Clint A. James
Bristol-Myers Squibb
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Publication
Featured researches published by Clint A. James.
Journal of Medicinal Chemistry | 2014
Makonen Belema; Van N. Nguyen; Carol Bachand; Dan H. Deon; Jason Goodrich; Clint A. James; Rico Lavoie; Omar D. Lopez; Alain Martel; Jeffrey L. Romine; Edward H. Ruediger; Lawrence B. Snyder; Denis R. St. Laurent; Fukang Yang; Juliang Zhu; Henry S. Wong; David R. Langley; Stephen P. Adams; Glenn H. Cantor; Anjaneya Chimalakonda; Aberra Fura; Benjamin M. Johnson; Jay O. Knipe; Dawn D. Parker; Kenneth S. Santone; Robert A. Fridell; Julie A. Lemm; Donald R. O’Boyle; Richard J. Colonno; Min Gao
The biphenyl derivatives 2 and 3 are prototypes of a novel class of NS5A replication complex inhibitors that demonstrate high inhibitory potency toward a panel of clinically relevant HCV strains encompassing genotypes 1-6. However, these compounds exhibit poor systemic exposure in rat pharmacokinetic studies after oral dosing. The structure-activity relationship investigations that improved the exposure properties of the parent bis-phenylimidazole chemotype, culminating in the identification of the highly potent NS5A replication complex inhibitor daclatasvir (33) are described. An element critical to success was the realization that the arylglycine cap of 2 could be replaced with an alkylglycine derivative and still maintain the high inhibitory potency of the series if accompanied with a stereoinversion, a finding that enabled a rapid optimization of exposure properties. Compound 33 had EC50 values of 50 and 9 pM toward genotype-1a and -1b replicons, respectively, and oral bioavailabilities of 38-108% in preclinical species. Compound 33 provided clinical proof-of-concept for the NS5A replication complex inhibitor class, and regulatory approval to market it with the NS3/4A protease inhibitor asunaprevir for the treatment of HCV genotype-1b infection has recently been sought in Japan.
Archive | 2003
Tao Wang; John F. Kadow; Nicholas A. Meanwell; Kap-Sun Yeung; Zhongxing Zhang; Zhiwei Yin; Zhilei Qiu; Daniel H. Deon; Clint A. James; Edward H. Ruediger; Carol Bachand
Archive | 2009
Carol Bachand; Makonen Belema; Daniel H. Deon; Andrew C. Good; Jason Goodrich; Clint A. James; Rico Lavoie; Omar D. Lopez; Alain Martel; Nicholas A. Meanwell; Van N. Nguyen; Jeffrey L. Romine; Edward H. Ruediger; Lawrence B. Snyder; R Laurent Denis; Fukang Yang; David R. Langley; Gan Wang; Lawrence G. Hamann
Archive | 2008
Carol Bachand; Makonen Belema; Daniel H. Deon; Andrew C. Good; Jason Goodrich; Clint A. James; Rico Lavoie; Omar D. Lopez; Alain Martel; Nicholas A. Meanwell; Van N. Nguyen; Jeffrey L. Romine; Edward H. Ruediger; Lawrence B. Snyder; R Laurent Denis; Fukang Yang; David R. Langley; Gan Wang; Lawrence G. Hamann
Archive | 2006
Tao Wang; John F. Kadow; Nicholas A. Meanwell; Zhongxing Zhang; Zhiwei Yin; Clint A. James; Edward H. Ruediger; Bradley C. Pearce
Bioorganic & Medicinal Chemistry Letters | 2003
Gene M. Dubowchik; Jodi A. Michne; Dmitry Zuev; Wendy S. Schwartz; Paul Michael Scola; Clint A. James; Edward H. Ruediger; Sokhom S. Pin; Kevin D. Burris; Lynn A. Balanda; Qi Gao; Dedong Wu; Lawrence K. Fung; Tracey Fiedler; Kaitlin E. Browman; Matthew T. Taber; Jie Zhang
Archive | 2009
Carol Bachand; Belema Makonen; Daniel H. Deon; Andrew C. Good; Jason Goodrich; Clint A. James; Rico Lavoie; Omar D. Lopez; Alain Martel; Nicholas A. Meanwell; Van N. Nguyen; Jeffrey L. Romine; Edward H. Ruediger; Lawrence B. Snyder; R Laurent Denis; Fukang Yang; David R. Langley; Gan Wang; Lawrence G. Hamann
Tetrahedron Letters | 2006
Clint A. James; Brigitte Poirier; Christiane Grisé; Alain Martel; Edward H. Ruediger
Tetrahedron Letters | 2013
Gan Wang; Clint A. James; Nicholas A. Meanwell; Lawrence G. Hamann; Makonen Belema
Archive | 2009
Carol Bachand; Makonen Belema; Daniel H. Deon; Andrew C. Good; Jason Goodrich; Clint A. James; Rico Lavoie; Omar D. Lopez; Alain Martel; Nicholas A. Meanwell; Van N. Nguyen; Jeffrey L. Romine; Edward H. Ruediger; Lawrence B. Snyder; R Laurent Denis; Fukang Yang; David R. Langley; Gan Wang; Lawrence G. Hamann