Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;:129.
We would like to report that using computer-aided design tools and x-ray
structures of the HIV-1 protease/inhibitor complex, a novel class of
nonpeptide cyclic ureas as HIV protease inhibitors has been designed and
synthesized. These cyclic ureas are the first subnanomolar Ki nonpeptide
and also the first inhibitors to displace the structural water commonly
found in the x-ray structures of other complexes. Confirmation of
binding was obtained via x-ray structures. Currently DMP323 is
undergoing extensive studies including Phase-1 clinical trial. Ki=0.27nM
Cell RNA assay IC90=57nM F% oral bioavailability in dog at 5 mg/Kg=37%
(diagram: see text).
Blood Proteins/*METABOLISM Cell Line Cytopathogenic Effect, Viral
Human HIV Protease Inhibitors/METABOLISM/*PHARMACOLOGY