Granted Patent B2

US 8,129,386 · App. 12/414,257 · Granted Mar 6, 2012

Abstract

Claims (237)

1. A method for treating or controlling asthma, atopic dermatitis, rhinitis, allergic diseases, chronic obstructive pulmonary disease (COPD), septic shock, joint diseases, an autoimmune pathology, rheumatoid arthritis, Grave's disease, diabetes, cancer, myocardial contractility disorders, or thromboembolism in a human or animal, the method comprising administering to the human or animal an effective amount of a compound of formula (I)

wherein

X represents CR 5 R 6 or NH;

Y 1 represents CR 3 or N;

Chemical bond between Y 2 —Y 3 represents a single bond or double bond, with the proviso that when the Y 2 —Y 3 represents a double bond, Y 2 and Y 3 independently represent CR 4 or N, and

when Y 2 —Y 3 represents a single bond, Y 2 and Y 3 independently represent CR 3 R 4 or NR 4 ;

Z 1 , Z 2 , Z 3 and Z 4 independently represent CH, CR 2 or N;

R l represents

C 1-6 alkyl optionally substituted by mono-, di- or tri- halogen, phenyl, methoxyphenyl, phenoxy, or thienyl,

C 1-6 alkoxy optionally substituted by mono-, di- or tri- halogen, phenyl, methoxyphenyl, phenoxy, or thienyl

or

one of the following carbocyclic and heterocyclic rings selected from the group consisting of cyclopropyl, cyclohexyl, piperidinyl, piperazinyl, pyrrolyl, pyrazolyl, furyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, isoimidazolyl, pyrazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1-benzothiophenyl, benzothiazolyl, benzimidazolyl, 3H-imidazo[4,5-b]pyridinyl, benzotriazolyl, indolyl, indazolyl, imidazo[1,2-a]pyridinyl, quinolinyl, and 1,8- naphthyridinyl,

wherein

said carbocyclic and heterocyclic rings optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxy, halogen, nitro, cyano, carboxy, amino, N—(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N—(C 1-6 acyl)amino, N—(C 1-6 alkoxycarbonyl)amino, N-(formyl)-N—(C 1-6 alkyl)amino, N[N,N-di(C 1-6 alkyl)amino methylene]amino, N[N,N-di(C 1-6 alkyl)amino (C 1-6 alkylene)methylene]amino, N—[N,N-di(C 1-6 alkyl)amino C 2-6 alkylenyl]amino, C 1-6 alkylthio, C 1-6 alkylanesulfonyl, sulfamoyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, pyrrolyl, imidazolyl, pyrazolyl, pyrrolidinyl, pyridyl, phenyl C 1-6 alkoxycarbonyl,

thiazolyl optionally substituted by pyridyl, piperazinyl optionally substituted by C 1-6 alkyl or C 1-6 alkoxy and

C 1-6 alkyl optionally substituted by mono-, di- or tri- halogen;

R 2 represents hydroxy, halogen, nitro, cyano, carboxy, amino, N—(C 1-6 alkyl)amino, N-(hydroxy C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N-(hydroxy C 1-6 alkyl)-N- (C 1-6 alkyl)amino, C 2-6 alkenyl, C 1-6 alkoxycarbonyl, aminocaronyl, C 1-6 acyloxy, aminoC 1-6 acyloxy, furyl, morpholino, phenyl, piperidino, aryl,

pyrrolidinyl optionally substituted by C 1-6 acylamino,

piperidino optionally substituted by hydroxy, C 1-6 alkyl, carboxy, aminocarbonyl, N—(C 1-6 alkyl)aminocarbonyl, or N,N-di(C 1-6 alkyl)aminocarbonyl,

