Patent ID: 6579982
Filing Date: 2003-06-17
Classification: A61P,C07D

Abstract:
A compound of the formula wherein R1 is hydrogen, (C1-C4)perfluoroalkyl, (C1-C8)alkyl, (C3-C8)cycloalkyl, tetrahydrofuranyl, tetrahydropyranyl, N-methyl-3-azetidinyl, piperazinyl, piperidinyl, 1,3-oxazolidin-4-on-5-yl, 1,3-oxazolidin-2,4-dion-5-yl, 4,5-dihydro-1,2-oxazolidin-3-on-4-yl, 1,3-thiazolidin-4-on-5-yl, 1,3-thiazolidin-2,4-dion-5-yl, 1,3-imidazolidin-4-on-5-yl, 1,3-imidazolidin-2,4-dion-5-yl, 1,2-pyrazolidin-3-on-4-yl, tetrahydro-1,3-oxazin-4-on-5-yl, tetrahydro-1,3-oxazin-2,4-dion-5-yl, morpholinyl, morpholin-3-on-2-yl, morpholin-3,5-dion-2-yl, 2,3-dihydro-1,4-oxazin-3-on-2-yl, tetrahydro-1,3-thiazin-4-on-5-yl, tetrahydro-1,3-thiazin-2,4-dion-5-yl, thiomorpholinyl, thiomorpholin-3-on-2-yl, thiomorpholin-3,5-dion-2-yl, 2,3-dihydro-1,4-thiazin-3-on-2-yl, hexahydro-1,2-diazin-3-on-4-yl, 4,5-dihydro-2H-pyridazin-3-on-4-yl, hexahydro-1,3-diazin-2,4-dion-5-yl, piperazin-2-on-3-yl, piperazin-2,6-dion-3-yl, tetrahydro-1,3,4-thiadiazin-5-on-6-yl, 5,6-dihydro-1,3,4-thiadiazin-5-on-6-yl, 1,3,4-oxadiazin-5-on-6-yl, 5,6-dihydro-1,2,4-oxadiazin-5-on-6-yl, tetrahydro-1,2,4-oxadiazin-5-on-6-yl, 1,2,4-triazin-5-on-6-yl, tetrahydro-1,2,4-oxadiazin-5-on-6-yl, 5,6-dihydro-1-2,4-oxadiazin-5-on-6-yl, 1,2,4-oxadiazin-3,5-dion-6-yl, or 1,2,4-triazin-6-on-5-yl; wherein said (C1-C8)alkyl may optionally contain one to three heteroatoms independently selected from oxygen, >NR5 and sulfur; wherein said (C1-C8)alkyl or (C3-C8)cycloalkyl may also optionally be substituted by one to two substituents independently selected from (C1-C4)alkyl, (C6-C10)aryl, pyridyl, furyl, pyrroyl, thienyl, isothiazolyl, imidazoly, benzimidazolyl, tetrazolyl, pyrazinyl, pyrimidyl, quinolyl, isoquinolyl, benzofuryl, isobenzofuryl, benzothienyl, pyrazoly, indolyl, isoindolyl, purinyl, carbazolyl, isoxazolyl, thiazolyl, oxazolyl, benzthiazoly, benzoxazolyl, OH, NH2, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, (C3-C8)cycloalkylamino, (C3-C8)cycloalkyl(C1-C4)alkylamino, (C1-C4)alkoxy, â€”CONH2, â€”CONHR4, â€”CON(R4)2, (C3-C8)cycloakyl, tetrahydrofuranyl, tetrahydropyrany, N-methyl-3-azetidinyl, piperazinyl, piperidinyl, 1,3-oxazolidin-4-on-5-yl, 1,3-oxazolidin-2,4-dion-5-yl, 4,5-dihydro-1,2-oxazolidin-3-on-4-yl, 1,3-thiazolidin-4-on-5-yl, 1,3-thiazolidin-2,4-dion-5-yl, 1,3-imidazolidin-4-on-5-yl, 1,3-imidazolidin-2,4-dion-5-yl, 1,2-pyrazolidin-3-on-4-yl, tetrahydro-1,3-oxazin-4-on-5-yl, tetrahydro-1,3-oxazin-2,4-dion-5-yl, morpholinyl, morpholin-3-on-2-yl, morpholin-3,5-dion-2-yl, 2,3-dihydro-1,4-oxazin-3-on-2-yl, tetrahydro-1,3-thiazin-4-on-5-yl, tetrahydro-1,3-thiazin-2,4-dion-5-yl, thiomorpholinyl, thiomorpholin-3-on-2-yl, thiomorpholin-3,5-dion-2-yl, 2,3-dihydro-1,4-thiazin-3-on-2-yl, hexahydro-1,2-diazin-3-on-4-yl, 4,5-dihydro-2H-pyridazin-3-on-4-yl, hexahydro-1,3-diazin-2,4-dion-5-yl, piperazin-2-on-3-yl, or piperazin-2,6-dion-3-yl; R2 and R3 are hydrogen; X is selected from the group consisting of oxygen, sulfur, >SO2, >S&boxH;O, >NR4, â€”CH2Oâ€”, â€”OCH2â€”, â€”CH2Sâ€”, â€”CH2(S&boxH;O)â€”, â€”CH2SO2â€”, â€”SCH2â€”, â€”SOCH2â€”, â€”SO2CH2â€”, â€”(R4)CH2â€”, â€”CH2N(R4)â€”, â€”(R4)SO2â€” and