biostudies-literatureOkello MNCRRNCRR NIH HHSNIAID NIH HHSGeorgia Research AllianceNIAIDUniversity of GeorgiaTerry Endowment4112-6https://www.ebi.ac.uk/biostudies/studies/S-EPMC3701953biostudies-literatureUnknown23(14)While some examples are known of integrase inhibitors that exhibit potent anti-HIV activity, there are very few cases reported of integrase inhibitors that show significant differences in anti-HIV activity that result from distinctions in cis- and trans-configurations as well as enantiomeric stereostructure. We describe here the design and synthesis of two enantiomeric trans-hydroxycyclopentyl carboxamides which exhibit notable difference in anti-HIV activity. This difference is explained through their binding interactions within the active site of the HIV-1 integrase intasome. The more active enantiomer 3 (EC50 25nM) was relatively stable in human liver microsomes. Kinetic data revealed that its impact on key cytochrome P450 isozymes, as either an inhibitor or an activator, was minor, sugBioorganic & medicinal chemistry lettersNotable difference in anti-HIV activity of integrase inhibitors as a consequence of geometric and enantiomeric configurations.PMC3701953R01 AI043181RO1 AI 43181R01 AI 43181IS10RR016621Nair VOkello MMishra SNishonov MfalseNotable difference in anti-HIV activity of integrase inhibitors as a consequence of geometric and enantiomeric configurations.While some examples are known of integrase inhibitors that exhibit potent anti-HIV activity, there are very few cases reported of integrase inhibitors that show significant differences in anti-HIV activity that result from distinctions in cis- and trans-configurations as well as enantiomeric stereostructure. We describe here the design and synthesis of two enantiomeric trans-hydroxycyclopentyl carboxamides which exhibit notable difference in anti-HIV activity. This difference is explained through their binding interactions within the active site of the HIV-1 integrase intasome. The more active enantiomer 3 (EC50 25nM) was relatively stable in human liver microsomes. Kinetic data revealed that its impact on key cytochrome P450 isozymes, as either an inhibitor or an activator, was minor, sug2013-01-01T00:00:00Z2013 Jul2025-04-04T18:55:13.144Z2019-03-27T01:12:33ZS-EPMC37019532374647410.1016/j.bmcl.2013.05.050