New pyridazin-3(2h)-one derivatives

Abstract

Pyridazin-3(2H)-one derivatives of formula (I) are found to inhibit PDE-4: wherein R 1 , R 2 and R 4 are organic radicals, R 3 is a cyclic group, and R 5 is an ester or an aryl or heteroaryl group.

1 - 28 . (canceled) 
   
   
       29 . A method for treating a subject afflicted with a pathological condition or disease, comprising administering to the said subject an effective amount of a compound of formula (I), wherein the pathological condition or disease is chosen from chronic obstructive pulmonary disease, rheumatoid arthritis, and irritable bowel disease: 
     
       
         
         
             
             
         
       
     
     wherein
 R 1  and R 2  represent independently from each other: 
 a hydrogen atom; 
 a group chosen from acyl, hydroxycarbonyl, alkoxycarbonyl, carbamoyl, monoalkylcarbamoyl and dialkylcarbamoyl; 
 an alkyl, alkenyl or alkynyl group, wherein said alkyl, alkenyl or alkynyl group is optionally substituted by one or more substituents chosen from halogen atoms, hydroxy, alkoxy, aryloxy, alkylthio, oxo, amino, mono- and di-alkylamino, acylamino, carbamoyl and mono- and di-alkylcarbamoyl groups; 
 an aryl or heteroaryl group, wherein said aryl or heteroaryl group is optionally substituted by one or more substituents chosen from halogen atoms, hydroxy, hydroxyalkyl, hydroxycarbonyl, alkoxy, alkylenedioxy, alkoxyacyl, aryloxy, acyl, acyloxy, alkylthio, amino, nitro, cyano, mono- and di-alkylamino, acylamino, carbamoyl, mono- and di-alkylcarbamoyl, difluoromethyl, trifluoromethyl, difluoromethoxy and trifluoromethoxy groups; 
 a saturated or unsaturated heterocyclic group, which is optionally substituted by one or more substituents chosen from halogen atoms, hydroxy, hydroxyalkyl, hydroxycarbonyl, alkoxy, alkylenedioxy, alkoxyacyl, aryloxy, acyl, acyloxy, alkylthio, oxo, amino, nitro, cyano, mono- and di-alkylamino, acylamino, carbamoyl, mono- and di-alkylcarbamoyl, difluoromethyl, trifluoromethyl, difluoromethoxy and trifluoromethoxy groups; 
 a group of formula
   —(CH 2 ) n —R 6    
 
 wherein n is an integer from 0 to 4 and R 6  represents:
 a cycloalkyl or cycloalkenyl group; 
 an aryl group, which is optionally substituted by one or more substituents chosen from halogen atoms, alkyl, hydroxy, alkoxy, alkylenedioxy, alkylthio, amino, mono- and di-alkylamino, nitro, acyl, hydroxycarbonyl, alkoxycarbonyl, carbamoyl, mono- and di-alkylcarbamoyl, cyano, trifluoromethyl, difluoromethoxy and trifluoromethoxy groups; 
 or a 3- to 7-membered ring having from 1 to 4 heteroatoms chosen from nitrogen, oxygen and sulphur, which ring is optionally substituted by one or more substituents chosen from halogen atoms, alkyl, hydroxy, alkoxy, alkylenedioxy, amino, mono- and di-alkylamino, nitro, cyano and trifluoromethyl groups; 
 
 R 3  represents a monocyclic or polycyclic aryl or heteroaryl group, which is optionally substituted by one or more substituents chosen from:
 halogen atoms; 
 alkyl and alkylene groups, which are optionally substituted by one or more substituents chosen from halogen atoms; phenyl, hydroxy, hydroxyalkyl, alkoxy, aryloxy, alkylthio, oxo, amino, mono- and di-alkylamino, acylamino, hydroxycarbonyl, alkoxycarbonyl, carbamoyl, and mono- and di-alkylcarbamoyl groups; 
 phenyl, hydroxy, hydroxyalkyl, alkoxy, cycloalkoxy, nitro, aryloxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulfamoyl, acyl, amino, mono- and di-alkylamino, acylamino, hydroxycarbonyl, alkoxycarbonyl, carbamoyl, mono- and di-alkylcarbamoyl, ureido, N′-alkylureido, N′,N′-dialkylureido, alkylsulphamido, aminosuphonyl, mono- and di-alkylaminosulphonyl, cyano, difluoromethoxy and trifluoromethoxy groups; 
 
