translation agency

Computer-aided design and discovery of potent, nonpeptidal cyclic ureas as HIV protease inhibitors.
Lam PY; Eyermann CJ; Jadhav PK; Hodge CN; Ru Y; Delucca GV; Bacheler LT;
December 30, 1995
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 HIV-1/PATHOGENICITY ABSTRACT