Potent and selective bicyclic lactam inhibitors of thrombin: Part 3: P1' modifications

J S Plummer; K A Berryman; C Cai; W L Cody; J DiMaio; A M Doherty; S Eaton; J J Edmunds; D R Holland; D Lafleur; S Levesque; L S Narasimhan; J R Rubin; S T Rapundalo; M A Siddiqui; A Susser; Y St-Denis; P Winocour

doi:10.1016/s0960-894x(99)00096-7

Potent and selective bicyclic lactam inhibitors of thrombin: Part 3: P1' modifications

Bioorg Med Chem Lett. 1999 Mar 22;9(6):835-40. doi: 10.1016/s0960-894x(99)00096-7.

Authors

J S Plummer¹, K A Berryman, C Cai, W L Cody, J DiMaio, A M Doherty, S Eaton, J J Edmunds, D R Holland, D Lafleur, S Levesque, L S Narasimhan, J R Rubin, S T Rapundalo, M A Siddiqui, A Susser, Y St-Denis, P Winocour

Affiliation

¹ Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.

PMID: 10206546
DOI: 10.1016/s0960-894x(99)00096-7

Abstract

The synthesis and antithrombotic activity of a series of nonpeptide bicyclic thrombin inhibitors are described. We have explored the SAR around the P1' site. Modification of the P1' site has been found to affect potency and selectivity.

MeSH terms

Animals
Disease Models, Animal
Heterocyclic Compounds / chemistry
Inhibitory Concentration 50
Kinetics
Lactams / pharmacology*
Models, Chemical
Models, Molecular
Rats
Thrombin / antagonists & inhibitors*
Thrombosis / drug therapy

Substances

Heterocyclic Compounds
Lactams
Thrombin