Squalene synthetase inhibitor agents

A compound of Formula I

• or a pharmaceutically acceptable salt of said compound
• wherein A is phenyl or naphthyl, said phenyl or naphthyl optionally mono-, di- or tri-substituted independently with R3, R9 and R10;
• X is oxy or thio;
• Y is oxy, thio 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 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 e and f 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 a five, six or seven membered carbocyclic ring or can be taken together to form methylenedioxyl, ethylenedioxyl or propylenedioxyl ring;
• R4 is phenyl, (C1-C7)alkyl, (C1-C7)alkenyl or (C3-C4)cycloalkylmethyl wherein said phenyl, (C1-C7)alkyl, (C1-C7)alkenyl or (C3-C4)cycloalkylmethyl are optionally mono-, di-, or tri-substituted independently with 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, or 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, partially unsaturated or fully 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, aminocarbonyl, cyano, hydroxyaminocarbonyl, —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, N(R12)COR15,
• mono-N-or di-N,N-(C1-C6)alkylaminocarbonyl wherein each of said (C1-C6)alkyl is optionally mono- or di-substituted independently with V or V1 , or —C(O)N(H)—(C0-C4)alkyl-R20
• wherein said (C0-C4)alkyl may optionally be mono-substituted with carboxyl and
• wherein R20 is a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;
• wherein said R20 substituent is optionally mono-, di- or tri-substituted independently with halo, (C2-C6)alkenyl, (C1-C6)alkyl, hydroxy, (C1-C6)alkoxy, (C1-C4)alkylthio, amino, nitro, cyano, oxo, carboxy, (C1-C6)alkyloxycarbonyl, mono-N- or di-N,N-(C1-C6)alkylamino wherein said (C1-C6)alkyl substituent is optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C1-C6)alkoxy, (C1-C4)alkylthio, amino, nitro, cyano, oxo, carboxy, (C1-C6)alkyloxycarbonyl, mono-N- or di-N,N-(C1-C6)alkylamino, wherein said (C1-C6)alkyl substituent is also optionally substituted with from one to nine flourines;
• R12, R13 and R14 are each independently H or (C1-C4)alkyl;
• R15 is H or (C1-C4)alkyl;
• R5 is H, 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;
• 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 with carboxyl or mono- or di-substituted with methyl;
• T forms a four to seven membered mono- or di-aza, saturated ring, said ring optionally containing thio and said ring optionally mono-substituted on carbon with hydroxyl;
• and
• V and V1 are each independently hydrogen, hydroxyl, amino, mono-N- or di-N,N-(C1-C4)alkylamino, carbamoyl, mono-N- or di-N,N-(C1-C4)alkylcarbamoyl, carboxyl, (C1-C4)alkoxy, fluorinated (C1-C4)alkoxy having from 1 to 9 fluorines, (C1-C4)alkoxycarbonyl, aminocarbonyl, cyano, thiol, sulfamoyl, (C1-C4)alkylthio, (C1-C4)alkylsulfonyl, (C1-C4)alkylsulfinyl, (C1-C4)alkylsulfonylamino, fluorinated (C1-C4)alkylsulfonylamino having from 1 to 9 fluorines, mono-N- or di-N,N-(C1-C4)alkylaminosulfonyl, (C1-C4)alkanoylamino, fluorinated (C1-C4)alkanoylamino having from 1 to 9 fluorines, ureido, mono-N- or di-N,N-(C1-C4)alkyl ureido, imidazolyl, pyridyl, tetrazol-5-yl, 4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl, tetrazol-5-yl-aminocarbonyl, 3-oxoisoxazolidin-4-yl-aminocarbonyl or (C0-C6)alkyl said (C0-C6) alkyl optionally mono- or di-substituted independently with carboxyl or (C1-C4)alkoxycarbonyl.