WO 2007/026950 PCT/JP2006/317691 DESCRIPTION PYRIDAZINONE DERIVATIVES USED FOR THE TREATMENT OF PAIN FIELD OF THE INVENTION The present invention relates to a pyridazinone derivative compound and a salt thereof, which are useful for medicaments. BACKGROUND ART Rheumatoid arthritis (RA) is a systemic inflammatory disease which causes mainly in the arthrosynovia. Today Methotrexate (MTX) is used generally as a disease-modified anti-rheumatic drugs (DMARD), but the efficacy for inflammatory responses or arthritis mutilans is not enough. On the other hand, the biologies, which targeted cytokines (TNF, IL-1, IL-6), has been revealed recently its efficacy for RA, and it has been proved the importance of these cytokines in the manifestation of RA. In particular, the monoclonal TNF antibody Remicade and soluble TNF receptor fusion protein Enbrel, which inhibit the TNF function, are worthy of note because of the unprecedented efficacy not only for inflammatory response but for arthritis mutilans. Though the fact above suggests that the importance of the treatment for RA in future, these biologies have fundamental drawbacks related to patient cost, efficacy of production, limitation of administration to hypodermal or intravenous injection, and so on. So, the anti-RA drugs in the next generation are expected to overcome these problems, that is to be an orally small-molecule drug, which blocks or modulates selectively the function of these cytokines. In particular p38 Examples of the substituents for the above-mentioned "substituted lower alkylene" formed together by R10 and R11 may include: (1) arylalkoxycarbonyl [e.g., (Ce-n) aryl (Ci_6) alkoxycarbonyl such as benzyloxycarbonyl, phenetyloxycarbonyl, etc.]; (2) acyl [e.g., (Ci_7) alkanoyl such as formyl, acetyl, propionyl, butyryl, etc., (C6-i4)acyl such as benzoyl, etc.], etc. Preferred examples of the "substituted or unsubstituted lower alkylene" formed by R10 and R11 may include (C2-6) alkylene in which one or more carbon atom(s) may be replaced with heteroatom(s) selected from an oxygen atom and a nitrogen atom, which is optionally substituted by (C6-14) aryl (Ci_6) alkoxycarbonyl or (C1-7) alkanoyl. Alternatively, R9 and R10 may be taken together to form lower- alkylene or a bond. Examples of the "lower alkylene" formed by R9 and R10 may include (C2-6) alkylene, in which preferred are propylene, etc. (Definitions of R12, R13 and R14) In the above-mentioned formula (I) , R12 is selected from the group consisting of hydrogen, halogen, hydroxy, formyl, cyano, substituted or unsubstituted lower alkyl, substituted or unsubstituted amino, substituted or unsubstituted lower alkoxy, saturated cyclic amino, substituted or unsubstituted carbamoyl, carboxy and substituted or unsubstituted lower alkoxycarbonyl, substituted or unsubstituted acyloxy. Examples of the "halogen" for R12 may include chloro, 21 WO 2007/026950 PCT/JP2006/317691 fluoro, bromo, iodo, etc., in which the preferred one may be fluoro, etc. Examples of the "lower alkyl" of the "substituted or unsubstituted lower alkyl" for R12 may include lower alkyl similar to those exemplified above for R1, in which the preferred one may be (C1-4) alkyl and more preferred one may be methyl, ethyl, isopropyl, etc. Examples of the substituents for the "substituted lower alkyl" for R12 may include: (1) hydroxy, hydroxyimino or tri(lower)alkylsilyloxy; (2) halogen (e.g., chloro, fluoro, bromo, iodo, etc.); (3) substituted or unsubstituted amino [e.g., amino, mono- or di-(substituted or unsubstituted lower alkyl)amino (e.g., mono-(Ci_6) alkylamino in which said (Ci_6) alkyl may be substituted by (C6_i4)aryl, (C3_a) cycloalkylcarbonyl or hydroxy (e.g., methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, neopentylamino, hydroxymethylamino, hydroxyethylamino, cyclopropanecarbonylamino, etc.), di-(C1-4) alkylamino in which one or both of said (C1-4) alkyl may be substituted by (C6-i4)aryl (e.g., dimethyl amino, diethylamino, ethylmethylamino, etc.), 2-hydroxyethylamino, 2- methoxyethy1amino, 2- (dimethylamino)ethylamino, 2-hydroxy- 1,1-dimethylethylamino, 2-hydroxy-l- (hydroxymethyl)ethylamino, (2-hydroxyethyl)methylamino, (2- methoxyethyl)methylamino, benzylmethylamino, tert- butylbenzylamino, dibenzylamino etc.), mono-(C2- 7)alkanoylamino (e.g., acetylamino, ethylcarbonylamino, propylcarbonylamino, isopropylcarbonylamino, butylcarbonylamino, pentylcarbonylamino, hexylcarbonylamino, etc.), (C3-B) cycloalkyl amino (e.g., cyclopropyl amino, cyclobutylamino, cyclopentylamino, cyclohexylamino, etc.), etc.]; (4) substituted or unsubstituted lower alkoxy (e.g., (Ci_ 6) alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, neopentyloxy, etc.), (C6-i4) aryl (Ci-e) alkoxy (e.g., benzyloxy, etc.), 2-hydroxyethyloxy, 2-hydroxy-l,1- 22 WO 2007/026950 PCT/JP2006/317691 dimethylethyloxy, 2-methoxyethyloxy, 2- (dimethylamino)ethyloxy, etc.); (5) saturated cyclic amino [e.g., 4-, 5- or 6-membered saturated cyclic amino which may further have heteroatom(s) selected from a nitrogen atom, an oxygen atom and a sulfur atom and/or oxo besides the amino nitrogen and may have substituent(s), such as azetidinyl (e.g., 3-hydroxy-l- azetidinyl, 3-amino-l-azetidinyl, 3-methylamino-l- azetidinyl, etc.), pyrrolidinyl (e.g., 1-pyrrolidinyl, 3- hydroxy-1-pyrrolidinyl, 3-amino-l-pyrrolidinyl, 3- methylamino~l-pyrrolidinyl, etc.), morpholinyl (e.g., morpholino, etc.), 4-(lower)alkyl-1-piperazinyl (e.g., 4- methyl-1-piperazinyl, 4-isopropyl-l-piperazinyl, etc.), 4- (mono- or di-(lower)alkylamino)-1-piperidinyl (e.g., 4- (dimethylamino)-1-piperidinyl, etc.), oxopyrrolidinyl (e.g., 2-oxo-l-pyrrolidinyl, etc.), etc.]; (6) substituted or unsubstituted carbamoyl [e.g., carbamoyl, (lower) alkylcarbamoyl (e.g., (Ci-4) alkylcarbamoyl such as methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, etc.), (C3- e)cycloalkylcarbamoyl (e.g., cyclopropylcarbamoyl, etc.), etc.]; (7) carboxy; (8) lower alkoxycarbonyl [e.g., (C1-6) alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl, propyloxycarbonyl, tert- butoxycarbonyl, pentyloxycarbamoyl, hexyloxycarbamoyl, etc.), etc.]; (9) lower alkylureido [e.g., (Ci-6) alkylureido (e.g., methylureido, ethylureido, etc.)] (10) lower acyloxy [e.g., (C1-7) alkanoyloxy (e.g., formyloxy, acetyloxy, ethylcarbonyloxy, propylcarbonyloxy, butylcarbonyloxy, pentylcarbonyloxy, hexylcarbonyloxy, etc.], etc. The number of the substituent may be one, two or more. Where the number of the substituent is two or more, the substituents may be the same or different. 23 WO 2007/026950 PCT/JP2006/317691 Examples of the "substituted or unsubstituted amino"', "saturated cyclic amino", ""substituted or unsubstituted lower alkoxy", "substituted or unsubstituted carbamoyl" and "lower alkoxycarbonyl" for R12 may be similar to the "substituted or unsubstituted amino", "saturated cyclic amino", "substituted or unsubstituted lower alkoxy", "substituted or unsubstituted carbamoyl" and "substituted or unsubstituted lower alkoxycarbonyl" exemplified above as the substituents of the "substituted lower alkyl" for R12. Examples of the "acyloxy" for the "substituted or unsubstituted acyloxy" for R12 may include lower acyloxy similar to those exemplified above as the substituent (10) for the "substituted lower alkyl" for R12 mentioned above. Examples of the substituents for the "substituted acyloxy" for R12 may be similar to those exemplified as the substituents for the "substituted lower alkyl" for R12. Preferable examples for R12 may include hydrogen; halogen; hydroxy; carboxy; formyl; cyano; hydroxycyano; (Ci-e) alkyl optionally substituted by hydroxy, hydroxyimino, halogen, (Ci_6) alkoxy, (C1-7) alkanoyloxy, amino, mono- or di- (C1-6) alkyl amino (in which one or both of said (Ci_6) alkyl is (are) optionally substituted by hydroxy, (C1-6) alkoxy, (C6-i4) aryl or (C3_6) cycloalkyl-carbonyl), (C) alkylureido, morpholino, (C1-7) alkanoyloxy, or 4- to 6-membered cyclic amino optionally substituted by hydroxy, (Ci_6) alkyl or di (Ci-6) alkylamino; mono- or di- (C1-6) alkylamino; 4- to 6- membered cyclic amino; (C1-6) alkoxy optionally substituted by (C6_14)aryl; carbamoyl optionally substituted by (C3- 6)cycloalkyl or hydroxy (C1-6) alkyl; (Ci_6) alkoxycarbonyl; (Ci_ 6)alkoxycarbonyloxy, etc. Among the above-mentioned substituents, suitable examples of R12 may include hydrogen, fluoro, hydroxy, formyl, cyano, methyl, aminomethyl, tert-butylaminomethyl, dimethylaminomethyl, diethylaminomethyl, dibenzylaminomethyl, benzylmethylaminomethyl, benzyl(tert- buthyl)aminomethyl, methoxycarbonylmethyl, 3- hydroxyazetinylmethyl, 4-methylpiperazinylmethyl, 24 WO 2007/026950 PCT/JP2006/317691 pyrrolidinylmethyl, hydroxymethyl, hydroxyethylaminoiuethyl, methoxyethylaminomethyl, iodomethyl, methylaminomethyl, morpholinomethyl, (2-hydroxyethyl)methylaminomethyl, acetyloxymethyl, 4-(dimethylamino)-1-piperidinylmethyl, ethoxycarbonylmethyl, cyclopropylcarbamoylmethyl, ethylureidomethyl, hydroxyiminomethyl, dimethylamino, isopropylamino, 3-hydroxy-l-azetidinyl, piperidino, morpholino, benzyloxy, neopentyloxy, carboxy, methoxycarbonyl, ethoxycarbonyi, tert-butoxycarbonyi, carbamoyl, cyclopropylcarbamoyl, etc. R13 is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted lower alkyl, carboxy and substituted or unsubstituted lower alkoxycarbonyl. Examples of the "halogen" and "substituted or unsubstituted lower alkoxycarbonyl" for R13 may be similar to those exemplified for R11. Examples of the "lower alkyl" of the "substituted or unsubstituted lower alkyl" for R13 may include lower alkyl similar to those exemplified above for R1, in which the preferred one may be (C1-4) alkyl, and more preferred one may be methyl, ethyl, isopropyl, etc. Examples of the substituents for the "substituted lower alkyl" for R13 may include (1) hydroxy; (2) halogen (e.g., chloro, fluoro, bromo, iodo, etc.); (3) substituted or unsubstituted amino [e.g., amino, mono- or di-(substituted or unsubstituted lower alkyl)amino (e.g., mono- (C1-6) alkyl amino (e.g., methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, neopentyl amino, etc.), di-(C1-4) alkylamino (e.g., dimethylamino, diethylamino, ethylmethylamino, etc.), 2- hydroxyethylamino, 2-methoxyethylamino, 2- (dimethylamino)ethylamino, 2-hydroxy-l,1-dimethylethylamino, 2-hydroxy-l-(hydroxymethyl)ethylamino, (2- hydroxyethyl)me thylamino, (2-methoxyethy1)methylamino, etc.), mono-(C2-7) alkanoylamino (e.g., acetylamino, 25 WO 2007/026950 PCT/JP2006/317691 ethylcarbonylamino, propylcarbonylamino, isopropylcarbonylamino, butylcarbony1amino, pentylcarbonylamino, hexylcarbonylamino, etc.), (C3_ e)cycloalkylamino (e.g., cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, etc.), etc.]; (4) substituted or unsubstituted lower alkoxy [e.g., (Ci_ 4) alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, etc.), 2-hydroxyethyloxy, 2-hydroxy-l,1- dimethylethyloxy, 2-methoxyethyloxy, 2- (dimethylamino)ethyloxy, etc.]; (5) lower alkanoyloxy [e.g., (Ci_7) alkanoyloxy [e.g., formyloxy, acetyloxy, ethylcarbonyloxy, propylcarbonyloxy, butylcarbonyloxy, pentylcarbonyloxy, hexylcarbonyloxy, etc.]; etc. The number of the substituent may be one, two or more. Where the number of the substituent is two or more, the' substituents may be the same or different. Suitable examples of R13 may include hydrogen, halogen (e.g., fluoro, etc.), (Ci-6) alkyl optionally substituted by hydroxy, fluoro, halogen, (Ci-6) alkoxy or (Ci_7) alkanoyl (e.g., methyl, hydroxymethyl, fluoromethyl, methoxymethyl, acetyloxymethyl, etc.), in which preferred are hydrogen, halogen or (Ci-e) alkyl optionally substituted by hydroxy or (CI-T) alkanoyloxy (e.g., hydroxymethyl, acetyloxymethyl, etc.), etc. R14 is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted lower alkyl, carboxy and substituted or unsubstituted lower alkoxycarbonyl. The "halogen", "substituted or unsubstituted lower alkyl" and "substituted or unsubstituted lower alkoxycarbonyl" for R14 may be similar to those exemplified for R11. Preferably, R14 is hydrogen. Alternatively, R12 and R13 may be taken together to form (1) substituted or unsubstituted lower alkylene [e.g., 26 WO 2007/026950 PCT/JP2006/317691 (C2-e) alkylene (e.g., ethylene, propylene, butylene, pentylene, hexylene, etc., in which the preferred one may be ethylene, propylene, butylene, etc.)]; (2) substituted or unsubstituted lower alkylidene [e.g., (Ci_6) alkylidene such as methylidene, ethylidene, propylidene, butylidene, pentylidene, hexylidene, etc., in which the preferred one may be methylidene, ethylidene, propan-2-ylidene, etc.];, (3)oxo, or (4)hydroxyimino. The term "lower alkylene" in the phrase "substituted or unsubstituted lower alkylene" for R12 and R13 refers to alkylene group as defined above in which one or more carbon atom(s)' is (are) replaced by one or more heteroatom(s) selected from a nitrogen atom, an oxygen atom and a sulfur atom Examples of the substituents for the above-mentioned "substituted lower alkylene" formed by R12 and R13 may include (1) substituents for "substituted or unsubstituted lower alkyl" for R12; and (2) substituted or unsubstituted lower alkyl [e.g., substituted or unsubstituted (Ci-6) alkyl (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, pentyl, hexyl, etc.), examples of the substituent may include the substituents for the "substituted or unsubstituted lower alkyl" for R12] . 27 Suitable examples of the "substituted or unsubstituted lower alkylene" formed by R12 and R13 may include following groups such as, but not limited to, WO 2007/026950 PCT/JP2006/317691 Examples of the substituents for the above-mentioned "substituted lower alkylidene" formed by Rlz and R13 may be similar to those exemplified for the "substituted or unsubstituted alkylene" formed by R12 and R13. Suitable examples of the "substituted or unsubstituted lower alkylidene" formed by R12 and R13 may include (Ci_6) alkylidene optionally substituted by hydroxy, such as the following groups, but not limited to, Alternatively, R11 and R13 or R13 and R14 may be taken together to form a bond. (Definition of R15) 28 In an embodiment of the present invention, R6 and R7 are taken together to form the following structure (A), (Bl) or (B2). WO 2007/026950 PCT/JP2006/317691 In the above-mentioned formula (A), R15 is selected from the group consisting of hydroxy, substituted or unsubstituted lower alkyl, substituted or unsubstituted amino, substituted or unsubstituted lower alkoxy, saturated cyclic amino, lower substituted or unsubstituted carbamoyl, carboxy and substituted or unsubstituted lower alkoxycarbonyl. Examples of the "lower alkyl" of the "substituted or unsubstituted lower alkyl" for R15 may include lower alkyl similar to those exemplified for R1 above, in which the preferred one may be (Ci_4) alkyl and more preferred one may be methyl, ethyl, isopropyl, etc. Examples of the substituents for the "substituted lower alkyl" for R15 may include: (1) hydroxy; (2) substituted or unsubstituted amino [e.g., amino, monp- or di-(substituted or unsubstituted lower alkyl)amino (e.g., mono- (Ci_6) alkylamino such as methylamino, ethylamino, propylamine, isopropylamino, butylamino, tert-butylamino, neopentyl amino, etc.; di- (Ci_4) alkylamino such as dimethylamino, diethylamino, ethylmethylamino, etc.; 2- hydroxyethylamino, 2-methoxyethylamino, 2- (dimethylamino)ethylamino, 2-hydroxy-l, 1-dimethylethylamino, 2-hydroxy-l-(hydroxymethyl)ethylamino, (2- hydroxyethyl)methylamino, (2-methoxyethyl)methylamino, etc.), mono-(C2-5) alkanoylamino (e.g., acetylamino, ethylcarbonylamino, propylcarbonylamino, isopropylcarbonylamino, butylcarbonylamino, etc.), (C3_ 6)cycloalkylamino (e.g., cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, etc.), etc.]; (3) substituted or unsubstituted lower alkoxy [e.g., (Ci_ 4)alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, etc.), 2-hydroxyethyloxy, 2-hydroxy-l,1- dimethylethyloxy, 2-methoxyethyloxy, 2- (dimethylamino)ethyloxy, etc.]; (4) saturated cyclic amino [e.g., 4-, 5- or 6-membered saturated cyclic amino which may further have heteroatom(s) 29 WO 2007/026950 PCT/JP2006/317691 selected from a nitrogen atom, an oxygen atom and a sulfur atom and/or oxo besides the amino nitrogen and may have substituent(s), such as azetidinyl (e.g., 3-hydroxy-l- azetidinyl, 3-amino-l-azetidinyl), pyrrolidinyl (e.g., 1- pyrrolidinyl, etc.), morpholinyl (e.g., morpholino, etc.), 4-(lower)alkyl-1-piperazinyl (e.g., 4-methyl-l-piperazinyl, 4-isopropyl-l-piperazinyl, etc.), oxopyrrolidinyl (e.g., 2- oxo-1-pyrrolidinyl, etc.), etc.]; (5) substituted or unsubstituted carbamoyl [e.g., carbamoyl, (lower) alkylcarbamoyl (e.g., (Ci_4) alkyl carbamoyl such as methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, etc.), etc.], (6) carboxy; (7) lower alkoxycarbonyl [e.g., (Ci-6) alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl), etc.], etc. The number of the substituent may be one, two or more. Where the number of the substituent is two or more, the substituents may be the same or different. Examples of the "substituted or unsubstituted amino", "substituted or unsubstituted lower alkoxy", "saturated cyclic amino", "substituted or unsubstituted carbamoyl" and "lower alkoxycarbonyl" for R15 may be similar to the "substituted or unsubstituted amino", "substituted or unsubstituted lower alkoxy", "saturated cyclic amino", "substituted or unsubstituted carbamoyl" and "lower alkoxycarbonyl" exemplified above as the substituents for the "substituted lower alkyl" for R15. Suitable examples of R15 may include dime thylaminomethyl, methylaminomethyl, hydroxymethyl, morpholino, 3-hydroxy-l- azetidinyl, etc. (Definitions of R16 and R1"7) In the above-mentioned formula (Bl), R16 is selected from the group consisting of hydrogen, halogen, hydroxy, substituted or unsubstituted lower alkyl, substituted or 30 WO 2007/026950 PCT/JP2006/317691 unsubstituted amino, saturated cyclic amino, substituted or unsubstituted lower alkoxy, substituted or unsubstituted carbamoyl, carboxy and lower alkoxycarbonyl. Examples of the "halogen" for R16 may include chloro, fluoro, bromo, iodo, etc., in which the preferred one may be fluoro, etc. Examples of the "lower alkyl" of the "substituted or unsubstituted lower alkyl" for R16 may include lower alkyl similar to those exemplified for R1 above, in which the preferred one may be (d-4) alkyl and more preferred one may be methyl, ethyl, isopropyl, etc. Examples of the substituents for the "substituted lower alkyl" for R16 may include: (1) hydroxy or tri(lower)alkylsilyloxy; (2) halogen (e.g., chloro, fluoro, bromo, iodo, etc.); (3) substituted or unsubstituted amino [e.g., amino, mono- or di-(substituted or unsubstituted lower alkyl)amino (e.g., mono- (Ci_6) alkylamino (e.g., methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, neopentylamino, etc.), diy (Ci-j) alkylamino (e.g., dimethyl amino, diethylamino, ethylmethylamino, etc.), 2- hydroxyethylamino, 2-methoxyethylamino, 2- (dime thy lamin.o) ethylamino, 2-hydroxy-l, 1-dimethylethylamino, 2-hydroxy-l- (hydroxymethyl) ethylamino, (2- hydroxyethyl) methylamino, (2-methoxyethyl) methylamino, etc.), mono-(C2-5) alkanoylamino (e.g., acetylamino, ethylcarbonylamino, propylcarbonylamino, isopropylcarbonylamino, butylcarbonylamino, etc.), (C3_ e)cycloalkylamino (e.g., cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, etc.), etc.]; (4) substituted or unsubstituted lower alkoxy (e.g., (Ci_ 4)alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, etc.), 2-hydroxyethyloxy, 2-hydroxy-l,1- dimethylethyloxy, 2-methoxyethyloxy, 2- (dimethylamino)ethyloxy, etc.); (5) saturated cyclic amino [e.g., 4-, 5- or 6-membered saturated cyclic amino which may further have heteroatom(s) 31 WO 2007/026950 PCT/JP2006/317691 selected from a nitrogen atom, an oxygen atom and a sulfur atom and/or oxo besides the amino nitrogen and may have substituent(s), such as azetidinyl (e.g., 3-hydroxy-l- azetidinyl, 3-amino-l-azetidinyl, 3-methylamino-1- azetidinyl, etc.), pyrrolidinyl (e.g., 1-pyrrolidinyl, 3- hydroxy-1-pyrrolidinyl, 3-amino-1-pyrrolidinyl, 3- methylamino-1-pyrrolidinyl, etc.), morpholinyl (e.g., morpholino, etc.), 4-(lower)alkyl-1-piperazinyl (e.g., 4- methyl-1-piperazinyl, 4-isopropyl-l-piperazinyl, etc.), 4- (mono- or di-(lower)alkylamino)-1-piperidinyl (e.g., 4- (dimethylamino)-1-piperidinyl, etc.), oxopyrrolidinyl (e.g., 2-oxo-l-pyrrolidinyl, etc.), etc.]; (6) substituted or unsubstituted carbamoyl [e.g., carbamoyl, (lower) alkyl carbamoyl (e.g., (Ci_4) alkylcarbamoyl such as methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, etc.), etc.]; (7) carboxy; (8) lower alkoxycarbonyl [e.g., (Ci_4) alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, etc.), etc.], etc. The number of the substituent may be one or two or more. Where the number of the substituent is two or more, the substituents may be the same or different. Examples of the "substituted or unsubstituted amino", "saturated cyclic amino", "substituted or unsubstituted lower alkoxy", "substituted or unsubstituted carbamoyl" and "lower alkoxycarbonyl" for R16 may be similar to the "substituted or unsubstituted amino", "saturated cyclic amino", "substituted or unsubstituted lower alkoxy", "substituted or unsubstituted carbamoyl" and "lower alkoxycarbonyl" exemplified as the substituents of the "substituted or unsubstituted lower alkyl" for R7. Suitable examples of R16 may include hydrogen, fluoro, hydroxy, dimethylaminomethyl, hydroxymethyl, iodomethyl, 4- (dimethylamino)-1-piperidinylmethyl, dimethylamino, piperidino, isopropylamino, methylaminomethyl, morpholinomethyl, (2-hydroxyethyl)methylaminomethyl, morpholino, carboxy, methoxycarbonyl, tert-butoxycarbonyl, 32 WO 2007/026950 PCT/JP2006/317691 3-hydroxy-l-azetidinyl, etc. In the above-mentioned formula (Bl), R17 is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted lower alkyl, carboxy and lower alkoxycarbonyl. Examples of the "halogen" for R17 may include chloro, fluoro, bromo, iodo, etc., in which the preferred one may be fluoro, etc. Examples of the "lower alkyl" of the "substituted or unsubstituted lower alkyl" for R17 may include lower alkyl similar to those exemplified for R1 above, in which the preferred one may be (C1-4) alkyl, and more preferred one may be methyl, ethyl, isopropyl, etc. Examples of the substituents for the "lower alkyl" for R17 may include (1) hydroxy; (2) halogen (e.g., chloro, fluoro, bromo, iodo, etc.); (3) substituted or unsubstituted amino [e.g., amino, mono- or di-(substituted or unsubstituted lower alkyl)amino (e.g., mono-(C1-6) alkylamino (e.g., methylamino, ethylamino, propylamino, isopropylamino, butylamino, t-butylamino, neopentylamino, etc.), di-(C1-4) alkylamino (e.g., dimethylamino, diethylamino, ethylmethylamino, etc.), 2- hydroxyethylamino, 2-methoxyethylamino, 2- (dimethylamino)ethylamino, 2-hydroxy-l,1-dimethylethylamino, 2-hydroxy-l-(hydroxymethyl)ethylamino, (2- hydroxyethyl)methylamino, (2-methoxyethyl)methylamino, etc.), mono-(C2-5) alkanoylamino (e.g., acetylamino, ethylcarbonylamino, propylcarbonylamino, isopropylcarbonylamino, butylcarbonylamino, etc.), (C3- a) cycloalkylamino (e.g., cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, etc.), etc.]; (4) substituted or unsubstituted lower alkoxy [e.g., (Ci_ 4)alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, etc.), 2-hydroxyethyloxy, 2-hydroxy-l,1- dimethylethyloxy, 2-methoxyethyloxy, 2- (dimethylamino) ethyloxy, etc.], etc. The number of the 33 WO 2007/026950 PCT/JP2006/317691 substituent may be one or two or more. Where the number of the substituent is two or more, the substituents may be the same or different. Suitable examples of R17 may include