Patent ID: 6537987
Filing Date: 2003-03-25
Classification: A61P,C07D

Abstract:
A compound of Formula I or the pharmaceutically acceptable cationic and anionic salts or stereoisomers thereof whereinX is oxy, thio, â€”S(O)â€” or â€”S(O)2â€”; Y is carbonyl or methylene; R1 and R2 are each independently hydrogen, halo, hydroxyl, trifluoromethyl, (C1-C4)alkyl, fluorinated (C1-C4)alkyl having from 1 to 9 fluorines, (C1-C4)alkoxy, fluorinated (C1-C4)alkoxy having from 1 to 9 fluorines, (C1-C4)alkylthio, (C1-C4)alkylsulfinyl, (C1-C4)alkylsulfonyl, phenyl, amino, mono-N- or di-N,N-(C1-C4)alkylamino, carboxyl, (C1-C4)alkoxycarbonyl, carbamoyl, mono-N- or di-N,N-(C1-C4)alkylcarbamoyl, (C1-C4)alkanoylamino, fluorinated (C1-C4)alkanoylamino having from 1 to 9 fluorines, (C1-C4)alkylsulfonylamino or fluorinated (C1-C4)alkylsulfonylamino having from 1 to 9 fluorines, (C1-C6)alkanoyl, (C1-C6)alkanoyl(C1-C6)alkyl, oxazolyl, thiazolyl, isoxazolyl, pyrazolyl or isothiazolyl wherein said preceding heterocycles are carbon linked or wherein R1 and R2 can be taken together to form a five, six or seven membered carbocyclic ring or can be taken together to form methylenedioxyl, ethylenedioxyl or propylenedioxyl and such rings formed by taking R1 and R2 together are fused at the 7 and 8 positions; R3, R9 and R10 are each independently hydrogen, halo, hydroxyl, trifluoromethyl, (C1-C4)alkyl, fluorinated (C1-C4)alkyl having from 1 to 9 fluorines, (C1-C4)alkoxy, fluorinated (C1-C4)alkoxy having from 1 to 9 fluorines, (C1-C4)alkylthio, (C1-C4)alkylsulfinyl, (C1-C4)alkylsulfonyl, phenyl, amino, mono-N- or di-N,N-(C1-C4)alkylamino, carboxyl, (C1-C4)alkoxycarbonyl, carbamoyl, mono-N- or di-N,N-(C1-C4)alkylcarbamoyl, (C1-C4)alkanoylamino, fluorinated (C1-C4)alkanoylamino having from 1 to 9 fluorines, (C1-C4)alkylsulfonylamino or fluorinated (C1-C4)alkylsulfonylamino having from 1 to 9 fluorines, (C1-C6)alkanoyl, (C1-C6)alkanoyl(C1-C6)alkyl, oxazolyl, thiazolyl, isoxazolyl, pyrazolyl or isothiazolyl wherein said preceding heterocycles are carbon linked or wherein R3 and R9 can be taken together to form methylenedioxyl, ethylenedioxyl or propylenedioxyl and such rings formed by taking R3 and R9 together are fused at the 2â€² and 3â€² or 3â€² and 4â€² positions; R4 is (C1-C7)alkyl, (C1-C7)alkenyl or (C3-C4)cycloalkylmethyl or said (C1-C7)alkyl, (C1-C7)alkenyl or (C3-C4)cycloalkylmethyl is optionally mono-, di-, or tri-substituted wherein the substituents are independently chosen from hydroxyl, oxo, (C1-C4)alkyl, amino, carboxy, thiol, (C1-C4)alkoxy, fluorinated (C1-C4)alkoxy having from 1 to 9 fluorines, (C1-C4)alkylthio, (C1-C4)alkylsulfinyl, (C1-C4)alkylsulfonyl, mono-N- or di-N,N-(C1-C4)alkylamino, mono-N- or di-N,N-(C1-C4)alkylaminocarbonyl, mono-N- or di-N,N-(C1-C4)alkylaminosulfonyl; or R4 is (C1-C7)alkyl substituted with 1 to 15 fluorines or (C3-C4)cycloalkylmethyl substituted with 1 to 9 fluorines; or R4 is het(C1-C6)alkyl wherein het is a 4-7 member saturated or unsaturated heterocycle containing independently one to three O, N or S atoms and said het is optionally mono-substituted with (C1-C4)alkyl, (C1-C4)alkoxy, hydroxyl, halo, amino or mono-N- or di-N,N-(C1-C4)alkylamino; Z is carboxyl, (C1-C4)alkoxycarbonyl, mono-N- or di-N,N-(C1-C4)alkylaminocarbonyl, aminocarbonyl, cyano, hydroxyaminocarbonyl, â€”C(O)N(H)SO2R5, tetrazol-5-yl, 4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl, tetrazol-5-yl-aminocarbonyl, 3-oxoisoxazolidin-4-yl-aminocarbonyl, N(R12)CONR13R14, N(R12)CO2(C1-C4)alkyl or N(R12)COR15; Z1 is H, carboxyl, hydroxyl, (C1-C4)alkoxy or (C1-C4)alkoxycarbonyl; R12, R13 and R14 are each independently H or (C1-C4)alkyl; R15 is (C1-C4)alkyl; R5 is amino or mono-N- or di-N,N-(C1-C4)alkylamino; or R5 is (C1-C4)alkyl optionally substituted with 1 to 9 fluorines, amino, mono-N- or di-N,N-(C1-C4)alkylamino, carboxyl, (C1-C4)alkoxycarbonyl, carbamoyl or mono-N- or di-N,N-(C1-C4)alkylcarbamoyl; or R5 is phenyl optionally mono- or di-substituted independently with methyl, methoxyl, fluoro, trifluoromethoxyl, carboxyl, (C1-C4)alkoxycarbonyl, methylthio, methylsulfinyl, methylsulfonyl, (C1-C4)alkylsulfonylamino or mono-N- or di-N,N-(C1-C4)alkylaminosulfonyl; or R5 is thiazolyl, isothiazolyl, thienyl, furyl, pyridinyl or any of said heterocycles optionally mono-substituted by carboxyl, or mono- or di-substituted with methyl; and T forms a four to seven membered mono-aza, saturated ring, said ring optionally containing thio or oxo and said ring optionally mono-substituted on carbon with hydroxyl, (C1-C4)alkoxy or carboxyl with the proviso that the compound of Formula I is not N-[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxyl-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetyl]piperidine-4-carboxylic acid.