OA10459A - Substituted n-(indole-2-carbonyl)-beta-alanimamides and derivatives as antidiabetic agents - Google Patents

Substituted n-(indole-2-carbonyl)-beta-alanimamides and derivatives as antidiabetic agents Download PDF

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OA10459A
OA10459A OA60836A OA60836A OA10459A OA 10459 A OA10459 A OA 10459A OA 60836 A OA60836 A OA 60836A OA 60836 A OA60836 A OA 60836A OA 10459 A OA10459 A OA 10459A
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alkyl
hydroxy
mono
chloro
alkoxy
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OA60836A
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Bernard Hulin
Judith Lee Treadway
William Holt Martin
Dennis Jay Hoover
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Pfizer
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Claims (32)

  1. - 105 - 010459 C L A I M S
    1. A compound of Formula I
    Formula I and the pharmaceutically acceptable salts and prodrugs15 thereof wherein the dotted line (---) is an optional bond; A is -C(H)=, —C ( (C-^-C^) alkyl) = or -C(halo)= when the dotted line (---) is a bond, or A is methylene or - CH((C^-C4) alkyl)- when the dotted line (---) is not a bond; 20 R^, R10 or R^^ are each independently H, halo, 4-, 6- or 7-nitro, cyano, (C^-C4)alkyl, (C^-C^)alkoxy,fluoromethyl, difluoromethyl or trifuloromethyl; R2 is H; Rj is H or (C^-Cjj) alkyl; 25 R4 is H, methyl, ethyl, n-propyl, hydroxy(C-j_- Cg)alkyl, (C^-Cj)alkoxy(C^-Cj)alkyl, phenyl(C^-C^)alkyl,phenylhydroxy(C^-C^)alkyl, phenyl(C^-C4)alkoxy(C^-C4)alkyl,thien-2- or -3-yl (C-^-C4) alkyl or fur-2- or -3-yl (Ci“C4) alkylwherein said R4 rings are mono-, di- or tri-substituted 30 independently on carbon with H, halo, (C^-C4)alkyl, (C-^-C4)alkoxy, trifluoromethyl, hydroxy, amino or cyano; or R4 is pyrid-2-, -3- or -4-yl (C^-C,^) alkyl, thiazol- 2-, -4- or -5-yl(C^-C4)alkyl, imidazol -1-, -2-, -4- or -5-yl(C1-C4)alkyl, pyrrol-2- or -3-yl(C^-C4)alkyl, oxazol-2-, 35 -4- or -5-yl-(Cj-C,^)alkyl, pyrazol-3-, -4- or -B-yliC^- C4) alkyl, isoxazol-3-, -4- or -5yl (C-j_-C4) alkyl, isothiazol- CASE: PC 9160 ADO - 106 - 010459 3-, -4- or -5-yl(C^-C^alkyl, pyridazin-3- or -4-yl-(C1-C4)alkyl, pyrimidin-2-, -4-, -5- or -6-yl (C-^-C^) alkyl,pyrazin-2- or -3-yl (¢^-04) alkyl or 1,3,5-triazin-2-yl(Cj-C4)alkyl, wherein said preceding R4 heterocycles are 5 optionally mono- or di-substituted independently with halo,trifluoromethyl, (C1-C4)alkyl, (C^-C4)alkoxy, amino orhydroxy and said mono- or di-substituents are bonded tocarbon; Rg is H, hydroxy, fluoro, (C^-Cg)alkyl, (Cj-tû C5)alkoxy, (Cj-Cg)alkanoyl, amino(¢^-04)alkoxy, mono-N- or di-N,N- (C1-C4) alkylamino(¢^-04) alkoxy, carboxy (0-^-04) alkoxy,(C2-C5) alkoxy-carbonyl(0^-04)alkoxy, benzyloxycarbonyl(Cj-C4)alkoxy, or