hydrogen, methyl, hydroxymethyl, fluoro, fluoromethyl, methoxymethyl, etc. Alternatively, R16 and R17 are taken together to form lower alkylene or lower alkylidene. Examples of the "lower alkylene" for R16 and R17 may include (C2-6) alkylene such as ethylene, propylene, butylene, pentylene, hexylene, etc., in which the preferred one may be ethylene, propylene, butylene, etc. Examples of the "lower alkylidene" for R16 and R17 may include (Ci-6) alkylidene such as methylidene, ethylidene, propylidene, butylidene, pentylidene, hexylene, etc., in which the preferred one may be methylidene, ethylidene, propan-2-ylidene, etc. (Definition of R18) In the above-mentioned formula (Bl), R18 is hydrogen or substituted or unsubstituted lower alkyl; provided that when both R16 and R17 are simultaneously hydrogen, R18 is substituted or unsubstituted lower alkyl. Examples of the "lower alkyl" of the "substituted or unsubstituted lower alkyl" for R18 may include lower alkyl similar to those exemplified for R1 above, in which the preferred one may be (C1-4) alkyl and more preferred one may be ethyl, propyl, etc. Examples of the substituents for the "substituted lower alkyl" for R18 may include (1) hydroxy; (2) carboxy; (3) halogen (chloro, fluoro, bromo, iodo); (4) (lower) alkoxycarbonyl [e.g., (Ci_6) alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, t-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, etc.), etc.]; (5) substituted or unsubstituted amino [e.g., amino, mono- 34 WO 2007/026950 PCT/JP2006/317691 or di-(substituted or unsubstituted lower alkyl)amino (e.g., mono- (Ci-6) alkylamino (e.g., methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, neopentyl amino, etc.), di- (C1-4) alkylamino (e.g., dimethylamino, diethylamino, ethylmethylamino, etc.), 2- hydroxyethylamino, 2-methoxyethylamino, 2- (dimethylamino)ethylamino, 2-hydroxy-l,1-dimethylethylamino, 2-hydroxy-l- (hydroxymethyl) ethylamino, (2- hydroxyethyl)methylamino, (2-methoxyethyl)methylamino, etc.), mono-(C2-5) alkanoyl amino (e.g., acetylamino, ethylcarbonylamino, propylcarbonylamino, isopropylcarbonylamino, butylcarbonylamino, etc.), (C3_ 8)cycloalkylamino (e.g., eyelopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, etc.), etc.]; (6) substituted or unsubstituted lower alkoxy [e.g., (Ci- 4)alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, etc.), 2-hydroxyethyloxy, 2-hydroxy-l,1- dimethylethyloxy, 2-methoxyethyloxy, 2- (dimethylamino)ethyloxy, etc.]; (7) saturated cyclic amino [e.g., 4, 5- or 6-membered saturated cyclic amino which may further have heteroatom(s) selected from a nitrogen atom, an oxygen atom and a sulfur atom and/or oxo besides the amino nitrogen and may have substituent(s), such as azetidinyl (e.g., 3-hydroxy-l- azetidinyl, 3-amino-l-azetidinyl, 3-methy1amino-1- azetidinyl, etc.), pyrrolidinyl (e.g., 1-pyrrolidinyl, 3- hydroxy-1-pyrrolidinyl, 3-amino-l-pyrrolidinyl, 3- methylamino-1-pyrrolidinyl, etc.), morpholinyl (e.g., morpholino, etc.), 4-(lower)alkyl-1-piperazinyl (e.g., 4- methyl-1-piperazinyl, 4-isopropyl-l-piperazinyl, etc.), 4- (mono- or di-(lower)alkylamino)-1-piperidinyl (e.g., 4- (dimethylamino)-1-piperidinyl, etc.), oxopyrrolidinyl (e.g., 2-oxo-l-pyrrolidinyl, etc.), etc.]; (8) lower alkylsulfonyloxy [e.g., (Ci-6) alkylsulfonyloxy (e.g., methylsulfonyloxy, ethylsulfonyloxy, propylsulfonyloxy, butylsulfonyloxy, pentylsulfonyloxy, hexylsulfonyloxy, etc.), etc.]; 35 WO 2007/026950 PCT/JP2006/317691 (9) substituted or unsubstituted arylsulfonyloxy (e.g., p- toluenesulfonyloxy, benzenesulfonyloxy, mesitylenesulfonyloxy, etc.), etc. The number of the substituent may be one or two or more. Where the number of the substituent is two or more, the substituents may be the same or different. ., ,. . . Suitable examples of R18 may include hydrogen, methyl, ethyl, t.ert-butoxycarbonylethyl, carboxyethyl, hydroxypropyl, methoxyethyl, hydroxyethyl, dimethylaminopropyl, etc. (Definition of R19) In the above-mentioned formula (B2) , R19 is hydrogen or substituted or unsubstituted lower alkyl. Examples of the "lower alkyl" of the "substituted or unsubstituted lower alkyl" for R19 may include lower alkyl similar to those exemplified for R1 above, in which the preferred one may be (Ci_4) alkyl and more preferred one may be ethyl, propyl, etc. Examples of the substituents for the "substituted lower alkyl" for R19 may include (1) hydroxy; (2) carboxy; (3) (lower) alkoxycarbonyl [e.g., (Ci_6) alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, etc.), etc.]; (4) saturated cyclic amino [e.g., 4-, 5- or 6-membered saturated cyclic amino which may further have heteroatom(s) selected from a nitrogen atom, an oxygen atom and a sulfur atom and/or oxo besides the amino nitrogen and may have substituent(s), such as azetidinyl (e.g., 3-hydroxy-l- azetidinyl, 3-amino-l-azetidinyl, etc.), morpholinyl (e.g., morpholino, etc.), etc.]; (5) (saturated cyclic amino)carbonyl [e.g., a group in which the saturated cyclic amino as exemplified in (4) above is attached to a carbonyl group (e.g., 36 WO 2007/026950 PCT/JP2006/317691 morpholinocarbonyl, etc.), etc.]; (6) (lower) alkylsulfonyloxy [e.g., (Ci-6) alkylsulfonyloxy (e.g., methylsulfonyloxy, ethylsulfonyloxy, propylsulfonyloxy, butylsulfonyloxy, pentylcarbonyloxy, hexylcarbonyloxy, etc.), etc.]; (7) substituted or unsubstituted amino [e.g., amino, mono- or di-(substituted or unsubstituted lower alkyl)amino (e.g., mono- (Ci-6) alkylamino (e.g., methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, neopentyl amino, etc.), di- (C1-4) alkylamino (e.g., dimethylamino, diethylamino, ethylmethylamino, etc.), 2- hydroxyethylamino, 2-methoxyethylamino, 2- (dimethylamino)ethylamino, 2-hydroxy-l,1-dimethylethylamino, 2-hydroxy-l- (hydroxymethyl)ethylamino, (2- hydroxyethy1) methylamino, (2-methoxyethyl)methylamino, etc.), mono-(C2-5) alkanoylamino (e.g., acetylamino, ethylcarbonylamino, propylcarbonylamino, isopropylcarbonylamino, butylcarbonylamino, etc.), (C3- 8)cycloalkylamino (e.g., cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, etc.), etc.], (8) substituted or unsubstituted arylsulfonyloxy (e.g., p- toluenesulfonyloxy, benzenesulfonyloxy, mesitylenesulfonyloxy, etc.); (9) halogen (e.g., chloro, fluoro, bromo, iodo, etc.), etc The number of the substituent may be one or two or more. Where the number of the substituent is two or more, the substituents may be the same or different. Suitable examples of R19 may include methyl, ethyl, propyl, methoxyethyl, methoxypropyl, hydroxyethyl, ethoxycarbonylethyl, carboxyethyl, hydroxypropyl, morpholinocarbonylethyl, methylsulfonyloxypropyl, morpholinopropyl, methylaminopropyl, dimethylaminopropyl, etc. Specific examples of the preferred compound of the present invention may be exemplified by Examples below. 37 WO 2007/026950 PCT/JP2006/317691 In order to show the usefulness of the compound (I) of the present invention, the pharmacological test results of the representative compounds of the present invention are shown in the following. Test 1: Inhibition of TNF-a production in THP-1 cells [I] Test method THP-1 cells, a human monocytic cell line, were maintained in RPMI 1640 (Sigma R8758) supplemented with penicillin (50 U/ml), streptomycin (50 ng/ml) and 10% fetal bovine serum (Moregate BioTech.) at 37°C, 5% C02 in a humidified incubator. Initial stock solutions of test compounds were made in DMSO. All cells, reagents and test compounds were diluted into culture media. THP-1 cells (1 x 105 cells/well final) and lipopolysaccharide (LPS; 10 u.g/mL final; Sigma L-4005, from E. coli serotype 055:B5) were added to 96 well polypropylene culture plates (Sumilon, MS-8196F5; sterile) containing test compound or 0.1% DMSO vehicle. The cell mixture was incubated for 20 hours in a humidified incubator at 37°C, 5% C02. The culture supernatants were harvested and TNF-a levels from LPS stimulated cells in the presence of 100 nM test compound was calculated compared with control cells stimulated in the presence of 0.1% DMSO. [II] Test compounds 6-{2-(2,4-Difluorophenyl)-6-[(dimethy1amino)methyl]- 4,5, 6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl}-2-(2- methylphenyl)-3(2H)-pyridazinone (Example 1) 6-{2-(2,4-Difluorophenyl)-6- [(dimethylamino)methyl]pyrazolo[1,5-a]pyrimidin-3-yl}-2-(2- methylphenyl)-3(2H)-pyridazinone (Example 2) 6-[l-Ethyl-6-(4-fluorophenyl)-2,3-dihydro-lH- imidazo[l,2-b]pyrazol-7-yl]-2-(2-methylphenyl)-3(2H)- pyridazinone (Example 6) 6-[2-(4-Fluorophenyl)-6, 6-bis(hydroxymethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2- 38 WO 2007/026950 PCT/JP2006/317691 methylphenyl)pyridazin-3(2H)-one (Example 35) 6-[2-(2,4-Difluorophenyl)-6-(hydroxymethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2- methylphenyl)pyrida2in-3(2H)-one (Example 37) 6-{2-(4-Fluorophenyl)-6-[(4-methylpiperazin-l- yl)methyl]-4,5,6,7-tetrahydropyrazolo[l, 5-a]pyrimidin-3- yl}-2-(2-methylphenyl)pyridazin-3(2H)-one dihydrochloride (Example 47) 6-{2-(2,4-difluorophenyl)-6-[(dimethylamino)methyl]- 4,5,6,7-tetrahydropyrazolo[l,5-a]pyrimidin-3-yl}-2-(2- methylphenyl)-4,5-dihydropyridazin-3(2H)-one (Example 55) N-cyclopropyl-2-(4-fluorophenyl)-3-[1-(2- methylphenyl)-6-oxo-l,6-dihydropyridazin-3-yl]-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-6-carboxamide (Example 57) 6-[6,6-Difluoro-2-(4-fluorophenyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one (Example 85) 6-{6-[(tert-Butylamino)methyl]-2-(2,4- difluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin- 3-yl}~2-(2-methylphenyl)pyridazin-3(2H)-one (Example 98) 6-[l-Acetyl-2'-(4-fluorophenyl)-4", 5'- dihydrospiro[piperidine-4,6'-pyrazolo[1,5-a]pyrimidin]-3'- yl]-2-(2-methylphenyl)pyridazin-3(2H)-one (Example 107) 6-[(5S)-2-(4-Fluorophenyl)-5-(hydroxymethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one (Example 123) 6-[(5S)-2-(4-Fluorophenyl)-5-(hydroxymethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one (Example 124) Ethyl 3-(4-fluorophenyl)-2-[1-(2-methylphenyl)-6-oxo- 1, 6-dihydropyridazin-3-yl]-3-oxopropanoate (Example 125) 6-(5-Isopropyl-2-phenyl-4, 5,6,7- tetrahydropyrazolo[1,5-a]pyrazin-3-yl) -2-(2- methylphenyl)pyridazin-3(2H)-one (Example 130) [III] Test results Table 1 : Inhibition of TNF-a production 39 WO 2007/026950 PCT/JP2006/317691 in THP-1 cells at 100 nM Test compounds (Example Nos.) % inhibition of control Example 1 88 Example 2 98 Example 6 80 Example 35 90 Example 37 94 Example 47 95 Example 55 98 Example 57 97 Example 85 88 Example 98 86 Example 107 90 Example 123 94 Example 124 94 Example 125 83 Example 130 70 Test 2: Inhibition of hind paw swelling in adjuvant-induced arthritis rats [I] Test method Arthritis was induced by injection of 0.5 mg of Mycobacterium tuberculosis (Difco Laboratories, Detroit, Mich.) in 50 \iL of liquid paraffin into the right hind footpad of female Lewis rats aged 7 weeks (day 0). Normal untreated rats were used as negative controls. Animals were randomized and grouped (n5) for drug treatment based on an increase of left hind paw volume and body weight on day 15. Test compounds were suspended in vehicle (0.5% methylcellulose) and orally administered once a day from days 15 to 24. The volume of the left hind paw was measured on day 25 by a water displacement method using a plethymometer for rats (MK-550; Muromachi Kikai Co., Ltd., 40 WO 2007/026950 PCT/JP2006/317691 Tokyo, Japan). [II] Test compounds 6-[2-(4-Fluorophenyl)-6-(hydroxymethyl)-4,5,6,7- tetrahydropyrazolo[l,5-a]pyrimidin-3-yl]-2-(2- methylphenyl)-3(2H)-pyridazinone (Example 3) 6-[2-(4-Fluorophenyl)-6-hydroxy-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl] -2- (2- methylphenyl)-3(2H)-pyridazinone (Example 18) 6-[2-(2,4-Difluorophenyl)-6-(hydroxymethyl)-4,5, 6, 7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one (Example 37) 6-[2'-(4-Fluorophenyl)-2,3,4',5,5',6- hexahydrospiro[pyran-4,6'-pyrazolo[1,5-a]pyrimidin]-3'-yl]- 