Patent ID: 6818640
Filing Date: 2004-11-16
Classification: A61P,C07D

Abstract:
A compound of the formula (II): whereinR1 is trimethylene optionally substituted C1-C10 alkyl, C2-C10 alkylene, C3-C7 cycloalkyl, C1-C10 alkoxy, C1-C10 alkylthio, C1-C10 alkylamino, acylamino, C6-C14 aryl, C6-C14 aryloxy, halogen, hydroxy, amino, nitro, C1-C10 alkylsulfonyl, C6-C14 arylsulfonyl, cyano, hydroxyamino, carboxy, C1-C10 alkoxycarbonyl, acyl, C6-C14 aryl-C1-C10 alkyl, mercapto, hydrazine, amino, or guanidino; R2 is a group of the formula: â€”C(&boxH;R5)â€”R6 wherein: R5 is O or S; R6 is: C1-C10 alkoxy; C1-C10 alkylthio; C6-C14 aryl-C1-C10 alkyloxy optionally substituted with (i) C1-C10 alkyl, (ii) C1-C10 alkoxy, (iii) C1-C10 alkylthio, (iv) amino optionally substituted with C1-C10 alkyl or acyl, (v) C6-C14 aryl optionally substituted with C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylthio, amino optionally substituted with C1-C10 alkyl or acyl, C6-C14 aryl, C6-C14 aryloxy, C3-C7 cycloalkyl, halogen, hydroxy, nitro, C1-C10 alkyl substituted with one or more halogen, C1-C10 alkoxy substituted with one or more halogen, carbamoyl optionally substituted with C1-C10 alkyl or acyl, carboxy, C1-C10 alkoxy-carbonyl, C1-C10 alkylsulfinyl, C1-C10 alkylsulfonyl, C1-C10 alkyloxy-C1-C10 alkyl, C1-C10 alkylthio-C1-C10 alkyl, C1-C10 alkyl substituted with amino optionally substituted with C1-C10 alkyl or acyl, C1-C10 alkyloxy-C1-C10 alkyloxy, C1-C9 heteroaryl having one to four nitrogen, oxygen, and/or sulfur atoms, C1-C9 non-aromatic ring having one to four nitrogen, oxygen, and/or sulfur atoms, C1-C10 alkoxyimino-C1-C10 alkyl, formyl, C1-C10 alkylcarbonyl, C6-C14 arylcarbonyl, C1-C9 non-aromatic heterocyclic group selected from the group consisting of 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidino, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-imidazolinyl, 2-imidazolinyl, 4-imidazolinyl, 1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1-pyrazolinyl, 3-pyrazolinyl, 4-pyrazolinyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, piperdino, 2-piperidyl, 3-piperidyl, 4-piperidyl, piperazino, 2-piperazinyl, 2-morpholinyl, 3-morpholinyl, morpholino, and tetrahydropyranyl, C6-C14 arylsulfonyl, cyano, hydroxyimino, C6-C14 aryl-C1-C10 alkyl, mercapto, hydrazino, amidino, guanidino, isocyano, isocyanato, thiocyanato, isothiocyanato, sulfamoyl, formyloxy, formyl substituted with halogen, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfoamino, azido, ureido, amidino, guanidino, oxo, thioxo, (vi) C6-C14 aryloxy optionally substituted with C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylthio, amino optionally substituted with C1-C10 alkyl or acyl, C6-C14 aryl, C6-C14 aryloxy, C3-C7 cycloalkyl, halogen, hydroxy, nitro, C1-C10 alkyl substituted with one or more halogen, C1-C10 alkoxy substituted with one or more halogen, carbamoyl optionally substituted with C1-C10 alkyl or acyl, carboxy, C1-C10 alkoxy-carbonyl, C1-C10 alkylsulfinyl, C1-C10 alkylsulfonyl, C1-C10 alkyloxy-C1-C10 alkyl, C1-C10 alkylthio-C1-C10 alkyl, C1-C10 alkyl substituted with amino optionally substituted with C1-C10 alkyl or acyl, C1-C10 alkyloxy-C1-C10 alkyloxy, C1-C9 heteroaryl having one to four nitrogen, oxygen, and/or sulfur atoms, C1-C9 non-aromatic ring having one to four nitrogen, oxygen, and/or sulfur atoms, C1-C10 alkoxyimino-C1-C10 alkyl, formyl, C1-C10 alkylcarbonyl, C6-C14 arylcarbonyl, C1-C9 non-aromatic heterocyclic group selected from the group consisting of 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidino, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-imidazolinyl, 2-imidazolinyl, 4-imidazolinyl, 1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1-pyrazolinyl, 3-pyrazolinyl, 4-pyrazolinyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, piperdino, 2-piperidyl, 3-piperidyl, 4-piperidyl, piperazino, 2-piperazinyl, 2-morpholinyl, 3-morpholinyl, morpholino, and tetrahydropyranyl, C6-C14 arylsulfonyl, cyano, hydroxyimino, C6-C14 aryl-C1-C10 