RU98109710A - 2-ALKYL-PYRROLIDINES, PHARMACEUTICAL COMPOSITION AND METHOD FOR INHIBITING LIVER-Glucose PRODUCTION IN LIVER - Google Patents

Claims (30)

1. The use of compounds of formula I

where R ¹ represents hydrogen, acyl, alkene, cycloalkyl or alkyl, which is optionally substituted by one or more of the following groups: hydroxyl, alkoxy, amino, N-alkylamino, N, N-dialkylamino, halogen, cycloalkyl, optionally substituted phenyl or alkoxycarbonyl , R ² represents hydrogen and alkyl, R ³ and R ⁴ that are the same or different, independently represent hydrogen, halogen, hydroxyl, mercapto or amino, which are optionally substituted by alkyl or aralkyl, and R ⁵ represents alkyl, substituted hydroxyl om, halogen, amino, N-alkylamino, N, N-dialkylamino or mercapto, or their salts or hydrates thereof, as a liver glycogen phosphorylase inhibiting agent.  2. The use according to claim 1, wherein the compound of formula I contains at least 2 hydroxyl groups.  3. Use according to any one of the preceding paragraphs, wherein the compound of formula I contains at least 3 hydroxyl groups. 4. The use according to any one of the preceding paragraphs, moreover, in the compound of formula I, two substituents, denoted by the symbols R ³ and R ⁵ , are located on one side of the plane formed by a 5-membered ring containing nitrogen, and R ⁴ is located on the opposite side of the plane formed 5 membered nitrogen ring. 5. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ¹ is hydrogen, acyl, or alkyl, which is optionally substituted with one or more of the following groups: hydroxyl, alkoxy, amino, N-alkylamino, N, N-dialkylamino, phenyl or alkoxycarbonyl. 6. The use of the preceding paragraph, wherein in the compound of formula IR ¹ is hydrogen, or alkyl, preferably methyl. 7. The use of the preceding paragraph, wherein in the compound of formula IR ¹ is hydrogen.  8. Use according to any one of the preceding paragraphs, wherein in the compound of formula I, an optionally substituted phenyl group is phenyl substituted with one or more of the following groups: halogen, hydroxy, alkoxy, trifluoroalkyl or cyano. 9. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ² is hydrogen or alkyl, preferably methyl. 10. Use according to any one of the preceding paragraphs, moreover, in the compound of the formula IR ² is hydrogen. 11. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ³ is hydrogen, hydroxyl, halogen or amino. 12. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ³ is hydroxyl, halogen or amino. 13. The compounds of the preceding paragraph, wherein R ³ is hydroxyl or halogen, preferably fluorine. 14. Use according to the preceding paragraphs, wherein R ³ is hydroxyl. 15. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ⁴ is hydrogen, hydroxyl, halogen or amino. 16. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ⁴ is hydroxyl, halogen or amino. 17. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ⁴ is hydrogen or halogen, preferably fluorine. 18. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ⁴ is hydroxyl or halogen, preferably fluorine. 19. The use of the preceding paragraph, wherein R ⁴ is hydroxyl. 20. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ⁵ is hydroxyalkyl. 21. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ⁵ is hydroxymethyl, hydroxyethyl or hydroxypropyl, preferably hydroxymethyl. 22. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ⁵ is hydroxymethyl. 23. Use according to any one of the preceding paragraphs, wherein in the compound of formula IR ⁵ is hydroxymethyl or benzyloxymethyl, preferably hydroxymethyl.  