Literature DB >> 12039587

Optimization of the beta-aminoester class of factor Xa inhibitors. Part 2: Identification of FXV673 as a potent and selective inhibitor with excellent In vivo anticoagulant activity.

Kevin R Guertin1, Charles J Gardner, Scott I Klein, Allison L Zulli, Mark Czekaj, Yong Gong, Alfred P Spada, Daniel L Cheney, Sebastian Maignan, Jean-Pierre Guilloteau, Karen D Brown, Dennis J Colussi, Valeria Chu, Christopher L Heran, Suzanne R Morgan, Ross G Bentley, Christopher T Dunwiddie, Robert J Leadley, Henry W Pauls.   

Abstract

Further optimization of the beta-aminoester class of factor Xa (fXa) inhibitors is described culminating in the identification of 9c (FXV673), a potent and selective factor Xa inhibitor with excellent in vivo anticoagulant activity. An X-ray structure of FXV673 bound to human fXa is also presented. Based on its selectivity, potent in vivo activity and favorable pre-clinical safety profile, FXV673 was selected for further development and is currently undergoing clinical trials.

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Year:  2002        PMID： 12039587     DOI： 10.1016/s0960-894x(02)00213-5

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  9 in total

1.  Role of the active-site solvent in the thermodynamics of factor Xa ligand binding.

Authors:  Robert Abel; Tom Young; Ramy Farid; Bruce J Berne; Richard A Friesner
Journal:  J Am Chem Soc       Date:  2008-02-12       Impact factor: 15.419

2.  Virtual Screening and X-ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 Group.

Authors:  Guyan Liang; Xin Chen; Suzanne Aldous; Su-Fen Pu; Shujaath Mehdi; Elaine Powers; Andrew Giovanni; Sathapana Kongsamut; Tianhui Xia; Ying Zhang; Rachel Wang; Zhongli Gao; Gregory Merriman; Larry R McLean; Isabelle Morize
Journal:  ACS Med Chem Lett       Date:  2012-01-11       Impact factor: 4.345

Review 3.  Heterocyclic N-Oxides - An Emerging Class of Therapeutic Agents.

Authors:  A M Mfuh; O V Larionov
Journal:  Curr Med Chem       Date:  2015       Impact factor: 4.530

4.  Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19.

Authors:  Jonathan H Shrimp; John Janiszewski; Catherine Z Chen; Miao Xu; Kelli M Wilson; Stephen C Kales; Philip E Sanderson; Paul Shinn; Rick Schneider; Zina Itkin; Hui Guo; Min Shen; Carleen Klumpp-Thomas; Samuel G Michael; Wei Zheng; Anton Simeonov; Matthew D Hall
Journal:  ACS Infect Dis       Date:  2022-06-01       Impact factor: 5.578

5.  Structures of beta-amino ester enolates: new strategies using the method of continuous variation.

Authors:  Lara R Liou; Anne J McNeil; Gilman E S Toombes; David B Collum
Journal:  J Am Chem Soc       Date:  2008-12-24       Impact factor: 15.419

6.  Molecular dynamics simulations of Factor Xa: insight into conformational transition of its binding subsites.

Authors:  Narender Singh; James M Briggs
Journal:  Biopolymers       Date:  2008-12       Impact factor: 2.505

7.  Enantiomeric characterization and structure elucidation of Otamixaban.

Authors:  Jian Shen; Jiping Yang; Winfried Heyse; Harald Schweitzer; Norbert Nagel; Doris Andert; Chengyue Zhu; Vincent Morrison; Gregory A Nemeth; Teng-Man Chen; Zhicheng Zhao; Timothy A Ayers; Yong-Mi Choi
Journal:  J Pharm Anal       Date:  2013-11-26

8.  A Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19.

Authors:  Jonathan H Shrimp; John Janiszewski; Catherine Z Chen; Miao Xu; Kelli M Wilson; Stephen C Kales; Philip E Sanderson; Paul Shinn; Zina Itkin; Hui Guo; Min Shen; Carleen Klumpp-Thomas; Samuel G Michael; Wei Zheng; Anton Simeonov; Matthew D Hall
Journal:  bioRxiv       Date:  2022-02-07

9.  Thermodynamics of Water in an Enzyme Active Site: Grid-Based Hydration Analysis of Coagulation Factor Xa.

Authors:  Crystal N Nguyen; Anthony Cruz; Michael K Gilson; Tom Kurtzman
Journal:  J Chem Theory Comput       Date:  2014-04-03       Impact factor: 6.006
  9 in total

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