts.

[0045] In certain embodiments, the present invention is, p and q is 2, compound or to a pharmacologically acceptable salt thereof represented by the general formula (I) of the present invention.

[0046] In certain embodiments, the present invention, p is 1, q is 3 (a or p is 3, q ​​is 1), the compound or a general formula (I) of the present invention It relates pharmacologically acceptable salts.

[0047] In certain embodiments, the present invention is, R 1 is a hydrogen atom; protecting group; C 1 -C 6 alkyl group (which is heavy hydrogen atom, a halogen atom, a cyano group, -CONR 11 R 12 , -OR 13 , -COOR 14 , -NR 15 R 16 and -S (O) n R 17 may be substituted with at least one substituent selected from the group consisting of); C 2 -C 6 alkenyl group; C 3 -C 8 cycloalkyl group (which includes at least one -OR 13 may be substituted by); C 1 -C 6 alkoxy -C 1 -C 6 alkyl group (which, -OR 13 and - NR 15 R 16May be substituted with at least one substituent selected from the group consisting of); - CONR 11 R 12 ; heterocyclyl or heterocyclyl -C 1 -C 6 alkyl group (wherein the heterocyclyl moiety is a halogen atom, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, R 13 O-C 1 -C 6 alkyl group, halo -C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, an oxo group, -COOR 14 and -S (O) n R 17It may be substituted with at least one substituent selected from the group consisting of); or an aryl group, wherein, R 11 and R 12 are independently hydrogen atom or a C 1 -C 6 an alkyl group, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 14 is a hydrogen atom or a C 1 -C 6 alkyl group, R 15 and R 16 are independently and a hydrogen atom, C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, -COOR 14 or -S (O) n R 17 is, R 17 is, C 1 -C 6An alkyl group and n is 0, 1 or 2, the compound or to a pharmacologically acceptable salt thereof represented by the general formula (I) of the present invention.

[0048] 特定の実施態様において、本発明は、Ｒ１が、水素原子、置換もしくは非置換のＣ１－Ｃ６アルキル基、Ｃ２－Ｃ６アルケニル基、置換もしくは非置換のＣ３－Ｃ８シクロアルキル基、置換もしくは非置換のＣ１－Ｃ６アルコキシ－Ｃ１－Ｃ６アルキル基又は置換もしくは非置換のヘテロシクリル基であり、ここで、上記「置換」は、重水素原子、ハロゲン原子、－ＯＲ１３及び－Ｓ（Ｏ）ｎＲ１７からなる群より選択される少なくとも１個の置換基で置換されていることを意味し、Ｒ１３は、水素原子、Ｃ１－Ｃ７アシル基又は保護基であり、Ｒ１７は、Ｃ１－Ｃ６アルキル基である、本発明の一般式（Ｉ）で示される化合物又はその薬理上許容される塩に関する。

[0049] 特定の実施態様において、本発明は、Ｒ１が、水素原子、Ｃ１－Ｃ６アルキル基（これは、重水素原子、ハロゲン原子、－ＯＲ１３及び－Ｓ（Ｏ）ｎＲ１７からなる群より選択される少なくとも１個の置換基で置換されていてもよい）、Ｃ２－Ｃ６アルケニル基、Ｃ３－Ｃ８シクロアルキル基（これは、少なくとも１個の－ＯＲ１３で置換されていてもよい）；Ｃ１－Ｃ６アルコキシ－Ｃ１－Ｃ６アルキル基（これは、少なくとも１個の－ＯＲ１３で置換されていてもよい）又はヘテロシクリル基（前記ヘテロシクリル部分は、ハロゲン原子及び－Ｓ（Ｏ）ｎＲ１７からなる群より選択される少なくとも１個の置換基で置換されていてもよい）であり、ここで、Ｒ１３は、水素原子、Ｃ１－Ｃ７アシル基又は保護基であり、Ｒ１７は、Ｃ１－Ｃ６アルキル基であり、そしてｎは、０、１又は２である、本発明の一般式（Ｉ）で示される化合物又はその薬理上許容される塩に関する。

[0050] 特定の実施態様において、本発明は、Ｒ１が、Ｃ１－Ｃ４アルキル基、又は重水素原子、フッ素原子及びヒドロキシ基からなる群より選択される少なくとも１個の置換基で置換されたＣ１－Ｃ４アルキル基である、本発明の一般式（Ｉ）で示される化合物又はその薬理上許容される塩に関する。