 R 5  represents a group —COOR 7  or a monocyclic or polycyclic aryl or heteroaryl group, wherein said —COOR 7  or monocyclic or polycyclic aryl or heteroaryl group is optionally substituted by one or more substituents chosen from:
 halogen atoms; 
 alkyl and alkenyl groups, which are optionally substituted by one or more substituents chosen from halogen atoms, phenyl, hydroxy, hydroxyalkyl, alkoxy, aryloxy, alkylthio, oxo, amino, mono- and di-alkylamino, acylamino, hydroxycarbonyl, alkoxycarbonyl, carbamoyl, and mono- and di-alkylcarbamoyl groups; and 
 phenyl, hydroxy, alkylenedioxy, alkoxy, cycloalkyloxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulfamoyl, amino, mono- and di-alkylamino, acylamino, nitro, acyl, hydroxycarbonyl, alkoxycarbonyl, carbamoyl, mono- and di-alkylcarbamoyl, ureido, N′-alkylureido, N′,N′-dialkylureido, alkylsulphamido, aminosuphonyl, mono- and di-alkylaminosulphonyl, cyano, difluoromethoxy and trifluoromethoxy groups; 
 
 wherein R 7  represents an alkyl, which is optionally substituted by one or more substituents chosen from halogen atoms, hydroxy, alkoxy, aryloxy, alkylthio, oxo, amino, mono- and di-alkylamino, acylamino, hydroxycarbonyl, alkoxycarbonyl, carbamoyl, mono- and di-alkylcarbamoyl groups, and a group of formula
   —(CH 2 ) n —R 6    
 wherein n and R 6  are as defined above; and 
 
 R 4  represents:
 a hydrogen atom; 
 a hydroxy, alkoxy, amino, mono- or di-alkylamino group; 
 an alkyl, alkenyl or alkynyl group, wherein said alkyl, alkenyl or alkynyl group is optionally substituted by one or more substituents chosen from halogen atoms, hydroxy, alkoxy, aryloxy, alkylthio, oxo, amino, mono- and di-alkylamino, acylamino, hydroxycarbonyl, alkoxycarbonyl, carbamoyl and mono- and di-alkylcarbamoyl groups; 
 or a group of formula
   —(CH 2 ) n —R 6    
 
 wherein n and R 6  are as defined above 
 
 or a N-oxide obtainable from heteroaryl radicals present in the structure when said heteroradical comprise at least one N atom or a pharmaceutically acceptable salt thereof; 
 with the proviso that when R 5  is neither an optionally substituted heteroaryl group nor a group COOR 7 , R 3  is an optionally substituted heteroaryl group. 
 
   
   
       30 . The method according to  claim 29 , wherein in the compound of formula (I), R 2  represents a hydrogen atom or an aryl group, which is optionally substituted by one or more substituents chosen from halogen atoms, nitro, C 1 -C 4  alkoxy, C 1 -C 4  hydroxyalkyl and —CO 2 —(C 1 -C 4  alkyl) groups. 
   
   
       31 . The method according to  claim 30 , wherein in the compound of formula (I), R 2  is a hydrogen atom or a phenyl group, which is unsubstituted or substituted with 1 or 2 unsubstituted substituents chosen from fluorine atoms, chlorine atoms, and nitro, C 1 -C 4  hydroxyalkyl and —CO 2 —(C 1 -C 2  alkyl) groups. 
   
   
       32 . The method according to  claim 29 , wherein in the compound of formula (I), R 1  represents a group chosen from:
 a (C 1 -C 4 ) alkyl group, which is optionally substituted by one or more hydroxy groups; and   groups of formula
   —(CH 2 ) n —R 6    
   wherein n is an integer from 1 to 3 and R 6  represents a (C 3 -C 6 ) cycloalkyl group.   
   
   
       33 . The method according to  claim 32 , wherein in the compound of formula (I), R 1  is an unsubstituted C 1 -C 4  alkyl, an unsubstituted C 1 -C 4  hydroxyalkyl or an unsubstituted cyclopropyl-(C 1 -C 4  alkyl)- group. 
   