24. The use of the compounds of formula I, as defined by any of the preceding paragraphs, for the manufacture of a pharmaceutical composition for the treatment of diabetes.  25. The use of the compounds of formula I, as defined by any of the preceding paragraphs, for the manufacture of a pharmaceutical composition that suppresses the production of glucose by the liver.  26. A pharmaceutical composition comprising compounds of formula I as defined by any of the preceding claims in combination with a pharmaceutically acceptable carrier.  27. A method of treating diabetes, which comprises administering an effective amount of a compound of formula I, as defined by any of the preceding paragraphs, to a patient in need of such treatment.  28. A method for inhibiting the production of glucose in the liver, which comprises administering an effective amount of a compound of formula I, as defined in any of the preceding paragraphs, to a patient in need of such treatment.  29. Use of the compound according to any of the preceding claims for use, composition or method, which is 3,4-dihydroxy-2-hydroxymethylpyrrolidine, 3,4-dihydroxy-2-hydroxymethyl-1-methylpyrrolidine, 1-cyclopropylmethyl-3,4 -dihydroxy-2-hydroxymethylpyrrolidine, 3,4-dihydroxy-2-hydroxymethyl-1-propylpyrrolidine, 1-butyl-3,4-dihydroxy-2-hydroxymethylpyrrolidine, 3,4-dihydroxy-2-hydroxymethyl-1- (2, 2,2-trifluoroethyl) pyrrolidine, 1-benzyl-3,4-dihydroxy-2-hydroxymethylpyrrolidine, 3,4-dihydroxy-2-hydroxymethyl-1- (2-hydroxyethyl) pyrrolidine, 3,4-dihydroxy-2-hydroxymethyl-1- (1,3-dihydroxyprop-2-yl) pyrrolidine, 3,4-dihydroxy-2-hydroxymethyl-1- (2,3-dihydroxyprop-1-yl) pyrrolidine, 1- (2-aminoethyl) -3,4-dihydroxy-2-2-hydroxymethylpyrrolidine, preferably 3,4-dihydroxy-2-hydroxymethylpyrrolidine and any of its optical isomers.  30. Use of the compound of the preceding paragraph, which is (2R, 3R, 4R) -3,4-dihydroxy-2-hydroxymethylpyrrolidine, (2R, 3R, 4R) -3,4-dihydroxy-2-hydroxymethyl-1-methylpyrrolidine , (2R, 3R, 4R) -1-cyclopropylmethyl-3,4-dihydroxy-2-hydroxymethylpyrrolidine, (2R, 3R, 4R) -3,4-dihydroxy-2-hydroxymethyl-1-propylpyrrolidine, (2R, 3R, 4R) -1-butyl-3,4-dihydroxy-2-hydroxymethylpyrrolidine, (2R, 3R, 4R) -3,4-dihydroxy-2-hydroxymethyl-1 (2,2,2-trifluoroethyl) pyrrolidine, (2R , 3R, 4R) -1-benzyl-3,4-dihydroxy-2-hydroxymethylpyrrolidine, (2R, 3R, 4R) -3,4-dihydroxy-2-hydroxymethyl-1- (2-hydroxyethyl) pyrrolidine, (2R, 3R, 4R) -3,4-dihydroxy-2-hydroxymethyl-1- (2,3-dihydroxyprop-1-yl) pyrrolidine, (2R, 3R, 4R) -3,4-dihydroxy-2-hydroxymethyl -1- (1,3-dihydroxyprop-2-yl) pyrrolidine, (2R, 3R, 4R) -1- (2-aminoethyl) -3,4-dihydroxy-2-hydroxymethylpyrrolidine, (2S, 3S, 4S) - 3,4-dihydroxy-2-hydroxymethylpyrrolidine, (2S, 3S, 4S) -3,4-dihydroxy-2-hydroxymethyl-1-methylpyrrolidine, (2S, 3S, 4S) -1-cyclopropylmethyl-3,4-dihydroxy- 2-hydroxymethylpyrrolidine, (2S, 3S, 4S) -3,4-dihydroxy-2-hydroxymethyl-1-propylpyrrolidine, (2S, 3S, 4S) -1-butyl-3,4-dihydroxy-2-hydroxymethyl-pyrrolidine, (2S, 3S, 4S) -3,4-dihydroxy-2-hydroxymethyl-1- (2,2,2-trifluoroethyl) pyrrolidine, (2S, 3S, 4S) -1-benzyl-3,4-dihydroxy-2-hydroxymethylpyrrolidine, (2S, 3S, 4S) -3,4-dihydroxy-2-hydroxymethyl-1- (2-hydroxyethyl) pyrrolidine, ( 2S, 3S, 4S) -3,4-dihydroxy-2-hydroxymethyl-1- (2,3-dihydroxyprop-1-yl) pyrrolidine, (2S, 3S, 4S) -3,4-dihydroxy-2-hydroxymethyl- 1- (1,3-dihydroxyprop-2-yl) pyrrolidine, (2S, 3S, 4S) -1- (2-aminoethyl) -3,4-dihydroxy-2-hydroxymethylpyrrolidine, preferably (2R, 3R, 4R) - 3,4-dihydroxy-2-hydroxymethylpyrrolidine.