2-(2-methylphenyl)pyridazin-3(2H)-one (Example 63) 6-[2'-(4-Fluorophenyl)-4',5'-dihydrospiro[1,3- dioxolane-2,6'-pyrazolo[1,5-a]pyrimidin]-3'-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one (Example 86) 6-[(6R)-2-(4-Fluorophenyl)-6-hydroxy-4,5,6,7- tetrahydropyrazolo[l,5-a]pyrimidin-3-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one (Example 100) 6-[(5S)-2-(4-fluorophenyl)-5-(hydroxymethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one (Example 123) 6-[(5S)-2- (4-fluorophenyl)-5-(hydroxymethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one (Example 124) 6-[2-(4-Fluorophenyl)-6, 6-dimethyl-4,5,6,7- teterahydropyrazolo[l,5-a]pyrimidin-3-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one (Example 132) 41 WO 2007/026950 PCT/JP2006/317691 [III] Test results Table 2: Inhibition of hind paw swelling in adjuvant- induced arthritis rats Test compounds Dose (mg/kg) % inhibition of vehicle-treated •rats Example 1 0.3 51.2 Example 3 1 56.4 Example 18 1 46.1 Example 37 1 63.6 Example 63 1 39.5 Hxample 86 1 48.1 Example 100 0.5 40.2 . Example 123 1 62.3 Example 124 1 50.6 Example 132 1 60.4 The compound (I) and a salt thereof of the present invention are useful as inhibitors of cytokines' production or their transduction, and through inhibiting the p38a MAPK they possess pharmacological actions such as analgesic action, anti-inflammatory, anti arthritis mutilans action, or the like, and for the prevention and/or the treatment of pain, rheumatoid arthritis, other conditions associated with inflammation, Crohn's disease, inflammatory bowel disease, psoriasis, or the like. The pharmaceutical composition of the present invention can be used in the form of a pharmaceutical preparation, for example, in a solid, semisolid or liquid form, which contains the compound (I) or a pharmaceutically acceptable salt thereof as an active ingredient in admixture with an organic or inorganic carrier or excipient suitable for rectal, pulmonary (nasal or buccal inhalation), nasal, ocular, external (topical), oral or parenteral (including subcutaneous, intravenous and intramuscular) administrations or insufflation. The active ingredient may be compounded, for example, with the usual non-toxic, 42 WO 2007/026950 PCT/JP2006/317691 pharmaceutical! acceptable carriers for tablets, pellets, troches, capsules, suppositories, creams, ointments, aerosols, powders for insufflation, solutions, emulsions, suspensions, and any other form suitable for use. In addition, auxiliary, stabilizing agents, thickening agents, coloring agents and perfumes may be used where necessary. The compound (I) or a pharmaceutically acceptable salt thereof is included in a pharmaceutical composition in an amount sufficient to produce the desired aforesaid pharmaceutical effect upon the process or condition of diseases. For applying the composition to a mammal (e.g., human being, mouse, rat, swine, dog, cat, horse, bovine, etc., especially human being), it is preferable to apply the composition by intravenous, intramuscular, pulmonary or oral administration, or insufflation. While the dosage of therapeutically effective amount of the compound (I) varies depending on the age and condition of each individual patient to be treated, in the case of intravenous administration, a daily dose of 0.01-100 mg of the compound (I) per kg weight of a mammal, in the case of intramuscular administration, a daily dose of 0.1-100 mg of the compound (I) per kg weight of a mammal, and in case of oral administration, a daily dose of 0.5-100 mg of the compound (I) per kg weight of a mammal is generally given for the prevention and/or treatment of the aforesaid diseases. Hereinafter the reactions for preparing the compound [I] of the present invention are explained in more detail with referring to the Preparations and Examples. However, the Preparations and Examples are given only for the purpose of illustration of the present invention, and the invention should not be restricted by the Preparations and Examples in any way. The abbreviations, symbols and terms used in the Preparations and Examples have the following meanings. 43 WO 2007/026950 PCT/JP2006/317691 AcOH acetic acid CDCI3 chloroform-d CHCI3 chloroform CH2C12 dichloromethane CH3CN acetonitrile EtOAc or AcOEt ethyl acetate MeOH methanol EtOH ethanol PrOH propanol i-PrOH or IPA isopropyl alcohol BuOH butanol t-(or tert-)BuOH t-(or tert-)butanol DME 1,2-dimethoxyethane DMF N,N-dimethylformamide DMSO dimethyl sulfoxide Et3N triethylamine IPE diisopropyl ether TFA trifluoroacetic acid THF tetrahydrofuran HOBt or HOBT 1-hydroxybenzotriazole EDCI or WSCD l-ethyl-3-[3'- (dimethylamino)propyl]carbodiimide Pd/C palladium on carbon MCPBA or mCPBA 3-chloroperoxybenzoic acid min minute(s) hr or h hour(s) rt room temperature cone. concentrated aq aqueous (ex. aq NaHC03 solution) HC1 hydrochloric acid CuBr2 copper (II) bromide Na2C03 sodium carbonate NaOH sodium hydroxide Na2SC>4 sodium sulfate Preparation 1 To a solution of 3-chloro-6-methylpyridazine (51 g) 44 WO 2007/026950 PCT/JP2006/317691 and ethyl 4-fluorobenzoate (66.7 g) in THF (200 ml) was added dropwise lithium bis(trimethylsilyl)amide (793 ml, 1.0 M in THF) over the period of 30 min while maintaining the temperature below 15°C. After stirring for 30 min at room temperature, the mixture was recooled in an ice bath, and neutralized by addition of cold water (250 ml) and 6 N HC1 (175 ml) . A solid was separated from the mixture and collected to give 2-(6-chloro-3-pyridazinyl)-1-(4- fluorophenyl)ethanone (36.6 g) as the first crop. The organic layer was separated from the mother liquor and washed with brine (150 ml, twice) , dried over Na2SC>4, filtered and concentrated to form a suspension. This suspension was dissolved under reflux. To the solution was added hexane (600 ml) and the resulted suspension was aged for 1 hour with stirring at room temperature. The resulted solid was collected and washed with hexane (200 ml) to afford 2-(6-chloro-3-pyridazinyl)-1-(4- fluorophenyl)ethanone (51.3 g) as the second crop. Mass ESI (+) 251 (M+l) XH-NMR (300 MHz, DMSO-d6) 5 4.85 (2H, s) , 7.42 (2H, t, J=9 Hz), 7.78 (1H, d, J=8.7 Hz), 7.93 (1H, d, J=8.7 Hz), 8..13- 8.22 (2H, m) Preparation 2 A mixture of 2-(6-chloro-3-pyridazinyl)-1-(4- fluorophenyl)ethanone (30.0 g) and sodium acetate (19.6 g) in AcOH (240 ml) was stirred for 3 hours at 135°C. After cooling to room temperature, cold water (400 ml) was added to this mixture. A solid separated from the mixture was collected, washed with water and dried in vacuo to give 6- [2-(4-fluorophenyl)-2-oxoethyl]-3(2H)-pyridazinone (17 g) as a gray solid. Mass ESI(+) 233 (M+l) 1H-NMR (300MHz, DMSO-d6) 5 4.43 (2H, s), 6.87 (1H, d, J=10 Hz), 7.36-7.43 (3H, m), 8.09-8.14 (2H, m) Preparation 3 A mixture of 6-[2-(4-fluorophenyl)-2-oxoethyl]-3(2H)- pyridazinone (4.8 g), ethylene glycol (9.6 ml) and 45 WO 2007/026950 PCT/JP2006/317691 toluenesulfonic acid hydrate (393 mg) in toluene (96 ml) was refluxed for 6 h with azeotropic removal of water. After concentration, the residue was partitioned between EtOAc and saturated aqueous NaHC03- The organic layer was washed with brine, dried over NaaSC, filtered and evaporated in vacuo to give a solid. The solid was triturated with hexane, collected and dried in vacuo to afford 6-{[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]methyl}- 3(2H)-pyridazinone (3.04 g) as a white solid. XH-NMR (200 MHz, DMSO-d6) 5 3.10 (2H, s) , 3.67-3.74 (2H, m) , 3.89-3.97 (2H, m), 6.76 (1H, d, J=9.8 Hz), 7.11-7.20 (2H, m), 7.28 (1H, d, J=9.8 Hz), 7.33-7.40 (2H, m), 12.76 (1H, s) Preparation 4 A mixture of 6-{[2-(4-fluorophenyl)-1,3-dioxolan-2- yl]methyl}-3(2H)-pyridazinone (2.0 g), 2- methylbenzeneboronic acid (2.46 g), copper (II) acetate (263 mg) and pyridine (2.93 ml) in DMF (30 ml) was stirred for 14 hours at room temperature. The mixture was partitioned between EtOAc and HzO. The separated organic layer was washed with brine, dried over NaaSOo filtered and evaporated in vacuo. The. residue was purified by column chromatography on Si02 (eluent; 1% to 8% methanol in dichloromethane) to give 6-{[2-(4-fluorophenyl)-1,3- dioxolan-2-yl]methyl}-2- (2-methylphenyl)-3(2H)-pyridazinone (2.17 g) as an amorphous solid. XH-NMR (200 MHz, DMSO-d6) 5 1.83 (3H, s) , 3.16 (2H, s) , 3.70-3.84 (2H, m) , 3.89-4.04 (2H, m), 6.95-7.07 (2H, m) , 7.09-7.23 (2H, m), 7.24-7.41 (5H, m), 7.46 (1H, d, J=9.5 Hz) Preparation 5 To a solution of 6-{[2-(4-fluorophenyl)-1,3-dioxolan- 2-ylJmethyl}-2-(2-methylphenyl)-3(2H)-pyridazinone (2.16 g) in THF (20 ml) was added cone. HC1 (2 ml) at room temperature. After stirring for 14 hours, the mixture was concentrated and partitioned between EtOAc and water. The organic layer was washed with 3% aqueous NaHC03 and brine, 46 WO 2007/026950 PCT/JP2006/317691 dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by column chromatography on Si02 (eluent; 30% to 50% EtOAc in dichloromethane) to give 6-[2- (4-fluorophenyl)-2-oxoethyl]-2-(2-methylphenyl)-3(2H)- pyridazinone (1.64 g) as a pale yellow waxy solid. 1H-NMR (200 MHz, DMSO-d6) 5-2.01 (3H, s) , 4.51 (2H, s) , 7.08 (1H, d, J=9.6 Hz), 7.20-7.47 (6H, m) , 7.53 (1H, d, J=9.6 Hz), 8.05-8.18 (2H, m) Preparation 6 To a solution of 6-[2-(4-fluorophenyl)-2-oxoethyl]-2- (2-methylphenyl)-3(2H)-pyridazinone (500 mg) in AcOH (4 ml) was added pyridinium tribromide (595 mg) portionwise at room temperature. After 3 h, the mixture was partitioned between EtOAc (8 ml) and water (16 ml) . The separated organic layer was washed with water, 3% aqueous Na2S203, 3% aqueous NaHCC>3 (two times) and brine, dried over Na2S04, filtered and concentrated in vacuo to give 6-[l-bromo-2-(4- fluorophenyl)-2-oxoethyl]-2-(2-methylphenyl)-3(2H)- pyridazinone (566 mg) as a pale yellow solid. 1H-NMR (200 MHz, DMSO-d6) 8 1.89 (3H, s) , 7.08 (1H, s) , 7.15-7.48 (7H, m), 7.80 (1H, d, J=9.7 Hz), 7.08-8.20 (2H, m) Preparation 7 2-(6-Chloro-3-pyridazinyl)-1-(2,4- difluorophenyl)ethanone was obtained according to a similar manner to Preparation 1. 1H-NMR (200 MHz, DMSO-d6) 5 4.74 (1.6H, d, J=2.5 Hz), 6.25 (0.2H, s), 7.18-7.37 (1H, m) , 7.39-7.56 (1H, m) , 7.75-7.87 (1.2H, m), 7.88-8.11 (2H, m) Preparation 8 6-[2-(2,4-Difluorophenyl)-2-oxoethyl]-3(2H)- pyridazinone was obtained according to a similar manner to Preparation 2. XH-NMR (200 MHz, DMS0-d6) 5 4.32 (2H, d, J=3.0 Hz), 6.86 (1H, dd, J=1.5, 10.0 Hz), 7.27 (1H, dt, J=2.5, 8.0 Hz), 7.38 (1H, d, J=10.0 Hz), 7.40-7.53 (1H, m), 7.91-8.08 (1H, m), 12.91 (1H, brs) 47 WO 2007/026950 PCT/JP2006/317691 Preparation 9 6-{[2-(2,4-Difluorophenyl)-l,3-dioxolan-2-yl]methyl}- 3(2H)-pyridazinone was obtained according to a similar manner to Preparation 3. 