Design, synthesis, and SAR of substituted acrylamides as factor Xa inhibitors

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 modificati...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2002-06, Vol.12 (11), p.1511-1515
Main Authors: Song, Yonghong, Clizbe, Lane, Bhakta, Chhaya, Teng, Willy, Li, Wenhao, Wu, Yanhong, Jia, Zhaozhong Jon, Zhang, Penglie, Wang, Lingyan, Doughan, Brandon, Su, Ting, Kanter, James, Woolfrey, John, Wong, Paul, Huang, Brian, Tran, Katherine, Sinha, Uma, Park, Gary, Reed, Andrea, Malinowski, John, Hollenbach, Stan, Scarborough, Robert M., Zhu, Bing-Yan
Format: Article
Language:English
Subjects:
Acrylamides - chemical synthesis
Acrylamides - chemistry
Acrylamides - pharmacology
Animals
Antithrombin III - chemical synthesis
Antithrombin III - chemistry
Antithrombin III - pharmacology
Binding Sites
Biological and medical sciences
Biological Availability
Blood. Blood coagulation. Reticuloendothelial system
Disease Models, Animal
Drug Design
Factor Xa Inhibitors
Ligands
Medical sciences
Models, Molecular
Pharmacology. Drug treatments
Rabbits
Rats
Stereoisomerism
Structure-Activity Relationship
Templates, Genetic
Thrombosis - drug therapy
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Substituted acrylamides were used as templates that bridge P1 and P4 moieties, resulting in a series of potent (sub-nanomolar) and selective factor Xa inhibitors. Compounds in this series show good in vivo efficacy in animal models.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(02)00199-3