Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications. Qiao, J. X., Wang, T. C., Wang, G. Z., Cheney, D. L., He, K., Rendina, A. R., Xin, B., Luettgen, J. M., Knabb, R. M., Wexler, R. R., & Lam, P. Y. S. Bioorg.~Med.~Chem.~Lett., 17(18):5041--5048, 2007. ![Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper abstract bibtex 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 Ki of 0.50 nM, PT EC2x of 2.1 $[$mu$]$M in human plasma, bioavailability of 25% and t1/2of 2.7 h in dogs. Further biochemical characterization of compound 31 is also presented.
@article{Qiao:2007aa,
Abstract = {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 Ki of 0.50 nM, PT EC2x of 2.1 {$[$}mu{$]$}M in human plasma, bioavailability of 25{\%} and t1/2of 2.7 h in dogs. Further biochemical characterization of compound 31 is also presented.},
Author = {Qiao, Jennifer X. and Wang, Tammy C. and Wang, Gren Z. and Cheney, Daniel L. and He, Kan and Rendina, Alan R. and Xin, Baomin and Luettgen, Joseph M. and Knabb, Robert M. and Wexler, Ruth R. and Lam, Patrick Y. S.},
Date-Added = {2007-12-11 17:01:03 -0500},
Date-Modified = {2007-12-11 17:01:03 -0500},
Journal = {Bioorg.~Med.~Chem.~Lett.},
Keywords = {sar; sali; Factor Xa inhibitors; Enantiopure cyclicdiamine derivatives; SAR; Human liver microsomal stability},
Local-Url = {file://localhost/Users/rguha/Documents/articles/qiao-fxainhib.pdf},
Number = {18},
Pages = {5041--5048},
Title = {Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications},
Ty = {JOUR},
Url = {http://www.sciencedirect.com/science/article/B6TF9-4P61N4W-D/2/77fe4de70b86a1d098c913a0174be52e},
Volume = {17},
Year = {2007},
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