carbonyloxy wherein said carbonyloxy is carbon-carbon linked with phenyl, thiazolyl, imidazolyl, lH-indolyl, 15 furyl, pyrrolyl, oxazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridazinyl, pyrmidinyl, pyrazinyl or 1,3,5-trizinyl and wherein said preceding Rg rings are optionallymono-substituted with halo, (Cjl-C4)alkyl, (0-^-04) alkoxy,hydroxy, amino or trifluoromethyl and said mono-substituents 20 are bonded to carbon; R? is H, fluoro or (C^-Cg)alkyl; orRg and R7 can be taken together to be oxo; Rg is carboxy, (C^-Cg)alkoxycarbonyl, C(O)NRgRg or c(o)r12, 25 wherein Rg is H, (C^-Cg)alkyl, hydroxy or (Cj-Cg)alkoxy; andRg is H, (C^-Cg)alkyl, hydroxy, (C^-Cg)alkoxy, methylene-perfluorinatediCj-Cg)alkyl, phenyl, pyridyl,thienyl, furyl, pyrrolyl, pyrrolidinyl, oxazolyl, thiazolyl, 30 imidazolyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, isozazolyl, isothiazolyl, pyranyl, piperidinyl, morpholinyl,pyridazinyl, pyrimidinyl, pyrazinyl, piperazinyl or 1,3,5-triazinyl wherein said preceding Rg rings are carbon-nitrogenlinked; or 35 Rg is mono-, di- or tri-substituted (C-^-Cg) alkyl, wherein said substituents are independently H, hydroxy,amino, mono-N- or di-N,N-(C^-Cg)alkylamino; or Rg is mono- or di-substituted (C^-Cg)alkyl, wherein - 107 - 010459 said substituents are independently phenyl, pyridyl, furyl,pyrrolyl, pyrrolidinyl, oxazolyl, thiazolyl, imidazolyl,pyrazolyl, pyrazolinyl, pyrazolidinyl, isoxazolyl,isothiazolyl, pyranyl, pyridinyl, piperidinyl, morpholinyl, 5 pyridazinyl, pyrimidinyl, pyrazinyl, piperazinyl or 1,3,5-triazinyl wherein the nonaromatic nitrogen-containing Rgrings are optionally mono-substituted on nitrogen with (C^-Cg)alkyl, benzyl, benzoyl or (C-^-Cg) alkoxycarbonyl and 10 wherein the Rg rings are optionally mono-substituted oncarbon with halo, (C^-C^) alkyl, (C-^-C^) alkoxy, hydroxy,amino, or mono-N- and di-N,N (C^-Cg)alkylamino provided thatno quaternized nitrogen is included and there are nonitrogen-oxygen, nitrogen-nitrogen or nitrogen-halo bonds; 15 R-^2 is piperazin-l-yl, 4- (C1-C4)alkylpiperazin-l-yl, 4-formylpiperazin-l-yl,morpholino, thiomorpholino, 1-oxothiomorpholino, 1,1-dioxo-thiomorpholino, thiazolidin-3-yl, 1-oxo-thiazolidin-3-yl, 1,l-dioxo-thiazolidin-3-yl, 2-((^- 20 Cg)alkoxycarbonylpyrrolidin-1-yl, oxazolidin-3-yl or2(R)-hydroxymethylpyrrolidin-l-yl;or R^2 is 3- and/or 4-mono- or di- substitutedoxazetidin-2-yl, 2-, 4-, and/or 5- mono- or di- substituted 25 oxazolidin-3-yl, 2-, 4-, and/or 5- mono- or di- substitutedthiazolidin-3-yl, 2-, 4-, and/or 5- mono- or di- substitutedl-oxothiazolidin-3-yl, 2-, 4-, and/or 5- mono- or di-substituted 1,l-dioxothiazolidin-3-yl, 3- and/or 4-, mono- ordi- substituted pyrrolidin-l-yl, 