1H-NMR (200 MHz, DMSO-d6) 5 3.19 (2H, s) , 3.72-3.87 (2H, m) , 3.88-4.02 (2H, m) , 6.76 (1H, d, J=10.0.Hz), 7.01 (1H, dt, J=2.5, 8.5Hz), 7.17-7.42 (3H, m) , 12.73 (1H, brs) Preparation 10 A mixture of 6-{[2-(2,4-difluorophenyl)-1,3-dioxolan- 2-yl]methyl}-3(2H)-pyridazinone (8.00 g), 2- methylbenzeneboronic acid (7.39 g) , copper (II) acetate (988 mg) and pyridine (10.75 g) in DMF (80 ml) was stirred at room temperature for 2 days. The mixture was partitioned between EtOAc (120 ml) and 3% aqueous NaHC03 (160 ml) . The organic layer was washed with 3% aqueous citric acid (x 2), 0.5 N NaOH (x 2) and brine, dried over Na2S04, filtered and evaporated in vacuo. The residue was purified by column chromatograph on Si02 (eluent; EtOAc/Hex (w/w) = 1/1 to 2/1) to give 6-{[2-(2,4-difluorophenyl)- 1, 3-dioxolan-2-yl]methyl}-2-(2-methylphenyl)-3(2H)- pyridazinone (8.29 g) as a waxy solid. -NMR (200 MHz, DMSO-d6) 5 1.81 (3H, s) , 3.24 (2H, s) , 3.74-3.90 (2H, m), 3.93-4.08 (2H, m) , 6.92-7.09 (3H, m), 7.14-7.39 (5H, m), 7.47 (1H, d, J=9.6 Hz) Preparation 11 6-[2-(2,4-Difluorophenyl)-2-oxoethyl]-2-(2- methylphenyl)-3(2H)-pyridazinone was obtained according to a similar manner to Preparation 5. lH-NMR (200 MHz, DMSO-d6) 5 2.00 (3H, s) , 4.40 (2H, d, J=2.6 Hz), 7.08 (1H, d, J=9.6 Hz), 7.19-7.58 (7H, m), 7.94- 8.09 (1H, m) Preparation 12 6-[l-Bromo-2-(2,4-difluorophenyl)-2-oxoethyl]-2-(2- methylphenyl)-3(2H)-pyridazinone was obtained according to a similar manner to Preparation 6. hl-NMR (200 MHz, DMSO-d6) 5 1.81 (3H, s) , 6.76 (1H, s) , 6.99-7.58 (7H, m), 7.80 (1H, d, J=9.7 Hz), 7.98-8.14 (1H, 48 WO 2007/026950 PCT/JP2006/317691 m) Preparation 13 A mixture of 4-methyl-4-phenylthiosemicarbazide (544 mg), 3-(dimethylaminomethyl)azetidine dihydrochloride (561 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.94 ml) in acetonitrile (2 mL) was stirred at 90°C for 3 hours. The mixture was cooled to room temperature. To the mixture was added water (20 mL), and the mixture was washed with ether (20 mL). The aqueous layer was extracted with chloroform (40 mL x 2) . The extracts were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The oily residue was crystallized from diisopropyl ether to give 3-[(dimethylamino)methyl]-1- azetidinecarbothiohydrazide (248 mg) as gray powder. -NMR (500 MHz, CDC13) 6 2.22 (s, 6H) , 2.52 (d, 2H, J=7.5 Hz), 2.80-2.85 (m, 1H), 3.78 (dd, 2H, J=5.5 Hz, 10.0 Hz), 4.20 (t, 2H, J=8.5Hz), 6.39 (brs, 1H). Preparation 14 To a solution of 2-hydrazinoethanol (0.88 mL) in ethanol (8 mL) was added dropwise a solution of ethyl 3- isothiocyanatopropionate (1.42 mL) in ethanol (8 mL) at room temperature. The mixture was stirred at room temperature tovernight. The solvent was removed under reduced pressure. The residue was purified by flash column chromatography (gradient elution: methanol/chloroform (w/w) = 0% to 6%) to give ethyl 3-({[l-(2- hydroxyethyl)hydrazino]carbonothioyl}amino)propanoate (2.40 g) as colorless oil. -NMR (500 MHz, CDC13) 6 1.27 (3H, t, J=7.5 Hz), 1.62 (1H, brs), 2.36 (1H, brs), 2.66 (2H, t, J=5.9 Hz), 3.90 (2H, q, J=6.0 Hz), 4.02-4.05 (2H, m), 4.08 (2H, s), 4.17 (2H, q, J=7.3 Hz), 4.30 (2H, t, J=5.0 Hz), 8.36 (1H, brs). Preparation 15 6-[5-(Ethylamino)-3-(4-fluorophenyl)-1-(2- hydroxyethyl)-lH-pyrazol-4-yl]-2-(2-methylphenyl)-3(2H)- pyridazinone was obtained according to a similar manner to Example 1 mentioned below. 49 WO 2007/026950 PCT/JP2006/317691 Mass ESI (+) 434 (M+l) XH-NMR (500 MHz, CDC13) 5 1.03 (3H, t, J=6.7 Hz), 2.22 (3H, s), 3.04-3.09 (2H, m) , 3.83 (1H, brs), 4.01-4.03 (2H, m) , 4.18 (2H, t, J=4.7 Hz), 5.15 (1H, brs), 6.87 (1H, d, J=9.8 Hz), 7.02 (1H, d, J=9.8 Hz), 7.13 (2H, t,. J=8.2 Hz), 7.28- 7.39 (4H, m), 7.48 (2H, dd, J=5.6, 8.8 Hz) Preparation 16 6-[5-(Ethylamino)-3-(4-fluorophenyl)-1-(3- hydroxypropyl)-lH-pyrazol-4-yl]-2-(2-methylphenyl)-3(2H)- pyridazinone was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 448 (M+l) XH-NMR (500MHz, CDC13) 5 1.04 (3H, t, J=7.8 Hz), 2.02-2.06 (2H, m), 2.23 (3H, s), 3.04-3.10 (2H, m) , 3.55-3.63 (3H, m) , 4.24 (2H, t, J=6.8 Hz), 5.21 (1H, brs), 7.14 (2H, t, J=8.4 Hz), 7.29-7.40 (4H, m), 7.48 (2H, dd, J=5.5, 8.7 Hz) Preparation 17 Ethyl 3-({3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4- [1- (2-methylphenyl)-6-oxo-l,6-dihydro-3-pyridazinyl]-1H- pyrazol-5-yl}amino)propanoate was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 506 (M+l) aH-NMR (500 MHz, CDC13) 5 1.19 (3H, t, J=7.0 Hz), 2.24 (3H, s), 2.36 (2H, t, J=6.5 Hz), 3.31 (2H, dd, J=6.4, 12.7 Hz), 3.65 (1H, t, J=6.0 Hz), 4.01-4.08 (4H, m) , 4.20 (2H, t, J=4.6 Hz), 5.18 (1H, t, J=7.1 Hz), 6.89 (1H, d, J=9.6 Hz), 7.01 (1H, d, J=9.5 Hz), 7.13 (2H, dd, J=8.8, 8.8 Hz), 7.36- 7.70 (4H, m), 7.47 (2H, dd, J=5.5, 8.7 Hz) Preparation 18 tert-Butyl 3-[{3-(4-fluorophenyl)-4-[1-(2- methylphenyl)-6-oxo-l,6-dihydro-3-pyridazinyl]-lH-pyrazol- 5-yl}(3-hydroxypropyl)amino]propanoate was obtained according to a similar manner to Example 1 mentioned below. aH-NMR (500 MHz, CDCI3) 8 1.42 (6H, s), 1.45 (3H, s) , 1.74- 1.79 (2H, m), 2.10 (3H, s), 2.41 (2H, t, J=7.5 Hz), 3.31 (2H, t, J=6.9 Hz), 3.42 (2H, t, J=7.5 Hz), 3.61 (2H, t, J=5.3 Hz), 6.98 (1H, d, J=9.6 Hz), 7.03 (2H, dd, J=8.6, 8.6 50 WO 2007/026950 PCT/JP2006/317691 Hz), 7.17 (1H, d, J=6.4 Hz), 7.28-7.42 (6H, m) Preparation 19 N-Ethyl-1-(3-hydroxypropyl)hydrazinecarbothioamide was obtained according to a similar manner to Preparation 14. -NMR (CDC13) 6 1.23 (3H, t, J=7.3 Hz), 1.65-1.66 (1H, m) , 1.82-1.86 (2H, m), 3.55-3.64 (5H, m) , 3.73 (2H, s) , 4.28 (2H, t, J=5.9 Hz), 7.81 (1H, brs) jTrepctidLj-un u 6-[l-Bromo-2-(2,4-difluorophenyl)-2-oxoethylj-3(2H)- pyridazinone was obtained according to a similar manner to Preparation 6. -NMR (200 MHz, DMS0-d6) 5 6.69 (1H, s) , 6.93-7.11 (1H, m) , 7.29 (1H, dt, J=2.7, 8.7 Hz), 7.38-7.53 (1H, m), 7.64 (1H, d, J=9.9Hz), 8.08 (1H, dt, J=6.6, 8.9 Hz), 13.08-13.27 (1H, m) Preparation 21 To a suspension of LiAlH4 (543 mg) in THF (20 mL) was added dropwise a solution of 4-(hydroxymethyl)tetrahydro- 2H-thiopyran-4-carbonitrile (1.50 g) in THF (20 mL) at 0°C. The mixture was stirred for Ih at the same temperature and the reaction was quenched by slow addition of H2O (0.5 mL), 10% aqueous NaOH (0.5 mL) and H20 (0.5 mL x 3) with ice cooling. After 10 min with stirring, the insoluble materials were filtered off and the filter cake was washed with EtOAc. The filtrate was dried over MgS04, filtered and concentrated in vacuo to give [4- (aminomethyl)tetrahydro-2H-thiopyran-4-ylJmethanol (1.30 g) as a pale yellow oil. Mass ESI (+) 162 (M+l) Preparation 22 To a mixture of [4-(aminomethyl)tetrahydro-2H- thiopyran-4-yl]methanol (1.20 g) in CH2C12 (20 mL) and aqueous NaHC03 (1.25 g in 10 mL of H20) was added O-phenyl chlorothiocarbonate (1.54 g) portionwise and the mixture was stirred for 30 min vigorously at room temperature. The organic layer was separated and the aqueous solution was 51 WO 2007/026950 PCT/JP2006/317691 extracted with CHC13. The combined organic layer was washed with brine, dried over MgS04, filtered and concentrated in vacuo. The residue was purified by column chromatography (eluent: Hex/EtOAc=l/l) to give O-phenyl {[4-(hydroxymethyl)tetrahydro-2H-thiopyran-4- yl] methyl}thiocarbamate (740 mg) as a colorless oil. Mass ESI (+) 320 (M+Na) Preparation 23 To a solution of O-phenyl {[4- (hydroxymethyl)tetrahydro-2H-thiopyran-4- yl]methyl}thiocarbamate (740 mg) in i-PrOH (10 mL) was added hydrazine monohydrate (1.25 g) and the mixture was stirred for 3 h at room temperature. The whole mixture was diluted with brine and CHCI3. The aqueous layer was extracted with CHC13. The combined organic layer was washed with 0.5 M aqueous NaOH and brine, dried over MgS04/ filtered and concentrated to give N-{[4- (hydroxymethyl)tetrahydro-2H-thiopyran-4- yl]methyl}hydrazinecarbothioamide (300 mg) as a white solid. Mass ESI (+) 258 (M+Na) Preparation 24 6-[5-{[ (2S)-2-(Benzyloxy)-3-hydroxypropyl]amino}-3- (4-fluorophenyl)-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 526 (M+l) 1H-NMR (CDCI3) 5 2.20 (3H, s) , 3.40-3.65 (5H, m), 4.49 (2H, s), 6.00 (1H, br), 6.82 (1H, d, J=9.9 Hz), 6.97 (1H, d, J=9.9 Hz), 7.15-7.25 (4H, m), 7.25-7.36 (7H, m), 7.41-7.48 (2H, m) Preparation 25 6-[5-{[ (2S)-2-(Benzyloxy)-3-hydroxypropyl]amino}-3- (2, 4-difluorophenyl)-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 544 (M+l) 1H-NMR (CDCI3) 5 2.19 (3H, s) , 3.39-3.67 (5H, m), 4.45-4.58 52 WO 2007/026950 PCT/JP2006/317691 (2H, m), .6.12 (1H, br), 6.85 (1H, d, J=9.9 Hz), 6.95-7.06 (2H, m), 6.95 (1H, dd, J=1.4, 9.9 Hz), 7.20-7.26 (2H, m), 7.26-7.37 (7H, m), 7.41-7.51 (1H, m) Preparation 26 6-[5-{[ (2R)-2-(Benzyloxy)-3-hydroxypropyl]amino}-3- (4-fluorophenyl)-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H) -one was obtained according to a similar manner to Example 1 mentioned below. Mace ET l4-\ S9fi (M+1 ) -NMR (CDC13) 5 2.20 (3H, s) , 3.41-3.64 (5H, m), 4.49 (2H, s), 6.00 (1H, t, J=6.2 Hz), 6.81 (1H, d, J=9.9 Hz), 6.97 (lfi, d, J=9.9 Hz), 7.16-7.24 (4H, m), 7.25-7.36 (7H, m), 7.42-7.48 (2H, m) Preparation 27 6-[5-{[(2R) -2-(Benzyloxy)-3-hydroxypropyl]amino}-3- (2, 4-difluorophenyl)-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 544 (M+1) -NMR (CDCI3) 5 2.18 (3H, s) , 3.39-3.67 (5H, m) , 4.42-4.53 (2H, m), 6.08 (1H, br), 6.85 (1H, d, J=10.1 Hz), 6.93-7.03 (2H, m), 6.94 (1H, dd, J=1.4, 10.1 Hz), 7.18-7.23 (2H, m), 7.24-7.35 (7H, m) , 7.39-7.47 (1H, m) Preparation 28 6-[3-(2,4-Difluorophenyl)-5-{[(2S)-2-(2,2- dimethylpropoxy)-3-hydroxypropyl]amino}-lH-pyrazol-4-yl]-2- (2~methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 544 (M+1) -NMR (CDCI3) 6 2.18 (3H/ s) , 3.39-3.67 (5H, m) , 4.42-4.53 (2H, m), 6.08 (1H, br), 6.85 (1H, d, J=10.1 Hz), 6.93-7.03 (2H, m), 6.94 (1H, dd, J=1.4, 10.1 Hz), 7.18-7.23 (2H, m), 7.24-7.35 (7H, m), 7.39-7.47 (1H, m) Preparation 29 Ethyl 3-({3-(2,4-difluorophenyl)-4-[1- (2- methylphenyl)-6-oxo-l,6-dihydropyridazin-3-yl]-lH-pyrazol- 53 WO 2007/026950 PCT/JP2006/317691 5-yl}amino) -2- (hydroxymethyl)propanoate was obtained according to a similar manner to Example 1 mentioned below. H-NMR (CDC13) 8 1.11 (3H, d, J=6.9 Hz), 2.20 (3H, s), 2.66-2.70 (1H, m) , 3.65-3.68 (2H, m) , 3.76-3.82 (2H, m) , 3.92-4.03 (2H, m), 6.03 (1H, brs), 6.85 (1H, d, J=9.2 Hz), 6.92-7.01 (3H, m) , 7.29-7.43 (5H, m). Preparation 30 Ethyl 3-({3-(4-fluorophenyl)-4-[1-(2-methylphenyl)-6- oxo-1,6-dihydropyridazin-3-yl]-lK-pyrazol-5-yl}amino)-2- (hydroxymethyl)propanoate was obtained according to a similar manner to Example 1 mentioned below. XH-NMR (CDCI3) 5 1.12 (3H, d, J=7.2 Hz), 2.22 (3H, s) , 2.69-2.73 (1H, m), 3.66-3.72 (2H, m) , 3.77-3.83 (2H, m) , 3.91-4.04 (2H, m), 5.98 (1H, brs), 6.82 (1H, d, J=10.1 Hz), 6.97 (1H, d, JKL0.1 Hz), 7.20 (2H, dd, J=8.6, 8.6 Hz), 7.34-7.38 (4H, m), 7.45 (2H, dd, J=5.4, 8.5 Hz). Preparation 31 Ethyl 3-({3-(2,4-difluorophenyl)-4-[1- (2- methylphenyl)-6-oxo-l,6-dihydropyridazin-3-yl]-lH-pyrazol- 5-yl}amino)butanoate was obtained according to a similar manner to Example 1 mentioned below. -NMR (CDCI3) 5 1.18-1.23 (6H, m) , 2.22 (3H, s) , 2.41-2.46 (1H, m), 259-2.64 (1H, m), 3.98-4.02 (1H, m), 4.10 (2H, q, J=7.3 Hz), 6.07 (1H, brs), 6.86 (1H, d, J=9.2 Hz), 6.95- 7.06 (3H, m), 7.30-7.38 (4H, m), 7.50 (1H, dd, 7.8, 16.5 Hz) Preparation 32 6-[5-{[3-tert-Butoxy-2-(hydroxymethyl)propyl]amino}- 3-(4-fluorophenyl)-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. H-NMR (CDCI3) 5 1.11 (9H, s), 1.86-1.90 (1H, m) , 2.20 (3H, s), 3.36 (2H, d, J=5.9 Hz), 3.40 (2H, dd, J=6.4, 6.4 Hz), 3.61 (2H, ddd, J=4.1, 11.0, 28.0 Hz), 5.98 (1H, brs), 6.81 (1H, d, J=9.7 Hz), 6.98 (1H, d, J=10.2 Hz), 7.17 (2H, dd, J=8.7, 8.7 Hz), 7.34-7.38 (4H, m) , 7.46 (2H, dd, J=5.0, 8.2 Hz) 54 WO 2007/026950 PCT/JP2006/317691 Preparation 33 6-[3-(2,4-Difluorophenyl)-5-({[1- (hydroxymethyl)cyclopropyl]methyl}amino)-lH-pyrazol-4-yl]- 2-(2-methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI ( + ) 464 (M+l) 1H-NMR (CDC13) 5 0.33-0.38 (4H, m) , 2.22 (3H, s) , 3.22 (2H, s), 3.35 (2H, brs), 6.24 (1H, brs) , 6.86 (1H, d, J=9.5 Hz), 6.95-7.03 (3H, m) , 7.33-7.39 (4H, m) ,- 7.46 (1H, dd, J=8.2, 14.5 Hz) Preparation 34 6-[3-(4-Fluorophenyl)-5-({[1- (hydroxymethyl)cyclopropyl]methyl}amino)-lH-pyrazol-4-yl]- 2-(2-methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 446 (M+l) -NMR (CDCI3) 5 0.33-0.38 (4H, m) , 2.24 (3H, s) , 3.23 (2H, d, J=5.9 Hz), 3.32 (2H , brs), 6.11 (1H, brs), 6.83 (1H, d, J=9.6 Hz), 6.99 (1H, d, J=9.6 Hz), 7.18 (2H , dd, J=8.5, 8.5 Hz), 7.33-7.39 (4H, m), 7.45 (2H, dd, J=5.1, 8.8 Hz) Preparation 35 6-[5-({[1-(Hydroxymethyl)cyclopropyl]methyl}amino)-3- (3-methylphenyl)-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 442 (M+l) 1H-NMR (CDCI3) 5 0.33-0.37 (4H, m) , 2.24 (3H, s) , 2.42 (3H, s), 3.24 (2H, brs), 3.31 (2H, brs), 6.09 (1H, brs), 6.81 (1H, d, J=10.2 Hz), 7.05 (1H, d, J=10.5 Hz), 7.24-7.40 (8H, m) Preparation 36 6-[3-(2,4-Difluorophenyl)-5-({[1- (hydroxymethyl)cyclobutyl]methyl}amino)-lH-pyrazol-4-yl]-2- (2-methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 478 (M+l) H-NMR (CDCI3) 5 1.56-1.69 (4H, m) , 1.82-1.88 (2H, m) , 2.22 55 WO 2007/026950 PCT/JP2006/317691 (3H, s), 3.36 (2H, d, J=6.5 Hz), 3.47 (2H, s), 6.24 (1H, brs), 6.85 (1H, d, J=10.1 Hz), 6.94-7.05 (3H, m), 7.33-7.40 (4H, m), 7.46 (1H, dd, J=8.2, 14.7 Hz) Preparation 37 6-[3-(4-Fluorophenyl)-5-({[1- (hydroxymethyl) cyclobutyl]methyl}amino) -lH-pyrazol-4-yl]-2- (2-methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 460 (M+l) aH-NMR (CDC13) 5 1.55-1.70 (4H, m) , 1.83-1.89 (2H, m), 2.23 (3H, s), 3.37 (2H, d, J=6.5 Hz), 3.45 (2H, s), 6.11 (1H, brs), 6.82 (1H, d, J=10.2Hz), 6.99 (1H, d, J=9.9 Hz) , 7.19 (2H, dd, J=8.3, 8.3 Hz), 7.34-7.39 (4H, m), 7.45 (2H, dd, J=5.0, 8.7 Hz) Preparation 38 6-[3-(2,4-Difluorophenyl)-5-({[3-(hydroxymethyl)-1- isopropylazetidin-3-yl]methyl}amino)-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 and Example 123, successively, mentioned below. XH-NMR (CDCI3) 6 0.92 (6H, d, J=6.2 Hz), 2.20 (3H, s) , 2.39-2.45 (1H, m) , 2.98 (2H, d, J=8.2 Hz), 3.01 (2H, d, J=8.4 Hz), 3.56 (2H, d, J=6.4 Hz), 3.57 (2H , s) , 6.25 (1H, brs), 6.85 (1H, d, J=10.1Hz), 6.93-7.02 (3H, m) , 7.31-7.38 (4H, m) , 7.45 (1H, dd, J=8.6, 15.1 Hz) Preparation 39 6-{3-(2,4-Difluorophenyl)-5-f(2-hydroxy-l,1- dimethylethyl)amino]-lH-pyrazol-4-yl}-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 452 (M+l) aH-NMR (CDCI3) 8 1.11 (6H, s), 2.21 (3H, s), 3.55 (2H, m), 6.35 (1H, brs), 6.84 (1H, d, J=9.5Hz), 6.92-6.98 (3H, m), 7.31-7.37 (4H, m), 7.42 (1H, dd, J=7.8, 14.3 Hz) Preparation 40 6-[3-(2,4-Difluorophenyl)-5-{[(2S)-2- hydroxypropyl]amino}-lH-pyrazol-4-yl]-2-(2- 56 WO 2007/026950 PCT/JP2006/317691 methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. 