920036-07-3Relevant academic research and scientific papers
Searching for novel scaffold of triazole non-nucleoside inhibitors of HIV-1 reverse transcriptase
Fr?czek, Tomasz,Paneth, Agata,Kamiński, Rafa?,Krakowiak, Agnieszka,Paneth, Piotr
, p. 481 - 489 (2016/03/26)
Azoles are a promising class of the new generation of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). From thousands of reported compounds, many possess the same basic structure of an aryl substituted azole ring linked by a thioglycolamide chain with another aromatic ring. In order to find novel extensions for this basic scaffold, we explored the 5-position substitution pattern of triazole NNRTIs using molecular docking followed by the synthesis of selected compounds. We found that heterocyclic substituents in the 5-position of the triazole ring are detrimental to the inhibitory activity of compounds with four-membered thioglycolamide linker and this substitution seems to be viable only for compounds with shorter two-membered linker. Promising compound, N-(4-carboxy-2-chlorophenyl)-2-((4-benzyl-5-methyl-4H-1,2,4-triazol-3-yl)sulfanyl)acetamide, with potent inhibitory activity and acceptable aqueous solubility has been identified in this study that could serve as lead scaffold for the development of novel water-soluble salts of triazole NNRTIs.
The design and synthesis of diaryl ether second generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with enhanced potency versus key clinical mutations
Tucker, Thomas J.,Saggar, Sandeep,Sisko, John T.,Tynebor, Robert M.,Williams, Theresa M.,Felock, Peter J.,Flynn, Jessica A.,Lai, Ming-Tain,Liang, Yuexia,McGaughey, Georgia,Liu, Meiquing,Miller, Mike,Moyer, Gregory,Munshi, Vandna,Perlow-Poehnelt, Rebecca,Prasad, Sridhar,Sanchez, Rosa,Torrent, Maricel,Vacca, Joseph P.,Wan, Bang-Lin,Yan, Youwei
, p. 2959 - 2966 (2008/12/23)
Using a combination of traditional Medicinal Chemistry/SAR analysis, crystallography, and molecular modeling, we have designed and synthesized a series of novel, highly potent NNRTIs that possess broad antiviral activity against a number of key clinical mutations.
HIV reverse transcriptase inhibitors
-
Page/Page column 33, (2010/11/25)
Compounds having the structure: are HIV reverse transcriptase inhibitors, wherein A, X, Y, Z, R1 and R2 are defined herein. The compounds and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
