Indolylarylsulfones, a fascinating story of highly potent human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors

Abstract

Indolylarylsulfones are a potent class of human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors. In this review, the structure activity relationship (SAR) studies to improve the profile of sulfone L-737,126 discovered by Merck AG have been analysed with focus on introduction of the 3′,5′-dimethyl groups at the 3-phenylsulfonyl moiety, the 2-hydroxyethyl tail at the indole-2-carboxamide nitrogen, coupling of the carboxamide nitrogen with one or two glycinamide and alaninamide units, a fluorine atom at position 4 of the indole ring and correlation between configuration of the asymmetric centre and linker length. IAS derivatives look like promising drug candidates for the treatment of AIDS and related infections in combination with other antiretroviral agents.

Regioselective C–H Sulfonylation of 2H-Indazoles by Electrosynthesis

“…Organosulfones are an important class of compounds extensively used as agrochemicals, pharmaceuticals, and synthetic precursors due to their intriguing biological activities and versatile reactivities . In particular, heteroaryl sulfones are of great interest due to their eminent drug activities, namely, anti-HIV, antifungal, antibacterial, etc . As a result, the evolution of viable routes for the preparation of organosulfones has gained significant attention of medicinal and synthetic organic chemists …”

Recent Advances in the Design and Development of Non‐nucleoside Reverse Transcriptase Inhibitor Scaffolds

“…[52] Sincet hen, this chemicals caffold has been recognized as ap romising one in the design of NNRTIs and attracted considerable attention from researchers. [53] PreviousS AR and in silico studies of IASsr evealed that 1) introduction of two methyl groups into the 5'-a nd 7'-positions of the 3-phenylsulfonyl motif resulted in more potent IASs against the mutant strains of HIV-1; [54] 2) introductiono fadiverse group of substituents into the 2-carboxamide moiety, such as Mannich bases, amino acids, and hydroxy ethyl group, led to potent NNRTIs; [55] 3) IASs with an additional aromatic motif by one carbon or two carbon atoms apart from the nitrogeng roup of the 2-carboxamide moiety resulted in NNRTIs with ab road spectrum of activity against drug-resistant HIV-1 strains. [56] Based on the SAR analysis mentioned above and to obtain more potent NNRTIs, aseries of IASs were synthesized by introducingp henylo rp henylethyl groups bearing different substituentsi nto the nitrogen moiety of 2-carboxamide.…”

“…5‐Chloro‐3‐(benzenesulfonyl)indole‐2‐carboxamide ( L ‐737,126 ; 82 ) was reported in 1993 by Merck & Co. to inhibit wild‐type HIV‐1 replication at an EC 50 value of 1 n m . Since then, this chemical scaffold has been recognized as a promising one in the design of NNRTIs and attracted considerable attention from researchers …”

Novel indolylarylsulfone derivatives as covalent HIV-1 reverse transcriptase inhibitors specifically targeting the drug-resistant mutant Y181C

“…1). Derivatives of this molecule have shown inhibitory activities against the WT virus in the nanomolar range [10] (reviewed in [11]).…”