Substituted N-( indole-2-carbonyl-) amides and derivatives as glycogen phosphorylase inhibitors

A compound of Formula I

• and the pharmaceutically acceptable salts and prodrugs thereof wherein
• the dotted line ( - - - ) is an optional bond;
• A is —C(H)═, —C((C1-C4)alkyl)= or —C(halo)= when the dotted line ( - - - ) is a bond, or A is methylene or —CH((C1-C4)alkyl)- when the dotted line ( - - - ) is not a bond;
• R1, R10 or R11 are each independently H, halo, 4-, 6- or 7-nitro, cyano, (C1-C4) alkyl, (C1-C4) alkoxy, fluoromethyl, difluoromethyl or trifluoromethyl;
• R2 is H;
• R3 is H or (C1-C5) alkyl;
• R4 is pyrid-2-, -3- or -4-yl(C1-C4)alkyl, thiazol-2-, -4- or -5-yl(C1-C4)alkyl, imidazol -1-,-2-, -4- or -5-yl(C1-C4)alkyl, pyrrol-2- or -3-yl(C1-C4)alkyl, oxazol-2-, -4- or -5-yl-(C1-C4)alkyl, pyrazol-3-, -4- or -5-yl(C1-C4)alkyl, isoxazol-3-, -4- or -5-yl(C1-C4)alkyl, or isothiazol-3-, -4- or -5-yl(C1-C4)alkyl, wherein said preceding R4 heterocycles are optionally mono- or di-substituted independently with halo, trifluoromethyl, (C1-C4)alkyl, (C1-C4)alkoxy, amino or hydroxy and said mono-or di-substituents are bonded to carbon;
• R5 is H hydroxy, fluoro, (C1-C5)akyl, (C1-C5)alkoxy, (C1-C6)alkanoyl, amino (C1-C4)alkoxy, mono-N- or di-N,N-(C1-C4)alkylamino (C1-C4)alkoxy, carboxy (C1-C4)alkoxy, (C1-C5)alkoxy-carbonyl (C1-C4)alkoxy, benzyloxycarbonyl(C1-C4)alkoxy, or carbonyloxy wherein said carbonyloxy is carbon—carbon linked with phenyl, and wherein said preceding R5 ring is optionally mono-substituted with halo, (C1-C4)alkyl, (C1-C4)alkoxy, hydroxy, amino or trifluoromethyl;
• R7 is H, fluoro or (C1-C5)alkyl;
• or
• R5 and R7 can be taken together to be oxo;
• R6 is carboxy, (C1-C8)alkoxycarbonyl, C(O)NR8R9 or C(O)R12,
• wherein
• R8 is H, (C1-C3) alkyl, hydroxy or (C1-C3) alkoxy;
• and
• R9 is H, (C1-C8) alkyl, hydroxy, (C1-C8) alkoxy, methylene-perfluorinated(C1-C8)alkyl, phenyl, pyridyl, thienyl, furyl, pyrrolyl, pyrrolidinyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, pyranyl, or piperidinyl, wherein said preceding R9 rings are carbon-nitrogen linked;
• or
• R9 is mono-, di- or tri-substituted (C1-C5)alkyl, wherein said substituents are independently H, hydroxy, amino, mono-N- or di-N,N-(C1-C5)alkylamino;
• or
• R9 is mono- or di-substituted (C1-C5)alkyl, wherein said substituents are independently phenyl, pyridyl, furyl, pyrrolyl, pyrrolidinyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, pyranyl, pyridinyl, piperidinyl, or 1,3,5-triazinyl,
• wherein the nonaromatic nitrogen-containing R9 rings are optionally mono-substituted on nitrogen with (C1-C6)alkyl, benzyl, benzoyl or (C1-C6)alkoxycarbonyl and wherein the R9 rings are optionally mono-substituted on carbon with halo, (C1-C4)alkyl, (C1-C4)alkoxy, hydroxy, amino, or mono-N- and di-N,N (C1-C5)alkylamino provided that no quaternized nitrogen is included and there are no nitrogen-oxygen, nitrogen—nitrogen or nitrogen-halo bonds;
• R12 is thiazolidin-3-yl, 1-oxo-thiazolidin-3-yl, 1,1-dioxo-thiazolidin-3-yl, 2-(C1C6)alkoxycarbonylpyrrolidin-1-yl, oxazolidin-3-yl or 2(R)-hydroxymethylpyrrolidin-1-yl;
• or
• R12 is 3- and/or 4-mono-or di-substituted oxazetidin-2-yl, 2-, 4-, and/or 5- mono- or di-substituted oxazolidin-3-yl, 2-, 4-, and/or 5- mono- or di- substituted thiazolidin-3-yl, 2-, 4-, and/or 5- mono- or di- substituted 1-oxothiazolidin-3-yl, 2-, 4-, and/or 5- mono- or di- substituted 1,1-dioxothiazolidin-3-yl, 3- and/or 4-, mono- or di-substituted pyrrolidin-1-yl, 3-, 4- and/or 5-, mono-, di- or tri-substituted piperidin-1-yl, 3-, 4-, and/or 5- mono-, di-, or tri-substituted piperazin-1-yl, 3-substituted azetidin-1-yl, 4- and/or 5-, mono- or di-substituted 1,2-oxazinan-2-yl, 3- and/or 4-mono- or di-substituted pyrazolidin-1-yl, 4- and/or 5-, mono- or di-substituted isoxazolidin-2-yl, 4- and/or 5-, mono- and/or di-substituted isothiazolidin-2-yl wherein said R12 substituents are independently H, halo, (C1-C5)-alkyl, hydroxy, amino, mono-N- or di-N,N-(C1-C5)alkylamino, formyl, oxo, hydroxyimino, (C1-C5)alkoxy, carboxy, carbamoyl, mono-N-or di-N,N-(C1-C4)alkylcarbamoyl, (C1-C4)alkoxyimino, (C1-C4)alkoxymethoxy, (C1-C6)alkoxycarbonyl, carboxy(C1-C5)alkyl or hydroxy (C1-C5) alkyl;
• with the proviso that if R4 is H, methyl, ethyl or n-propyl, R5 is OH;
• with the proviso that if R5 and R7 are H, then R4 is not H, methyl, ethyl, n-propyl, hydroxy(C1-C3)alkyl or (C1-C3)alkoxy(C1-C3)alkyl and R6 is C(O)NR8R9, C(O)R12 or (C1-C4)alkoxycarbonyl.