3-, 4- and/or 5-, mono-, di- 30 or tri-substituted piperidin-l-yl, 3-, 4-, and/or 5- mono-,di-, or tri-substituted piperazin-l-yl, 3-substitutedazetidin-l-yl, 4- and/or 5-, mono- or di-substituted 1,2-oxazinan-2-yl, 3- and/or 4-mono- or di-substitutedpyrazolidin-l-yl, 4- and/or 5-, mono- or di-substituted 35 isoxazolidin-2-yl, 4- and/or 5-, mono- and/or di-substitutedisothiazolidin-2-yl wherein said R·^ substituents areindependently H, halo, (C^-Cg)-alkyl, hydroxy, amino, mono-N-or di-N,N-(Cj-Cg)alkylamino, formyl, oxo, hydroxyimino, 108 - 010459 (C^-Cg) alkoxy, carboxy, carbamoyl, mono-N or di-NiN-ÎCj^-C4)alkylcarbamoyl, (Cj-C^alkoxyimino, (Cj-C^)alkoxymethoxy,(Ci-C6) alkoxycarbonyl, carboxy (Cj^-Cg) alkyl or hydroxy(Cj-C5)alkyl; with the proviso that if R4 is H, methyl, ethyl orn-propyl, Rg is OH; with the proviso that if Rg and Ry are H, then R4is not H, methyl, ethyl, n-propyl, hydroxy(C1-C3)alkyl or(C1-C3)alkoxy(Ci-C3)alkyl and Rg is C(O)NRgRg, C(O)R12 or(C^-C4)alkoxycarbonyl
  2. 2. A compound as recited in claim 1, wherein R^ is 5-H, 5-halo, 5-methyl, 5-trifluoromethyl or 5-cyano; R10 and Ru are each independently H or halo; A is -C(H)=; R2 and R3 are H; R4 is phenyl (C.£-C2) alkyl wherein said phenyl groupeare mono-, di- or tri-substituted independently with H orhalo or mono- or di- substituted independently with H, halo,(C1-C4)alkyl, (^-04)alkoxy, trifluoromethyl, hydroxy, aminoor cyano; or R4 is thien-2- or -3-yl(C^-Cj)alkyl, pyrid-2-, -3-or -4-yl (C-^-Cjj) alkyl, thiazol-2-, -4- or -5-yl(Cj-C^alkyl,imidazol -1-, -2-, -4- or -5-yl (C^Cg)alkyl, fur-2- or -3-yl (Ci-C2) alkyl, pyrrol-2- or -3-yl (Cj.-C^alkyl, oxazol-2-, -4- or -5-yl-(C^-C2)alkyl, pyrazol-3-, -4- or -S-yltC^-C2)alkyl, isoxazol-3-, -4- or -5-yl(C^C^alkyl wherein saidpreceding R4 heterocycles are optionally mono- or di-substituted independently with halo, trif luoromethyl, (C-j_-C4)alkyl, (C1-C4)alkoxy, amino or hydroxy and said mono- ordi-substituents are bonded to carbon; Rg is hydroxy; Rg is C(O)NRqR9 or C(O)R12; and R? is H.
  3. 3. A compound as recited in claim 2, whereinthe carbon atom a has (S) stereochemistry;the carbon atom b has (R) stereochemistry; R4 is phenyl(C^-C2)alkyl, thien-2-yl(C^-C2)alkyl, 109 - Û10459 thien-3-yl-(C-j_-C2) alkyl, fur-2-yl-(C-£-C2) alkyl or fur-3-yl-(Ci-C2)alkyl wherein said rings are mono- or di- substitutedindependently with H or fluoro; Rg is C(O)NRgRj; Rg is (C^-Cg)alkyl, hydroxy or (C-^-Cg) alkoxy; and Rg is H, (C-^-Cg) alkyl, hydroxy, hydroxy(C^-Cg)alkyl, (ci_cg)alkoxy, pyridyl, morpholinyl, piperazinyl,pyrrolidinyl, piperidinyl, imidazolyl or thiazolyl or (C·^-C4)alkyl mono-substituted with pyridyl, morpholinyl,piperazinyl, pyrrolidinyl, piperidinyl, imidazolyl orthiazolyl.