piperazinyl optionally substituted by

C 1-6 alkyl,

C 1-6 alkyl optionally substituted by cyano, mono-, di- or tri-halogen, hydroxy, amino, N—(C 1-6 alkyl)amino, N-(hydroxy C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, C 3-6 cycloalkyl, tetrazolyl, tetrahydropyranyl, morpholino, phthalimidyl, 2-oxo-1,3oxazolidinyl, phenyl, —C(O)—R 201 , pypyrrolidinyl optionally substituted by C 1-6 acylamino,

piperidino optionally substituted by hydroxy, C 1-6 alkyl, carboxy, aminocarbonyl, N—(C 1-6 alkyl)aminocarbonyl, or N, N-di(C 1-6 alkyl)aminocarbonyl, or piperazinyl optionally substituted by C 1-6 alkyl,

wherein

R 201 represents hydroxy, amino, N—(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N-(halobenzyl)amino, C 1-6 alkyl, C 1-6 alkoxy, tetrazolyl, tetrahydropyranyl, morpholino,

pyrrolidinyl optionally substituted by C 1-6 acylamino, piperidino optionally substituted by

hydroxy, C 1-6 alkyl, carboxy, aminocarbonyl, N—(C 1-6 alkyl)aminocarbonyl, or N,N-di(C 1-6 alkyl)aminocarbonyl,

or

piperazinyl optionally substituted by C 1-6 alkyl, C 1-6 alkoxy optionally substituted by cyano, mono-, di- or tri- halogen, hydroxy, C 1-6 alkoxy, hydroxy C 1-6 alkoxy, amino, N—(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, pyrrolyl, tetrazolyl, tetrahydropyranyl, morpholino, phthalimidyl, 2-oxo-1,3oxazolidinyl, phenyl, —C(O)—R 201 ,

pyrrolidinyl optionally substituted by C 1-6 acylamino, piperidino optionally substituted by hydroxy, C 1-6 alkyl, carboxy, aminocarbonyl, N—(C1-6-alkyl)aminocarbonyl, or N,N-di(C 1-6alkyl)aminocarbonyl,

or

piperazinyl optionally substituted by C 1-6 alkyl,

wherein

R 201 represents hydroxy, amino, N—(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N-(halobenzyl)amino, C 1-6 alkyl, C 1-6 alkoxy, amino C 2-6 alkylenyl, tetrazolyl, tetrahydropyranyl, morpholino, pyrrolidinyl optionally substituted by C 1-6 acylamino, piperidino optionally substituted by hydroxy, C 1-6 alkyl, carboxy, aminocarbonyl, N—(C 1-6 alkyl)aminocarbonyl, or N,N-di(C 1-6 alkyl)aminocarbonyl,

or

piperazinyl optionally substituted by C 1-6 alkyl;

R 3 represents hydrogen, halogen, C 1-6 alkyl optionally substituted by aminocarbonyl, arylC 1-6 alkoxy, or mono-, di- or tri-halogen;

R 4 represents hydrogen or C 1-6 alkyl;

R 5 represents hydrogen or C 1-6 alkyl; and

R 6 represents hydrogen, halogen or C 1-6 alkyl,

a tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof.

2. The method of claim 1 , wherein

X represents CR 5 R 6 or NH;

Y 1 represents N;

Y 2 and Y 3 represent CR 3 R 4 ;

Chemical bond between Y 2 —Y 3 represents a single bond.

Z 4 represents CH;

Z 1 , Z 2 and Z 3 independently represent CH, CR 2 or N;

R 1 represents

C 1-6 alkyl optionally substituted by mono-, di- or tri- halogen, phenyl, methoxyphenyl, phenoxy, or thienyl,

