title: Design, synthesis, and SAR of substituted acrylamides as factor Xa inhibitors.
abstract: Substituted acrylamides were used as templates that bridge P1 and P4 binding elements, resulting in a series of potent (sub-nanomolar) and selective factor Xa inhibitors. In this template, cis-geometry of P1 and P4 ligands is highly preferred. SAR on the substituting groups, as well as on modification of P1 and P4 moieties is described. Compounds in this series show good in vivo efficacy in animal models.
authors.affiliation: Millennium Pharmaceuticals, Inc., 256 East Grand Avenue, South San Francisco, CA 94080, USA. yonghong.song@mpi.com
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Song
authors.forename: Lane
authors.initials: L
authors.lastname: Clizbe
authors.forename: Chhaya
authors.initials: C
authors.lastname: Bhakta
authors.forename: Willy
authors.initials: W
authors.lastname: Teng
authors.forename: Wenhao
authors.initials: W
authors.lastname: Li
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhaozhong Jon
authors.initials: ZJ
authors.lastname: Jia
authors.forename: Penglie
authors.initials: P
authors.lastname: Zhang
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.forename: Brandon
authors.initials: B
authors.lastname: Doughan
authors.forename: Ting
authors.initials: T
authors.lastname: Su
authors.forename: James
authors.initials: J
authors.lastname: Kanter
authors.forename: John
authors.initials: J
authors.lastname: Woolfrey
authors.forename: Paul
authors.initials: P
authors.lastname: Wong
authors.forename: Brian
authors.initials: B
authors.lastname: Huang
authors.forename: Katherine
authors.initials: K
authors.lastname: Tran
authors.forename: Uma
authors.initials: U
authors.lastname: Sinha
authors.forename: Gary
authors.initials: G
authors.lastname: Park
authors.forename: Andrea
authors.initials: A
authors.lastname: Reed
authors.forename: John
authors.initials: J
authors.lastname: Malinowski
authors.forename: Stan
authors.initials: S
authors.lastname: Hollenbach
authors.forename: Robert M
authors.initials: RM
authors.lastname: Scarborough
authors.forename: Bing-Yan
authors.initials: BY
authors.lastname: Zhu
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000990:Antithrombin III / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D001682:Biological Availability; D004195:Disease Models, Animal; D015195:Drug Design; D065427:Factor Xa Inhibitors; D008024:Ligands; D008958:Models, Molecular; D011817:Rabbits; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013698:Templates, Genetic; D013927:Thrombosis / Q000188:drug therapy
chemical_list: D000178:Acrylamides; D065427:Factor Xa Inhibitors; D008024:Ligands; D000990:Antithrombin III