  4. 4. À compound as recited in claim 3, selected from
  5. 5-Chloro-lH-indole-2-carboxylic acid [(IS)-((R)- hydroxy-dimethylcarbamoylmethyl) -2-phenyl-ethyl] -amide, 5,6-Dichloro-lH-indole-2-carboxylic acid {(1S)-[ (R) -hydroxy- (methoxy-methylcarbamoyl) -methyl] -2-phenyl-ethyl}-amide,
    5-Chloro-lH-indole-2-carboxylic acid {(1S)-[(R)-hydroxy- (methoxy-methylcarbamoyl) -methyl] -2-phenyl-ethyl}-amide,
    5-Chloro-lH-indole-2-carboxylic acid ((1S)-{(R)-hydroxy- [(2-hydroxy-ethylmethyl-carbamoyl] -methyl}-2-phenyl-ethyl) -amide,
    5-Chloro-lH-indole-2-carboxylic acid {(IS)-[(R)-hydroxy- (methyl-pyridin-2-yl-carbamoyl) -methyl] -2-phenyl-ethyl}-amide or
    5-Chloro-lH-indole-2-carboxylic acid ((1S)-{(R)-hydroxy- [methyl- (2-pyridin-2-yl-ethyl) -carbamoyl] -methyl}-2-phenyl-ethyl)-amide.
    5. The compound as recited in claim 3, wherein 5^ is 5-chloro; R10 and Ru are H; R4 is benzyl; Rg is methyl; and Rg is methyl. The compound as recited in claim 3, wherein R^ is 5-chloro; R^ is H; 6 110 - 010459 ς1Ο is 6-chloro; 10 15 20 30 10 R4 is benzyl; Rg is methyl; and Rg is methoxy. The compound as recited in daim 3, whereinR^ is 5-chloro; R-£q and R-^-j. are H' R4 is benzyl; Rg is methyl; andRg is methoxy. The compound as recited in claim 3, whereinR^ is 5-chloro; R^q and R^jl are H; R4 is benzyl; Rg is methyl; andRg is 2 -(hydroxy)ethyl. The compound as recited in claim 3, whereinRj is 5-chloro; R1Q and R^-£ are H; R4 is benzyl; Rg is methyl; andRg is pyridin-2-yl. The compound as recited in claim 3, whereinR^ is 5-chloro; 25 l10 and R1;£ are H; R4 is benzyl; Rg is methyl; andRg is 2-(pyridin-2-yl)ethyl.
  6. 11. A compound as recited in claim 2, wherein the carbon atom a is (S) stereochemistry;the carbon atom b is (R) stereochemistry; R4 is phenyl(Cj-C2)alkyl, thien-2-yl-(Cj-C2)alkyl,thien-3-yl-(C.].-C2)alkyl, fur-2-yl-(Cj-Cj)alkyl or fur-3-yl-(Ci-C2)alkyl wherein said rings are mono- or di- substitutedindependently with H or fluoro; Rç is C(O)R12; and R12 is morpholino, 4-(C^-C^)alkylpiperazin-l-yl, 3-substituted azetidin-l-yl, 3- and/or 4-, mono- or di- 35 111 010459 10 15 20 25 30 35 substituted pyrrolidin-l-yl, 4- and/or 5- mono- or di-substituted isoxazolidin-2-yl, 4- and/or 5-, mono- or di-substituted 1,2-oxazinan-2-yl wherein said substituents areeach independently H, halo, hydroxy, amino, mono-N- or di-N,N-(Cj-Cg)alkylamino, oxo, hydroxyimino or alkoxy.
  7. 12. A compound as recited In claim 1 selected from
    5-Chloro-l-H-indole-2-carboxylic acid [(lS)-benzyl (2R)-hydroxy-3-(4-methylpiperazin-l-yl)-3-oxo-propyl]-amidehydrochloride,
    5-Chloro-lH-indole-2-carboxylic acid [ (IS)-benzyl-(2R)-hydroxy-3-(3-hydroxyazetidin-l-yl)-3-oxo-propyl]-amide,
    5-Chloro-lH-indole-2-carboxylic acid ( (IS)-benzyl-(2R)-hydroxy-3-isoxazolidin-2-yl-3-oxo-propyl)-amide,
    5-Chloro-lH-indole-2-carboxylic acid ((IS)-benzyl-(2R)-hydroxy-3-[1,2]oxazinan-2-yl-3-oxo-propyl)-amide,
    5-Chloro-lH-indole-2-carboxylic acid [ (IS)-benzyl-(2R)-hydroxy-3-((3S)-hydroxy-pyrrolidin-l-yl)-3-oxo-propyl]-amide,
    5-Chloro-lH-indole-2-carboxylic acid [(IS)-benzyl- 3-((3S,4S)-dihydroxypyrrolidin-l-yl)-(2R)-hydroxy-3-oxo-propyl] -amide,
    5-Chloro-lH-indole-2-carboxylic acid[(lS)-benzyl-3((3R,4S)-dihydroxypyrrolidin-l-yl)-(2R)-hydroxy-3-oxo-propyl]-amide or
    5-Chloro-lH-indole-2-carboxylic acid ( (IS)-benzyl-(2R)-hydroxy-3-morpholin-4-yl-3-oxo-propyl)-amide.
  8. 13. The compound as recited in claim 11, wherein R-]_ is 5-chloro; Rjq and R^ are H; R4 is benzyl; and R^2 is 4-methylpiperazin-l-yl.
  9. 14. The compound as recited in claim 11, wherein R-^ is 5-chloro; R10 and R-j^ are H; R4 is benzyl; and R^2 is 3-hydroxyazetidin-l-yl. The compound as recited in claim 11, wherein R^ is 5-chloro; 15 112 Ο 1 0 459 Rjq and are H; R4 is benzyl; and R-^2 is isoxazolidin-2-yl.
  10. 16. The compound as recited in claim 11, wherein 5 R"L is 5-chloro; R10 and R1:1 are H; R4 is benzyl; and r12 is (1/2)-oxazinan-2-yl.
  11. 17. The compound as recited in claim 11, wherein 10 R·^ is 5-chloro; R10 and R1;L are H; R4 is benzyl; and R^2 is 3(S)-hydroxypyrrolidin-l-yl.
  12. 18. The compound as recited in claim 11, wherein 15 R^ is 5-chloro; Rjq and Rjj are H; R4 is benzyl; and R12 is (3S,4S)-dihydroxypyrrolidin-l-yl.
  13. 19. The compound as recited in claim 11, wherein 20 Ri is 5-chloro; R10 and Ru are H; R4 is benzyl; and R12 is (3R,4S)-dihydroxypyrrolidin-l-yl.
  14. 20. The compound as recited in claim 11, wherein 25 Ri is 5-chloro; RlO and Ru are H; R4 is benzyl; andR-^2 is morpholino.
  15. 21. A compound as recited in claim 1, wherein 30 R]_ is H, halo, methyl or cyano; R10 and R^ are each independently H or halo; A is -C(H)=; R2 and R^ are H; R4 is phenyl (0.^-02) alkyl wherein said phenyl groupe35 are mono-, di- or tri-substituted independently with H or halo or mono- or di- substituted independently with H, halo,{C1-C4)alkyl, (Ci-C4)alkoxy, trifluoromethyl, hydroxy, aminoor cyano; or 113- 10 15 20 25 30 0 î Ο459 R4 is thien-2- or -3-yl (C-^·^) alkyl, pyrid-2-, -3-or -4-yl(C^-C2)alkyl, thiazol-2-, -4- or -5-yl(Cj-C2)alkyl,imidazol -1-, -2-, -4- or -5-yl(C^-Cg)alkyl, fur-2- or -3-yl(C^-C2)alkyl, pyrrol-2- or -3-yl(¢2-03)alkyl, oxazol-2-, -4- or -5-yl-(C^-C^)alkyl, pyrazol-3-, -4- or -5-yl(0^-C2)alkyl, isoxazol-3-, -4- or -5-yl(Cj-C^)alkyl wherein saidpreceding R4 heterocycles are optionally mono- or di-substituted independently with halo, trifluoromethyl, (C^-C4)alkyl, (Cj-C4)alkoxy, amïno or hydroxy and said mono- ordi-substituents are bonded to carbon; Rg is hydroxy; Rg is carboxy or (C-^-Cg) alkoxycarbonyl; and R7 is H, fluoro or (C^-Cg)alkyl.