[0051] 特定の実施態様において、本発明は、一般式（ＩＩ）で示される化合物又はその薬理上許容される塩に関する。 一般式（ＩＩ）： [化7]

一般式（ＩＩ）において、Ｒ１、ｐ及びｑは、一般式（Ｉ）における定義と同じである。

[0052] 特定の実施態様において、本発明は、ｐ及びｑが１である、本発明の一般式（ＩＩ）で示される化合物又はその薬理上許容される塩に関する。

[0053] 特定の実施態様において、本発明は、ｐが１であり、ｑが２である（又はｐが２であり、ｑが１である）、本発明の一般式（ＩＩ）で示される化合物又はその薬理上許容される塩に関する。

[0054] 特定の実施態様において、本発明は、ｐ及びｑが２である、本発明の一般式（ＩＩ）で示される化合物又はその薬理上許容される塩に関する。

[0055] 特定の実施態様において、本発明は、ｐが１であり、ｑが３である（又はｐが３であり、ｑが１である）、本発明の一般式（ＩＩ）で示される化合物又はその薬理上許容される塩に関する。

[0056] In certain embodiments, the present invention is, R 1 is a hydrogen atom; protecting group; C 1 -C 6 alkyl group (which is heavy hydrogen atom, a halogen atom, a cyano group, -CONR 11 R 12 , -OR 13 , -COOR 14 , -NR 15 R 16 and -S (O) n R 17 may be substituted with at least one substituent selected from the group consisting of); C 2 -C 6 alkenyl group; C 3 -C 8 cycloalkyl group (which includes at least one -OR 13 may be substituted by); C 1 -C 6 alkoxy -C 1 -C 6 alkyl group (which, -OR 13 and - NR 15 R 16May be substituted with at least one substituent selected from the group consisting of); - CONR 11 R 12 ; heterocyclyl or heterocyclyl -C 1 -C 6 alkyl group (wherein the heterocyclyl moiety is a halogen atom, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, R 13 O-C 1 -C 6 alkyl group, halo -C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, an oxo group, -COOR 14 and -S (O) n R 17It may be substituted with at least one substituent selected from the group consisting of); or an aryl group, wherein, R 11 and R 12 are independently hydrogen atom or a C 1 -C 6 an alkyl group, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 14 is a hydrogen atom or a C 1 -C 6 alkyl group, R 15 and R 16 are independently and a hydrogen atom, C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, -COOR 14 or -S (O) n R 17 is, R 17 is, C 1 -C 6An alkyl group and n is 0, 1 or 2, the compound or to a pharmacologically acceptable salt thereof represented by the general formula (I) of the present invention.

[0057] In certain embodiments, the present invention is, R 1 is a hydrogen atom, a substituted or unsubstituted C for 1 -C 6 alkyl group, C 2 -C 6 alkenyl group, a substituted or unsubstituted C for 3 -C 8 cycloalkyl group, a substituted or unsubstituted C 1 -C 6 alkoxy -C 1 -C 6 alkyl group or a substituted or unsubstituted heterocyclyl group, wherein the above-mentioned "substituted", a deuterium atom, a halogen atom, -OR 13 and -S (O) n R 17 means that it is substituted with at least one substituent selected from the group consisting of, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group in and, R 17 is, C 1 -C 6 alkyl group, the compound or to a pharmacologically acceptable salt thereof represented by the general formula (II) of the present invention.

[0058] In certain embodiments, the present invention is, R 1 is a hydrogen atom, C 1 -C 6 alkyl group (which is heavy hydrogen atom, a halogen atom, -OR 13 and -S (O) n R 17 group consisting of more may be substituted with at least one substituent selected), C 2 -C 6 alkenyl group, C 3 -C 8 cycloalkyl group (which, at least one -OR 13 substituted with may be); C 1 -C 6 alkoxy -C 1 -C 6 alkyl group (which includes at least one -OR 13 may be substituted with) or heterocyclyl group (wherein the heterocyclyl moiety, and a halogen atom -S (O) n R 17 are optionally substituted with at least one substituent selected from the group consisting of wherein, R 13 is a hydrogen atom, C 1 -C 7An acyl group or a protecting group, R 17 is C 1 -C 6 alkyl group, and n is 0, 1 or 2, a compound represented by the general formula (I) of the present invention or a pharmacologically on acceptable salt thereof.