   
       34 . The method according to  claim 29 , wherein in the compound of formula (I), R 3  represents a monocyclic or polycyclic aryl or heteroaryl group, wherein said monocyclic or polycyclic aryl or heteroaryl group is optionally substituted by one or more substituents chosen from:
 halogen atoms;   alkyl and alkylene groups, wherein said alkyl and alkylene groups are optionally substituted by one or more substituents chosen from halogen atoms;   phenyl, hydroxy, hydroxycarbonyl, hydroxyalkyl, alkoxycarbonyl, alkoxy, cycloalkoxy, nitro, aryloxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulfamoyl, acyl, amino, mono- or di-alkylamino, acylamino, hydroxycarbonyl, alkoxycarbonyl, carbamoyl, mono- and di-alkylcarbamoyl, ureido, N′-alkylureido, N′,N′-dialkylureido, alkylsulphamido, aminosuphonyl, mono- and di-alkylaminosulphonyl, cyano, difluoromethoxy and trifluoromethoxy groups;   
   
   
       35 . The method according to  claim 34 , wherein in the compound of formula (I), R 3  represents a group chosen from monocyclic or polycyclic aryl or heteroaryl groups, wherein said monocyclic or polycyclic aryl or heteroaryl groups are optionally substituted by one or more substituents chosen from:
 halogen atoms;   (C 1 -C 4 ) alkyl groups, which are optionally substituted by one or more hydroxy groups;   and (C 1 -C 4 ) alkoxy, nitro, hydroxy, hydroxycarbonyl, carbamoyl, (C 1 -C 4  alkoxy)-carbonyl and cyano groups.   
   
   
       36 . The method according to  claim 35 , wherein in the compound of formula (I), R 3  represents a phenyl group, a naphthyl group or a 5- to 14-membered monocylic or polycyclic heteroaryl group containing 1, 2 or 3 heteroatoms chosen from N, O and S, the phenyl, naphthyl and heteroaryl groups being unsubstituted or substituted with 1 or 2 unsubstituted substituents chosen from:
 halogen atoms;   C 1 -C 4  alkyl and C 1 -C 4  hydroxyalkyl groups; and   C 1 -C 4  alkoxy, nitro, hydroxy, hydroxycarbonyl, carbamoyl, (C 1 -C 4  alkoxy)-carbonyl and cyano groups.   
   
   
       37 . The method according to  claim 36 , wherein in the compound of formula (I), R 3  represents a phenyl group, a naphtyl group or a substituted or unsubstituted heteroaryl group chosen from substituted or unsubstituted oxadiazolyl, oxazolyl, pyridyl, pyrrolyl, imidazolyl, thiazolyl, thiadiazolyl, thienyl, furanyl, quinolinyl, isoquinolinyl, indolyl, benzoxazolyl, naphthyridinyl, benzofuranyl, pyrazinyl, pyrimidinyl and pyrrolopyridyl radicals. 
   
   
       38 . The method according to  claim 29 , wherein in the compound of formula (I), R 4  represents:
 an unsubstituted mono-(C 1 -C 4  alkyl)amino or unsubstituted di-(C 1 -C 4  alkyl)amino group;   a C 1 -C 4  alkyl group which is unsubstituted or substituted by one or more substituents chosen from hydroxy, C 1 -C 4  alkoxy, amino, mono-(C 1 -C 4  alkyl)amino and di-(C 1 -C 4  alkyl)amino groups;   an unsubstituted phenyl-(C 1 -C 4  alkyl)- group; or   a group of formula   
     wherein n is 2 and R 6  represents a radical chosen from phenyl, pyridyl and thienyl, optionally substituted by one or more substituents chosen from halogen atoms, alkyl, hydroxy, alkoxy, alkylenedioxy, amino, mono- and di-alkylamino, nitro, ciano and trifluoromethyl groups. 
   
   
       39 . The method according to  claim 38 , wherein in the compound of formula (I), R 4  represents an alkyl group having from 1 to 6 carbon atoms and which is optionally substituted by one or more substituents chosen from halogen atoms and hydroxy groups. 
   
   
       40 . The method according to  claim 29 , wherein in the compound of formula (I), R 5  represents a group COOR 7  or a monocyclic or polycyclic aryl or heteroaryl group, wherein said —COOR 7  or monocyclic or polycyclic aryl or heteroaryl group is optionally substituted by one or more substituents chosen from halogen atoms, C 1 -C 4  alkyl groups, C 1 -C 4  alkoxycarbonyl groups, hydroxycarbonyl groups and C 1 -C 4  alkoxy groups. 
   
   
       41 . The method according to  claim 40 , wherein in the compound of formula (I), R 5  represents a group COOR 7  or a monocyclic or polycyclic aryl or heteroaryl group, wherein said COOR 7  or a monocyclic or polycyclic aryl or heteroaryl group is optionally substituted by one or more substituents chosen from halogen atoms and C 1 -C 4  alkoxy groups. 
   
   
       42 . The method according to  claim 40 , wherein in the compound of formula (I), R 5  represents —CO 2 R 7 , wherein R 7  represents an unsubstituted C 1 -C 4  alkyl group, or R 5  represents a phenyl group or a 5- to 10-membered monocyclic or polycyclic heteroaryl group containing 1 or 2 heteroatoms chosen from N, O and S, the phenyl and heteroaryl groups being unsubstituted or substituted by 1 or 2 substituents chosen from C 1 -C 4  alkoxy groups and halogen atoms. 
   
