180462-76-4Relevant articles and documents
Novel azapeptide inhibitors of hepatitis C virus serine protease
Bailey, Murray D.,Halmos, Ted,Goudreau, Nathalie,Lescop, Ewen,Llinàs-Brunet, Montse
, p. 3788 - 3799 (2007/10/03)
Azapeptides are known inhibitors of several serine and cysteine proteases. In seeking different classes of inhibitors for the HCV serine protease, a series of novel azapeptide-based inhibitors were investigated which incorporated noncleavable P1/P1′ aza-a
Aza-peptide analogs as potent human immunodeficiency virus type-1 protease inhibitors with oral bioavailability
F?ssler, Alexander,Bold, Guido,Capraro, Hans-Georg,Cozens, Robert,Mestan, Jürgen,Poncioni, Bernard,R?sel, Johannes,Tintelnot-Blomley, Marina,Lang, Marc
, p. 3203 - 3216 (2007/10/03)
A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition- state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P2'P3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P3 and an ethyl carbamate in P3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED50 values 150-fold following oral application in mice.