[0059] In certain embodiments, the present invention is, R 1 is, C 1 -C 4 C substituted with an alkyl group, or a deuterium atom, at least one substituent selected from the group consisting of fluorine atom and hydroxy group 1 -C 4 alkyl group, compound or to a pharmacologically acceptable salt thereof represented by the general formula (II) of the present invention.

[0060] In certain embodiments, the present invention provides a compound or to a pharmacologically acceptable salt thereof represented by the general formula (III). Formula (III):

Formula 8

In the general formula (III), R 1 , R 2 , p and q are as defined in the general formula (I).

[0061] In certain embodiments, the present invention is, p and q are 1, compound or to a pharmacologically acceptable salt thereof represented by the general formula (III) of the present invention.

[0062] In certain embodiments, the present invention, p is 1, q is 2 (a or p is 2, q is 1), the compound or a general formula (III) of the present invention It relates pharmacologically acceptable salts.

[0063] In certain embodiments, the present invention is, p and q is 2, compound or to a pharmacologically acceptable salt thereof represented by the general formula (III) of the present invention.

[0064] In certain embodiments, the present invention, p is 1, q is 3 (a or p is 3, q ​​is 1), the compound or a general formula (III) of the present invention It relates pharmacologically acceptable salts.

[0065] In certain embodiments, the present invention is, R 2 is a hydrogen atom, a halogen atom, C 1 -C 6 alkyl group (which, halogen atom, -OR 13 and C 1 -C 6 selected from the group consisting of an alkoxy group at least one of which may be substituted with a substituent), C is 3 -C 8 cycloalkyl group, C 1 -C 6 alkoxy group or a cyano group, wherein, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, compound or to a pharmacologically acceptable salt thereof represented by the general formula (III) of the present invention.

[0066] In certain embodiments, the present invention is, R 2 is a hydrogen atom, a fluorine atom, a chlorine atom, C 1 -C 4 alkyl group, at least one C is substituted with a fluorine atom 1 -C 4 alkyl group, at least one C substituted with hydroxy 1 -C 4 alkyl group, at least one of the protected C substituted with hydroxy 1 -C 4 alkyl group, at least one C 1 -C 4 alkoxy group substituted C 1 -C 4 alkyl group, C 3 -C 6 cycloalkyl group, C 1 -C 4 alkoxy group or a cyano group, a compound represented by the general formula (III) or a pharmacologically acceptable of the invention relates to a salt it is.

WE CLAIM

[Claim 1]General formula (I):[Formula 1] {wherein, R 1 represents a hydrogen atom, protecting group, substituted or unsubstituted C for 1 -C 6 alkyl group, a substituted or unsubstituted C 2 -C 6 alkenyl group, substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C for 1 -C 6 alkoxy -C 1 -C 6 alkyl group, -CONR 11 R 12 , substituted or unsubstituted heterocyclyl groups, substituted or unsubstituted heterocyclyl -C 1 -C 6 alkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted C 7 -C 16 aralkyl group; X is, N or C-R 2 are, here , R 2 is a hydrogen atom, a halogen atom, a substituted or unsubstituted C

1 -C 6 alkyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C 1 -C 6 alkoxy group or a cyano group; p and q are, independently of one another, 1 the sum of to 3 is a natural number, provided that p and q is a natural number of 2 to 4; wherein the "substituted", a deuterium atom, a halogen atom, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, R 13 O-C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7Acyl group, a cyano group, an oxo group, -CONR 11 R 12 , -OR 13 , -COOR 14 , -NR 15 R 16 and -S (O) n R 17 at least one substituent selected from the group consisting of in means that it is substituted, R 11 and R 12 are independently hydrogen atom or a C 1 -C 6 alkyl group, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protected a group, R 14 is a hydrogen atom or a C 1 -C 6 alkyl group, R 15 and R 16 are independently hydrogen atom, C 1 -C 6 alkyl group, C 7 -C 16Aralkyl groups, C 1 -C 7 acyl group, -COOR 14 or -S (O) n R 17 is, R 17 is C 1 -C 6 alkyl group, and n is 0, 1 or 2 there} compound or pharmacologically acceptable salt thereof represented by.