â€”SO2N(R4)â€”; R4 wherever it occurs is independently selected from hydrogen and (C1-C4)alkyl; R5 wherever it occurs is independently selected from hydrogen, (C1-C4)alkyl, (C6-C10)aryl, pyridyl, furyl, pyrroyl, thienyl, isothiazolyl, imidazolyl, benzimidazolyl, tetrazolyl, pyrazinyl, pyrimidy, quinolyl, isoquinolyl, benzofuryl, isobenzofuryl, benzothienyl, pyrazolyl, indolyl, isoindolyl, purinyl, carbazolyl, isoxazolyl, thiazolyl, oxazolyl, benzthiazolyl, benzoxazolyl, OH, â€”CONH2, â€”CONHR4, â€”CON(R4)2 and (C3-C8)cycloalkyl; Y is selected from the group consisting of a bond, oxygen, sulfur, >SO2, >S&boxH;O, >NH, â€”CH2â€”, â€”CH2Oâ€”, â€”OCH2â€”, â€”CH2Sâ€”, â€”CH2(S&boxH;O)â€”, â€”CH2SO2â€”, â€”SCH2â€”, â€”SOCH2â€”, â€”SO2CH2â€”, â€”NHCH2â€”, â€”CH2NHâ€”, â€”2CH2â€”, â€”CH&boxH;CHâ€”, â€”NHSO2â€” â€”SO2NHâ€”; Ar1 is (C6-C10)aryl, pyridyl, furyl, pyrroyl, thienyl, isothiazolyl, imidazolyl, benzimidazolyl, tetrazolyl, pyrazinyl, pyrimidyl, quinoly, isoquinolyl, benzofuryl, isobenzofuryl, benzothienyl, pyrazolyl, indolyl, isoindolyl, purinyl, carbazolyl, isoxazolyl, thiazolyl, oxazolyl, benzthiazolyl or benzoxazolyl; and Z is (C6-C10)aryl, (C3-C8)cycloalkyl, (C3-C8)cycloalky(C1-C4)alkyl, pyridyl, furyl, pyrroyl, isothiazolyl, imidazolyl, benzimidazolyl, tetrazolyl, pyrazinyl, pyrimidyl, quinolyl, isoquinolyt, benzofuryl, isobenzofuryl, benzothienyl, pyrazolyl, indolyl, isoindolyl, purinyl, carbazolyl, isoxazolyl, thiazolyl, oxazolyl, benzthiazolyl or benzoxazolyl; wherein said (C3-C8)cycloalkyl moiety of said (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C4)alkyl may optionally be replaced by tetrahydrofuranyl, tetrahydropyranyl, N-methyl-3-azetidinyl, piperazinyl, piperidinyl, 1,3-oxazolidin-4-on-5-yl, 1,3-oxazolidin-2,4-dion-5-yl, 4,5-dihydro-1,2-oxazolidin-3-on-4-yl, 1,3-thiazolidin-4-on-5-yl, 1,3-thiazolidin-2,4-dion-5-yl, 1,3-imidazolidin-4-on-5-yl, 1,3-imidazolidin-2,4-dion-5-yl, 1,2-pyrazolidin-3-on-4-yl, tetrahydro-1,3-oxazin-4-on-5-yl, tetrahydro-1,3-oxazin-2,4-dion-5-yl, morpholinyl, morpholin-3-on-2-yl, morpholin-3,5-dion-2-yl, 2,3-dihydro-1,4-oxazin-3-on-2-yl, tetrahydro-1,3-thiazin-4-on-5-yl, tetrahydro-1,3-thiazin-2,4-dion-5-yl, thiomorpholinyl, thiomorpholin-3-on-2-yl, thiomorpholin-3,5-dion-2-yl, 2,3-dihydro-1,4-thiazin-3-on-2-yl, hexahydro-1,2-diazin-3-on-4-yl, 4,5-dihydro-2H-pyridazin-3-on-4-yl, hexahydro-1,3-diazin-2,4-dion-5-yl, piperazin-2-on-3-yl, piperazin-2,6-dion-3-yl, tetrahydro-1,3,4-thiadiazin-5-on-6-yl, 5,6-dihydro-1,3,4-thiadiazin-5-on-6-yl, 1,3,4-oxadiazin-5-on-6-yl, 5,6-dihydro-1,2,4-oxadiazin-5-on-6-yl, tetrahydro-1,2,4-oxadiazin-5-on-6-yl, 1,2,4-triazin-5-on-6-yl, tetrahydro-1,2,4-oxadiazin-5-on-6-yl, 5,6-dihydro-1,2,4-oxadiazin-5-on-6-yl, 1,2,4-oxadiazin-3,5-dion-6-yl, or 1,2,4-triazin-6-on-5-yl; Ar1 and Z may be optionally substituted on any of the ring carbon atoms capable of forming an additional bond by one to three substituents independently selected from F, Cl, Br, CN, OH, (C1-C4)alkyl, (C1-C4)perfluoroalkyl, (C1-C4)perfluoroalkyloxy, (C1-C4)alkyloxy, and (C3-C8)cycloalkyloxy; or a pharmaceutically acceptable salt thereof.