  16. 22. A compound as recited in claim 21, whereinthe carbon atom a is (S) stereochemistry;the carbon atom b is (R) stereochemistry; R4 is phenyl (C^-C2) alkyl, thien-2-yl-(0-^-03) alkyl,thien-3-yl-(Cj-C2)alkyl, fur-2-yl-(C;£-C2) alkyl or fur-3-yl-(C1-C2)alkyl wherein said rings are mono- or di- substitutedindependently with H or fluoro; Rj0 and Rjj are H; Rg is carboxy; and R7 is H.
  17. 23. The compound as recited in claim 22, wherein Rj_ is 5-chloro; R10 and Ru are H; and R4 is benzyl.
  18. 24. A compound as recited in claim 1, wherein Rj is H, halo, methyl or cyano; Rlo and Rjj are each independently H or halo; A is -C(H)=; R2 and Rg are H; R4 is phenyl(C1-C2)alkyl wherein said phenyl groupeare mono-, di- or tri-substituted independently with H orhalo or mono- or di- substituted independently with H, halo,(C1-C4) alkyl, (C-^-C^) alkoxy, trif luoromethyl, hydroxy, aminoor cyano; or R4 is thien-2- or -3-yl(C^-C2)alkyl, pyrid-2-, -3- 35 0î0459 114 or -4-yl (C]-C2)alkyl, thiazol-2-, -4- or -5-yl (Cj-C^alkyl, imidazol -1-, -» 2-, -4- or -5-yl (Cj-C2)alkyl, fur-2- or 3-yl (Cj-C^alkyl, pyrrol-2- or -3-yl (Cj-C2)alkyl, oxazol-2-, -4- or -5-yl-(C1-C2) alkyl, pyrazol-3-, -4- or -5-yl-(Cj-C2) alkyl, isoxazol-3-, -4- or -5-yl (Cj-C2) alkyl wherein saidpreceding R4 heterocycles are optionally mono- or di-substitutedindependently with halo, trifluoromethyl, (Cj-C^) alkyl, (Cj-C4) alkoxy,amino or hydroxy and said mono- or di-substituents are bonded tocarbon; R5 is fluoro, (C,-C4) alkyl, (Q-Cj) alkoxy,amino (CrC4) alkoxy, mono-N- or di-N,N-(C1-C4)alkylamino (Cj-C4)alkoxy, carboxy (Cj-C4) alkoxy, (Cj-C5) alkoxy-carbonyl (Cj-C4) alkoxy,benzyloxycarbonyl (Cj-C4) alkoxy; R6 is carboxy or (Cj-Cg) alkoxycarbonyl; and R7 is H, Fluoro or (Cj-C6) alkyl.
  19. 25. A compound as recited in claim 1, wherein Ri is H, halo, methyl or cyano; R1O and Rj j are each independently H or halo; Ais -C(H)=; R2 and R3 are H; R4 is phenyl (Cj-C2) alkyl wherein said phenyl groups are mono-,di- or tri-substituted independently with H or halo or mono- or di-substituted independently with H, halo, (Cj-C4) alkyl, (Cj-C4) alkoxy,trifluoromethyl, hydroxy, amino or cyano; or R4 is thien-2- or -3-yl (Cj.C2) alkyl, pyrid-2-, -3- or -4-yl (Cj-C2) alkyl, thiazol-2-, -4- or -5-yl (Cj-C2) alkyl, imidazol -1-, -2-, -4- or -5-yl (Cj-C^) alkyl, fur-2- or -3-yl (Cj-C2)alkyl, pyrrol-2- or -3-yl (Cj-C^) alkyl, oxazol-2-, -4- or -5-yl- (Cj-C2) alkyl,pyrazol-3-, -4- or -5-yl (Cj-Cj) alkyl, isoxazol-3-, -4- or -5-yl (Cj-C^) alkylwherein said preceding R4 heterocycles are optionally mono- or di-substituted independently with halo, trifluoromethyl, (CrC4) alkyl, (CrC4)alkoxy, amino or hydroxy and said mono- or di-substituents are bondedto carbon; R5 is fluoro, (CrC4) alkyl, (C,-C5) alkoxy, amino (Ci-C4) alkoxy,mono-N- or di-N,N- (Cj-C4) alkylamino (Cj-C4) alkoxy, carboxy (Cj-C4)alkoxy, (CrC5) alkoxy-carbonyl (Cj-C4) alkoxy, benzyloxycarbonyl (CrC4)alkoxy; 115 010459 R* is C(O)NRiiR9 or C(O)R12; andR7 is H, Fluoro or (Cj-C6)alkyl.
