title: Chlorothiophenecarboxamides as P1 surrogates of inhibitors of blood coagulation factor Xa.
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.
authors.affiliation: Merck KGaA, Preclinical Pharmaceutical Research, 64271 Darmstadt, Germany. mederski@merck.de
authors.forename: Werner W K R
authors.initials: WW
authors.lastname: Mederski
authors.forename: Bertram
authors.initials: B
authors.lastname: Cezanne
authors.forename: Christoph
authors.initials: C
authors.lastname: van Amsterdam
authors.forename: Karl-Ulrich
authors.initials: KU
authors.lastname: Bühring
authors.forename: Dieter
authors.initials: D
authors.lastname: Dorsch
authors.forename: Johannes
authors.initials: J
authors.lastname: Gleitz
authors.forename: Joachim
authors.initials: J
authors.lastname: März
authors.forename: Christos
authors.initials: C
authors.lastname: Tsaklakidis
mesh_terms: D000818:Animals; D004285:Dogs; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors; D013876:Thiophenes; D015951:Factor Xa