766556-65-4Relevant academic research and scientific papers
Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications
Qiao, Jennifer X.,Wang, Tammy C.,Wang, Gren Z.,Cheney, Daniel L.,He, Kan,Rendina, Alan R.,Xin, Baomin,Luettgen, Joseph M.,Knabb, Robert M.,Wexler, Ruth R.,Lam, Patrick Y.S.
, p. 5041 - 5048 (2008/02/13)
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 μM in human plasma, bioavailability of 25% and t1/2of 2.7 h in dogs. Further biochemical characterization of compound 31 is also presented.
CYCLIC DIAMINES AND DERIVATIVES AS FACTOR XA INHIBITORS
-
, (2008/06/13)
The present application describes cyclic diamino compounds, derivatives thereof, and pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.
LACTAM-CONTAINING CYCLIC DIAMINES AND DERIVATIVES AS FACTOR XA INHIBITORS
-
Page/Page column 119, (2010/02/08)
The present application describes lactam-containing cyclic diamines and derivatives thereof of Formula I: or pharmaceutically acceptable salt forms thereof, wherein M is a non-aromatic carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trysin-like serine proteases, specifically factor Xa.