Claim 2

Formula (II): [Chemical Formula 2] {wherein,

R 1 represents a hydrogen atom, protecting group, substituted or unsubstituted C for 1 -C 6 alkyl group, a substituted or unsubstituted C 2 -C 6 alkenyl group, substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C for 1 -C 6 alkoxy -C 1 -C 6 alkyl group, -CONR 11 R 12 , substituted or unsubstituted heterocyclyl groups, substituted or unsubstituted heterocyclyl -C 1 -C 6 alkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted C 7 -C 16 aralkyl group; p and q are, independently of one another, from 1 to 3 is a natural number, provided that the sum of p and q is a natural number of 2 to 4; wherein said "substituted", a deuterium atom, a halogen atom, C 1 -C

6 alkyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, R 13 O-C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, a cyano group, an oxo group, -CONR 11 R 12 , -OR 13 , -COOR 14 , -NR 15 R 16 and -S (O) n R 17 consisting of It means that it is substituted with at least one substituent selected from the group, R 11 and R12 is independently hydrogen atom or a C 1 -C 6 alkyl group, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 14 is a hydrogen atom or a C 1 - C 6 alkyl group, R 15 and R 16 are independently hydrogen atom, C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, -COOR 14 or - S (O) n R 17 is, R 17 is C 1 -C 6 alkyl group, and n is 0, 1 or 2} the compound of claim 1 represented by or a pharmacologically acceptable salt thereof.

Claim 3

R 1 is a hydrogen atom, a substituted or unsubstituted C for 1 -C 6 alkyl group, C 2 -C 6 alkenyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C 1 - C 6 alkoxy -C 1 -C 6 alkyl group or a substituted or unsubstituted heterocyclyl group, wherein said "substituted", a deuterium atom, a halogen atom, -OR 13 and -S (O) n R 17 means that it is substituted with at least one substituent selected from the group consisting of, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 17 is C 1 - C 6 alkyl group, and n is 0, 1 or 2, compound or pharmacologically acceptable salt thereof according to claim 2.

Claim 4

p and q are 1, compound or a pharmacologically acceptable salt thereof according to claim 3.

Claim 5

R 1 is, C 1 -C 4 alkyl group, or a deuterium atom, C substituted with at least one substituent selected from the group consisting of fluorine atom and hydroxy group 1 -C 4 alkyl group, wherein compound or pharmacologically acceptable salt thereof according to claim 4.

Claim 6

Formula (III): [Chemical Formula 3] {wherein,

R 1 represents a hydrogen atom, protecting group, substituted or unsubstituted C for 1 -C 6 alkyl group, a substituted or unsubstituted C 2 -C 6 alkenyl group, substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C for 1 -C 6 alkoxy -C 1 -C 6 alkyl group, -CONR 11 R 12 , substituted or unsubstituted heterocyclyl groups, substituted or unsubstituted heterocyclyl -C 1 -C 6 alkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted C 7 -C 16 aralkyl group; R 2 represents a hydrogen atom, a halogen atom, a substituted or unsubstituted C of 1 -C 6

Alkyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C 1 -C 6 alkoxy group or a cyano group; p and q are, independently of one another, natural numbers of 1 to 3 although, provided that the sum of p and q is a natural number of 2 to 4; wherein said "substituted", a deuterium atom, a halogen atom, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkoxy -C 1 -C 6 alkyl group, R 13 O-C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1 -C 7 acyl group, a cyano group, an oxo group, -CONR 11R 12 , -OR 13 , -COOR 14 , -NR 15 R 16 and -S (O) n R 17 means that it is substituted with at least one substituent selected from the group consisting of, R 11 and R 12 is independently hydrogen atom or a C 1 -C 6 alkyl group, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 14 is a hydrogen atom or a C 1 -C 6 alkyl group, R 15 and R 16 are independently hydrogen atom, C 1 -C 6 alkyl group, C 7 -C 16 aralkyl group, C 1-C 7 acyl group, -COOR 14 or -S (O) n R 17 is, R 17 is C 1 -C 6 alkyl group, and n is 0, 1 or 2} represented by compound or pharmacologically acceptable salt thereof according to claim 1.

