Discovery of LB30057, a benzamidrazone-based selective oral thrombin inhibitor.

Abstract

Systematic variation of the so-called P-pocket moiety of benzamidrazone-based selective thrombin inhibitors led to the discovery of LB30057. It is potent (Ki = 0.38 nM for human thrombin), selective (Ki = 3290 nM for bovine trypsin), and orally bioavailable (58% oral bioavailability in dogs). LB30057 was efficacious in thrombosis animal models.

• Authors: Y S Oh, M Yun, S Y Hwang, S Hong, Y Shin, K Lee, K H Yoon, Y J Yoo, D S Kim, S H Lee, Y H Lee, H D Park, C H Lee, S K Lee, S Kim
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 8 Issue 6 Pg. 631-4 (Mar 17 1998) ISSN: 0960-894X [Print] England
• PMID: 9871573 (Publication Type: Journal Article)

Chemical References

• Benzamides
• LB 30057
• Thrombin

Topics

• Animals
• Benzamides (pharmacokinetics, therapeutic use)
• Biological Availability
• Cattle
• Disease Models, Animal
• Dogs
• Half-Life
• Humans
• Models, Molecular
• Rats
• Structure-Activity Relationship
• Thrombin (antagonists & inhibitors)
• Thrombosis (drug therapy)