C 1-6 alkoxy optionally substituted by phenyl phenoxy, thienyl or mono-, di- or tri- halogen,

or

one of the following carbocyclic and heterocyclic rings selected from the group consisting of cyclopropyl, cyclopentyl, cyclohexyl, piperidinyl, piperazinyl, pyrrolyl, pyrazolyl, furyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, isoimidazolyl, pyrazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1-benzothiophenyl, benzothiazolyl, benzimidazolyl, 3H-imidazo[4,5-b]pyridinyl, benzotriazolyl, indolyl, indazolyl, imidazo[1,2-a]pyridinyl, quinolinyl, and 1,8-naphthyridinyl,

wherein

said carbocyclic and heterocyclic rings optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxy, halogen, nitro, cyano, carboxy, amino, N—(C 1-6 alkyl)amino, N-(hydroxy C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N—(C 1-6 acyl)amino, N—(C 1-6 alkoxycarbonyl)amino, N-(formyl)-N—(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl) amino (C 2-6 alkenyl) amino, N—(C 1-6 alkane)sulfonyl amino, N[N,N-di(C 1-6 alkyl)amino methylene]amino, C 1-6 alkylthio, C 1-6 alkanesulfonyl, sulfamoyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, pyrrolyl, imidazolyl, pyrazolyl, pyrrolidinyl, pyridyl, phenyl C 1-6 alkoxycarbonyl, thiazolyl optionally substituted by pyridyl, piperazinyl optionally substituted by C 1-6 alkyl or C 1-6 alkoxy and C 1-6 alkyl optionally substituted by mono-, di- or tri- halogen;

R 2 represents halogen, hydroxy, nitro, cyano, amino, N—(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N-(hydroxyC 1-6 alkyl)-N—(C 1-6 alkyl)amino, (C 2-6 )alkenyl, C 1-6 alkoxycarbonyl, aminocarbonyl, furyl, piperidino, morpholino, phenyl, pyrrolidinyl optionally substituted by N—(C 1-6 acyl)amino, or N—(C 1-6 alkyl)carbonylamino, piperidino optionally substituted by hydroxy, piperazinyl optionally substituted by C 1-6 alkyl, phenylC 1-6 alkyl, C 1-6 alkoxycarbonyl, or aminocarbonyl;

C 1-6 alkyl optionally substituted by amino, cyano, C 1-6 alkoxycarbonyl, morpholino, or mono-, di- or tri- halogen,

or

C 1-6 alkoxy optionally substituted by hydroxy, cyano, carboxy, C 1-6 alkoxy, C 1-6 acyl, C 1-6 alkoxycarbonyl, amino, N—(C 1-6 alkyl)amino, N—(C 1-6 -alkyl)aminocarbonyl, N,N-di(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)aminocarbonyl, aminocarbonyl, aminoC 1-6 alkylcarbonyl, N-(halo-benzyl)aminocarbonyl, hydroxy C 1-6 alkoxy, C 3-6 cycloalkyl, morpholino, morpholinocarbonyl, pyrrolidinyl, pyrrolyl, piperidino, phthalimidyl,

or

piperazinyl optionally substituted by benzyl;

R 3 represents hydrogen;

R 4 represents hydrogen;

R 5 represents hydrogen; and

R 6 represents hydrogen.

3. The method of claim 1 , wherein

X represents CR 5 R 6 or NH;

Y 1 represents N;

Y 2 and Y 3 represent CR 3 R 4 ;

Chemical bond between Y 2 —Y 3 represents a single bond

Z 4 represents CH;

Z 1 , Z 2 and Z 3 independently represent N, CH or CR 2 ;

R l represents cyclopropyl, cyclopentyl, cyclohexyl, 2-furyl, 3-furyl, imidazolyl, pyrimidinyl, pyridazinyl, piperazinyl, 1,2,3-thiadiazolyl, 1,3-benzothiazolyl, quinolyl, 3 H-imidazo[4,5-b]pyridinyl, 1H-pyrrol-2-yl optionally substituted by C 1-6 alkyl, 1H-pyrrol-3-yl optionally substituted by C 1-6 alkyl, pyrazolyl optionally substituted by 1 or 2 C 1-6 alkyl, isoxazolyl optionally substituted by 1 or 2 C 1-6 alkyl, 2-thienyl optionally substituted by chloro, nitro, cyano, or C 1-6 alkyl, 3-thienyl optionally substituted by chloro, nitro, cyano, or C 1-6 alkyl, piperidinyl optionally substituted by C 1-6 alkoxycarbonyl, or benzyloxycarbonyl, phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of fluoro, chloro, hydroxy, nitro, cyano, carboxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, amino, N—(C 1-6 alkyl)amino, N—(C 1-6 acyl)amino, N—(C 1-6 alkoxycarbonyl)amino, N,N-di(C 1-6 alkyl)amino, N-(formyl)-N—C 1-6 alkyl amino, C 1-6 alkylthio, C 1-6 alkanesulfonyl, sulfamoyl, pyrrolyl, imidazolyl, pyrazolyl, and piperazinyl optionally substituted by C 1-6 alkyl,

pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of chloro, hydroxy, carboxy, C 1-6 alkoxy, C 1-6 alkylthio, amino, N—(C 1-6 alkyl)amino, N-(hydroxyC 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N—(C 1-6 acyl)amino, N—(C 1-6 alkane)sulfonyl amino, N[N,N-di(C 1-6 alkyl)amino methylene]amino, and C 1-6 alkyl optionally substituted by tri halogen,

pyrazinyl optionally substituted by C 1-6 alkyl, 1,3-thiazolyl optionally substituted by 1 or 2 substituents selected from the group consisting of C 1-6 alkyl, pyridyl and N—(C 1-6 alkoxycrbonyl)amino,

indolyl optionally substituted by C 1-6 alkyl,

benzimidazolyl optionally substituted by C 1-6 alkyl or tri-halo C 1-6 alkyl,

1,2,3-benzotriazolyl optionally substituted by C 1-6 alkyl,

1,8-naphthyridinyl optionally substituted by C 1-6 alkyl optionally substituted by tri halogen,

C 1-6 alkyl optionally substituted by tri- halogen, phenyl, phenoxy, or thienyl,

or

C 1-6 alkoxy optionally substituted by phenyl, phenoxy, or thienyl;

R 2 represents fluoro, chloro, bromo, hydroxy, nitro, vinyl, cyano, amino, aminoacetoxy, N—(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N-(hydroxyC 1-6 alkyl)-N—(C 1-6 alkyl)amino, 2-furyl, piperidino, morpholino, phenyl, pyrrolidinyl optionally substituted by acetamido,

piperidino optionally substituted by hydroxy, piperazinyl optionally substituted by methyl, benzyl, C 1-6 alkoxycarbonyl, or aminocarbonyl,

C 1-6 alkyl optionally substituted by cyano, tri-fluoro, carboxy, methoxycarbonyl, aminocarbonyl, tert-butoxycarbonyl, tetrahydropyranyl, or morpholino, C 1-6 alkoxy optionally substituted by hydroxy, cyano, methoxy, methoxycarbonyl, tert-butoxycarbonyl, carboxy, aminoacetyl, dimethylamino, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, fluorobenzylaminocarbonyl, cyclopropyl, pyrrolidinyl, piperidino , tetrahydropyranyl, morpholino, morpholinocarbonyl, 2-oxo-1,3-oxazolidin-4-yl, phthalimid-N-yl, or hydroxy C 1-6 alkyleneoxy,

R 3 represents hydrogen;

R 4 represents hydrogen;

R 5 represents hydrogen; and

R 6 represents hydrogen.

4. The method of claim 1 , wherein

X represents CR 5 R 6 or NH;

Y l represents N;

Y 2 and Y 3 represent CR 3 R 4 ;

Chemical bond between Y 2 —Y 3 represents a single bond

Z 3 and Z 4 represent CH;

Z 1 and Z 2 independently represent CH or CR 2 ;