Claim 7

R 1 is a hydrogen atom, a substituted or unsubstituted C for 1 -C 6 alkyl group, C 2 -C 6 alkenyl group, a substituted or unsubstituted C 3 -C 8 cycloalkyl group, a substituted or unsubstituted C 1 - C 6 alkoxy -C 1 -C 6 alkyl group or a substituted or unsubstituted heterocyclyl group, wherein said "substituted", a deuterium atom, a halogen atom, -OR 13 and -S (O) n R 17 means that it is substituted with at least one substituent selected from the group consisting of, R 13 is a hydrogen atom, C 1 -C 7 acyl group or a protecting group, R 17 is C 1 - C 6 alkyl group, and n is 0, 1 or 2, compound or pharmacologically acceptable salt thereof according to claim 6. [8.] R 2 is a halogen atom, a compound or a pharmacologically acceptable salt thereof according to claim 7.

Claim 9

R 2 is a fluorine atom, compound or pharmacologically acceptable salt thereof according to claim 8.

Claim 10

p and q are 1, compound or pharmacologically acceptable salt thereof according to claim 9.

Claim 11

R 1 is, C 1 -C 4 alkyl group, or a deuterium atom, C substituted with at least one substituent selected from the group consisting of fluorine atom and hydroxy group 1 -C 4 alkyl group, wherein compound or pharmacologically acceptable salt thereof of claim 10, wherein.

