Synthesis, biological activity and modelling studies of two novel anti HIV PR inhibitors with a thiophene containing hydroxyethylamino core

Tetrahydrofuran, Tetrahydropyran, Triazoles and Related Heterocyclic Derivatives as HIV Protease Inhibitors

“…It is not surprising then that De Bonis and co-workers recently reported on NFV and SQV analogs that use thiopene as a P 1 phenyl substitute (45–48 Figure 9 ) . Initially, the thiophenes were directly attached to the PI scaffold resulting in a loss of potency ( 45 & 47 ; IC 50 = 5 and 30 μM, respectively, as compared with SQV = 0.0004 and NFV = 0.0019 μM), however, the addition of a methylene spacer greatly restored their inhibitory activity ( 46 & 48 ; IC 50 = 0.02 and 0.003 μM, respectively) [38,39]. Unfortunately, analogs containing the thiophene ring demonstrated a significant loss in enzyme inhibitory potency when assayed against a V32I mutant enzyme, similar to SQV.…”

“…Unfortunately, analogs containing the thiophene ring demonstrated a significant loss in enzyme inhibitory potency when assayed against a V32I mutant enzyme, similar to SQV. However, further structural refinements led to the incorporation of a benzothienyl moiety as a P 1 ligand producing 49 (Figure 9), which retained activity against V32I [38,39]. …”

3-(4-Methoxybenzyl)-1-benzothiophene

“…For the biological activity of thiophene derivatives, see: Bonini et al (2005); Brault et al (2005); Isloora et al (2010). For related structures, see: Gunasekaran et al (2009) ;Umadevi et al (2009).…”

Synthesis, Anticonvulsant Activity and <i>In silco</i> Studies of Schiff Bases of 2-Aminothiophenes via Guanidine- Catalyzed Gewald Reaction

“…Thiophene scaffold have a variety of biological activities such as antitubercular [1], antioxidant [2], anti-HIV-PR inhibitors [3], antimicrobial [4], multitargeted kinase inhibition [5], A 1 adenosine receptor allosteric enhancement [6]. Of Several approaches for the synthesis of 2-aminothiophenes have been reported including the use of microwave assisted synthesis [7], synthesis from thiomorpholides [8], coupling reaction [9], solid support [10], base-induced inter-and intra-molecular C-S and C-C bond formation [11] and ultrasonication [12].…”