Chlorothiophenecarboxamides as P1 surrogates of inhibitors of blood coagulation factor Xa

  • Bioorg Med Chem Lett. 2004 Dec 6;14(23):5817-22. doi: 10.1016/j.bmcl.2004.09.043.
Werner W K R Mederski  1 ,  Bertram Cezanne ,  Christoph van Amsterdam ,  Karl-Ulrich Bühring ,  Dieter Dorsch ,  Johannes Gleitz ,  Joachim März ,  Christos Tsaklakidis
Affiliations
  • 1. Merck KGaA, Preclinical Pharmaceutical Research, 64271 Darmstadt, Germany. [email protected]
PMID: 15501047 DOI: 10.1016/j.bmcl.2004.09.043
Abstract

Neutral chlorothiophenecarboxamides bearing an amino acid and a substituted aniline were synthesized and investigated for their Factor Xa inhibitory activity in vitro. From selected 2-methylphenyl morpholinones the solution properties were determined. The most soluble and active compounds were then investigated in different animal species to compare the pharmacokinetic parameters. This led to a potent, water soluble and orally bioavailable candidate for further development: EMD 495235.

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