   
       43 . The method according to  claim 42 , wherein in the compound of formula (I), R 5  represents a phenyl group, or a substituted or unsubstituted heteroaryl group chosen from substituted or unsubstituted oxadiazolyl, oxazolyl, pyridyl, pyrrolyl, imidazolyl, thiazolyl, thiadiazolyl, thienyl, furanyl, quinolinyl, isoquinolinyl, indolyl, benzoxazolyl, naphthyridinyl, benzofuranyl, pyrazinyl, pyrimidinyl and pyrrolopyridyl radicals. 
   
   
       44 . The method according to  claim 29 , wherein the compound of formula (I) is chosen from: 
     5-acetyl-2-ethyl-4-[(3-fluorophenyl)amino]-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3,5-dichlorophenyl)amino]-2-ethyl-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(1-naphthylamino)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     methyl 4-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-3-yl-2,3-dihydropyridazin-4-yl)amino]benzoate; 
     5-acetyl-2-ethyl-4-[(2-fluorophenyl)amino]-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(2-chlorophenyl)amino]-2-ethyl-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-3-ylpyridazin-3(2H)-one; 
     3-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-3-yl-2,3-dihydropyridazin-4-yl)amino]benzonitrile; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-4-[(3,5-dichlorophenyl)amino]-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-4-[(2-fluorophenyl)amino]-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(2-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     3-{[5-acetyl-2-(cyclopropylmethyl)-3-oxo-6-pyridin-3-yl-2,3-dihydropyridazin-4-yl]amino}benzonitrile; 
     methyl 4-{[5-acetyl-2-(2-hydroxyethyl)-3-oxo-6-pyridin-3-yl-2,3-dihydropyridazin-4-yl]amino}benzoate; 
     5-acetyl-4-[(2-fluorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(2-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-pyridin-2-ylpyridazin-3(2H)-one; 
     3-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-2-yl-2,3-dihydropyridazin-4-yl)amino]benzonitrile; 
     5-acetyl-2-ethyl-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-2-ylpyridazin-3(2H)-one; 
     3-{[5-acetyl-2-(cyclopropylmethyl)-3-oxo-6-pyridin-2-yl-2,3-dihydropyridazin-4-yl]amino}benzonitrile; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-2-ylpyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-2-ylpyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-4-[(3,5-dichlorophenyl)amino]-6-pyridin-2-ylpyridazin-3(2H)-one; 
     3-{[5-acetyl-2-(2-hydroxyethyl)-3-oxo-6-pyridin-2-yl-2,3-dihydropyridazin-4-yl]amino}benzonitrile; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-2-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3,5-dichlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-2-ylpyridazin-3(2H)-one; 
     5-acetyl-2-(2-hydroxyethyl)-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-2-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(3-fluorophenyl)amino]-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(1-naphthylamino)-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(2-methylphenyl)amino]-6-pyridin-4-ylpyridazin-3(2H)-one; 
     methyl 4-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydropyridazin-4-yl)amino]benzoate; 
     5-acetyl-2-ethyl-4-[(2-methoxyphenyl)amino]-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(3-methoxyphenyl)amino]-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(2-fluorophenyl)amino]-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(2-chlorophenyl)amino]-2-ethyl-6-pyridin-4-ylpyridazin-3(2H)-one; 
     3-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydropyridazin-4-yl)amino]benzonitrile; 
     5-acetyl-2-ethyl-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-4-ylpyridazin-3(2H)-one; 
     4-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydropyridazin-4-yl)amino]benzoic acid; 
     5-acetyl-2-(cyclopropylmethyl)-4-[(2-fluorophenyl)amino]-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(2-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-4-ylpyridazin-3(2H)-one; 
     3-{[5-acetyl-2-(cyclopropylmethyl)-3-oxo-6-pyridin-4-yl-2,3-dihydropyridazin-4-yl]amino}benzonitrile; 
     5-acetyl-2-(cyclopropylmethyl)-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(2-fluorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(2-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-4-ylpyridazin-3(2H)-one; 
     3-{[5-acetyl-2-(2-hydroxyethyl)-3-oxo-6-pyridin-4-yl-2,3-dihydropyridazin-4-yl]amino}benzonitrile; 
     5-acetyl-2-(2-hydroxyethyl)-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-thien-2-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[bis(3-fluorophenyl)amino]-2-ethyl-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[bis-(4-methoxycarbonylphenyl)-amino]-2-ethyl-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-{bis[4-(hydroxymethyl)phenyl]amino}-2-ethyl-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[bis(3-nitrophenyl)amino]-2-ethyl-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[bis(3-fluorophenyl)amino]-2-ethyl-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[bis(3-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[bis(3,5-dichlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[bis(4-methoxycarbonylphenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[bis(3-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-2-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[bis(3-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-4-[(3,5-dichloropyridin-4-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(pyrazin-2-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(pyrimidin-2-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(quinolin-8-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(5-nitropyridin-2-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(1 h-indol-4-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-(1,3-benzothiazol-6-ylamino)-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(thianthren-1-ylamino)pyridazin-3(2H)-one; 
     methyl 3-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridazin-4-yl)amino]thiophene-2-carboxylate; 
     5-acetyl-2-ethyl-4-[(4-methylpyridin-2-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(1h-1,2,4-triazol-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(6-methoxypyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(2H-indazol-5-ylamino)-6-phenylpyridazin-3(2H)-one; 
     methyl 4-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridazin-4-yl)amino]thiophene-3-carboxylate; 
     5-acetyl-2-ethyl-6-phenyl-4-(pyridin-2-ylamino)pyridazin-3(2H)-one; 
     3-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridazin-4-yl)amino]thiophene-2-carboxylic acid; 
     5-acetyl-2-ethyl-4-[(3-methylcinnolin-5-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(2-methylquinolin-8-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(1 h-indol-5-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(isoquinolin-5-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(6-methoxyquinolin-8-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-[(5-bromoquinolin-8-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(4-methylpyrimidin-2-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-6-(3-chlorophenyl)-2-(cyclopropylmethyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(3-fluorophenyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-6-(3-fluorophenyl)-2-isopropyl-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-6-(3-fluorophenyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-fluorophenyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-6-(1 h-benzimidazol-2-yl)-4-[(3-chlorophenyl)amino]-2-ethylpyridazin-3(2H)-one; 
     5-acetyl-6-(1,3-benzoxazol-2-yl)-4-[(3-chlorophenyl)amino]-2-ethylpyridazin-3(2H)-one; 
     5-acetyl-6-(1,3-benzoxazol-2-yl)-2-ethyl-4-[(3-fluorophenyl)amino]pyridazin-3(2H)-one; 
     5-acetyl-6-benzooxazol-2-yl-4-[bis-(3-chlorophenyl)-amino]-2-ethyl-pyridazin-3(2H)-one; 
     5-acetyl-6-benzooxazol-2-yl-4-[bis-(3-fluorophenyl)-amino]-2-ethyl-pyridazin-3(2H)-one; 
     3-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-3-yl-2,3-dihydropyridazin-4-yl)amino]benzamide; 
     5-acetyl-2-ethyl-4-(isoquinolin-1-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-[(2-butylquinazolin-4-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-(1,2-benzisothiazol-3-ylamino)-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(pyridin-4-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(2-hydroxy-7h-purin-6-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(quinazolin-4-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-4-[(4-chloro-1H-indazol-3-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-[(7-chloroquinolin-4-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-[(4,6-dichloropyrimidin-2-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(6-hydroxy-2H-pyrazolo[3,4-d]pyrimidin-4-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(2-methylquinolin-4-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(1H-imidazol-2-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(quinolin-4-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-4-(cinnolin-4-ylamino)-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(thieno[2,3-d]pyrimidin-4-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(1H-indazol-6-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-(2-methoxypyridin-4-yl)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-{[4-(hydroxymethyl)phenyl]amino}-6-(6-methoxypyridin-3-yl)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(3-methoxyphenyl)amino]-6-thien-3-ylpyridazin-3(2H)-one; 
     5-acetyl-6-(1-benzofuran-5-yl)-2-ethyl-4-[(3-fluorophenyl)amino]pyridazin-3(2H)-one; 
     1-ethyl-5-[(3-methoxyphenyl)amino]-n,n-dimethyl-6-oxo-3-pyridin-3-yl-1,6-dihydropyridazine-4-carboxamide; 
     5-[(3-chlorophenyl)amino]-1-ethyl-n-methyl-6-oxo-3-pyridin-4-yl-1,6-dihydropyridazine-4-carboxamide; 
     2-ethyl-4-[(3-fluorophenyl)amino]-5-glycoloyl-6-pyridin-4-ylpyridazin-3(2H)-one; 
     2-ethyl-4-[(3-fluorophenyl)amino]-5-(methoxyacetyl)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-[(dimethylamino)acetyl]-2-ethyl-4-[(3-methoxyphenyl)amino]-6-pyridin-3-ylpyridazin-3(2H)-one; 
     2-ethyl-4-[(3-fluorophenyl)amino]-5-[(methylamino)acetyl]-6-pyridin-4-ylpyridazin-3(2H)-one; 
     3-{[2-ethyl-3-oxo-5-(3-phenylpropanoyl)-6-pyridin-4-yl-2,3-dihydropyridazin-4-yl]amino}benzamide; 
     ethyl 4-acetyl-5-[(3-chlorophenyl)amino]-1-ethyl-6-oxo-1,6-dihydropyridazine-3-carboxylate; 
     ethyl 4-acetyl-5-amino-1-ethyl-6-oxo-1,6-dihydropyridazine-3-carboxylate; 
     5-acetyl-6-(1,3-benzoxazol-2-yl)-2-ethyl-4-[(3-methoxyphenyl)amino]pyridazin-3(2H)-one; 