Claim 12

Compound, the following: 2-fluoro-3- {2- [3- (methoxyimino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 3- {2- [3- (ethoxy imino) azetidin-1-yl] pyrimidin-5-yl} -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(methoxy -d 3 ) imino] azetidin- yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(2-fluoroethoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamate Mimi Doyle carbamate, 3- (2- {3 - [(2,2-difluoro-ethoxy) imino] azetidin-1-yl} pyrimidine-5-y ) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(2,2,2-trifluoroethoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(3-fluoro-propoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro 3- {2- [3 - ({4 - [(tetrahydropyran-2-yl) oxy] butoxy} imino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro 3- (2- {3 - [(2-methoxyethoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl Cal Bas Mimi Doyle carbamate, [({L- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] methyl pivalate, 1- [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] -3-methoxypropane 2-yl acetate, 4 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino ) oxy] butane-1,2-diyl diacetate, 2 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] Chill} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] ethyl acetate, 2 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] ethyl propionate, 2 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] ethyl butyrate, 2 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] ethyl Ben Art, 2-fluoro-3- {5-fluoro-6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- (5-fluoro-6- {3 - [(methoxy -d 3 ) imino] azetidin-l-yl} pyridin-3-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- {6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {6- [3- (methoxyimino) azetidin-1-yl ] -5-methyl-pyridin-3-yl} benzyl carbamimidoyl carbamate, 3- {5-cyano-6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} -2-fluoro benzyl carbamimidoyl carbamate, 3- {5-chloro-6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} -2-fluoride Robenjiru carbamimidoyl carbamate, 3- {5- (difluoromethyl) -6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} -2-fluorobenzyl carbamimidoyl carbamate, 3 - {5-cyclopropyl-6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} -2-fluorobenzyl carbamimidoyl carbamate, 3- {5-ethyl-6- [3 - (methoxyimino) azetidin-1-yl] pyridin-3-yl} -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- {6- [3- (methoxyimino) azetidin-1-yl] 5- (methoxymethyl) pyridin-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {5-methoxy-6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [4 - (methoxyimino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 3- {2- [4- (ethoxyimino) piperidin-1-yl] pyrimidin-5-yl} -2 - fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [4- (isopropoxycarbonyl alkoximinoalkyl amino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro -3 - {2- [4- (propoxyimino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl-carba Mart, 3- (2- {4 - [(allyloxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [4 - ({2 - [(tetrahydropyran-2-yl) oxy] ethoxy} imino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(2-methoxyethoxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] piperidin-4-ylidene} amino) oxy] ethyl acetate, (E / Z)-2-fluoro-3- {2- [3- (methoxyimino) pyrrolidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [3- (hydroxyimino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(2-hydroxyethoxy) imino] azetidin -1 - yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(3-hydroxypropoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(4-hydroxy-butoxy) imino] azetidin-l-yl} Rimijin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[2- (2-hydroxyethoxy) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl ] benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[3-fluoro-2- (hydroxymethyl) propoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamate Mimi Doyle carbamate, 2-fluoro-3- (2- {3 - [(4-hydroxy-3-methoxy-butoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) Rimijin 2-yl] azetidin-3-ylidene} amino) oxy] -2- (hydroxymethyl) propyl acetate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] -2- (hydroxymethyl) propyl propionate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] -2- (hydroxymethyl) propyl butyrate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl ] azetidin-3-ylidene} amino) oxy] -2- (hydroxymethyl) propyl isobutyrate, 3 - [({1- [5 (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] -2- (hydroxymethyl) propyl pivalate, 3- [ ({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] -2- (hydroxymethyl ) propyl hexanoate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino ) oxy] -2- (hydroxymethyl) propyl benzoate, 2-fluoro-3- {5- (2-hydroxy Propan-2-yl) -6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(2-hydroxyethoxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- { 4 - [(3-hydroxypropoxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(4-hydroxy-butoxy) imino ] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(3-hydroxy-2,2-dimethyl propoxy) imino] piperidine -1 - yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(3-hydroxy 3-methylbutoxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(2-hydroxypropoxy) imino] piperidine - 1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(3-hydroxy-2-methyl-propoxy) imino] piperidin-1-yl} pyrimidine - 5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[3-hydroxy-2- (hydroxymethyl) propoxy] imino} azetidin-1-yl) pyrimidin-5-yl ] benzyl carbamimidoyl carbamate, 3- (2- {3 - [(2,3-dihydroxy-propoxy) imino] Zechijin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 3- (2- {3 - [(3,4-dihydroxy-butoxy) imino] azetidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 3- (6- {3- [(3,4-dihydroxy-butoxy) imino] azetidin-l-yl} -5-fluoro-3-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- {5-fluoro -6 - [3 - {[3-hydroxy-2- (hydroxymethyl) propoxy] imino} azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[3-hydroxy-2- (hydroxymethyl) propoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl Karubami Mi Doyle carbamate, 2-fluoro-3- [2- (4 - {[3-hydroxy-2- (hydroxymethyl) -2-methyl propoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- (2- {4 - [(2,3-dihydroxy-propoxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2- fluoro-3- [2- (3 - {[3-hydroxy-2- (methoxymethyl) propoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro -3 - (2- {3 - [(3-hydroxy-2-methoxypropoxy) imino] azetidin-1-yl} pyrimidine-5-y Le) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {3 - [(2-fluoro-3-hydroxy-propoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (5-fluoro-6- {3 - [(2-fluoro-3-hydroxy-propoxy) imino] azetidin-l-yl} pyridin-3-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- (2 - {3 - [(2-hydroxy-3-methoxypropoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [4- (hydroxymethyl imino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {5- Ruoro-6- [3- (hydroxyimino) azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate, tert-butyl 2 - [({l- [5- (3 - {[(carba