1374964-63-2Relevant academic research and scientific papers
Novel indole sulfides as potent HIV-1 NNRTIs
Brigg, Siobhan,Pribut, Nicole,Basson, Adriaan E.,Avgenikos, Moscos,Venter, Reinhardt,Blackie, Margaret A.,van Otterlo, Willem A.L.,Pelly, Stephen C.
, p. 1580 - 1584 (2016)
In a previous communication we described a series of indole based NNRTIs which were potent inhibitors of HIV replication, both for the wild type and K103N strains of the virus. However, the methyl ether functionality on these compounds, which was crucial for potency, was susceptible to acid promoted indole assisted SN1 substitution. This particular problem did not bode well for an orally bioavailable drug. Here we describe bioisosteric replacement of this problematic functional group, leading to a series of compounds which are potent inhibitors of HIV replication, and are acid stable.
Novel cyclopropyl-indole derivatives as HIV non-nucleoside reverse transcriptase inhibitors
Hassam, Mohammad,Basson, Adriaan E.,Liotta, Dennis C.,Morris, Lynn,Van Otterlo, Willem A. L.,Pelly, Stephen C.
supporting information; experimental part, p. 470 - 475 (2012/09/22)
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.
