title: Novel small molecule bradykinin B1 receptor antagonists. Part 1: benzamides and semicarbazides.
abstract: The synthesis and SAR of two series of bradykinin B(1) receptor antagonists is described. The benzamide moiety proved to be a suitable replacement for the aryl ester functionality of biaryl based antagonists. In addition, it was found that semicarbazides can effectively replace cyclopropyl amino acids. The compounds with the best overall profile were biaryl semicarbazides which display high antagonistic activity, low Caco-2 efflux and high oral bioavailability in the rat.
authors.affiliation: Jerini AG, Invalidenstrasse 130, 10115 Berlin, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Schaudt
authors.forename: Elsa
authors.initials: E
authors.lastname: Locardi
authors.forename: Gunther
authors.initials: G
authors.lastname: Zischinsky
authors.forename: Roland
authors.initials: R
authors.lastname: Stragies
authors.forename: Jochen R
authors.initials: JR
authors.lastname: Pfeifer
authors.forename: Christoph
authors.initials: C
authors.lastname: Gibson
authors.forename: Dirk
authors.initials: D
authors.lastname: Scharn
authors.forename: Uwe
authors.initials: U
authors.lastname: Richter
authors.forename: Holger
authors.initials: H
authors.lastname: Kalkhof
authors.forename: Klaus
authors.initials: K
authors.lastname: Dinkel
authors.forename: Karsten
authors.initials: K
authors.lastname: Schnatbaum
mesh_terms: D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D018938:Caco-2 Cells; D006801:Humans; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000378:metabolism; D012663:Semicarbazides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D001549:Benzamides; D065169:Bradykinin B1 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D012663:Semicarbazides