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 novel oxyindole-derived
HIV-1 protease
inhibitors were designed and synthesized based upon our X-ray crystal structure of
inhibitor 2
(TMC-114) bound to
HIV-1 protease
. The effects of substituents, spirocyclic rings, and ring sizes have been investigated. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease.
...
PMID:Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P2'-ligands. 1648 Aug 71
A series of potent
HIV-1 protease
inhibitors with a lipophilic adamantyl P1 ligand have been designed, synthesized, and evaluated. We have developed an enantioselective synthesis of adamantane-derived hydroxyethylamine isosteres utilizing Sharpless asymmetric epoxidation as the key step. Various inhibitors incorporating P1-adamantylmethyl in combination with P2 ligands such as 3-(R)-THF, 3-(S)-THF, bis-THF, and THF-THP were examined. The S1' pocket was also probed with phenyl and phenylmethyl ligands. Inhibitor 15d, with an isobutyl P1' ligand and a bis-THF P2 ligand, proved to be the most potent of the series. The cLogP value of inhibitor 15d is improved compared to
inhibitor 2
with a phenylmethyl P1-ligand. X-ray structural studies of 15d, 15h, and 15i with
HIV-1 protease
complexes revealed molecular insight into the inhibitor-protein interaction.
...
PMID:Probing Lipophilic Adamantyl Group as the P1-Ligand for HIV-1 Protease Inhibitors: Design, Synthesis, Protein X-ray Structural Studies, and Biological Evaluation. 2738 67