     5-acetyl-6-(1,3-benzoxazol-2-yl)-2-ethyl-4-{[4-(hydroxymethyl)phenyl]amino}pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(isoquinolin-4-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(1,6-naphthyridin-8-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(5-methoxypyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-pyridin-4-yl-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(isoquinolin-4-ylamino)-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-pyridin-4-yl-4-[(3,4,5-trifluorophenyl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(isoquinolin-4-ylamino)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-pyridin-3-yl-4-[(3,4,5-trifluorophenyl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(quinolin-5-ylamino)-6-thien-2-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(pyridin-3-ylamino)-6-thien-2-ylpyridazin-3(2H)-one; 
     4-[(5-acetyl-2-ethyl-3-oxo-6-thien-2-yl-2,3-dihydropyridazin-4-yl)amino]benzonitrile; 
     5-acetyl-2-ethyl-6-thien-2-yl-4-[(3,4,5-trifluorophenyl)amino]pyridazin-3(2H)-one; 
     5-Acetyl-4-(bis(4-cyanophenyl)amino)-2-ethyl-6-thien-2-ylpyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-4-(quinolin-5-ylamino)-6-thien-2-ylpyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-4-(pyridin-3-ylamino)-6-thien-2-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(quinolin-5-ylamino)-6-thien-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-thien-3-ylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(pyridin-3-ylamino)-6-thien-3-ylpyridazin-3(2H)-one; 
     4-[(5-acetyl-2-ethyl-3-oxo-6-thien-3-yl-2,3-dihydropyridazin-4-yl)amino]benzonitrile; 
     5-acetyl-2-ethyl-6-thien-3-yl-4-[(3,4,5-trifluorophenyl)amino]pyridazin-3(2H)-one; 
     2-ethyl-6-phenyl-5-(3-phenylpropanoyl)-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     2-ethyl-6-phenyl-5-(3-phenylpropanoyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     2-ethyl-4-(isoquinolin-4-ylamino)-6-phenyl-5-(3-phenylpropanoyl)pyridazin-3(2H)-one; 
     2-ethyl-6-phenyl-4-(quinolin-5-ylamino)-5-(3-thien-3-ylpropanoyl)pyridazin-3(2H)-one; 
     2-ethyl-6-phenyl-4-(pyridin-3-ylamino)-5-(3-thien-3-ylpropanoyl)pyridazin-3(2H)-one; 
     5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-(1H-imidazo[4,5-b]pyridin-2-yl)pyridazin-3(2H)-one; 
     5-acetyl-6-(1,3-benzothiazol-2-yl)-4-[(3-chlorophenyl)amino]-2-ethylpyridazin-3(2H)-one; 
     5-acetyl-6-(1-benzofuran-2-yl)-4-[(3-chlorophenyl)amino]-2-ethylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-pyridin-3-yl-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     4-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-3-yl-2,3-dihydropyridazin-4-yl)amino]benzoic acid; 
     5-acetyl-2-ethyl-4-[(1-oxidopyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     ethyl 3-(5-acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydro-pyridazin-4-ylamino)benzoate; 
     3-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydropyridazin-4-yl)amino]benzamide; 
     5-acetyl-2-ethyl-6-phenyl-4-(thieno[2,3-b]pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(6-fluoropyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(2-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-{[2-(dimethylamino)pyridin-3-yl]amino}-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridazin-4-yl)amino]pyridine-2-carboxylic acid; 
     5-acetyl-2-ethyl-4-[(2-methoxypyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(1H-indazol-4-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-[(2-chloropyridin-3-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-[(5-chloropyridin-3-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridazin-4-yl)amino]nicotinamide; 
     5-acetyl-2-ethyl-4-(1,7-naphthyridin-8-ylamino)-6-phenylpyridazin-3(2H)-one; 
     2-ethyl-5-glycoloyl-4-[(2-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     methyl 5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridazin-4-yl)amino]nicotinate; 
     5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridazin-4-yl)amino]nicotinic acid; 
     5-acetyl-2-ethyl-4-(1,5-naphthyridin-3-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(8-hydroxy-1,7-naphthyridin-5-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(thien-2-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-[(2-phenylpyridin-3-yl)amino]pyridazin-3(2H)-one; 
     ethyl {5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridazin-4-yl)amino]pyridin-2-yl}acetate; 
     5-acetyl-2-ethyl-4-[(6-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(6-hydroxypyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(2-fluoropyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-[(6-chloro-4-methylpyridin-3-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(3-hydroxypyridin-2-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(4-methoxypyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(isoquinolin-8-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(quinolin-7-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-4-[(5-chloropyridin-3-yl)amino]-2-ethyl-6-(3-fluorophenyl)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-fluorophenyl)-4-[(2-methoxypyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-fluorophenyl)-4-[(2-methylpyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-4-[(2-chloropyridin-3-yl)amino]-2-ethyl-6-(4-fluorophenyl)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-fluorophenyl)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-fluorophenyl)-4-[(2-fluoropyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-4-[(2-chloropyridin-3-yl)amino]-2-(cyclopropylmethyl)-6-(4-fluorophenyl)pyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-6-(4-fluorophenyl)-4-[(2-methoxypyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-6-(4-fluorophenyl)-4-[(2-methylpyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-6-(4-fluorophenyl)-4-[(2-fluoropyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-6-(4-fluorophenyl)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-6-(4-fluorophenyl)-4-[(pyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-[(2-methylpyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-6-(3-chlorophenyl)-4-[(2-chloropyridin-3-yl)amino]-2-ethylpyridazin-3(2H)-one; 
