The design of non-peptide human bradykinin B2 receptor antagonists employing the benzodiazepine peptidomimetic scaffold.
The Bradykinin B2 receptor antagonist HOE 140 (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg) has been used as a template for the de novo design and synthesis of a small number of non-peptide lead compounds based on the 1,4-benzodiazepin-2-one framework. Two of the compounds have been found to exhibit moderate K(i) values of 8.9 and 9.2 microM at the human Bradykinin B2 receptor.
Dziadulewicz
E K
EK
Novartis Institute for Medical Sciences, London, UK. ed.dziadulewicz@pharma.novartis.com
Brown
M C
MC
Dunstan
A R
AR
Lee
W
W
Said
N B
NB
Garratt
P J
PJ
D001920:Bradykinin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D015195:Drug Design; D006801:Humans; D018716:Molecular Mimicry; D043782:Receptor, Bradykinin B2
D065168:Bradykinin Receptor Antagonists; D043782:Receptor, Bradykinin B2; C065679:icatibant; D001920:Bradykinin