Back to Search
Start Over
Design, synthesis, and biological evaluation of piperidinyl-substituted [1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential anti-HIV-1 agents with reduced cytotoxicity.
- Source :
-
Chemical biology & drug design [Chem Biol Drug Des] 2021 Jan; Vol. 97 (1), pp. 67-76. Date of Electronic Publication: 2020 Aug 03. - Publication Year :
- 2021
-
Abstract
- Taking the previously reported compound BH-7d as the lead, we designed and synthesized a series of piperidinyl-substituted [1,2,4]triazolo[1,5-a]pyrimidines, and their anti-HIV activities as well as cytotoxicities were evaluated. Several compounds exhibited moderate anti-HIV (IIIB) potency, among which 2b was the most active one (EC <subscript>50</subscript>  = 4.29 μM). Structure-activity relationships derived from the antiretroviral results were analyzed. Additionally, most compounds demonstrated reduced cytotoxicity (CC <subscript>50</subscript>  > 200 μM) compared with those of BH-7d and etravirine. Molecular docking study further revealed the binding conformation of 2b in the binding pocket of HIV-1 reverse transcriptase.<br /> (© 2020 John Wiley & Sons Ltd.)
- Subjects :
- Anti-HIV Agents metabolism
Anti-HIV Agents pharmacology
Binding Sites
Cell Line
Cell Survival drug effects
HIV Reverse Transcriptase antagonists & inhibitors
HIV Reverse Transcriptase metabolism
HIV-1 drug effects
HIV-1 enzymology
Humans
Molecular Docking Simulation
Pyrimidines metabolism
Pyrimidines pharmacology
Reverse Transcriptase Inhibitors metabolism
Reverse Transcriptase Inhibitors pharmacology
Structure-Activity Relationship
Triazoles metabolism
Triazoles pharmacology
Anti-HIV Agents chemical synthesis
Drug Design
Pyrimidines chemistry
Reverse Transcriptase Inhibitors chemical synthesis
Triazoles chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1747-0285
- Volume :
- 97
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Chemical biology & drug design
- Publication Type :
- Academic Journal
- Accession number :
- 32725669
- Full Text :
- https://doi.org/10.1111/cbdd.13760