TENOFOVIR PRODRUG AND PHARMACEUTICAL USES THEREOF

• US 20150225433A1
• Filed: 07/10/2013
• Published: 08/13/2015
• Est. Priority Date: 08/30/2012
• Status: Active Grant

• Current Assignee: Jiangsu Hansoh Pharmaceutical Group Co., Ltd
• Original Assignee: Jiangsu Hansoh Pharmaceutical Company Limited
• Inventors: Zhang, Fuyao, Wei, Dong
• Granted Patent: US 9,908,908 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07F 9/65616 containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs

Abstract

The invention relates to a tenofovir prodrug and pharmaceutical uses thereof. In particular, the invention relates to a compound as shown in general formula (I):

and its isomer, pharmaceutically acceptable salt, hydrate or solvate, as well as their uses in preparing drugs for treating viral infectious diseases, especially HIV infection, hepatitis B, or diseases caused by hepatitis B virus, wherein the definition of each substituent in the general formula (I) is as defined in the specification.

Claims

1. A compound of general formula (I) or a stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof:

2. The compound of general formula (I) according to claim 1, or the stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein the phosphorus atom is chiral and the configuration is S or R, or a mixture of R and S.

3. The compound of general formula (I) according to claim 1, or the stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein the stereoisomer comprises a tautomer, cis-trans isomer, conformational isomer, mesomer, or enantiomeric or diastereomeric optical isomer.

4. The compound of general formula (I) according to claim 1, or the stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein the compound is:

5. The compound of general formula (I) according to claim 1, or the stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein the compound is:

7. A pharmaceutical composition comprising the compound of formula (I) or the stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof according to claim 1 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, wherein the pharmaceutically acceptable carrier is selected from the group consisting of water for injection, lyophilized powder excipient, and oral preparation excipient.

13. A pharmaceutical composition comprising the compound of formula (Ia) or the stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof according to claim 4 and a pharmaceutically acceptable carrier.

14. A pharmaceutical composition comprising the compound of formula (Ia) or the stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof according to claim 5 and a pharmaceutically acceptable carrier.

15. A method of treating a viral infection in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition according to claim 7.

16. The method according to claim 15, wherein the viral infection is selected from the group consisting of HIV infection, hepatitis B, and diseases caused by hepatitis B virus.

19. A method of treating a viral infection in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition according to claim 13.

20. The method according to claim 19, wherein the viral infection is selected from the group consisting of HIV infection, hepatitis B, and diseases caused by hepatitis B virus.

21. A method of treating a viral infection in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition according to claim 14.

22. The method according to claim 21, wherein the viral infection is selected from the group consisting of HIV infection, hepatitis B, and diseases caused by hepatitis B virus.

6. A compound of formula (Ia1) or a stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof:

11. A pharmaceutical composition comprising the compound of formula (Ia) or the stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof according to claim 6 and a pharmaceutically acceptable carrier.

12. The pharmaceutical composition according to claim 11, wherein the pharmaceutically acceptable carrier is selected from the group consisting of water for injection, lyophilized powder excipient, and oral preparation excipient.

17. A method of treating a viral infection in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition according to claim 11.

18. The method according to claim 17, wherein the viral infection is selected from the group consisting of HIV infection, hepatitis B, and diseases caused by hepatitis B virus.

9-10. -10. (canceled)