alkyl, mercapto, hydrazino, amidino, guanidino, isocyano, isocyanato, thiocyanato, isothiocyanato, sulfamoyl, formyloxy, formyl substituted with halogen, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfoamino, azido, ureido, amidino, guanidino, oxo, thioxo, (vii) C3-C7 cycloalkyl, halogen, hydroxy, nitro, C1-C10 alkyl substituted with one or more halogen, C1-C10 alkoxy substituted with one or more halogen, carbamoyl optionally substituted with C1-C10 alkyl or acyl, carboxy, C1-C10 alkoxy-carbonyl, C1-C10 alkylsulfinyl, C1-C10 alkylsulfonyl, C1-C10 alkyloxy-C1-C10 alkyl, C1-C10 alkylthio-C1-C10 alkyl, C1-C10 alkyl substituted with amino optionally substituted with C1-C10 alkyl or acyl, C1-C10 alkyloxy-C1-C10 alkyloxy, C1-C10 alkylthio-C1-C10 alkyloxy, (viii) C1-C9 heteroaryl having one to four nitrogen, oxygen, and/or sulfur atoms, optionally substituted with C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylthio, amino optionally substituted with C1-C10 alkyl or acyl, C6-C14 aryl, C6-C14 aryloxy, C3-C7 cycloalkyl, halogen, hydroxy, nitro, C1-C10 alkyl substituted with one or more halogen, C1-C10 alkoxy substituted with one or more halogen, carbamoyl optionally substituted with C1-C10 alkyl or acyl, carboxy, C1-C10 alkoxy-carbonyl, C1-C10 alkylsulfinyl, C1-C10 alkylsulfonyl, C1-C10 alkyloxy-C1-C10 alkyl, C1-C10 alkylthio-C1-C10 alkyl, C1-C10 alkyl substituted with amino optionally substituted with C1-C10 alkyl or acyl, C1-C10 alkyloxy-C1-C10 alkyloxy, C1-C9 heteroaryl having one to four nitrogen, oxygen, and/or sulfur atoms, C1-C9 non-aromatic ring having one to four nitrogen, oxygen, and/or sulfur atoms, C1-C10 alkoxyimino-C1-C10 alkyl, formyl, C1-C10 alkylcarbonyl, C6-C14 arylcarbonyl, C1-C9 non-aromatic heterocyclic group, selected from the group consisting of 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidino, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-imidazolinyl, 2-imidazolinyl, 4-imidazolinyl, 1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1-pyrazolinyl, 3-pyrazolinyl, 4-pyrazolinyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, piperdino, 2-piperidyl, 3-piperidyl, 4-piperidyl, piperazino, 2-piperazinyl, 2-morpholinyl, 3-morpholinyl, morpholino, and tetrahydropyranyl, C6-C14 arylsulfonyl, cyano, hydroxyimino, C6-C14 aryl-C1-C10 alkyl, mercapto, hydrazino, amidino, guanidino, isocyano, isocyanato, thiocyanato, isothiocyanato, sulfamoyl, formyloxy, formyl substituted with halogen, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfoamino, azido, ureido, amidino, guanidino, oxo, thioxo, (ix) C1-C9 nonaromatic ring having one to four nitrogen, oxygen, and/or sulfur atoms, optionally substituted with C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylthio, amino optionally substituted with C1-C10 alkyl or acyl, C6-C14 aryl, C6-C14 aryloxy, C3-C7 cycloalkyl, halogen, hydroxy, nitro, C1-C10 alkyl substituted with one or more halogen, C1-C10 alkoxy substituted with one or more halogen, carbamoyl optionally substituted with C1-C10 alkyl or acyl, carboxy, C1-C10 alkoxy-carbonyl, C1-C10 alkylsulfinyl, C1-C10 alkylsulfonyl, C1-C10 alkyloxy-C1-C10 alkyl, C1-C10 alkylthio-C1-C10 alkyl, C1-C10 alkyl substituted with amino optionally substituted with C1-C10 alkyl or acyl, C1-C10 alkyloxy-C1-C10 alkyloxy, C1-C9 heteroaryl having one to four nitrogen, oxygen, and/or sulfur atoms, C1-C9 non-aromatic ring having one to four nitrogen, oxygen, andlor sulfur atoms, C1-C10 alkoxyimino-C1-C10 alkyl, formyl, C1-C10 alkylcarbonyl, C6-C14 arylcarbonyl, C1-C9 non-aromatic heterocyclic group selected from the group consisting of 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidino, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-imidazolinyl, 2-imidazolinyl, 4imidazolinyl, 1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1-pyrazolinyl, 3-pyrazolinyl, 4-pyrazolinyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, piperdino, 2-piperidyl, 3-piperidyl, 4-piperidyl, piperazino, 2-piperazinyl, 2-morpholinyl, 