简介: |
Patrick Y. Lam is currently a medicinal chemistry and drug discovery consultant. He was recently a director in the Discovery Chemistry Department at Bristol-Myers Squibb Co. He received his Ph.D. from the University of Rochester (Dr. Louis Friedrich) in 1980 and was a postdoctoral fellow in UCLA (Prof. Mike Jung and the late Prof. Don Cram). He joined DuPont in 1984 and moved to BMS in 2001. In recent years, he has been involved with HIV protease inhibitors, antithrombotics and antisense oligonucleotide (ASO) therapeutics. His research interest is in the application of new technologies in synthetic methodology, nucleic acid therapeutics, combichem, molecular recognition, computer-aided drug design tools and structural biology to drug discovery in order to deliver clinical candidates with novel structures, ADME and biological properties.
Patrick discovered and/or led groups that discovered a total of seven clinical candidates. This includes the novel anticoagulant, Apixaban/Eliquis®, a Factor Xa inhibitor in various completed or on-going PIII clinical trials. Apixaban has been approved in EU for deep vein thrombosis prevention in orthopedic surgery patients. Patrick is the co-discoverer of the powerful Chan-Lam oxidative coupling reaction for the copper promoted N/O-arylation with boronic acids. Patrick has received numerous awards including four BMS Citation Awards for the most cited BMS chemistry publications in 2003, 2004, 2005 and 2010; BMS Ondetti-Cushman Innovation Award for FXa inhibitor research in 2003; DuPont-Merck Summit Award for HIV protease inhibitor research in 1993. He serves on the Editorial Board of Current Medicinal Chemistry, Medicinal Chemistry, Letters in Drug Design & Discovery, Medicinal Research Reviews; was a member of Long Range Planning Committee of ACS Medicinal Chemistry Division (1997-2000).
Abstract
Thrombosis is the leading cause of death in developed countries and there is significant need for novel antithrombotics with an improved safety profile. Preclinical data has demonstrated that blocking FXa is an effective approach for anticoagulation with improved safety profile. Utilizing structure-based drug design tools, we at Bristol-Myers Squibb have discovered a novel class of potent, selective and orally bioavailable Factor Xa inhibitors culminating in Apixaban. Apixaban is being evaluated in a series of ongoing or completed Phase III clinical trials and has recently been approved in EU to be used as a new anticoagulant for orthopedic surgery patients. This seminar will describethis successful drug discovery storystarting from drug design leading all the way to clinical trials and market. During this drug discovery process, we have also discovered the powerful copper-promoted C-X bond coupling via boronic acids: Chan-Lam oxidative coupling reaction. This reaction is complementary to Suzuki-Miyauru C-C bond coupling reaction.
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