R 1 represents cyclopropyl, cyclopentyl, cyclohexyl, 2-furyl, 3-furyl, imidazolyl, 1H-pyrrol-2-yl, 1H-pyrrol-3-yl, pyrimidinyl, pyridazinyl, piperazinyl, 1,2,3-thiadiazolyl, 1,3-benzothiazolyl, quinolyl, 3H-imidazo[4,5-b]pyridinyl,

pyrrolyl optionally substituted by C 1-6 alkyl, pyrazolyl optionally substituted by 1 or 2 C 1-6 alkyl, isoxazolyl optionally substituted by 1 or 2 C 1-6 alkyl, 2-thienyl optionally substituted by chloro, nitro, cyano, or C 1-6 alkyl, 3-thienyl optionally substituted by chloro, nitro, cyano, or C 1-6 alkyl,

piperidinyl optionally substituted by C 1-6 alkoxycarbonyl, or benzyloxycarbonyl,

phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of fluoro, chloro, hydroxy, nitro, cyano, carboxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, amino, N—(C 1-6 alkyl)amino, N—(C 1-6 acyl)amino, N—(C 1-6 alkoxycabonyl)amino, N,N-di(C 1-6 alkyl)amino, N-(formyl)-N—C 1-6 alkyl amino, C 1-6 alkylthio, C 1-6 alkanesulfonyl, sulfamoyl, pyrrolyl, imidazolyl, pyrazolyl, and piperazinyl optionally substituted by C 1-6 alkyl,

pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of chloro, hydroxy, carboxy, C 1-6 alkoxy, C 1-6 alkylthio, amino, N—(C 1-6 alkyl)amino, N-(hydroxyC 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N—(C 1-6 acyl)amino, N—(C 1-6 alkane)sulfonyl amino, N[N,N-di(C 1-6 alkyl)amino methylene]amino, and C 1-6 alkyl optionally substituted by tri halogen,

pyrazinyl optionally substituted by C 1-6 alkyl, 1,3-thiazolyl optionally substituted by

1 or 2 substituents selected from the group consisting of C 1-6 alkyl, pyridyl and N—(C 1-6 alkoxycrbonyl)amino, indolyl optionally substituted by C 1-6 alkyl, benzimidazolyl optionally substituted by C 1-6 alkyl or tri-halo C 1-6 alkyl, 1,2,3-benzotriazolyl optionally substituted by C 1-6 alkyl, 1,8-naphthyridinyl optionally substituted by C 1-6 alkyl optionally substituted by tri halogen,

C 1-6 alkyl optionally substituted by tri- halogen, phenyl, phenoxy, or thienyl,

or

C 1-6 alkoxy substituted by phenyl, phenoxy, or thienyl;

R 2 represents fluoro, chloro, bromo, hydroxy, nitro, vinyl, cyano, amino, amino-acetoxy, N-(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N-(hydroxyC 1-6 alkyl)-N—(C 1-6 alkyl)amino, 2-furyl, piperidino, morpholino, phenyl,

pyrrolidinyl optionally substituted by acetamido,

piperidino optionally substituted by hydroxy,

piperazinyl optionally substituted by methyl, benzyl, C 1-6 alkoxycarbonyl, or aminocarbonyl,

C 1-6 alkyl optionally substituted by cyano tri-fluoro, carboxy, methoxycarbonyl, aminocarbonyl, tert-butoxycarbonyl, tetrahydropyranyl, or morpholino,

or

C 1-6 alkoxy optionally substituted by hydroxy, cyano, methoxy, methoxycarbonyl, tert-butoxycarbonyl, carboxy, aminoacetyl, dimethylamino, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, fluorobenzylaminocarbonyl, cyclopropyl, pyrrolidinyl, piperidino, tetrahydropyranyl, morpholino, morpholinocarbonyl, 2-oxo-1,3-oxazolidin-4-yl, phthalimid-N-yl, or hydroxy C 1-6 alkyleneoxy;

R 3 represents hydrogen;

R 4 represents hydrogen;

R 5 represents hydrogen; and

R 6 represents hydrogen.