     5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-one; 
     methyl 5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridazin-4-yl)amino]quinoline-8-carboxylate; 
     5-acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(isoquinolin-4-ylamino)-6-(4-methoxyphenyl)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-methoxyphenyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-methoxyphenyl)-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-methoxy-phenyl)-4-(1-oxy-quinolin-5-ylamino)-2H-pyridazin-3-one 
     5-acetyl-2-ethyl-4-(isoquinolin-4-ylamino)-6-(3-methoxyphenyl)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(3-methoxyphenyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(3-methoxyphenyl)-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(3-methoxyphenyl)-4-[(1-oxidoquinolin-5-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(isoquinolin-4-ylamino)-6-(4-methylphenyl)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-methylphenyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-methylphenyl)-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-methylphenyl)-4-[(1-oxidoquinolin-5-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-methylphenyl)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(isoquinolin-4-ylamino)-6-(3-methylphenyl)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(3-methylphenyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(3-methylphenyl)-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(3-methylphenyl)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-one; 
     methyl 4-[4-acetyl-1-ethyl-5-(isoquinolin-4-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl]benzoate; 
     methyl 4-[4-acetyl-1-ethyl-6-oxo-5-(pyridin-3-ylamino)-1,6-dihydropyridazin-3-yl]benzoate; 
     4-[4-acetyl-1-ethyl-6-oxo-5-(pyridin-3-ylamino)-1,6-dihydropyridazin-3-yl]benzoic acid; 
     methyl 4-{4-acetyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-1,6-dihydropyridazin-3-yl}benzoate; 
     4-{4-acetyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-1,6-dihydropyridazin-3-yl}benzoic acid; 
     methyl 3-[4-acetyl-1-ethyl-6-oxo-5-(pyridin-3-ylamino)-1,6-dihydropyridazin-3-yl]benzoate; 
     3-[4-acetyl-1-ethyl-6-oxo-5-(pyridin-3-ylamino)-1,6-dihydropyridazin-3-yl]benzoic acid; 
     5-acetyl-4-[(3-chloro-4-fluorophenyl)amino]-2-ethyl-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[bis(3-chloro-4-fluorophenyl)amino]-2-ethyl-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[(3-chloro-4-fluorophenyl)amino]-2-ethyl-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-acetyl-4-[bis(3-chloro-4-fluorophenyl)amino]-2-ethyl-6-pyridin-3-ylpyridazin-3(2H)-one; 
     methyl [4-acetyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazin-1(6H)-yl]acetate; 
     [4-acetyl-6-oxo-3-phenyl-5-(quinolin-5-ylamino)pyridazin-1(6H)-yl]acetic acid; 
     5-acetyl-2-ethyl-4-[(3-methylpyridin-2-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(1H-pyrazol-3-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-phenyl-4-(9H-purin-6-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(3-methylisoxazol-5-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(8-hydroxyquinolin-5-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(1H-indazol-7-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-4-[(6-bromoquinolin-8-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(5-methylisoxazol-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-(isoxazol-3-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-6-phenyl-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-6-phenyl-4-(quinolin-8-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(1-methyl-1H-pyrazol-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(1-oxidoquinolin-5-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(2-oxidoisoquinolin-5-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-(quinolin-8-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-pyridin-4-yl-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-pyridin-3-yl-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(8-fluoroquinolin-5-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-6-(4-fluorophenyl)-4-(quinolin-8-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-fluorophenyl)-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-fluorophenyl)-4-(quinolin-8-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-(cyclopropylmethyl)-6-(4-fluorophenyl)-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-[(1-oxidoquinolin-5-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-4-[(2-methylquinolin-5-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-(isoquinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(4-fluorophenyl)-4-[(1-oxidoquinolin-5-yl)amino]pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(3-fluorophenyl)-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-acetyl-2-ethyl-6-(3-fluorophenyl)-4-[(1-oxidoquinolin-5-yl)amino]pyridazin-3(2H)-one; and 
     5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridazin-4-yl)amino]quinoline-8-carboxylic acid and pharmaceutically acceptable salts thereof. 
   