Mimi Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] acetate, 2 - [({l- [5- (3 - {[(Karubamimi Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] acetic acid, 3- [2- (3 - {[(dimethylcarbamoyl) oxy] imino} azetidine 1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate 2-fluoro-3- [2- (3 - {[2- (methylamino) -2-oxo-ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- ( 2- {3 - [(3-amino-3-oxopropoxy) imino] azetidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[3- (methylamino) -3-oxopropoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, ethyl 4 - [({l- [5- ( 3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy Butanoate, 4 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] butane acid, 2-fluoro-3- [2- (3 - {[4- (methylamino) -4-oxobutoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3 - [2- (3 - {[2- (dimethylamino) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- {2- [3- ({2- [benzyl (methyl) amino] ethoxy} imino) azetidin-1-yl] pyrimidin-5-yl} -2-fluorobenzyl Karubamimido Rukarubamato, 3- [2- (3 - {[3-acetamido-2- (hydroxymethyl) propoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- [ 2- (3 - {[3- (dimethylamino) -2- (hydroxymethyl) propoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- ( 2- {3 - [(3-acetamido-2-methoxy propoxy) imino] azetidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[2- (piperidin-1-yl) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl Ca Luba Mimi Doyle carbamate, 2-fluoro-3- (2- {3 - [(2-morpholinoethoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 3- [2 - (3 - {[2- (azetidin-1-yl) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- [2- (3- {[2- (3,3-difluoro-1-yl) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[2- (3-fluoro-1-yl) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl Carbamimidoyl carbamate 2-fluoro-3- [2- (3 - {[2- (3-Methoxy-1-yl) ethoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[(4-methyl-morpholin-2-yl) methoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- [ 2- (3 - {[(4-acetyl-2-yl) methoxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[(5-oxo tetrahydrofuran-2-yl) methoxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl Cal Ba Mimi Doyle carbamate, 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino ) oxy] cyclobutyl acetate, 2-fluoro-3- (2- {3 - [(3-hydroxy-cyclo-butoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 3- ( 2- {3 - [(benzyloxy) imino] azetidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (3 - {[( 4-methoxybenzyl) oxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carba-mer , 2-fluoro-3- [2- (3 - {[(1-methyl-3-yl) oxy] imino} azetidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- [2- (3 - {[(1-acetyl-3-yl) oxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- [2 - (3 - {[(1-benzyl-3-yl) oxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [3 - ({[1- (2,2,2-trifluoroethyl) azetidin-3-yl] oxy} imino) azetidin-1-yl] pyrimidin-5-yl} Ben Le carbamimidoyl carbamate, 2-fluoro-3- {2- [3 - ({[l- (methylsulfonyl) azetidin-3-yl] oxy} imino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 3- [2- (3 - {[(1-ethyl-3-yl) oxy] imino} azetidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carba Mimi Doyle carbamate, methyl 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino ) oxy] azetidine-1-carboxylate, 2-fluoro-3- (2- {3 - [(oxetan-3-yloxy) imino] azetidine Down-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 2- {3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] azetidin-1-yl} ethyl acetate, 2-fluoro-3- {2- [3 - ({[1- (2-hydroxyethyl) azetidin-3-yl] oxy} imino) azetidin-1-yl] pyrimidine - 5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [3 - ({[1- (2-methoxyethyl) azetidin-3-yl] oxy} imino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [3 - ({[1- (2-fluoroethyl) azetidin-3-yl] Carboxymethyl} imino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, ethyl 3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} - 2-fluorophenyl) pyrimidin-2-yl] piperidin-4-ylidene} amino) oxy] propanoate, 3- (2- {4 - [(3-amino-3-oxopropoxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[3- (methylamino) -3-oxopropoxy] imino} piperidin-1-yl ) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, ethyl 4 - [({l- [5- (3 - {[(Karubamimido Carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] piperidin-4-ylidene} amino) oxy] butanoate, 4 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] piperidin-4-ylidene} amino) oxy] butanoic acid, 3- [2- (4 - {[3- (dimethylamino) -3-oxopropoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 3- ( 2- {4 - [(2-acetamide ethoxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4- { [2-(N-methylacetamide) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2 - fluoro -3- [2- (4 - {[ 2- (N- methyl sulfonamide) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro - 3- [2- (4 - {[2- (methylsulfonamido) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- [2- (4 - {[ 2- (dimethylamino) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate 2-fluoro-3- [2- (4 - {[2- (methyl amino) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate 3- (2- {4 - [(2- Minoetokishi) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 3- (2- {4 - [(2-cyano-ethoxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 3- (2- {4 - [( 3-cyano-propoxy) imino] piperidin-1-yl} pyrimidin-5-yl) -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[2- (methylsulfonyl) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[3- (methylsulfonyl) propoxy] imino} piperidine -1 - yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[(1-methyl -1H Pyrazol-3-yl) methoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- [2-(4 - {[(1H-pyrazol-3-yl) methoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- {2- [4 - ({[1- (tetrahydropyran-2-yl) -1H- pyrazol-4-yl] methoxy} imino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 3- [2-(4 - {[(1H-pyrazol-4-yl ) methoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[(1-methyl -1H- pyrazol-4-yl) methoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 3- [2- (4 - {[ 2- (1H- pyrazol-1-yl) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluorobenzyl carbamimidoyl carbamate, 2- fluoro-3- (2- {4 - [(pyridin-4-ylmethoxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, 3- [2- (4 - {[2 - (2,5-dioxo-1-yl) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] -2-fluoro-benzyl carbamate ear de dolphins Rubamato, 2-fluoro-3- [2- (4 - {[2- (2-oxopyrrolidin-1-yl) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate , 2-fluoro-3- [2- (4 - {[2- (2-oxo-oxazolidine-3-yl) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro-3- [2- (4 - {[2- (3-oxomorpholino) ethoxy] imino} piperidin-1-yl) pyrimidin-5-yl] benzyl carbamimidoyl carbamate, 2-fluoro -3 - {2- [4- (phenoxyimine amino) piperidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate, 2-fluoro-3- (2- {4 - [(pyrimidin-5-yloxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate, or 2-fluoro-3- (2 - {4 - [(pyrimidin-2-yloxy) imino] piperidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate the compound or a pharmacologically acceptable salt thereof according to claim 1 .

