Triterpene derivative and medicinal composition

• US 5,885,992 A
• Filed: 12/19/1996
• Issued: 03/23/1999
• Est. Priority Date: 06/24/1994
• Status: Expired due to Fees

• Current Assignee: Nippon Shinyaku Company Limited
• Original Assignee: Nippon Shinyaku Company Limited
• Inventors: Ohgi, Tadaaki, Yoshifusa, Hiroto, Kandori, Kazuhisa
• Primary Examiner(s): Cook, Rebecca
• Application Number:
  US08/750,896
• Time in Patent Office: 824 Days
• Field of Search: 514/245, 514/460, 560/8, 560/129, 562/498
• US Class Current: 514/245
• CPC Class Codes: C07J 63/008 Expansion of ring D by one atom, e.g. D homo steroids
• CPC Class Codes: C07J 71/0005 Oxygen-containing hetero ring

Abstract

The invention is composed of a hederagenin derivative of the following formula or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising of this compound as an active ingredient. ##STR1## (wherein R¹ represents OR¹¹ or NR¹¹ R¹². R¹¹ and R¹² may be the same or different and each represents hydrogen, alkyl that may be substituted, cycloalkyl that may be substituted, alkenyl that may be substituted, alkinyl that may be substituted, aryl that may be substituted, or a heteroaromatic group that may be substituted,

R² and R³ may be the same or different and each represents hydrogen, alkyl that may be substituted, cycloalkyl that may be substituted, alkenyl that may be substituted, alkinyl that may be substituted, acyl that may be substituted, monoalkylcarbamoyl that may be substituted, dialkylcarbamoyl that may be substituted, or alkoxycarbonyl that may be substituted, or R² and R³ taken together represents carbonyl.)

The pharmaceutical composition of the invention is effective for the therapy of nephritis.

Claims

1. A method for treating an animal suffering from nephritis, which comprises administering to the sufferer an effective amount of a compound of formula (1) or a pharmaceutically acceptable salt thereof, or a solvate of said compound or said salt:

##STR13## wherein R¹ is OR¹¹ or NR¹¹ R¹², R¹¹ and R¹² are the same or different and each is (1) hydrogen, (2) alkyl optionally substituted, (3) cycloalkyl optionally substituted, (4) alkenyl optionally substituted, (5) alkynyl optionally substituted, (6) aryl optionally substituted, or (7) a heteroaromatic group optionally substituted;

R² and R³ is the same or different and each is (1) hydrogen, (2) alkyl optionally substituted, (3) cycloalkyl optionally substituted, (4) alkenyl optionally substituted, (5) alkynyl optionally substituted, (6) acyl optionally substituted, (7) monoalkylcarbamoyl optionally substituted, (8) dialkylcarbamoyl optionally substituted, or (9) alkoxy carbonyl optionally substituted, or R² and R³ taken together is carbonyl;

wherein the substituents on R¹¹, R¹², R², R³ are the same or different and are selected from (1) halogen, (2) OR¹³, (3) OCOR¹³, (4) COOR¹³, (5) cyano, (6) NR¹³ R¹⁴, (7) cycloalkyl, (8) aryl optionally substituted by halogen, alkyl, hydroxy, or amino, and (9) a heteroaromatic group optionally substituted by halogen, alkyl, hydroxy, or amino;

wherein R¹³ and R¹⁴ are the same or different and each is (1) hydrogen or (2) alkyl optionally substituted by hydroxy, alkoxy, amino, monoalkylamino, or dialkylamino.

2. The method of claim 1, wherein R¹ is hydroxy, acyloxyalkoxy, phenylalkoxy, alkoxyalkoxy, hydroxyalkoxy, haloalkoxy, di(hydroxyalkyl)aminoalkoxy, (alkoxyalkyl)amino, halogen-substituted phenylamino, (dialkylaminoalkyl)amino, di(hydroxyalkyl)aminoalkyl!amino, (carboxyalkyl)amino, (alkoxycarbonylalkyl)amino, (cyanoalkyl)amino, or diamino-substituted triazinylalkylamino, R² is hydrogen, and R³ is hydrogen.

3. The method of claim 1, wherein R¹ is hydroxy, (alkoxyalkyl)amino, halogen-substituted phenylamino, (dialkylaminoalkyl)amino, di(hydroxyalkyl)aminoalkyl!amino, (alkoxycarbonylalkyl)amino, or (cyanoalkyl)amino, R² is acetoxy, and R³ is acetoxy.

4. The method of claim 1, wherein R¹ is phenylalkoxy, R² is hydroxy, (alkoxycarbonylalkyl)carbamoyl, or (alkoxyalkyl)carbamoyl, and R³ is phenylalkyl.

