Synthesis and biological evaluation of both enantiomers of L-761,000 as inhibitors of cyclooxygenase 1 and 2

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 6, 1996, Pages 731-736

  Leblanc, Y ^a   Black, W C ^a   Chan, C C ^a   Charleson, S ^a   Delorme, D ^a   Denis, D ^a   Gauthier, J Y ^a   Grimm, E L ^a   Gordon, R ^a   Guay, D ^a   Hamel, P ^a   Kargman, S ^a   Lau, C K ^a   Mancini, J ^a   Ouellet, M ^a   Percival, D ^a   Roy, P ^a   Skorey, K ^a   Tagari, P ^a   Vickers, P ^a   Wong, E ^a   Xu, L ^a   Prasit, P ^a   more..

^a MERCK FROSST CENTRE FOR THERAPEUTIC RESEARCH   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

INDOMETACIN; L 761000; L 761065; L 761066; PROSTAGLANDIN SYNTHASE; PROSTAGLANDIN SYNTHASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ANTIPYRETIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG SYNTHESIS; ENANTIOMER; ENZYME INHIBITION; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT;

ANIMALIA;

EID: 0029980668     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00101-1     Document Type: Article

References (14)

1. See preceding paper
2. (a) Lien, E. J. J. Drug Targeting, 1995, 2, 527.
3. (b) Brossi, A. Med. Res. Rev., 1994, 14, 665.
4. (c) Waldeck, B. Chirality, 1993, 5, 350.
5. (a) Tracy, T. S. Ann. Pharmacother. 1995, 29, 161.
6. (b) Augustijns, P.; Verbeke, N. Clin. Pharmacokinet., 1993, 24, 259.
7. Corey, E. J.; Boaz, N. W. Tetrahedron Lett. 1985, 26, 6015.
8. Thijs, L.; Stokkingreef, E. H. M.; Lemmens, J. M.; Zwanenburg, B. Tetrahedron, 1985, 41, 2949.
9. Overberger, C. G.; Weise, J. K. J. Am. Chem. Soc. 1968, 90, 3525.
10. Randad, R. S.; Bhat, N. G.; Kulkami, G. H. Indian J. Chem. 1984, 23B, 947.
11. The value of the optical rotation for L-761,066 is-7.1° (c = 1, acetone).
12. Chan, C.-C.; Boyce, S.; Brideau, C.; Ford-Hutchinson, A. W.; Gordon, R.; Guay, D.; Hill, R. G.; Li, C.-S.; Mancini, J.; Penneton, M.; Prasit, P.; Rasori, R.; Riendeau, D.; Roy, P.; Tagari, P.; Vickers, P.; Wong, E.; Rodger, I. W. J. Pharmacol. Exp. Ther. 1995, 274, 1531.
13. 50's values have been observed in the COX-2 induction of different cell cultures. This partially explains why the ICso value for the racemate (L-761,000) is different than in the preceeding paper.
14. A clearance of 5.7 mL/kg/min was observed for the racemate L-761,000.