6-Aminocarbonyl purine 3',5'-cyclic nucleotides

• US 4,038,480 A
• Filed: 09/17/1973
• Issued: 07/26/1977
• Est. Priority Date: 09/17/1973
• Status: Expired due to Term

• Current Assignee: Viratek, Inc. (Bausch Health Cos., Inc.)
• Original Assignee: ICN Pharmaceuticals, Inc (Bausch Health Cos., Inc.)
• Inventors: Robins, Roland K., Boswell, Kay H., Shuman, Dennis A.
• Primary Examiner(s): Brown, Johnnie R.
• Application Number:
  US05/398,009
• Time in Patent Office: 1,408 Days
• Field of Search: 260/211.5 R, 536/27, 536/28
• US Class Current: 536/26.13
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids

Abstract

N⁶ -Carbamoyl and -carbonyl analogs of adenosine 3'"'"',5'"'"'-cyclic phosphate (cAMP) are prepared and variously demonstrated to exhibit kinase, adrenal steroidogenisis and lipolysis activation superior to cAMP, inhibit phosphodiesterase, and found to increase cardiac output or, in particular cases, to lower blood pressure.

Claims

1. A compound of structure ##STR3## wherein Y is COOR₁, CONHR₁, or CONHC₆ H₅, X is C₁ -C₁₈ acyl, Y or H, Z is H, bromine, or chlorine SR₂, R₁ is C₁ - C₆ alkyl and R₂ is H, phenyl, benzyl or C₁ - C₆ alkyl.

2. A compound according to claim 1 wherein X is acyl or H.

3. A compound according to claim 2 wherein Y is CONHR₁ or CONHC₆ H₅.

4. A compound according to claim 3 wherein Y is CONHC₆ H₅.

5. N⁶ -(N-methylcarbamoyl) adenosine 3'"'"',5'"'"'-cyclic phosphate.

6. N⁶ -(N-propylcarbamoyl) adenosine 3'"'"',5'"'"'-cyclic phosphate.

7. N⁶ -(N-phenylcarbamoyl) adenosine 3'"'"',5'"'"'-cyclic phosphate.

8. N⁶ -(ethoxycarbonyl) adenosine 3'"'"',5'"'"'-cyclic phosphate.

9. 8-Benzylthio-N⁶ -(N-phenylcarbamoyl) adenosine 3'"'"',5'"'"'-cyclic phosphate.

10. 8-Benzylthio-2'"'"'-O-butyryl-N⁶ -(N-phenylcarbamoyl) adenosine 3'"'"',5'"'"'-cyclic phosphate.

11. 2'"'"'-O-butyryl-N⁶ -(N-phenylcarbamoyl) adenosine 3'"'"',5'"'"'-cyclic phosphate.

12. A compound of the formula ##STR4## wherein Y is selected from the group consisting of COOR₁, CONHR₁ and CONHC₆ H₅ ;

X is selected from the group consisting of COOR₁, CONHR₁, CONHC₆ H₅, C₁ -C₄ acyl and H and R₁ is lower alkyl.

13. A compound according to claim 12 wherein X is acyl or H.

14. A compound according to claim 12 wherein X is H.

15. A compound according to claim 13 wherein Y is CONHR₁.

16. A compound according to claim 13 wherein Y is CONHC₆ H₅.

17. A compound according to claim 15 wherein R₁ is C₁ -C₃ alkyl.

18. A compound according to claim 16 wherein R₁ is C₁ -C₃ alkyl.

19. A compound according to claim 14 wherein Y is CONHR₁.

20. A compound according to claim 14 wherein Y is CONHC₆ H₅.

21. A compound according to claim 15 wherein R₁ is C₁ -C₃ alkyl.

22. A compound according to claim 16 wherein R₁ is C₁ -C₃ alkyl.