5. The method of claim 1, wherein R¹ is hydroxy, R² is (alkoxycarbonylalkyl)carbamoyl, or (alkoxyalkyl)carbamoyl, and R³ is hydrogen.

6. The method of claim 1, wherein R¹ is hydroxy or acyloxyalkoxy, and R² and R³ taken together is carbonyl.

7. The method of claim 1, wherein R¹ is hydroxy, 2-methoxyethylamino, or 2-acetoxyethoxy, R² is hydrogen, and R³ is hydrogen.

8. The method of claim 1, wherein said nephritis is proliferative glomulonephritis.

9. The method of claim 1, wherein said nephritis is chronic nephritis.

10. The method of claim 1, wherein the animal is a human.

11. A compound of formula (1) or a pharmaceutically acceptable salt thereof, or a solvate of said compound or said salt:

##STR14## wherein R¹ is OR¹¹ or NR¹¹ R¹², R¹¹ and R¹² are the same or different and each is (1) hydrogen, (2) alkyl optionally substituted, (3) cycloalkyl optionally substituted, (4) alkenyl optionally substituted, (5) alkynyl optionally substituted, (6) aryl optionally substituted, or (7) a heteroaromatic group optionally substituted;

R² and R³ may be the same or different and each is (1) hydrogen, (2) alkyl optionally substituted, (3) cycloalkyl optionally substituted, (4) alkenyl optionally substituted, (5) alkynyl optionally substituted, (6) acyl optionally substituted, (7) monoalkylcarbamoyl optionally substituted, (8) dialkylcarbamoyl optionally substituted, or (9) alkoxy-carbonyl optionally substituted, or R² and R³ taken together is carbonyl;

wherein the substituents on R¹¹, R¹², R², R³ are the same or different and are selected from (1) halogen, (2) OR¹³, (3) OCOR¹³, (4) COOR¹³, (5) cyano, (6) NR¹³ R¹⁴, (7) cycloalkyl, (8) aryl optionally substituted by halogen, alkyl, hydroxy, or amino, and (9) a heteroaromatic group optionally substituted by halogen, alkyl, hydroxy, or amino;

wherein R¹³ and R¹⁴ may be the same or different and each is (1) hydrogen or (2) alkyl optionally substituted by hydroxy, alkoxy, amino, monoalkylamino, or dialkylamino but exclusive of the compounds wherein R¹ is hydroxy or methoxy;

R² and R³ are the same or different and each is hydrogen, methyl, formyl, acetyl or benzoyl.

12. The compound, pharmaceutically acceptable salt, or solvate claimed in claim 11 wherein R¹ is hydroxy, acyloxyalkoxy, phenylalkoxy, alkoxyalkoxy, hydroxyalkoxy, haloalkoxy, di(hydroxyalkyl)aminoalkoxy, (alkoxyalkyl)amino, halogen-substituted phenylamino, (dialkylaminoalkyl)amino, di(hydroxyalkyl)aminoalkyl!amino, (carboxyalkyl)amino, (alkoxycarbonylalkyl)amino, (cyanoalkyl)amino, or diamino-substituted triazinylalkylamino, R² is hydrogen, and R³ is hydrogen.

13. The compound, pharmaceutically acceptable salt, or solvate claimed in claim 11 wherein R¹ is hydroxy, (alkoxyalkyl)amino, halogen-substituted phenylamino, (dialkylaminoalkyl)amino, di(hydroxyalkyl)aminoalkyl!amino, (alkoxycarbonylalkyl)amino, or (cyanoalkyl)amino, R² is acetoxy, and R³ is acetoxy.

14. The compound, pharmaceutically acceptable salt, or solvate claimed in claim 11 wherein R¹ is phenylalkoxy, R² is hydroxy, (alkoxycarbonylalkyl)carbamoyl, or (alkoxyalkyl)carbamoyl, and R³ is phenylalkyl.

15. The compound, pharmaceutically acceptable salt, or solvate claimed in claim 11 wherein R¹ is hydroxy, R² is (alkoxycarbonylalkyl)carbamoyl, or (alkoxyalkyl)carbamoyl, and R³ is hydrogen.

16. The compound, pharmaceutically acceptable salt, or solvate claimed in claim 11 wherein R¹ is hydroxy or acyloxyalkoxy, and R² and R³ taken together is carbonyl.

17. The compound, pharmaceutically acceptable salt, or solvate claimed in claim 11 wherein R¹ is 2-methoxyethylamino or 2-acetoxyethoxy, R² is hydrogen, and R³ is hydrogen.

18. A pharmaceutical composition for the treatment of an animal, including humans, suffering from nephritis, which comprises an effective amount of the compound, pharmaceutically acceptable salt or solvate of claim 11 and a pharmaceutically acceptable carrier therefor.