Novel cyclopropyl-indole derivatives as HIV non-nucleoside reverse transcriptase inhibitors
Date
2012
Authors
Hassam M.
Basson A.E.
Liotta D.C.
Morris L.
Van Otterlo W.A.L.
Pelly S.C.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
The HIV pandemic represents one of the most serious diseases to face mankind in both a social and economic context, with many developing nations being the worst afflicted. Due to ongoing resistance issues associated with the disease, the design and synthesis of anti-HIV agents presents a constant challenge for medicinal chemists. Utilizing molecular modeling, we have designed a series of novel cyclopropyl indole derivatives as HIV non-nucleoside reverse transcriptase inhibitors and carried out their preparation. These compounds facilitate a double hydrogen bonding interaction to Lys101 and efficiently occupy the hydrophobic pockets in the regions of Tyr181/188 and Val179. Several of these compounds inhibited HIV replication as effectively as nevirapine when tested in a phenotypic assay. © 2012 American Chemical Society.
Description
Keywords
cyclopropyl, HIV, indole, NNRTI, rational design
Citation
ACS Medicinal Chemistry Letters
3
6
470
475
3
6
470
475