Alan Xiangdong Wang
Bristol-Myers Squibb
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Alan Xiangdong Wang.
Journal of Medicinal Chemistry | 2014
Paul Michael Scola; Li-Qiang Sun; Alan Xiangdong Wang; Jie Chen; Ny Sin; Brian Lee Venables; Sing-Yuen Sit; Yan Chen; Anthony J. Cocuzza; Donna M. Bilder; Stanley V. D’Andrea; Barbara Zheng; Piyasena Hewawasam; Yong Tu; Jacques Friborg; Paul Falk; Dennis Hernandez; Steven Levine; Chaoqun Chen; Fei Yu; Amy K. Sheaffer; Guangzhi Zhai; Diana Barry; Jay O. Knipe; Yong-Hae Han; Richard Schartman; Maria Donoso; Kathy Mosure; Michael Sinz; Tatyana Zvyaga
The discovery of asunaprevir (BMS-650032, 24) is described. This tripeptidic acylsulfonamide inhibitor of the NS3/4A enzyme is currently in phase III clinical trials for the treatment of hepatitis C virus infection. The discovery of 24 was enabled by employing an isolated rabbit heart model to screen for the cardiovascular (CV) liabilities (changes to HR and SNRT) that were responsible for the discontinuation of an earlier lead from this chemical series, BMS-605339 (1), from clinical trials. The structure-activity relationships (SARs) developed with respect to CV effects established that small structural changes to the P2* subsite of the molecule had a significant impact on the CV profile of a given compound. The antiviral activity, preclincial PK profile, and toxicology studies in rat and dog supported clinical development of BMS-650032 (24).
Bioorganic & Medicinal Chemistry Letters | 2017
Alan Xiangdong Wang; Jie Chen; Qian Zhao; Li-Qiang Sun; Jacques Friborg; Fei Yu; Dennis Hernandez; Andrew C. Good; Herbert E. Klei; Ramkumar Rajamani; Kathy Mosure; Jay O. Knipe; Danshi Li; Jialong Zhu; Paul Levesque; Fiona McPhee; Nicholas A. Meanwell; Paul Michael Scola
The design and synthesis of a series of tripeptide acylsulfonamides as potent inhibitors of the HCV NS3/4A serine protease is described. These analogues house a C4 aryl, C4 hydroxy-proline at the S2 position of the tripeptide scaffold. Information relating to structure-activity relationships as well as the pharmacokinetic and cardiovascular profiles of these analogues is provided.
ACS Medicinal Chemistry Letters | 2018
Barbara Zheng; Stanley D'andrea; Li-Qiang Sun; Alan Xiangdong Wang; Yan Chen; Peter Hrnciar; Jacques Friborg; Paul Falk; Dennis Hernandez; Fei Yu; Amy K. Sheaffer; Jay O. Knipe; Kathy Mosure; Ramkumar Rajamani; Andrew C. Good; Kevin Kish; Jeffrey Tredup; Herbert E. Klei; Manjula Paruchuri; Alicia Ng; Qi Gao; Richard Rampulla; Arvind Mathur; Nicholas A. Meanwell; Fiona McPhee; Paul Michael Scola
The design and synthesis of potent, tripeptidic acylsulfonamide inhibitors of HCV NS3 protease that contain a difluoromethyl cyclopropyl amino acid at P1 are described. A cocrystal structure of 18 with a NS3/4A protease complex suggests the presence of a H-bond between the polarized C-H of the CHF2 moiety and the backbone carbonyl of Leu135 of the enzyme. Structure-activity relationship studies indicate that this H-bond enhances enzyme inhibitory potency by 13- and 17-fold compared to the CH3 and CF3 analogues, respectively, providing insight into the deployment of this unique amino acid.
Bioorganic & Medicinal Chemistry Letters | 2018
Brian Lee Venables; Ny Sin; Alan Xiangdong Wang; Li-Qiang Sun; Yong Tu; Dennis Hernandez; Amy K. Sheaffer; Min Lee; Cindy Dunaj; Guangzhi Zhai; Diana Barry; Jacques Friborg; Fei Yu; Jay O. Knipe; Jason Sandquist; Paul Falk; Dawn D. Parker; Andrew C. Good; Ramkumar Rajamani; Fiona McPhee; Nicholas A. Meanwell; Paul Michael Scola
A series of tripeptidic acylsulfonamide inhibitors of HCV NS3 protease were prepared that explored structure-activity relationships (SARs) at the P4 position, and their in vitro and in vivo properties were evaluated. Enhanced potency was observed in a series of P4 ureas; however, the PK profiles of these analogues were less than optimal. In an effort to overcome the PK shortcomings, modifications to the P3-P4 junction were made. This included a strategy in which one of the two urea N-H groups was either N-methylated or replaced with an oxygen atom. The former approach provided a series of regioisomeric N-methylated ureas while the latter gave rise to P4 reverse carbamates, both of which retained potent NS3 inhibitory properties while relying upon an alternative H-bond donor topology. Details of the SARs and PK profiles of these analogues are provided.
Synthetic Communications | 2009
Zhizhen Barbara Zheng; Alan Xiangdong Wang; Paul Michael Scola; Stanley D'andrea
Abstract A convenient and efficient synthetic route to 1-chloro-6-methoxy-isoquinolin-3-ol and its derivatives is reported. This new method involves carboxylation of 4-methoxy-2-methylbenzonitrile, subsequent conversion of the resulting 2-cyano-5-methoxy-phenylacetic acid to its acid chloride, and acid-promoted cyclization of the 2-cyano-5-methoxy-phenyl-acetyl chloride. This procedure offers a better overall yield than the previously reported route and is also less hazardous and more reproducible.
Journal of Medicinal Chemistry | 2014
Paul Michael Scola; Alan Xiangdong Wang; Andrew C. Good; Li-Qiang Sun; Keith D. Combrink; Jeffrey Allen Campbell; Jie Chen; Yong Tu; Ny Sin; Brian Lee Venables; Sing-Yuen Sit; Yan Chen; Anthony J. Cocuzza; Donna M. Bilder; Stanley V. D’Andrea; Barbara Zheng; Piyasena Hewawasam; Min Ding; Jan Willem Thuring; Jianqing Li; Dennis Hernandez; Fei Yu; Paul Falk; Guangzhi Zhai; Amy K. Sheaffer; Chaoqun Chen; Min S. Lee; Diana Barry; Jay O. Knipe; Wenying Li
Archive | 2007
Alan Xiangdong Wang; Barbara Zhizhen Zheng; Stanley D'andrea; Nicholas A. Meanwell; Paul Michael Scola
Archive | 2017
Srinivasan Thangathirupathy; Makonen Belema; Robert A. Fridell; Brett R. Beno; Nicholas A. Meanwell; Gan Wang; Alan Xiangdong Wang; Zhong Yang; Van N. Nguyen; Omar D. Lopez; John A. Bender
Archive | 2016
Paul Michael Scola; Juliang Zhu; Ningning Xu; Alan Xiangdong Wang; Li Sun; Mark G. Saulnier; Kyle E. Parcella; Eric Mull; Zhaoxing Meng; David R. Langley; Piyasena Hewawasam; Katherine A Grant Young; David B. Frennesson; Timothy P. Connolly; Kap Yeung
Archive | 2009
Ny Sin; Brian Lee Venables; Paul Michael Scola; Alan Xiangdong Wang