Novel small molecule bradykinin B1 receptor antagonists. Part 3: hydroxyurea derivatives.
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.
Schnatbaum
Karsten
K
Jerini AG, Invalidenstrasse 130, 10115 Berlin, Germany.
Schaudt
Marco
M
Stragies
Roland
R
Pfeifer
Jochen R
JR
Gibson
Christoph
C
Locardi
Elsa
E
Scharn
Dirk
D
Richter
Uwe
U
Kalkhof
Holger
H
Dinkel
Klaus
K
Zischinsky
Gunther
G
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*
D065169:Bradykinin B1 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D006918:Hydroxyurea