3-morpholinyl, morpholino, and tetrahydropyranyl, C6-C14 arylsulfonyl, cyano, hydroxyimino, C6-C14 aryl-C1-C10 alkyl, mercapto, hydrazino, amidino, guanidino, isocyano, isocyanato, thiocyanato, isothiocyanato, sulfamoyl, formyloxy, formyl substituted with halogen, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfoamino, azido, ureido, amidino, guanidino, oxo, thioxo, (x) C1-C10 alkoxyimino-C1-C10 alkyl, (xi) formyl, (xii) C1-C10 alkylcarbonyl, (xiii) C6-C14 arylcarbonyl, optionally substituted with C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylthio, amino optionally substituted with C1-C10 alkyl or acyl, C6-C14 aryl, C6-C14 aryloxy, C3-C7 cycloalkyl, halogen, hydroxy, nitro, C1-C10 alkyl substituted with one or more halogen, C1-C10 alkoxy substituted with one or more halogen, carbamoyl optionally substituted with C1-C10 alkyl or acyl, carboxy, C1-C10 alkoxy-carbonyl, C1-C10 alkylsulfinyl, C1-C10 alkylsulfonyl, C1-C10 alkyloxy-C1-C10 alkyl, C1-C10 alkylthio-C1-C10 alkyl, C1-C10 alkyl substituted with amino optionally substituted with C1-C10 alkyl or acyl, C1-C10 alkyloxy-C1-C10 alkyloxy, C1-C9 heteroaryl having one to four nitrogen, oxygen, and/or sulfur atoms, C1-C9 non-aromatic ring having one to four nitrogen, oxygen, and/or sulfur atoms, C1-C10 alkoxyimino-C1-C10 alkyl, formyl, C1-C10 alkylcarbonyl, C6-C14 arylcarbonyl, C1-C9 non-aromatic heterocyclic selected from the group consisting of 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidino, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-imidazolinyl, 2-imidazolinyl, 4-imidazolinyl, 1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1-pyrazolinyl, 3-pyrazolinyl, 4-pyrazolinyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, piperdino, 2-piperidyl, 3-piperidyl, 4-piperidyl, piperazino, 2-piperazinyl, 2-morpholinyl, 3-morpholinyl, morpholino, and tetrahydropyranyl, C6-C14 arylsulfonyl cyano, hydroxyimino, C6-C14 aryl-C1-C10 alkyl, mercapto, hydrazino, amidino, guanidino, isocyano, isocyanato, thiocyanato, isothiocyanato, sulfamoyl, formyloxy, formyl substituted with halogen, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfoamino, azido, ureido, amidino, guanidino, oxo, thioxo, (xiv) C1-C9 non-aromatic heterocyclic group selected from the group consisting of 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidino, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-imidazolinyl, 2-imidazolinyl, 4-imidazolinyl, 1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1-pyrazolinyl, 3-pyrazolinyl, 4-pyrazolinyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, piperdino, 2-piperidyl, 3-piperidyl, 4-piperidyl, piperazino, 2-piperazinyl, 2-morpholinyl, 3-morpholinyl, morpholino, and tetrahydropyranyl, optionally substituted with C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylthio, amino optionally substituted with C1-C10 alkyl or acyl, C6-C14 aryl, C6-C14 aryloxy, C3-C7 cycloalkyl, halogen, hydroxy, nitro, C1-C10 alkyl substituted with one or more halogen, C1-C10 alkoxy substituted with one or more halogen, carbamoyl optionally substituted with C1-C10 alkyl or acyl, carboxy, C1-C10 alkoxy-carbonyl, C1-C10 alkylsulfinyl, C1-C10 alkylsulfonyl, C1-C10 alkyloxy-C1-C10 alkyl, C1-C10 alkylthio-C1-C10 alkyl, C1-C10 alkyl substituted with amino optionally substituted with C1-C10 alkyl or acyl, C1-C10 alkyloxy-C1-C10 alkyloxy, C1-C9 heteroaryl having one to four nitrogen, oxygen, and/or sulfur atoms, C1-C9 non-aromatic ring having one to four nitrogen, oxygen, and/or sulfur atoms, C1-C10 alkoxyimino-C1-C10 alkyl, formyl, C1-C10 alkylcarbonyl, C6-C14 arylcarbonyl, C1-C9 non-aromatic heterocyclic group selected from the group consisting of 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidino, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-imidazolinyl, 2-imidazolinyl, 4-imidazolinyl, 1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1-pyrazolinyl, 3-pyrazolinyl, 4-pyrazolinyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, piperdino, 2-piperidyl, 3-piperidyl, 