5. The method of claim 1 , wherein

X represents CR 5 R 6 or NH;

Y 1 represents N;

Y 2 and Y 3 represent CR 3 R 4 ;

Chemical bond between Y 2 —Y 3 represents a single bond

Z 1 and Z 4 represent CH;

Z 2 and Z 3 independently represent CH or CR 2 ;

R l represents cyclopropyl, cyclopentyl, cyclohexyl, 2-furyl, 3-furyl, imidazolyl, 1H-pyrrol-2-yl, 1H-pyrrol-3-yl, pyrimidinyl, piperazinyl, pyridazinyl, 1,2,3-thiadiazolyl, 1,3-benzothiazolyl, quinolyl, 3H-imidazo[4,5-b]pyridinyl,

pyrrolyl optionally substituted by C 1-6 alkyl,

pyrazolyl optionally substituted by 1 or 2 C 1-6 alkyl,

isoxazolyl optionally substituted by 1 or 2 C 1-6 alkyl,

2-thienyl optionally substituted by chloro, nitro, cyano, or C 1-6 alkyl,

3-thienyl optionally substituted by chloro, nitro, cyano, or C 1-6 alkyl,

piperidinyl optionally substituted by C 1-6 alkoxycarbonyl, or benzyloxycarbonyl,

phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of fluoro, chloro, hydroxy, nitro, cyano, carboxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, amino, N—(C 1-6 alkyl)amino, N—(C 1-6 acyl)amino, N—(C 1-6 alkoxycabonyl)amino, N,N-di(C 1-6 alkyl)amino, N-(formyl)-N—C 1-6 alkyl amino, C 1-6 alkylthio, C 1-6 alkanesulfonyl, sulfamoyl, pyrrolyl, imidazolyl, pyrazolyl, and piperazinyl optionally substituted by C 1-6 alkyl,

pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of chloro, hydroxy, carboxy, C 1-6 alkoxy, C 1-6 alkylthio, amino, N—(C 1-6 alkyl)amino, N-(hydroxyC 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N—(C 1-6 acyl)amino, N—(C 1-6 alkane)sulfonyl amino, N[N,N-di(C 1-6 alkyl)amino methylene]amino, C 1-6 alkoxyphenylC 1-6 alkoxy, and C 1-6 alkyl optionally substituted by tri halogen,

pyrazinyl optionally substituted by C 1-6 alkyl,

1,3-thiazolyl optionally substituted by 1 or 2 substituents selected from the group consisting of C 1-6 alkyl, pyridyl and N—(C 1-6 alkoxycrbonyl)amino, indolyl optionally substituted by C 1-6 alkyl,

benzimidazolyl optionally substituted by C 1-6 alkyl or tri-halo C 1-6 alkyl,

1,2,3-benzotriazolyl optionally substituted by C 1-6 alkyl, 1,8-naphthyridinyl optionally substituted by C 1-6 alkyl optionally substituted by tri halogen,

C 1-6 alkyl optionally substituted by tri- halogen, phenyl, phenoxy, or thienyl,

or

C 1-6 alkoxy substituted by phenyl, phenoxy, or thienyl;

R 2 represents fluoro, chloro, bromo, hydroxy, nitro, vinyl, cyano, amino, aminoacetoxy, N—(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, N-(hydroxyC 1-6 alkyl)-N—(C 1-6 alkyl)amino, 2-furyl, piperidino, morpholino, phenyl,

pyrrolidinyl optionally substituted by acetamido, piperidino optionally substituted by hydroxy, piperazinyl optionally substituted by methyl, benzyl, C 1-6 alkoxycarbonyl, or aminocarbonyl,

C 1-6 alkyl optionally substituted by cyano, tri-fluoro, carboxy, methoxycarbonyl,

aminocarbonyl, tert-butoxycarbonyl, tetrahydropyranyl, or morpholino,

or

C 1-6 alkoxy optionally substituted by hydroxy, cyano, methoxy, methoxycarbonyl, tert-butoxycarbonyl, carboxy, aminoacetyl, dimethylamino, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, fluorobenzylaminocarbonyl, cyclopropyl, pyrrolidinyl, piperidino, tetrahydropyranyl, morpholino, morpholinocarbonyl, tetrazolyl, 2-oxo-1,3-oxazolidin-4y1, phthalimid-N-yl, or hydroxy C 1-6 alkyleneoxy;

R 3 represents hydrogen;

R 4 represents hydrogen;

R 5 represents hydrogen; and

R 6 represents hydrogen.

