title: Synthesis and evaluation of novel alpha-amino cyclic boronates as inhibitors of HCV NS3 protease.
abstract: We have designed and synthesized a novel series of alpha-amino cyclic boronates and incorporated them successfully in several acyclic templates at the P1 position. These compounds are inhibitors of the HCV NS3 serine protease, and structural studies show that they inhibit the NS3 protease by trapping the Ser-139 hydroxyl group in the active site. Synthetic methodologies and SARs of this series of compounds are described.
authors.affiliation: Anacor Pharmaceuticals, Inc., Palo Alto, CA 94303, USA. xli@anacor.com
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Li
authors.forename: Yong-Kang
authors.initials: YK
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Charles Z
authors.initials: CZ
authors.lastname: Ding
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Yasheen
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Plattner
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Baker
authors.forename: Xuelei
authors.initials: X
authors.lastname: Qian
authors.forename: Dazhong
authors.initials: D
authors.lastname: Fan
authors.forename: Liang
authors.initials: L
authors.lastname: Liao
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Ni
authors.forename: Gemma V
authors.initials: GV
authors.lastname: White
authors.forename: Jackie E
authors.initials: JE
authors.lastname: Mordaunt
authors.forename: Linos X
authors.initials: LX
authors.lastname: Lazarides
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Slater
authors.forename: Richard L
authors.initials: RL
authors.lastname: Jarvest
authors.forename: Pia
authors.initials: P
authors.lastname: Thommes
authors.forename: Malcolm
authors.initials: M
authors.lastname: Ellis
authors.forename: Colin M
authors.initials: CM
authors.lastname: Edge
authors.forename: Julia A
authors.initials: JA
authors.lastname: Hubbard
authors.forename: Don
authors.initials: D
authors.lastname: Somers
authors.forename: Paul
authors.initials: P
authors.lastname: Rowland
authors.forename: Pamela
authors.initials: P
authors.lastname: Nassau
authors.forename: Bill
authors.initials: B
authors.lastname: McDowell
authors.forename: Tadeusz J
authors.initials: TJ
authors.lastname: Skarzynski
authors.forename: Wieslaw M
authors.initials: WM
authors.lastname: Kazmierski
authors.forename: Richard M
authors.initials: RM
authors.lastname: Grimes
authors.forename: Lois L
authors.initials: LL
authors.lastname: Wright
authors.forename: Gary K
authors.initials: GK
authors.lastname: Smith
authors.forename: Wuxin
authors.initials: W
authors.lastname: Zou
authors.forename: Jon
authors.initials: J
authors.lastname: Wright
authors.forename: Lewis E
authors.initials: LE
authors.lastname: Pennicott
mesh_terms: D001897:Boronic Acids / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D020134:Catalytic Domain; D015195:Drug Design; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D015394:Molecular Structure; D012694:Serine / Q000737:chemistry; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D001897:Boronic Acids; D012694:Serine; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases