Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.23.16 (
HIV-1 protease
)
2,107
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Aza-peptide analogs as potent human immunodeficiency virus type-1 protease inhibitors with oral bioavailability. 875 43
