Anthranilamide-based N,N-dialkylbenzamidines as potent and orally bioavailable factor Xa inhibitors: P4 SAR

Penglie Zhang; Liang Bao; Jingmei Fan; Zhaozhong J Jia; Uma Sinha; Paul W Wong; Gary Park; Athiwat Hutchaleelaha; Robert M Scarborough; Bing-Yan Zhu

doi:10.1016/j.bmcl.2009.02.114

Anthranilamide-based N,N-dialkylbenzamidines as potent and orally bioavailable factor Xa inhibitors: P4 SAR

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2186-9. doi: 10.1016/j.bmcl.2009.02.114. Epub 2009 Mar 3.

Authors

Penglie Zhang¹, Liang Bao, Jingmei Fan, Zhaozhong J Jia, Uma Sinha, Paul W Wong, Gary Park, Athiwat Hutchaleelaha, Robert M Scarborough, Bing-Yan Zhu

Affiliation

¹ Millennium Pharmaceuticals, Inc, South San Francisco, CA 94080, USA.

PMID: 19297158
DOI: 10.1016/j.bmcl.2009.02.114

Abstract

Anthranilamide-based benzamidine compound 4 and its N-substituted analogs were designed and examined as factor Xa inhibitors using substituted benzamidines as unconventional S4 binding element. A group of N,N-dialkylbenzamidines (11, 17 and 24) have been discovered as potent factor Xa inhibitors with strong anticoagulant activity and promising oral PK profiles.

Publication types

Comparative Study

MeSH terms

Administration, Oral
Animals
Anticoagulants / administration & dosage*
Anticoagulants / chemical synthesis*
Anticoagulants / pharmacokinetics
Benzamidines / administration & dosage*
Benzamidines / chemical synthesis*
Benzamidines / pharmacokinetics
Biological Availability
Dogs
Factor Xa / pharmacokinetics
Factor Xa Inhibitors*
Humans
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship
ortho-Aminobenzoates / administration & dosage*
ortho-Aminobenzoates / chemical synthesis*
ortho-Aminobenzoates / pharmacokinetics

Substances

Anticoagulants
Benzamidines
Factor Xa Inhibitors
ortho-Aminobenzoates
Factor Xa
anthranilamide