4-piperidyl, piperazino, 2-piperazinyl, 2-morpholinyl, 3-morpholinyl, morpholino and tetrahydropyranyl, C6-C14 arylsulfonyl, cyano, hydroxyimino, C6-C14 aryl-C1-C10 alkyl, mercapto, hydrazino, amidino, guanidino, isocyano, isocyanato, thiocyanato, isothiocyanato, sulfamoyl, formyloxy, formyl substituted with halogen, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfoamino, azido, ureido, amidino, guanidino, oxo, thioxo, (xv) C6-C14 arylsulfonyl, (xvi) cyano, (xvii) hydroxyimino, (xviii) C6-C14 aryl-C1-C10 alkyl, (xix) mercapto, (xx) hydrazino, (xxi) amidino, (xxii) guanidino, (xxiii) isocyano, (xxiv) isocyanato, (xxv) thiocyanato, (xxvi) isothiocyanato, (xxvii) sulfamoyl, (xxviii) formyloxy, (xxix) formyl substituted with halogen, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfoamino, azido, ureido, amidino, guanidino, oxo, thioxo; C6-C14 aryl-C1-C10 alkylthio optionally substituted with the same substituents (i) to (xxix) as defined above for C6-C14 aryl-C1-C10 alkyloxy, C1-C10 alkoxy-C1-C10 alkyl; C1-C10 alkylthio-C1-C10 alkyl; or C1-C10 alkyl substituted with amino optionally substituted with C1-C10 alkyl or acyl; R3 and R4 each is independently hydrogen, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylthio, amino optionally substituted with C1-C10 alkyl or acyl, C6-C14 aryl optionally substituted with the same substituents (i) to (xxix) as defined above for C6-C14 aryl-C1-C10 alkyloxy; C6-C14 aryloxy optionally substituted with the same substituents (i) to (xxix) as defined above for C6-C14 aryl-C1-C10 alkyloxy, C3-C7 cycloalkyl, halogen, hydroxy, nitro, halo C1-C10 alkyl, halo C1-C10 alkoxy, carbamoyl optionally substituted C1-C10 alkyl or acyl, carboxy, C1-C10 alkoxycarbonyl, C1-C10 alkylsulfinyl, C1-C10 alkylsulfonyl, C1-C10 alkoxy-C1-C10 alkyl, C1-C10 alkylthio-C1-C10 alkyl, C1-C10 alkyl substituted with amino optionally substituted C1-C10 alkyl or acyl, C1-C10 alkoxy-C1-C10 alkoxy, C1-C10 alkylthio-C1-C10 alkoxy, C1-C9 heteroaryl having one to four nitrogen, oxygen, and/or sulfur atoms optionally substituted with the same substituents (i) to (xxix) as defined above for C6-C14 aryl-C1-C10 alkyloxy, C1-C9 non-aromatic heterocyclic group selected from the group consisting of 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidino, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-imidazolinyl, 2-imidazolinyl, 4-imidazolinyl, 1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1-pyrazolinyl, 3-pyrazolinyl, 4-pyrazolinyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, piperdino, 2-piperidyl, 3-piperidyl, piperazino, 2-piperazinyl, 2-morpholinyl, 3-morpholinyl, morpholino, and tetrahydropyranyl optionally substituted with the same substituents (i) to (xxix) as defined above for C6-C14 aryl-C1-C10 alkyloxy, C1-C10 alkoxyimino-C1-C10 alkyl, or a group of the formula: â€”C(&boxH;O)â€”RH wherein RH is hydrogen, C1-C10 alkyl, C6-C14 aryl optionally substituted with the same substituents (i) to (xxix) as defined above for C6-C14 aryl-C1-C10 alkyloxy or C1-C9 non-aromatic heterocyclic group selected from the group consisting of 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidino, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-imidazolinyl, 2-imidazolinyl, 4-imidazolinyl, 1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1-pyrazolinyl, 3-pyrazolinyl, 4-pyrazolinyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, piperdino, 2-piperidyl, 3-piperidyl, 4-piperidyl, piperazino, 2-piperazinyl, 2-morpholinyl, 3-morpholinyl, morpholino, and tetrahydropyranyl optionally substituted with the same substituents (i) to (xxix) as defined above for C6-C14 aryl-C1-C10 alkyloxy; or R3 and R4 taken together may form C2-C10 alkylenedioxy; m is an integer of 0 to 2; A is benzene optionally substituted with the same substituents (i) to (xxix) as defined above for C6-C14 aryl-C1-C10 alkyloxy, provided that when R5 is O and R6 is C1-C10 alkoxy, R1 is not unsubstituted trimethylene; a pharmaceutically acceptable salt thereof or a hydrate thereof.