   
       45 . The method according to  claim 44 , wherein the compound of formula (I) is chosen from: 
     5-Acetyl-2-ethyl-4-[(3-fluorophenyl)amino]-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-(1-naphthylamino)-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-Acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-(1-naphthylamino)-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-[(2-methylphenyl)amino]-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-[(3-methoxyphenyl)amino]-6-pyridin-4-ylpyridazin-3(2H)-one; 
     4-[(5-Acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydropyridazin-4-yl)amino]benzoic acid; 
     5-Acetyl-4-[(3-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-Acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-thien-2-ylpyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-6-phenyl-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-6-phenyl-4-(quinolin-8-ylamino)pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-(1H-indol-4-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-6-phenyl-4-(quinolin-5-ylamino)pyridazin-3(2H)-one; 
     5-Acetyl-6-(3-fluorophenyl)-2-isopropyl-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-Acetyl-2-(cyclopropylmethyl)-6-(3-fluorophenyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-6-(4-fluorophenyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-(isoquinolin-5-ylamino)-6-phenylpyridazin-3(2H)-one; 
     5-Acetyl-6-(1,3-benzoxazol-2-yl)-2-ethyl-4-[(3-fluorophenyl)amino]pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-[(1-oxidoquinolin-5-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-(isoquinolin-4-ylamino)-6-phenylpyridazin-3(2H)-one; 
     2-Ethyl-6-phenyl-5-(3-phenylpropanoyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-(isoquinolin-4-ylamino)-6-(3-methylphenyl)pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-(isoquinolin-4-ylamino)-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-(isoquinolin-4-ylamino)-6-(4-methylphenyl)pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-6-(4-fluorophenyl)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-[(5-Acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridazin-4-yl)amino]quinoline-8-carboxylic acid; 
     5-Acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     Methyl 3-[4-acetyl-1-ethyl-6-oxo-5-(pyridin-3-ylamino)-1,6-dihydropyridazin-3-yl]benzoate; 
     5-acetyl-2-ethyl-6-(3-methylphenyl)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-(pyridin-3-ylamino)-6-thien-3-ylpyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-[(2-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-one; 
     3-(4-Acetyl-5-amino-1-ethyl-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzoic acid methyl ester; 
     5-Acetyl-2-ethyl-6-(3-methylphenyl)-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-6-(3-fluorophenyl)-4-(pyridin-3-ylamino)-pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-pyridin-4-ylpyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-pyridin-3-ylpyridazin-3(2H)-one; 
     5-Acetyl-4-[(2-chloropyridin-3-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-6-pyridin-3-yl-4-(pyridin-3-ylamino)pyridazin-3(2H)-one; 
     5-Acetyl-2-ethyl-6-(4-methylphenyl)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-one; and 
     5-Acetyl-2-ethyl-6-phenyl-4-(thieno[2,3-b]pyridin-3-ylamino)pyridazin-3(2H)-one. 
   
   
       46 . The method according to  claim 29 , wherein the compound of formula (I) is ethyl 4-acetyl-5-amino-1-ethyl-6-oxo-1,6-dihydropyridazine-3-carboxylate.