1H-NMR (CDCI3) 8 1.11 (6H, s), 2.21 {3H, s) , 3.55 (2H, m) , 6.35 (1H, brs), 6.84 (1H, d, J=9.5Hz), 6.92-6.98 (3H, m) , 7.31-7.37 (4H, m) , 7.42 (1H, dd, J=7.8, 14.3 Hz) Preparation 41 6-[3-(2,4-Difluorophenyl)-5-{[(2R)-2- hydroxypropyl]amino}-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H)one.was obtained according to a similar manner to Example 1 mentioned below. aH-NMR (CDC13) 5 1.09 (3H, d, J=6.0 Hz), 2.20 (3H, s) , 3.10-3.17 (1H, m), 3.22-3.27 (1H, m), 3.88-3.94 (1H, m) , 6.16 (1H, brs), 6.85 (1H, d, J=9.6 Hz), 6.92-6.99 (3H, m), 7.32-7.37 (4H, m) , 7.43 (1H, dd, J=8.3, 15.6 Hz) Preparation 42 6-{3-(2,4-Difluorophenyl)-5-[(2S)-2- (hydroxymethyl)pyrrolidin-1-yl]-lH-pyrazol-4-yl}-2- (2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 464 (M+l) 1H-NMR (CDCI3) 5 1.68-1.74 (1H, m) , 1.81-1.91 (2H, m) , 2.02-2.10 (1H, m), 2.07 <3H, s) , 3.08 (1H, dd, J=6.9, 16.5 Hz), 3.40 (1H, dd, J=6.9, 15.1 Hz), 3.64 (1H, dd, J=6.4, 11.0 Hz), 3.75 (1H, dd, J=3.2, 11.0 Hz), 3.94-3.99 (1H, m), 6.82-6.91 (2H, m) , 6.96 (1H, d, J=9.6 Hz), 7.07-7.13 {1H, m), 7.27-7.35 (4H, m), 7.39 (1H, dd, J=8.4, 14.7 Hz) Preparation 43 6-[3-(4-Fluorophenyl)-5-{[(1R)-2-hydroxy-l- methylethyl]amino}-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H) -one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 420 (M+l) -NMR (CDCI3) 5 1.04 (3H, d, J=6.0 Hz), 2.23 (3H, s) , 3.36-3.45 (1H, m), 3.65 (2H, d, J=8.2 Hz), 6.01 (1H, brs), 6.83 (1H, d, J=9.6Hz), 6.98 (1H, d, J=9.6Hz), 7.14 (2H, dd, J=8.7 Hz, J=8.7 Hz), 7.28-7.42 (4H, m), 7.45 (2H, dd, J=5.5 Hz, J=8.7 Hz). 57 WO 2007/026950 PCT/JP2006/317691 Preparation 44 6-[3-(4-Fluorophehyl)-5-({[4- (hydroxymethyl)tetrahydro-2H-thiopyran-4-yl]methyl}amino)- lH-pyrazol-4-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 506 (M+l) -NMR (CDC13) 8 1.42 (4H, br) , 2.10 (3H, s), 2.41-2.44 <4H, m), 3.06 (2H, d, J=5 Hz), 3.12 (2H, d, J=6 Hz), 4.16 (1H, t, J=6 Hz), 5.57 (1H, br), 6.92 (1H, m), 7.03 (1H, m), 7.34- 7.40 (6H, m), 7.53 (2H, m) , 12.29 (1H, s) Preparation 45 6-[5-({[1-(Bromomethyl)cyclohexyl]methyl}amino)-3-(4- fluorophenyl)-lH-pyrazol-4-yl]-2-(2-methylphenyl)pyridazin- 3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 550 (M+l) -NMR (DMSO-ds) 6 1.12-1.38 (10H, m) , 2.09 (3H, s) , 3.11- 3.19 (2H, m), 6.92 (1H, d, J=10.0 Hz), 7.01 (1H, d, J=10.0 Hz), 7.32-7.41 (6H, m), 7.52-7.58 (2H, m) Preparation 46 6-[3-(4-Fluorophenyl)-5-({ [4- (hydroxymethyl)tetrahydro-2H-pyran-4-yl]methyl}amino)-1H- pyrazol-4-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 490 (M+l) 1H-NMR (CDCI3) 5 1.48-1.56 (2H, m) , 1.68-1.79 (2H, m) , 2.01 (2H, t, J=6 Hz), 2.25 (3H, s), 3.07-3.22 (2H, m), 3.60-3.75 (2H, m), 4.18 (2H, t, J=6 Hz), 6.79-6.83 (1H, m), 6.83 (1H, d, J=10 Hz), 7.06 (1H, d, J=10 Hz), 7.14-7.19 (2H, m), 7.35-7.39 (4H, m), 7.48-7.53 (2H, m) Preparation 47 6-{5-[({4-[(Benzyloxy)methyl]-1,1-dioxidotetrahydro- 2H-thiopyran-4-yl}methyl)amino]-3-(4-fluorophenyl)-lH- pyrazol-4-yl}-2-(2-methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 58 WO 2007/026950 PCT/JP2006/317691 mentioned below. Mass ESI (+) 628 (M+l) -NMR (CDC13) 5 1.83-1.96 (4H, m) , 2.18 (3H, s) , 2.78-2.84 (2H, m) , 3.04-3.08 (2H, m), 3.08 (2H, s), 3.50 (2H, d, J=6 Hz), 4.11 (2H, s), 6.35 (1H, br), 6.83 (1H, d, J=10 Hz), 6.92 (1H, d, J=10 Hz), 7.13-7.17 (4H, m), 7.27-7.43 (9H, m) Preparation 48 6-[5-{[(lS)-l-({[tert- Butyl(diphenyl)silyl]oxy}methyl)-3-hydroxypropyl]amino}-3- (4-fluorophenyl)-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. -NMR (DMSO-d6) 5 0.80 (9H, s) , 1.52-1.62 (1H, m) , 1.70- 1.83 (1H, m), 2.07 (3H, s) , 3.46-3.86 (5H, m) , 4.46 (1H, brs), 5.53 (1H, brs), 6.92 (1H, d, J=10 Hz), 7.03 (1H, d, J=10 Hz), 7.24-7.56 (18H, m), 12.27 (1H, brs) Preparation 49 6-[5-{[(lR)-l-({[tert- Butyl(diphenyl)silylJoxy}methyl)-3-hydroxypropyl]amino}-3- (4-fluorophenyl)-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. -NMR (DMSO-de) 5 0.80 (9H, s), 1.52-1.62 (1H, m) , 1.70- 1.83 (1H, m), 2.07 (3H, s), 3.46-3.86 (5H, m) , 4.46 (1H, brs), 5.53 (1H, brs), 6.92 (1H, d, J=10 Hz), 7.03 (1H, d, J=10 Hz), 7.24-7.56 (18H, m), 12.27 (1H, brs) Preparation 50 tert-Butyl 4-[{3-(4-fluorophenyl)-4-[1-(2- methylphenyl)-6-oxo-l,6-dihydropyridazin-3-yl]-lH-pyrazol- 5-yl}amino)methyl]-4-(hydroxymethyl)piperidine-l- carboxylate was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 611 (M+Na) Preparation 51 6-[3-(4-Fluoro£henyl)-5-{[4-(2- hydroxyethyl)tetrahydro-2H-pyran-4-yl]amino}-lH-pyrazol-4- yl]-2-(2-methylphenyl)pyridazin-3(2H)-one was obtained 59 WO 2007/026950 PCT/JP2006/317691 according to a similar manner to Example 1 mentioned below. Mass ESI (+) 472 (M+l) H-NMR (CDC13) 5 1.52-1.64 (2H, m) , 1.80-1.90 (2H, m) , 1.83-1.87 (2H, m), 2.24 (3H, s) , 3.09-3.28 (2H, m) , 3.38- 3.50 (2H, m), 3.71 (2H, d, J=6 Hz), 6.85 (1H, d, J=10 Hz), 6.97 (1H, d, J=10 Hz), 7.18-7.25 (2H, m) , 7.32-7.41 (4H, m) , 7.44-7.48 (2H, m) Preparation 52 6-{3-(4-Fluorophenyl)-5-[(3-hydroxy-2,2- dimethylpropyl)amino]-lH-pyrazol-4-yl}-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 448 (M+l) -NMR (CDCI3) 5 0.62 (6H, s) , 2.10 (3H, s) , 2.98-3.00 (4H, m), 4.59 (1H, t, J=6 Hz), 6.91-7.04 (2H, m), 7.34-7.39 (6H, m), 7.53 (2H, m) Preparation 53 6-{3-(4-Fluorophenyl)-5-[(2-hydroxyethyl)amino]-1H- pyrazol-4-yl}-2-(2-methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. -NMR (CDCI3) 5 2.22 (3H, s) , 3.45-3.52 (2H, m) , 3.72-3.78 (2H, m), 6.82 (1H, d, J=9.5 Hz), 6.89 (1H, d, J=10.0 Hz), 7.06-7.17 (2H, m) , 7.31-7.42 (8H, m) Preparation 54 6-[5-{[(lS)-2-(Benzyloxy)-l- {hydroxymethyl)ethyl]amino}-3-(4-fluorophenyl)-lH-pyrazol- 4-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 548 (M+Na) H-NMR (CDCI3) 8 2.18 (3H, s) , 3.27-4.41 (7H, m) , 6.52-7.63 (15H, m) Preparation 55 6-[5-{[(1R)-2-(Benzyloxy)-1- (hydroxymethyl)ethyl]amino}-3-(4-fluorophenyl)-lH-pyrazol- 4-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. 60 WO 2007/026950 PCT/JP2006/317691 Mass ESI (+) 548 (M+Na) -H-NMR (CDC13) 5 2.20 (3H, s) , 3.50 (2H, m) , 3.70 (2H, m) , 3.93 (1H, brs), 4.22 (2H, s) , 6.85 (1H, d), 7.08 (3H, m) , 7.19-7.43 (11H, m) Preparation 56 (2S)-2-({3-(4-Fluorophenyl)-4-[1-(2-methylphenyl)-6- oxo-1,6-dihydropyridazin-3-yl]-lH-pyrazol-5-yl}amino)-3- methylbutyl acetate was obtained according to a similar manner to Example 1 mentioned below. Mass ESI (+) 490 (M+l) -NMR (CDCI3) 5 0.54-0.66 (3H, m) , 0.80-0.90 (3H, m) , 1.78-1.88 (1H, m) , 1.98 (3H, s) , 2.22 (3H, s) , 3.46-3.64 (1H, m), 3.93-4.02 (1H, m) , 4.18-3.25 (1H, m) , 6.13-6.31 (1H, m), 6.82 (1H, d, J=9.5 Hz), 7.02 (1H, d, J=9.5 Hz), 7.20 (2H, dd, J=8.5 Hz, J=8.5 Hz), 7.30-7.39 (4H, m), 7.49 (2H, dd, J=5.5 Hz, J=8.5 Hz) Preparation 57 6-{5-[(3-Bromo-2,2-difluoropropyl)amino]-3-(4- fluorophenyl)-lH-pyrazol-4-yl}-2-(2-methylphenyl)pyridazin- 3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. -NMR (CDCI3) 5 2.23 (3H, s) , 3.55 (2H, t, J=13.5 Hz), 3.89 (2H, J=13.0 Hz, J=6.5Hz), 5.98 (1H, m), 6.85 (1H, d, J=9.5 Hz), 6.98 (1H, d, J=9.5 Hz), 7.24 (2H, dd, J=9.0 Hz, J=9.0 Hz), 7.31-7.42 (4H, m), 7.46 (2H, dd, J=5.5 Hz, J=9.0 Hz), 9.09 (1H, brs) Preparation 58 6-[5-({[2-(Bromomethyl)-1,3-dioxolan-2- yl]methyl}amino)-3-(4-fluorophenyl)-lH-pyrazol-4-yl]-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 1 mentioned below. XH-NMR (CDCI3) 8 2.23 (3H, s) , 3.39 (2H, s) , 3.54-3.66 (2H, m), 3.69-3.89 (2H, m) , 3.91-4.05 (2H, m), 6.07 (1H, brs), 6.83 (1H, d, J=10.0 Hz), 6.99 (1H, d, J=10.0 Hz), 7.20 (2H, dd, J=9.0 Hz, J=9.0 Hz), 7.33-7.43 (4H, m), 7.47 (2H, dd, J=5.5 Hz, J=9.0 Hz) Preparation 59 61 WO 2007/026950 PCT/JP2006/317691 6-{3-(2,4-Difluorophenyl)-5-[(3-hydroxy-l- methylpropyl)amino]-lH-pyrazol-4-yl}-2-(2- methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 10 mentioned below. 1H-NMR (CDC13) 5 1.09 (3H, d, J=5.5 Hz), 1.71-1.77 (2H, m), 2.23 (3H, s), 3.51-3.55 (1H, m) , 3.59-3.66 (2H, m) , 5.99 (1H, brs), 6.84 (1H, d, J=10.1 Hz), 6.90-6.98 (3H, m), 7.27-7.43 (5H, m) Preparation 60 6-[3-(4-Fluorophenyl)-5-({[4-(hydroxymethyl)-1,1- dioxidotetrahydro-2H-thiopyran-4-yl]methyl}amino)-1H- pyrazol-4-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one was obtained according to a similar manner to Example 95 . mentioned below. Mass ESI ( + ) 538 (M+l) 1H-NMR (DMSO-dg) 6 1.70 (4H, m) , 2.10 (3H, s) , 2.90-3.02 (4H, m), 3.16 (2H, s), 3.23 (2H, d, J=6 Hz), 6.94 (1H, . d, J=10 Hz), 7.06 (1H, d, J=10 Hz), 7.30-7.40 (6H, m) , 7.51- 7.55 (2H, m) Preparation 61 Benzyl 4-({3-(4-fluorophenyl)-4-[1-(2-methylphenyl)- 6-oxo-l,6-dihydropyridazin-3-yl]-lH-pyrazol-5-yl}amino)-4- (2-hydroxyethyl)piperidine-l-carboxylate was obtained according to a similar manner to Example 123 mentioned below. H-NMR (DMSO-d6) 5 1.36 (2H, t) , 1.91 (3H, brs), 2.07 (3H, s), 2.67 (2H, brs), 3.51 (2H, m), 4.21 (1H, t), 5.03 (2H, brs), 5.82 (1H, s), 6.55 (1H, s), 6.94 (1H, d), 7.03 (1H, d) , 7.25-7.46 (9H, m), 7.57 (2H, m), 7.69 (4H, m) Example 1 A mixture of 6-[l-bromo-2-(2,4-difluorophenyl)-2- oxoethyl]-2-(2-methylphenyl)-3(2H)-pyridazinone (210 mg), 3-[(dimethylamino)methyl]-1-azetidinecarbothiohydrazide (113 mg) in glacial acetic acid (1.5 mL) was heated at 55°C to 60°C for 1.5 h. The mixture was poured into water (20 mL), neutralized with sodium hydrogencarbonate and extracted with ethyl acetate (30 mL). The extract was 62 WO 2007/026950 PCT/JP2006/317691 concentrated under reduced pressure- The residue was purified by flash column chromatography on Si02 (eluent; 0% to 4% methanol in chloroform) to give 6-{2-(2,4- difluorophenyl)-6-[(dimethylamino)methyl]-4,5, 6, 7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl}-2-(2- methylphenyl)-3(2H)-pyridazinone (167 mg) as yellow amorphous solid. Mass ESI (+) 477 (M+l) 1H-NMR (500 MHz, CDC13) 5 2.21 (3H, s) , 2.24 (6H, s), 2,26- 2.43 (3H, m), 3.09(1H, t, J=B;9 Hz), 3.48 (1H, d, J=12.3 Hz), 3.82 (1H, dd, J=8.1 Hz, 12.4 Hz), 4.27 (1H, dd, J=5.6 Hz, 12.4Hz), 5.90 (1H, brs), 6.83 (1H, d, J=9.6Hz), 6.92- 6.97 (2H, m), 7.00-7.04 (1H, m) , 7.34-7.38 (4H, m), 7.55 (1H, dd, J=8.1 Hz, 14.7 Hz) Example 2 A mixture of 6-{2-(2,4-difluorophenyl)-6- [(dimethylamino)methyl]-4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl}-2-(2-methylphenyl)-3(2H)-pyridazinone (48 mg) and 2,3-dichloro-5,6-dicyano-p-benzoquinone (23 mg) in dioxane (1 mL) was stirred at room temperature overnight. To the mixture was added water (10 mL), and the mixture was extracted with ethyl acetate (15 mL). The extract was concentrated under reduced pressure. The residue was purified by flash column chromatography on SiOz (eluent; ethyl acetate to 4% MeOH in chloroform) to give 6-{2-(2,4- difluorophenyl)-6-[(dimethylamino)methyl]pyrazolo[1,5- a]pyrimidin-3-yl}-2-(2-methylphenyl)-3(2H)-pyridazinone as yellow oil (22 mg). Mass ESI (+) 473 (M+l) Hl-NMR (500 MHz, CDC13) 5 2.05 (3H, s) , 2.33 (6H, s) , 3.55 (2H, s), 6.67 (1H, t, J=10.2 Hz), 6.87 (1H, t, J=8.2 Hz), .7.01 (1H, d, J=7.8 Hz), 7.14-7.19 (1H, d, J=9.6Hz), 7.36 (3H, m), 7.52 (1H, dd, J=7.5 Hz, 15.2 Hz), 8.31 (2H, d, J=9.5 Hz), 8.64 (2H, d, J=6.9 Hz) Example 3 6-[2-(4-Fluorophenyl)-6-(hydroxymethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2- 63 WO 2007/026950 PCT/JP2006/317691 methylphenyl)-3(2H)-pyridazinone was obtained according to a similar manner to Example 1. Mass ESI (+) 432 (M+l) -NMR (500 MHz, ,CDC13) 6 1.69 (1H, brs), 2.23 (3H, s) , 2.40-2.50 (1H, m), 3.20-3.30 (1H, m) , 3.46-5.30 (1H, m) , 3.72-3.78 (2H, m) , 3.98 (1H, dd, J=7.3, 13.0 Hz), 4.25 (1H, dd, J=5.2, 13.0 Hz), 5.81 (1H, brs), 6.81 (1H, d, J=9.5 Hz), 7.02 (1H, d, J=9.5 Hz), 7.15 (2H, dd, J=8.2, 8.5 Hz), 7.31- 7.41 (4H, m), 7.50 (2H, dd, J=5.6, 8.2 Hz) Example 4 To a suspension of 6-[2-(4-fluorophenyl)-6- (hydroxymethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin- 3-yl]-2-(2-methylphenyl)~3(2H)-pyridazinone (0.216 mg) in tetrahydrofuran (2 mL) were added imidazole (85 mg) and triphenylphosphine (197 mg), and the suspension was stirred at room temperature for 5 minutes. To the suspension was added dropwise a solution of iodine (190 mg) in tetrahydrofuran (1 mL), and the mixture was stirred at room temperature for 1.5 h. To the reaction mixture were added EtOAc (50 mL), and the solution was washed successively with 3% aqueous Na2S203 (20 mL), saturated aqueous NaHC03 solution (20 mL) and brine (20 mL) . The organic layer was dried over' anhydrous MgSO and the insoluble substance was filtered off. The filtrate was concentrated in vacuo. The residue was purified by flash column chromatography (gradient elution: hexane/EtOAc (w/w) 0% to 100%) to give 6-[2-(4-fluorophenyl)-6-iodomethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2- methylphenyl)-3(2H)-pyridazinone (0.211 g) as yellow solid. -NMR (500 MHz, CDC13) 5 2.23 (3H, s) , 2.44-2.52 (1H, m) , 3.22-3.26 (1H, m) , 3.26 (2H, d, J=6.9Hz), 3.51-3.57 (1H, m) , 3.96 (1H, dd, J=7.6, 13.0 Hz), 4.34 (1H, dd, J=5.1, 13.0 Hz), 5.84 (1H, brs), 6.81 (1H, d, J=9.2 Hz), 7.02 (1H, d, J=9.2 Hz), 7.16 (2H, dd, J=8.2, 8.5 Hz), 7.32-7.42 (4H, m), 7.50 (2H, dd, J=5.0, 8.2 Hz) Example 5 To a suspension of 6-[2-(4-fluorophenyl)-6~ 64 WO 2007/026950 PCT/JP2006/317691 iodomethyl-{4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3- yl}]-2-(2-methylphenyl)]-3(2H)-pyridazinone (50 mg) in CH3CN (1 mL) were added 4-dimethylaminopiperidine (36 mg) and K2C03 (25.6 mg) , and the suspension was stirred at 80°C for 2.5 h. To the suspension was added 4- dimethylaminopiperidine (3 6 mg), and the suspension was additionally stirred for 8 h. To the reaction mixture were added EtOAc (30 mL), and the solution was extracted with 10% citric acid (20 mL x 2) . The extracts were combined, and the solution was basified with NaHCCK. The suspension was extracted with EtOAc (20 mL x 3), and the organic layers were combined. The solution was dried over anhydrous MgS04 and filtered off. The filtrate was concentrated in vacuo. To the residue was added 4 M HCl in EtOAc (2 mL) to give 6-[6-{[4-(dimethylamino)-1- piperidinyl]methyl}-2-(4-fluorophenyl)-4,5,6,7- tetrahydropyrazolo [1, 5-a]pyrimidin-3-yl] -2-.(2- methylphenyl)-3(2H)-pyridazinone dihydrochloride (25 mg). Mass ESI (+) 542 (M+l) XH-NMR (500 MHz, CDC13) 8 2.09 (3H, s) , 2.16-2.32 (4H, m) , 2.68-2.81 (7H, m) , 2.90-3.02 (2H, m) , 3.10-3.22 (3H, m), 3.47-3.54 (1H, m) , 3.62-4.07 (4H, m) , 4.30-4.41 (1H, m) , 6.10 (1H, brs), 6.95 (1H, d, J=9.5 Hz), 7.10 (1H, d, J=9.5 Hz), 7.24 (2H, dd, J=8.6, 8.9 Hz), 7.31-7.40 (4H, m) , 7.49 (2H, dd, J=5.5, 8.5 Hz), 10.8 (1H, brs), 11.1 (1H, brs) Example 6 A mixture of 6-[5-(ethylamino)-3-(4-fluorophenyl)-1- (2-hydroxyethyl)-lH-pyrazol-4-yl]-2-(2-methylphenyl)-3(2H)- pyridazinone (858 mg), imidazole (337 mg, 4.95 mmol) and triphenylphosphine (779 mg) in tetrahydrofuran (5.0 ml) was stirred at room temperature for 3 h. To the mixture was added dropwise a solution of iodine (754 mg) in THF (5.0 mL) . The mixture was stirred overnight. To the mixture were added THF (4.0 mL), imidazole (236 mg) and triphenylphosphine (545 mg) . The mixture was stirred at room temperature for 20 minutes. To the mixture was added dropwise a solution of iodine (754 mg) in THF (4.0 ml) at 65 WO 2007/026950 PCT/JP2006/317691 room temperature, and the mixture was stirred for 6 h. The resulting precipitate was removed by filtration. To the- filtrate was added EtOAc (50 ml) . The mixture was washed successively with 5% aqueous Na2S2C>3 solution (30 ml) , 5% aqueous NaHC03 solution (30 ml) and brine (30 mL) . The organic layer was concentrated under reduced pressure. The residue was purified by flash column chromatography (gradient elution: EtOAc/hexane = 50% to 85%). To the crystalline residue was added isopropyl ether, and the solid was filtered off. To the solid was added 10% HC1 (100 mL) and EtOAc (50 mL) . The aqueous layer was separated, washed with Et20 and neutralized with NaOH. The mixture was extracted with EtOAc (100 mL) . The extract was dried over anhydrous MgS04 and concentrated under reduced pressure. To the crystalline residue was added hexane, and the solid was filtered off to give 6-[l-ethyl-6-(4- fluorophenyl)-2,3-dihydro-lH-imidazo[l,2-b]pyrazol-7-yl]-2- (2-methylphenyl)-3(2H)-pyridazinone as pale yellow prisms (460 mg). Mass ESI (+) 416 (M+l) -NMR (500 MHz, CDC13) 5 0.97 (3H, t, J=6.8 Hz), 2.20 (3H, s), 3.27 (2H, q, J=6.9 Hz), 3.81 (2H, t, J=8.6 Hz), 4.20 (2H, t, J=8.2 Hz), 6.86 (1H, d, J=9.7 Hz), 6.97 (1H, d, J=9.7 Hz), 7.08 (2H, dd, J=8.7, 8.7 Hz), 7.26-7.36 (4H, m), 7.46 (2H, dd, J=5.5, 8.7 Hz) Example 7 A mixture of tert-butyl 3-[{3-(4-fluorophenyl)-4-[1- (2-methylphenyl)-6-oxo-l,6~dihydro-3-pyridazinyl]-1H- pyrazol-5-yl}(3-hydroxypropyl)amino]propanoate (175 mg), triphenylphosphine (126 mg) and diethyl azodicarboxylate (75 uL) in THF (6 ml) was stirred at room temperature for 24 h. The mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography (gradient elution: EtOAc/hexane = 20% to 95%) to give tert- butyl 3-[2-(4-fluorophenyl)-3-[1-(2-methylphenyl)-6-oxo- 1, 6-dihydro-3-pyridazinyl]-6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl]propanoate (153 mg) as yellow 66 WO 2007/026950 PCT/JP2006/317691 amorphous. XH-NMR (500 MHz, CDC13) 5 1.39 (9H, s) , 2.16 (3H, s) , 2.15- 2.23 (2H, m), 2.28 (2H, t, J=6.9 Hz), 3.28 (2H, t, J=5.6 Hz), 3.49-3.54 (2H, m), 4.14 (2H, t, J=6.5Hz), 6.92 (1H, d, J=9.6 Hz), 7.01 (2H, dd, J=8.7, 8.7 Hz), 7.12 (1H, d, J=9.6 Hz), 7.25-7.35 (4H, m), 7.39 (2H, dd, J=5.5, 8.8 Hz) Example 8 To a solution of tert-butyl 3-[2-(4-fluorophenyl)-3- [1- (2-methylphenyl) -6-oxo-l, 6-dihydro-3-pyridazinyl] -6, 7- dihydropyrazolofl,5~a]pyrimidin-4(5H)-yljpropanoate (145 mg) in chloroform (6 ml) was added trifluoroacetic acid (0.5 mL), and the mixture was stirred at room temperature for 2 h. To the mixture was added water (10 mL), and the mixture was neutralized with NaHC03. The organic layer was separated and concentrated under reduced pressure to give 3-[2-(4-fluorophenyl)-3-[1-(2-methylphenyl)-6-oxo-l,6- dihydro-3-pyridazinyl]-6,7-dihydropyrazolo[1, 5-a]pyrimidin- 4(5H)-yl]propanoic acid (110 mg) as yellow amorphous. 1H-NMR (500 MHz, CDCI3) 5 2.13 (3H, s) , 2.16-2.19 (2H, m) , 2.36 (2H, t, J=7.5 Hz), 3.26 (2H, t, J=5.5 Hz), 3.56 (2H, brs), 4.14 (2H, t, J=5.8 Hz), 6.96 (1H, d, J=9.6 Hz), 7.01 (2H, dd, J=8.7, 8.7 Hz), 7.11 (1H, d, J=9.6 Hz), 7.26-7.33 (4H, m), 7.37 (2H, dd, J=5.5, 8.7 Hz) Example 9 A mixture of ethyl 3-{6-(4-fluorophenyl)-7-[1-(2- methylphenyl)-6-oxo-l,6-dihydro-3-pyridazinyl]-2,3-dihydro- lH-imidazo[l,2-bJpyrazol-l-yl}propanoate (450 mg) and 10% aqueous NaOH solution (4 mL) in ethanol (10 mL) was stirred at 60°C for 50 minutes. The solvent was removed under reduced pressure. To the residue was added water (10 mL). The mixture was neutralized with citric acid and extracted with EtOAc (30 mL) . The extract was dried over anhydrous MgS04 and concentrated under reduced pressure to give 3-{6- (4-fluorophenyl)-7-[1-(2-methylphenyl)-6-oxo-l,6-dihydro-3- pyridazinyl]-2,3-dihydro-lH-imidazo[l,2-b]pyrazol-l- yl}propanoic acid (380 mg) as pale yellow powder. -NMR (500 MHz, CDCI3) 5 2.18 (3H, s) , 2.38 (2H, t, J=6.9 67 WO 2007/026950 PCT/JP2006/317691 Hz), 3.55 (2H, brs), 3.85 (2H, t, J=8.3 Hz), 4.20 (2H, t, J=7.9 Hz), 6.91 (1H, d, J=9.7 Hz), 6.98 (1H, d, J=9.7 Hz), 7.07 (2H, dd, J=8.6, 8.6 Hz), 7.27-7.33 (4H, m), 7.42 (2H, dd, J=5.0, 8.1 Hz) Example 10 To a solution, of 3-{6-(4-fluorophenyl)-7-[1-(2- methylphenyl)-6-oxo-l,6-dihydro-3~pyridazinyl]-2,3-dihydro- lH-imidazo[l,2-b]pyrazol-l-yl}propanoic acid (0.87 g) in THF (15 mL) was added NaBH4 (0.22 g), following BF3 - Et20 complex (0.72 mL) at room temperature. The mixture was stirred at room temperature for 5.5 h. To the mixture were added dichloromethane (50 mL) and aqueous saturated NaHC03 solution (30 mL) . The mixture was stirred at room temperature overnight. The organic layer was separated and concentrated under reduced pressure. The residue was purified by flash column chromatography (gradient elution: methanol/chloroform = 5% to 10%) to give 6~[6-(4- fluorophenyl)-1-(3-hydroxypropyl)-2, 3-dihydro-lH- imidazo[1,2-b]pyrazol-7-yl]-2-(2-methylphenyl)-3(2H)- pyridazinone as yellow amorphous (0.22 g) . Mass ESI (+) 446 (M+l) -NMR (500 MHz, CDC13) 5 1.34 (1H, brs), 1.61-1.67 (2H, m) , 2.21 (3H, s), 3.34-3.40 (4H, m), 3.83 (2H, t, J=8.7 Hz), 4.21 (2H, t, J=8.2 Hz), 6.85 (1H, d, J=9.8 Hz), 6.95 (1H, d, J=9.8 Hz), 7.08 (2H, dd, J=8.2, 8.2 Hz), 7.33-7.38 (4H, m) , 7.44 (2H, dd, J=5.5, 8.4 Hz) Example 11 To a suspension of 3-{6-(4-fluorophenyl)-7-[1-(2- methylphenyl)-6-oxo-l,6-dihydro-3-pyridazinyl]-2,3-dihydro- IH-imidazo[1,2-b]pyrazol-l-yl}propanoic acid (96 mg) in dichloromethane (5 mL) was added catalytic amount of DMF. To the mixture was added dropwise oxalyl chloride (23 \ih) at room temperature. The mixture was stirred at room temperature for 1.5 h. The solvent was removed under reduced pressure. The residue was dissolved in chloroform (5 mL) . To a solution of morpholine (55 uL) in chloroform (5 mL) was added slowly the solution of acid chloride in 68 WO 2007/026950 PCT/JP2006/317691 chloroform. The mixture was stirred for 40 minutes. To the mixture was added water (5 mL). The organic layer was separated and concentrated under reduced pressure. The residue was purified by flash column chromatography (methanol/chloroform = 8%) to give 6-{6-(4-fluorophenyl)-1- [3-(4-morpholinyl)-3-oxopropyl]-2, 3-dihydro-lH-imidazo[1,2- b]pyrazol-7-yl}-2-(2-methylphenyl)-3(2H)-pyridazinone (35 mg) as yellow amorphous. Mass ESI (+) 529 (M+l) 1H-NMR (500 MHz, CDC13) 5 2.21-2.27 (5H, m) , 2.92-2.96 (2H, m), 3.48-3.52 (6H, m) , 3.62 (2H, t, J=4.5Hz), 3.96 (2H, t, J=7.8 Hz), 4.16 (2H, t, J=8.1 Hz), 6.84 (1H, d, J=9.6 Hz), 6.93 (1H, d, J=9.5 Hz), 7.09 (2H, dd, J=8.1, 8.1 Hz), 7.30- 7.38 (4H, m) , 7.43 (2H, dd, J=5.5, 8.4 Hz) Example 12 To a mixture of 6-[6-(4-fluorophenyl)-1-(3- hydroxypropyl)-2,3-dihydro-lH-imidazo[1,2-b]pyrazol-7-yl]- 2- (2-methylphenyl) -3 (2H) -pyridazinone (178 mg) and triethylamine (78 uL) in dichloromethane (10 mL) was added methanesulfonyl chloride (37 uL) . The mixture was stirred for 1.5 h. To the mixture was added dichlorome thane (10 mL), and the mixture was washed with