Imidazotriazinone inhibitors of the Ca2+-calmodulin sensitive phosphodiesterase (PDE I)

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 1, 1997, Pages 89-94

  Hlasta, Dennis J ^a,b   Bode, Donald C ^a   Court, John J ^a   Desai, Ranjit C ^a   Pagani, Edward D ^a   Silver, Paul J ^a  

^a Sanofi Winthrop Inc   (United States)

^b R W JOHNSON PHARMACEUTICAL RES I   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4,5 DIHYDRO 6 [4 (1H IMIDAZOL 1 YL)PHENYL] 5 METHYL 3(2H) PYRIDAZINONE; ISOENZYME; MILRINONE; PHOSPHODIESTERASE I; PHOSPHODIESTERASE INHIBITOR; UNCLASSIFIED DRUG; WIN 61691; ZAPRINAST;

ARTICLE; DRUG DESIGN; DRUG SYNTHESIS; ENZYME INHIBITION; HYBRID; STRUCTURE ACTIVITY RELATION;

EID: 0031031796     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(96)00578-1     Document Type: Article

References (15)

1. Nicholson, C. D.; Challiss, R. A. J.; Shahid, M. Trends Pharmacol. Sci. 1991, 12, 19. Beavo, J. A.; Reifsnyder, D. H. Trends Pharmacol. Sci. 1990, 11, 150.
2. Nicholson, C. D.; Challiss, R. A. J.; Shahid, M. Trends Pharmacol. Sci. 1991, 12, 19. Beavo, J. A.; Reifsnyder, D. H. Trends Pharmacol. Sci. 1990, 11, 150.
3. Sharma, R. K.; Hickie, R. A. In Phosphodiesterase Inhibitors; Schudt, C.; Dent, G.; Rabe, K. F., Eds.; Academic: San Diego, 1996; Chap 4, pp 65-79.
4. Ahn, H. S.; Crim, W.; Romano, M.; Sybertz, E.; Pitts, B. Biochem. Pharmacol. 1989, 38, 3331.
5. Fredholm, B. B.; Lindgren, E.; Lindstrom, K.; Vernet, L. Acta Pharmacol. Toxicol. 1983, 53, 236.
6. Silver, P. J.; Dundore, R. L.; Bode, D. C.; deGaravilla, L.; Buchholz, R. A.; Van Aller, G.; Hamel, L. T.; Bacon, E.; Singh, B.; Lesher, G. Y.; Hlasta, D.; Pagani, E. D. J. Pharmacol. Exp. Ther. 1994, 271, 1143.
7. Reaction of 2a with three portions of bromine in acetic acid at it for 5 days gave 2e (20% yield): mp 250-252 °C.
8. + quench gave 2f (40% yield): mp 224-226 °C. The structure was determined by X-ray crystallography.
9. 2 and refluxed to give S (20% yield): mp 216-217 °C.
10. 3 and MeI in DMF at 40 °C gave 6 (90% yield): mp 169-171 °C.
11. Bastiaansen, L. A. M.; Godefroi, E. F. Synthesis 1978, 675.
12. Regel, E. Ann. 1977, 159.
13. A similar modeling analysis of a heterocyclic PDE inhibitor with cGMP has been described. Davis, A.; Warrington, B. H.; Vinter, J. G. J. Comput.-Aided Mol. Des. 1987, 1, 97.
14. Alousi, A. A.; Walton, L. H.; Lesher, G. Y.; Farah, A. E. Spec. Publ. - R. Soc. Chem. 1984, 50, 65. Lesher, G. Y.; Philion, R. E. U.S. Patent 4 313 951, 1982.
15. Alousi, A. A.; Walton, L. H.; Lesher, G. Y.; Farah, A. E. Spec. Publ. - R. Soc. Chem. 1984, 50, 65. Lesher, G. Y.; Philion, R. E. U.S. Patent 4 313 951, 1982.