title: Novel small molecule bradykinin B1 receptor antagonists. Part 3: hydroxyurea derivatives.
abstract: Hydroxy urea moieties are introduced as a new class of bradykinin B(1) receptor antagonists. First, the SAR of the lead compound was systematically explored. Subsequent optimization resulted in the identification of several biaryl-based hydroxyurea bradykinin B(1) receptor antagonists with low-nanomolar activity and very high oral bioavailability in the rat.
authors.affiliation: Jerini AG, Invalidenstrasse 130, 10115 Berlin, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Schnatbaum
authors.forename: Marco
authors.initials: M
authors.lastname: Schaudt
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: Elsa
authors.initials: E
authors.lastname: Locardi
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: Gunther
authors.initials: G
authors.lastname: Zischinsky
mesh_terms: D000818:Animals; D001682:Biological Availability; D065169:Bradykinin B1 Receptor Antagonists; D018938:Caco-2 Cells; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*
chemical_list: D065169:Bradykinin B1 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D006918:Hydroxyurea