1,2,3-Triazole-[2,5-Bis-O-(tert-butyldimethylsilyl)-.beta.-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO) Analogs: Synthesis and Anti-HIV-1 Activity

Abstract

Several 4- or 5-monosubsituted and 4,5-disubstituted 1,2,3-triazole analogues of the anti-HIV-1 lead compound [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D- ribofuranosyl]thymine]-3'-spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) (TSAO-T) have been prepared and evaluated as inhibitors of HIV-1-induced cytopathicity. These analogues have been prepared by 1,3-diplar cycloaddition of [2,5-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]- 3-spiro-5'-(4'-amino- and 4'-(N-acetylamino)-1',2'-oxathiole 2',2'-dioxide) (TSAO) azides to various substituted acetylenes. Several 4- and 5-substituted 1,2,3-triazole-TSAO analogues proved superior to the unsubstituted derivative by 1-2 orders of magnitude. In particular the 5-substituted amido-, (methylamido)-, and (dimethylamido)-1,2,3-triazole derivatives of TSAO were endowed with potent anti-HIV-1 activity (50% effective concentration: 0.056-0.52 microM). They show a similar resistance spectrum as previously noted for TSAO-T and related derivatives.

Micellar promoted multi-component synthesis of 1,2,3-triazoles in water at room temperature

“…Some alternative systems exist like the employment of mechano-chemical conditions in a ball milling apparatus using a copper vial at high temperature for at least 16 h or the use of a structurally well-defined copper(I) isonitrile complex, 31 insoluble in the reaction medium, that can be readily recovered by precipitation and filtration and recycled for at least five runs without significant loss of activity. Examples of purely homogeneous multicomponent reactions for triazole synthesis are indeed rare, involving the use of CuSO 4 at 100°C in water in the presence of an excess of azide that acts as a reducing agent. 32 Alternatively, examples operating at room temperature are based on well defined complexes like the original [Cu(NHC)X] system (X halogen atom) developed by Nolan 20 or the PTA-iminophosphorane Cu(I) complex (PTA = 1,3,5-triaza-7-phosphaadamantane) 33 both in water and mainly focused on the use of terminal aromatic alkynes.…”

Design, Synthesis and Docking Studies of Novel 1, 2, 3-Triazolyl Phenylthiazole Analogs as Potent Anti-HIV-1 NNRT Inhibitors

“…Genuine efforts have been made to integrate 1, 2, 3-triazole in existing drugs, still more research is needed to find lead molecule [18]. 1,2,3-triazole structural moiety is present in several compounds showing various biological activities including anti-HIV [19], anti-bacterial [20], anti-allergic [21], anticonvulsant [22], b-\lactamase inhibitory [23], and anti-tuberculosis activities [24], 1,2,3-triazole has been comprehensively studied due to its important applications in industrially interesting materials, such as dyes, anticorrosive agents, photo stabilizers, photographic materials, and agrochemicals [18]. Therefore, we found it interesting to design new molecules within the scope of synthetic procedure using phenylthiazole scaffold followed by suitable modification to generate diversified compounds for anti-HIV activity.…”

An Efficient Synthesis of Mono and Bis‐1,2,3‐triazole AZT Derivatives via Copper(I)‐catalyzed Cycloaddition

“…2 1,2,3-Triazole can serve as a suitable moieties in these drugs since it is stable to metabolic degradation and susceptible to hydrogen bonding beneficial for the affinity with molecular targets and solubility. 3,4 Compounds containing a 1,2,3-triazole moiety show various biological activities such as anti-HIV, 5 anti-microbial, 6 anti-allergic, 7 and selective b3 adrenergic receptor agonist. 8 Ribavirin (Fig.…”