Cyclic adenosine monophosphate 8-substituted derivatives

• US 4,048,307 A
• Filed: 09/24/1975
• Issued: 09/13/1977
• Est. Priority Date: 12/26/1974
• Status: Expired due to Term

• Current Assignee: Asahi Kasei Kogyo Kabushiki Kaisha
• Original Assignee: Asahi Kasei Kogyo Kabushiki Kaisha
• Inventors: Suzuki, Nobuyuki, Sowa, Tsuneo, Yokota, Takeshi, Sasaki, Yasuharu, Ono, Yasutaka
• Primary Examiner(s): Brown, Johnnie R.
• Application Number:
  US05/616,356
• Time in Patent Office: 720 Days
• Field of Search: 260/211.5 R, 536/27, 424/180
• US Class Current: 514/47
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids

Abstract

Novel cyclic adenosine monophosphate derivatives represented by the following general formula: ##STR1## wherein A stands for --S-- or --NH-- and n is an integer of from 2 to 12, ARE SUPERIOR TO KNOWN CYCLIC ADENOSIENE DERIVATIVES IN BIOLOGICAL AND PHARMACOLOGICAL ACTIVITIES, ESPECIALLY PDE-inhibiting activity and membrane permeability. Accordingly, these derivatives are very effective for remedying and controlling diseases caused by disorder of the intracellular cyclic adenosine monophosphate level, such as asthma and scabies. These derivaives can readily be synthesized by reacting an 8-halogeno cyclic adenosine monophosphate of the following general formula ##STR2## wherein X is a halogen atom such as bromine, with an alkali metal salt of a linear alkylmercaptan having 3 to 13 carbon atoms in the alkyl group or a linear alkylamine having 3 to 13 carbon atoms in the alkyl group.

Claims

1. A cyclic adenosine monophosphate represented by the formula, or its pharmaceutically acceptable non-toxic inorganic or organic salt:

##STR6## wherein A stands for --S-- or --NH-- and n is an integer of from 5 to 12.

5. An 8-alkylamino cyclic adenosine monophosphate according to claim 1 wherein A is --NH--.

6. An 8-alkylamino cyclic adenosine monophosphate according to claim 5 wherein n is an integer of 5 to 8.

7. An 8-alkylamino cyclic adenosine monophosphate according to claim 5 wherein n is an integer of 9 to 12.

16. An 8-alkylamino cyclic adenosine monophosphate according to claim 5 wherein n is 5.

17. An 8-alkylamino cyclic adenosine monophosphate according to claim 5 wherein n is 6.

18. An 8-alkylamino cyclic adenosine monophosphate according to claim 5 wherein n is 7.

19. An 8-alkylamino cyclic adenosine monophosphate according to claim 5 wherein n is 8.

20. An 8-alkylamino cyclic adenosine monophosphate according to claim 5 wherein n is 9.

21. An 8-alkylamino cyclic adenosine monophosphate according to claim 5 wherein n is 10.

22. An 8-alkylamino cyclic adenosine monophosphate according to claim 5 wherein n is 11.

23. An 8-alkylamino cyclic adenosine monophosphate according to claim 5 wherein n is 12.

24. A pharmaceutical composition comprising an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 1 and a pharmaceutically acceptable carrier therefor.

28. A pharmaceutical composition comprising an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 5 and a pharmaceutically acceptable carrier therefor.

29. A pharmaceutical composition comprising an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 6 and a pharmaceutically acceptable carrier therefor.

30. A pharmaceutical composition comprising an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 7 and a pharmaceutically acceptable carrier therefor.

31. A method of treating diseases caused by disorder of the intracellular cyclic adenosine monophosphate level which comprises administering to a patient suffering from such disease an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 1.

35. A method of treating diseases caused by disorder of the intracellular cyclic adenosine monophosphate level which comprises administering to a patient suffering from such disease an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 5.

36. A method of treating diseases caused by disorder of the intracellular cyclic adenosine monophosphate level which comprises administering to a patient suffering from such disease an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 6.

37. A method of treating diseases caused by disorder of the intracellular cyclic adenosine monophosphate level which comprises administering to a patient suffering from such disease an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 7.

2. An 8-alkylmercapto cyclic adenosine monophosphate according to claim 2, wherein A is --S--.

3. An 8-alkylmercapto cyclic adenosine monophosphate according to claim 2 wherein n is an integer of from 5 to 8.

4. An 8-alkylmercapto cyclic adenosine monophosphate according to claim 2 wherein n is an integer of from 9 to 12.

8. An 8-alkylmercapto cyclic adenosine monophosphate according to claim 2 wherein n is 5.

9. An 8-alkylmercapto cyclic adenosine monophosphate according to claim 2 wherein n is 6.

10. An 8-alkylmercapto cyclic adenosine monophosphate according to claim 2 wherein n is 7.

11. An 8-alkylmercapto cyclic adenosine monophosphate according to claim 2 wherein n is 8.

12. An 8-alkylmercapto cyclic adenosine monophosphate according to claim 2 wherein n is 9.

13. An 8-alkylmercapto cyclic adenosine monohosphate according to claim 2 wherein n is 10.

14. An 8-alkylmercapto cyclic adenosine monophosphate according to claim 2 wherein n is 11.

15. An 8-alkylmercapto cyclic adenosine monophosphate according to claim 2 wherein n is 12.

25. A pharmaceutical composition comprising an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 2 and a pharmaceutically acceptable carrier therefor.

26. A pharmaceutical composition comprising an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 3 and a pharmaceutically acceptable carrier therefor.

27. A pharmaceutical composition comprising an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 4 and a pharmaceutically acceptable carrier therefor.

32. A method of treating diseases caused by disorder of the intracellular cyclic adenosine monophosphate level which comprises administering to a patient suffering from such disease an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 2.

33. A method of treating diseases caused by disorder of the intracellular cyclic adenosine monophosphate level which comprises administering to a patient suffering from such disease an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 3.

34. A method of treating diseases caused by disorder of the introcellular cyclic adenosine monophosphate level which comprises administering to a patient suffering from such disease an effective amount of a cyclic adenosine monophosphate or pharmaceutically acceptable non-toxic inorganic or organic salt thereof according to claim 4.