successive water (10 mL) and 5% aqueous NaHCC>3 solution (10 mL) . The mixture was dried over anhydrous MgS04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (gradient elution: methanol/chloroform = 0% to 10%) to give 3-[6-(4-fluorophenyl)-7-(1-(2- WO 2007/026950 PCT/JP2006/317691 CLAIMS 1. A pyridazinone derivative compound shown by the following formula (I): wherein R1 is selected from the group consisting of hydrogen, substituted or unsubstituted lower alkyl and substituted or unsubstituted aryl; R2 is selected from the group consisting of substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; R3 is lower alkyl; P is 0, 1 or 2; and R4 and R5 are each hydrogen or taken together to form a bond; R6 and R7 are taken together to form a group of the formula: wherein R8 is hydrogen, X is oxygen or N-R9, in which R9 is hydrogen, substituted or unsubstituted lower alkanoyl or substituted or unsubstituted lower alkyl; or 135 WO 2007/026950 PCT/JP2006/317691 R8 and R9 may be taken together to form a bond; m and n are each 0, 1 or 2; R10 and R12 are each selected from the group consisting of hydrogen, halogen, hydroxy, formyl, cyano, substituted or unsubstituted lower alkyl, substituted or unsubstituted amino, substituted or unsubstituted lower alkoxy, saturated cyclic amino, substituted or unsubstituted carbamoyl, carboxy, substituted or unsubstituted lower alkoxycarbonyl and substituted or unsubstituted acyloxy; R11, R13 and R14 are each selected from the group consisting of hydrogen, halogen, substituted or unsubstituted lower alkyl, carboxy and substituted or unsubstituted lower alkoxycarbonyl; R10 and Ru or R12 and R13 may be taken together to form pxo, hydroxyimino, substituted or unsubstituted lower alkylene in which one or more carbon(s) may be replaced by hetero atom(s), or substituted or unsubstituted lower alkylidene; R9 and R10 may be taken together to form lower alkylene or a bond; R11 and R13 or R13 and R" may be taken together to form a bond; provided that when n=l and R10, R11, R12, R13 and R14 are simultaneously hydrogen, R9 is substituted or unsubstituted lower alkyl or substituted or unsubstituted lower alkanoyl, 136 WO 2007/026950 PCT/JP2006/317691 or a pharmaceutically acceptable salt thereof. 2. The pyridazinone derivative compound of claim 1, wherein R1 is hydrogen or substituted or unsubstituted aryl ; R2 is substituted or unsubstituted aryl; p is 0; R4 and R5 are each hydrogen or taken together to form a bond; and R6 and R7 are taken together to form a group of the formula: wherein R8 is hydrogen; X is oxygen or N-R9, in which R9 is hydrogen, substituted or unsubstituted lower alkanoyl or substituted or unsubstituted lower alkyl; or R8 and R9 may be taken together to form a bond; m and n are each 0, 1 or 2; R10 and R12 are each selected from the group consisting of hydrogen, halogen, hydroxy, formyl, cyano, substituted or unsubstituted lower alkyl, substituted or unsubstituted amino, substituted or unsubstituted lower alkoxy, saturated cyclic amino, substituted or unsubstituted carbamoyl, carboxy substituted or unsubstituted lower alkoxycarbonyl and 137 WO 2007/026950 PCT/JP2006/317691 substituted or unsubstituted acyloxy; R11, R13 and R14 are each selected from the group consisting of hydrogen, halogen and substituted or unsubstituted lower alkyl; R10 and R11 or R12 and R13 may be taken together to form oxo, hydroxyimino, substituted or unsubstituted lower alkylene in which one or more carbon(s) may be replaced by hetero atom(s), or substituted or unsubstituted lower alkylidene; R9 and R10 may be taken together to form lower alkylene or a bond; Ru-and R13 or R13 and R14 may be taken together to form a bond, provided that when n=l and R10, R11, R12, R13 and R14 are simultaneously hydrogen, R9 is substituted or unsubstituted lower alkyl or substituted or unsubstituted lower alkanoyl, or a pharmaceutically acceptable salt thereof. 3. The pyridazinone derivative compound of claim 2, wherein R1 is hydrogen or (C6-i4)aryl optionally substituted by (Ci_6) alkyl or (Ci_ e)alkylamiriosulfonyl; R2 is (C6-i4)aryl optionally substituted by 1 to 3 substituent(s) selected from halogen, (Ci_ 6) alkyl and (Ci_6) alkoxy; p is 0; R4 and R5 are each hydrogen or taken together to form a bond; and R6 and R7 are taken together to form a group of the formula: 138 WO 2007/026950 PCT/JP2006/317691 wherein R8 is hydrogen; X is oxygen or N=R9, in which R9 is hydrogen, (Ci_ 5)alkyl optionally substituted by carboxy, hydroxy, {Ci_6)alkoxycarbonyl, morpholino, morpholinocarbonyl or (Ci_6) alkylsulfonyloxy, or (C2-7) alkanoyl; or R8 and R9 are taken together to form a bond; m and n are each 0, 1 or 2; R10 is hydrogen, or (C1-6) alkyl optionally substituted by (C6-i4)aryl(C1-6)alkoxy/ di (C6-14) aryl (Ci-6) alkylsilyloxy or hydroxy; R11 is hydrogen or (Ci_6) alkyl; R12 is selected from the group consisting of hydrogen; halogen; hydroxy; carboxy; formyl; cyano; (C1-6) alkyl optionally substituted by hydroxy, hydroxyimino, halogen, (Ci_6) alkoxy, (Ci- 7) alkanoyloxy, amino, mono- or di-(Ci_ 6) alkylamino (wherein one or both of said (Ci- 6)alkyl is(are) optionally substituted by 139 WO 2007/026950 PCT/JP2006/317691 hydroxy, (C6-i4)aryl or (C3_6) cycloalkyl- carbonyl), (Ci-6) alkylureido, morpholino, or 4- to 6-membered cyclic amino optionally substituted by hydroxy, (Ci_6)alkyl or di (Ci_ 6) alkylamino; mono- or di- (Ci_6) alkylamino; 4- to 6-membered cyclic amino; Ci_6 alkoxy optionally substituted by (Ce_ i4)aryl; carbamoyl optionally substituted by (C3- 6)cycloalkyl or hydroxy (Ci_6) alkyl; (Ci_6) alkoxy-carbonyl; and (CI_G) alkoxy-carbonyloxy; R13 is hydrogen, or (Ci-6) alkyl optionally substituted by hydroxy or (Ci--?) alkanoyloxy; R14 is hydrogen; R10 and R11 may be taken together to form (C2- 6)alkylene in which one or more carbon atom(s) may be replaced with heteroatom(s) , which is optionally substituted by (C6-14) aryl (d.- 6) alkoxycarbonyl or (Ci_7) alkanoyl; R12 and R13 may be taken together to form C2-6 alkylene in which one or more carbon atom(s) may be replaced with heteroatom(s) , which is optionally substituted by (Ci-6) alkyl optionally substituted by hydroxy, or (Ci- 7) alkanoyl optionally substituted by Ci_6 alkoxy; (Ci-6) alkylidene optionally substituted by hydroxy; oxo; or hydroxyimino; 140 WO 2007/026950 PCT/JP2006/317691 R9 and R10 may be taken together to form (C2-s) alkylene or a bond; R11 and R13 may be taken together to form a bond; or R13 and R14 may be taken together to form a bond; provided that when n=l and R10, R11, R12, R13 and R14 are simultaneously hydrogen, R9 is substituted or unsubstituted lower alkyl or substituted or unsubstituted lower alkanoyl; or a pharmaceutically acceptable salt thereof. 4. The compound of claim 1, wherein R1 is selected from the group consisting of hydrogen, substituted or unsubstituted lower alkyl and substituted or unsubstituted aryl; R2 is selected from the group consisting of substituted or unsubstituted aryl and substituted or unsubstituted thienyl; R3 is lower alkyl; p is 0, 1 or 2; R4 and R5 are taken together to form a bond; and R6 and R7 are taken together to form a group of the formula: wherein R15 is selected from the group consisting of hydroxy, substituted or unsubstituted lower alkyl, substituted or unsubstituted amino, substituted or unsubstituted lower alkoxy, saturated cyclic amino, substituted or 141 WO 2007/026950 PCT/JP2006/317691 unsubstituted carbamoyl, carboxy and substituted or unsubstituted lower alkoxycarbonyl/ R16 is selected from the group consisting of hydrogen, halogen, hydroxy, substituted or unsubstituted lower alkyl, substituted or unsubstituted amino, saturated cyclic amino, substituted or unsubstituted lower alkoxy, substituted or unsubstituted carbamoyl, carboxy and substituted or unsubstituted lower alkoxycarbony1; R17 is selected from the group consisting of hydrogen, halogen and substituted or unsubstituted lower alkyl; or R16 and R17 are taken together to form lower alkylene or lower alkylidene; R18 is hydrogen or substituted or unsubstituted lower alkyl, provided that when both R16and R17 are simultaneously hydrogen, R18 is substituted or unsubstituted lower alkyl; and R19 is hydrogen or substituted or unsubstituted lower alkyl, or a pharmaceutically acceptable salt thereof. 5. The compound of claim 4, wherein R1 is hydrogen or substituted or unsubstituted aryl; R2 is substituted or unsubstituted aryl; p is 0; R4 and R5 are taken together to form a bond; and R6 and R7 are taken together to form a group of the formula: 142 WO 2007/026950 PCT/JP2006/317691 wherein R15 is substituted or unsubstituted lower aikyi; R15 is selected from the group consisting of hydrogen, hydroxy, substituted or unsubstituted lower alkyl, substituted or unsubstituted amino and saturated cyclic amino; R17 is hydrogen; R1B is hydrogen or substituted or unsubstituted lower alkyl; and R19 is hydrogen or substituted or unsubstituted lower alkyl, or a pharmaceutically acceptable salt thereof. 6. The compound of claim 5, wherein R1 is selected from the group consisting of hydrogen and (C6-i4)aryl optionally substituted by (Ci_6) alkyl or (Ci_6) alkylaminosulfonyl; R2 is (C6-i4)aryl optionally substituted by 1 to 3 substituent (s) selected from halogen, (Ci_6) alkyl and (Ci-6)alkoxy; p is 0; R4 and R5 are taken together to form a bond; and R6 and R7 are taken together to form a group of the formula: 143 WO 2007/026950 PCT/JP2006/317691 wherein R15 is mono- or di- (Ci-S) alkylamino- (Ci_6) alkyl or hydroxy (Ci_6) alkyl; R16 is selected from the group consisting of hydrogen; hydroxy; Ci-6 alkyl optionally substituted by hydroxy, halogen, methylamino, dimethylamino, (2- hydroxyethyl)methylamino, morpholino or 4- (dimethylamino)-1-piperidinyl; mono- or di- (Ci-6) alkylamino; and piperidino; R17 is hydrogen; R18 is hydrogen or (Ci-6) alkyl optionally substituted by (Ci-6) alkoxycarbonyl, carboxy or hydroxy; and R19 is (Ci-6) alkyl optionally substituted by carboxy, hydroxy, (Ci-6) alkoxycarbonyl, morpholino, morpholinocarbonyl or (Ci_5) alkylsulf onyloxy, or a pharmaceutically acceptable salt thereof. 7. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable carrier. 8. The pharmaceutical composition of claim 7, which is for the prevention or the treatment of a disease selected from the group consisting of pain, rheumatoid arthritis, other conditions associated with inflammation, Crohn's disease, inflammatory bowel disease and psoriasis. 144 WO 2007/026950 PCT/JP2006/317691 9. A method for preventing or treating a disease selected from the group consisting of pain, rheumatoid arthritis, other conditions associated with inflammation, Crohn's disease, inflammatory bowel disease and psoriasis, which comprises administering an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to a mammal in need thereof. 10. Use of the compound of claim 1 or a pharmaceutically acceptable salt thereof for the production of a pharmaceutical composition for the prevention or the treatment of a disease selected from the group consisting of pain, rheumatoid arthritis, other conditions associated with inflammation, Crohn's disease, inflammatory bowel disease and psoriasis. 145 A pyridazinone derivative compound shown by the following formula (I): wherein R1 is selected from hydrogen, etc.; R2 is selected from substituted or unsubstituted aryl, etc.; R3 is hydrogen, etc.;p is 0,1 or 2; R4 and R5 are each hydrogen, etc.; R6 and R7 are taken together to form a group of the formula: wherein R8 is hydrogen; X is selected from oxygen, etc; R10 is selected from hydrogen, etc.; R11 is selected from hydrogen, etc.; R12 is selected from hydrogen, etc.; R13 is selected from hydrogen, etc.; R14 is selected from hydrogen, etc.; m and n are each 0, 1, or 2, or a pharmaceutically acceptable salt thereof, which is useful as a medicament.