6. The method of claim 1 , wherein

X represents CR 5 R 6 or NH;

Y 1 represents N;

Y 2 and Y 3 represent CR 3 R 4 ;

Chemical bond between Y 2 —Y 3 represents a single bond

Z 3 and Z 4 represent CH;

Z 1 and Z 2 independently represent CH or CR 2 ;

R l represents 3H-imidazo[4,5-b]pyridinyl, benzimidazolyl

pyridyl optionally substituted by hydroxy, amino, acetamido, methoxybenzyloxy or methylsulfonylamino,

or

1,3-thiazolyl optionally substituted by 1 or 2 methyl;

R 2 represents fluoro, chloro, bromo, morpholino, piperazinyl, methylpiperazinyl, methyl, tri-fluoro methyl, or C 1-6 alkoxy optionally substituted by hydroxy, cyano, carboxy, dimethylaminocarbonyl, tetrahydropyranyl, morpholino, morpholinocarbonyl, tetrazolyl, or phthalimid-N-yl;

R 3 represents hydrogen;

R 4 represents hydrogen;

R 5 represents hydrogen; and

R 6 represents hydrogen.

7. The method of claim 1 , wherein

X represents CR 5 R 6 or NH;

Y l represents N;

Y 2 and Y 3 represent CR 3 R 4 ;

Chemical bond between Y 2 —Y 3 represents a single bond;

Z 1 , Z 3 and Z 4 represent CH;

Z 2 represents CR 2 ;

R l represents 3H-imidazo[4,5-b]pyridinyl, benzimidazolyl pyridyl optionally substituted by hydroxy, amino, acetamido, methoxybenzyloxy or methylsulfonylamino,

or

1,3-thiazolyl optionally substituted by 1 or 2 methyl,

R 2 represents fluoro, chloro, bromo, morpholino, piperazinyl, methylpiperazinyl, methyl, tri-fluoro methyl, C 1-6 alkoxy optionally substituted by hydroxy, cyano, carboxy, dimethylaminocarbonyl, tetrahydropyranyl, morpholino, morpholinocarbonyl, tetrazolyl, or phthalimid-N-yl;

R 3 represents hydrogen;

R 4 represents hydrogen;

R 5 represents hydrogen; and

R 6 represents hydrogen.

8. The method of claim 1 , wherein said compound is selected from the group consisting of:

N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide;

2-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1-pyridin-3-ylethylenol;

N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide;

6-(acetamido)-N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide;

N-{5-[2-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1-hydroxyvinyl]pyridin-2-yl}acetamide;

2-({5-[2-hydroxy-2-pyridin-3-ylvinyl]-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl}oxy)-N,N-dimethylacetamide;

2-[7-methoxy-8-(tetrahydro-2H-pyran-2-ylmethoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]-1-pyridin-3-ylethylenol;

2-[8-(2-hydroxyethoxy)-7-methoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl]-1-pyridin-3-ylethylenol;

({5-[2-hydroxy-2-pyridin-3-ylvinyl]-7-methoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-8-yl}oxy)acetic acid;

4-({5-[2-hydroxy-2-pyridin-3-ylvinyl]-7-methoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-8-yl}oxy)butanoic acid;

({5-[2-hydroxy-2-pyridin-3-ylvinyl]-7-methoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-8-yl}oxy)acetonitrile;

2-[7-methoxy-8-(2H-tetrazol-5-ylmethoxy)-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl]-1-pyridin-3-ylethylenol;