Claim 13

2-fluoro-3- {2- [3- (methoxyimino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate or a pharmaceutically acceptable salt thereof.

Claim 14

3- {2- [3- (ethoxyimino) azetidin-1-yl] pyrimidin-5-yl} -2-fluorobenzyl carbamimidoyl carbamate or a pharmaceutically acceptable salt thereof.

Claim 15

2-fluoro-3- (2- {3 - [(methoxy -d 3 ) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate or a pharmaceutically acceptable salt thereof.

Claim 16

2-fluoro-3- (2- {3 - [(2-fluoroethoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate or a pharmaceutically acceptable salt thereof.

Claim 17

2-fluoro-3- {5-fluoro-6- [3- (methoxyimino) azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate or a pharmaceutically acceptable salt thereof.

Claim 18

2-fluoro-3 - (5-fluoro-6- {3 [(methoxy -d 3 is) imino] azetidin-l-yl} pyridin-3-yl) benzyl carbamimidoyl carbamate or a pharmacologically acceptable salt.

Claim 19

3- (6- {3 - [(3,4-dihydroxy-butoxy) imino] azetidin-l-yl} -5-fluoro-3-yl) -2-fluorobenzyl carbamimidoyl carbamate or a pharmacologically acceptable salt.

Claim 20

2-fluoro-3- {5-fluoro-6- [3 - {[3-hydroxy-2- (hydroxymethyl) propoxy] imino} azetidin-1-yl] pyridin-3-yl} benzyl carbamimidoyl carbamate or a pharmaceutically acceptable salt thereof.

Claim 21

2-fluoro-3 - acceptable (2- {3 [(2-fluoro-3-hydroxy-propoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate or a pharmacologically salt.

Claim 22

3 - [({l- [5- (3 - {[(carba ear Doi carbamoyl) oxy] methyl} -2-fluorophenyl) pyrimidin-2-yl] azetidin-3-ylidene} amino) oxy] cyclobutyl acetate or a pharmacologically acceptable salt thereof.

Claim 23

2-fluoro-3- (2- {3 - [(3-hydroxy-cyclo-butoxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate or a pharmaceutically acceptable salt thereof.

Claim 24

2-fluoro-3- {2- [3 - ({[l- (methylsulfonyl) azetidin-3-yl] oxy} imino) azetidin-1-yl] pyrimidin-5-yl} benzyl carbamimidoyl carbamate or a pharmacologically acceptable salt thereof.

Claim 25

2-fluoro-3- (2- {3 - [(oxetan-3-yloxy) imino] azetidin-1-yl} pyrimidin-5-yl) benzyl carbamimidoyl carbamate or a pharmaceutically acceptable salt thereof.

Claim 26

Salts pharmacologically acceptable salt is a salt of an organic acid, is pharmacologically acceptable compound according to any one of claims 1 to 25.

Claim 27

Salts pharmacologically acceptable salt is a salt of a dicarboxylic acid, is pharmacologically acceptable compound according to any one of claims 1 to 25.

Claim 28

A compound according to any one of claims 1 to 27 or a salt thereof pharmacologically acceptable, containing an additive acceptable at least one pharmacologically, pharmaceutical compositions.

Claim 29

Prevented by VAP-1 inhibition, relief and / or for the treatment of the disease being treated, the pharmaceutical composition according to claim 28.

Claim 30

The disease is diabetic nephropathy, the pharmaceutical composition according to claim 29.

Claim 31

The disease is non-alcoholic steatohepatitis, the pharmaceutical composition according to claim 29.

Claim 32

Prevented by VAP-1 inhibitor, for use in the treatment of alleviation and / or the disease being treated, the compound or pharmacologically acceptable salt thereof according to any of claims 1-27.

Claim 33

Prevented by VAP-1 inhibition, relief and / or for the manufacture of a medicament for the treatment of the disease being treated, the use of a compound or a pharmacologically acceptable salt thereof according to any one of claims 1-27.

Claim 34

The compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 27 in a therapeutically effective amount, comprising administering to a patient in need thereof, preventing the VAP-1 inhibitor, alleviating and / or method treatment of the disease being treated.