Chlorothiophenecarboxamides as P1 surrogates of inhibitors of blood coagulation factor Xa.

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.

Halothiophene benzimidazoles as P1 surrogates of inhibitors of blood coagulation factor Xa.

Neutral weak halothiophene benzimidazole inhibitors of the serine protease factor Xa were identified via screening of a compound library. The X-ray crystal structure of representative 3a bound to human fXa confirmed the S1 binding mode. Starting from 3a a series of halothiophene benzimidazoles was synthesized and investigated for their factor Xa inhibitory activity.

A general synthesis of 1-aryl carbamoyl-2-alkyl-4-aryl substituted semicarbazides as nonbasic factor Xa inhibitors.

An efficient four-step synthesis of 1-aryl-carbamoyl-2-alkyl-4-aryl-semicarbazides starting from benzophenone hydrazone is described leading to moderately active neutral factor Xa inhibitors.

Benzofuro[3,2-b]pyridines as mixed ET(A)/ET(B) and selective ET(B) endothelin receptor antagonists.

The discovery, synthesis and structure-activity relationships of a series of novel benzofuro[3,2-b]pyridines as non-selective endothelin ET(A)/ET(B) as well as selective ET(B) receptor antagonists are described. The most potent non-selective inhibitor 7s displayed an IC50 of 21 nM and 41 nM for ET(A) and ET(B) receptors, respectively, whereas 7ee merely showed affinity for the ET(B) receptor (IC50 = 3.6 nM).