  20. 26. A use of a compound as claimed in claim 1, for préparation of amédicament for treatment of a glycogen phosphorylase dépendent disease or condition in a mammalsuifering from a glycogen phosphorylase dépendent disease or condition.
  21. 27. A use as claimed in claim 26, wherein said glycogen phosphorylasedisease or condition is hyperglycemia.
  22. 28. A use as claimed in claim 26, wherein said glycogen phosphorylasedisease or condition is diabètes.
  23. 29. A use as claimed in claim 26, wherein said glycogen phosphorylasedisease or condition is hypercholesterolemia.
  24. 30. A use as claimed in claim 26, wherein said glycogen phosphorylasedisease or condition is atherosclerosis.
  25. 31. A use as claimed in claim 26, wherein said glycogen phosphorylasedisease or condition is hyperinsulinemia.
  26. 32. A use as claimed in claim 26, wherein said glycogen phosphorylasedisease or condition is hypertension.
  27. 33. A use as claimed in claim 26, wherein said glycogen phosphorylasedisease or condition is hyperlipidemia.
  28. 34. A use as claimed in claim 26, wherein said glycogen phosphorylasedisease or condition is a myocardîal ischémie injury in a mammal at risk for perioperativemyocardial ischémie injury.
  29. 35. Use of a glycogen phosphorylase inhibitor for préparation of amédicament for preventing a myocardial ischémie injury in a mammal at risk for perioperativemyocardial ischémie injury.
  30. 36. A pharmaceutical composition which comprises a therapeutically effectiveamount of a compound of claim 1 and a pharmaceutically acceptable carrier.
  31. 37. The pharmaceutical composition as récited in claim 36, for the treatment ofglycogen phosphorylase dépendent diseases or conditions in mammals which comprises aglycogen phosphorylase dépendent disease or condition treating amount of a compound ofclaim 1 and a pharmaceutically acceptable carrier.
  32. 38. A pharmaceutical composition which comprises a therapeutically effectiveamount of 116 010459 « F a) a glycogen phosphorylase inhibitor as recited in claim 1 ; b) an antidiabetic agent selected from insulin and insulin analogs; insulinotropin; Sulfonylureas and analogs; Biguanides; a2-Antagonists and Imidazolines; insulinsecretagogues; Glitazones; Fatty Acid Oxidation inhibitors; cc-Glucosidase inhibitors; β-Antagonists; Phosphodiesterase Inhibitors; Lipid-lowering Agents; Antiobesity Agents;Vanadate and vanadium complexes and peroxovanadium complexes; Amylin Antagoniste;Glucagon Antagonists; Gluconeogenesis Inhibitors; Somatostatin Analogs; Antilipotic Agents;and c) optionally a pharmaceutically acceptable carrier.
OA60836A 1995-06-06 1996-06-06 Substituted n-(indole-2-carbonyl)-beta-alanimamides and derivatives as antidiabetic agents OA10459A (en)

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CA002223625A CA2223625C (fr) 1995-06-06 1995-06-06 (indole-2-carbonyl-)-amides substitues en n et leurs derives, servant d'inhibiteurs de la glycogene phosphorylase
PCT/IB1995/000443 WO1996039385A1 (fr) 1995-06-06 1995-06-06 (indole-2-carbonyl-)-amides substitues en n et leurs derives, servant d'inhibiteurs de la glycogene phosphorylase

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