2-[7-methoxy-8-(4-morpholin-4-yl-4-oxobutoxy)-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl]-1-pyridin-3-ylethylenol;

5-[1-hydroxy-2-(8-morpholin-4-yl-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)vinyl]pyridin-3-ol ;

N-(2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)-5-hydroxynicotinamide;

6-(acetamido)-N-(7,9-dimethoxy-8-methyl-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)nicotinamide;

N-(8 ,9-dimethoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)-5-hydroxynicotinamide;

5-hydroxy-N-(7-methoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)nicotinamide;

N-(7, 8-dimethoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)-5-[(4-methoxybenzyl)oxy]nicotinamide;

N-(7, 8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-5-hydroxynicotinamide;

5-hydroxy-N-[8-(trifluoromethyl)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]nicotinamide;

N-{8-[3-(1 ,3-dioxo-1 ,3-dihydro-2H-isoindo1-2-yl)propoxy]-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl}nicotinamide;

N-(7-bromo-8-methoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)nicotinamide;

6-amino-N-(8-methoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)nicotinamide;

1-(1H-benzimidazol-5-yl)-2-(8,9-dimethoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)ethylenol;

2-(8,9-dimethoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)-1-(2,4-dimethyl-1 ,3-thiazol-5-yl)ethylenol;

N-(9-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide;

N-(8-bromo-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)nicotinamide;

N-(8-bromo-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide;

N-(8-methoxy-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide;

N-(8-methyl-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide;

N-[8-(trifluoromethyl)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]-1H-benzimidazole-5-carboxamide;

N-(7-fluoro-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide;

N-(7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide;

N-(8-chloro-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide;

6-(acetamido)-N-(8-morpholin-4-yl-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)nicotinamide;

1-(1H-benzimidazol-5-yl)-2-(8-morpholin-4-yl-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)ethylenol;

N-{5-[1-hydroxy-2-(8-morpholin-4-yl-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)vinyl]pyridin-2-yl}acetamide;

6-methyl-N-(8-morpholin-4-yl-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl)nicotinamide;

1-(1H-benzimidazol-5-yl)-2[8-(4-methylpiperazin-1-yl)-2,3-dihydroimidazo[1 ,2-c]quinazolin-5-yl]ethylenol;

N-(2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-3H-imidazo[4,5-b]pyridine-6-carboxamide;

N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-3H-imidazo[4,5-b]pyridine-6-carboxamide;

N-[7-(trifluoromethyl)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]-1H-benzimidazole-5-carboxamide;

N-(7,9-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide;

N-{5[2-(7,9-dimethoxy-8-methyl-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1-hydroxyvinyl]pyridin-2-yl}acetamide;

N-{5[2-(7-bromo-9-methyl-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1-hydroxyvinyl]pyridin-2-yl}acetamide; and

2-(8,9-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1-pyridin-3-ylethylenol.

9. The method of claim 1 , wherein the compound is administered for treating or controlling asthma, rhinitis, allergic diseases, or an autoimmune pathology.

10. The method of claim 4 , wherein the compound is administered for treating or controlling asthma, rhinitis, allergic diseases, or an autoimmune pathology.

11. The method of claim 6 , wherein the compound is administered for treating or controlling asthma, rhinitis, allergic diseases, or an autoimmune pathology.

12. The method of claim 8 , wherein the compound is administered for treating or controlling asthma, rhinitis, allergic diseases, or an autoimmune pathology.

13. The method of claim 1 , wherein the compound is administered for treating or controlling diabetes, cancer, or myocardial contractility disorders.

14. The method of claim 4 , wherein the compound is administered for treating or controlling diabetes, cancer, or myocardial contractility disorders.

15. The method of claim 6 , wherein the compound is administered for treating or controlling diabetes, cancer, or myocardial contractility disorders.

16. The method of claim 8 , wherein the compound is administered for treating or controlling diabetes, cancer, or myocardial contractility disorders.

Assignments (9)