Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications.

Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications. Research Abstract Details 

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Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications. Abstract Text:

Jennifer X Qiao,Tammy C Wang,Gren Z Wang,Daniel L Cheney,Kan He,Alan R Rendina,Baomin Xin,Joseph M Luettgen,Robert M Knabb,Ruth R Wexler,Patrick Y S Lam,Jennifer X Qiao,Tammy C Wang,Gren Z Wang,Daniel L Cheney,Kan He,Alan R Rendina,Baomin Xin,Joseph M Luettgen,Robert M Knabb,Ruth R Wexler,Patrick Y S Lam,

We previously reported a series of enantiopure cis-(1R,2S)-cyclopentyldiamine derivatives as potent and selective inhibitors of Factor Xa (FXa). Herein, we describe our approach to improve the metabolic stability of this series via core modifications. Multiple resulting series of compounds demonstrated similarly high FXa potency and improved metabolic stability in human liver microsomes compared with the cyclopentyldiamide 1. (3R,4S)-Pyrrolidinyldiamide 31 was the best overall compound with human FXa K(i) of 0.50 nM, PT EC(2x) of 2.1 microM in human plasma, bioavailability of 25% and t(1/2)of 2.7h in dogs. Further biochemical characterization of compound 31 is also presented.

Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications. Publishing Authors By Initials

JX Qiao,TC Wang,GZ Wang,DL Cheney,K He,AR Rendina,B Xin,JM Luettgen,RM Knabb,RR Wexler,PY Lam,JX Qiao,TC Wang,GZ Wang,DL Cheney,K He,AR Rendina,B Xin,JM Luettgen,RM Knabb,RR Wexler,PY Lam,

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Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Bioorganic & medicinal chemistry letters

VOLUME: 17

Page Numbers: 5041-8

Journal Abbreviation: Bioorg. Med. Chem. Lett.

ISSN: 0960-894X

DAY: 13

MONTH: 07

YEAR: 2007

Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications. Information

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LANGUAGE: eng

NlmUniqueID: 9107377

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Grant and Affiliation Information for Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications.

AFFILIATION: Bristol-Myers Squibb Company, Research and Development, PO Box 5400, Princeton, NJ 08643-5400, USA. jennifer.qiao@bms.com

Country: England

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MEDLINETA: Bioorg Med Chem Lett

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