Design and synthesis of conformationally restricted capsaicin analogues based in the 1, 3, 4-thiadiazole heterocycle reveal a novel family of transient receptor potential vanilloid 1 (TRPV1) antagonists

Novel Scaffolds for Modulation of TRPV1 Identified with Pharmacophore Modeling and Virtual Screening

“…Pharmacophoric comparison of (1) capsaicin [7], (2) capsazepine [7], (3) benzylthiourea derivatives [33], (4) piperidine carboxamide derivatives [35], (5) 1,3,4-thiadiazole derivatives [36] according to three structural sections of TRPV1 ligands: (A) polar head, (B) linker and (C) hydrophobic tail.…”

“…So far, several pharmacophore-like models were proposed for different classes of TRPV1 antagonists. They were derived from a set of unique chemical scaffolds, and highlight three important pharmacophores of TRPV1 ligands: a polar head (A), a linker (B) and a hydrophobic tail (C) (Figure 1) [7,33–36]. In the work of Kim [37], the pharmacophore was derived from a 3D QSAR analysis of substituted capsazepines.…”

Synthesis of 6- Tert -Octyl and 6,8-Di Tert -Butyl Coumarins, Two Coumarins of Biological Interest

“…8 Our working group has designed and synthesized structures analogous to capsaicin, which incorporate an increasing the conformational restriction on the amide bond. (Figure 2, III, region: A) with the incorporation of the heterocyclic, such as the azoles 9 or a chalcone 10 (Figure 2; IV and V respectively) and the action of these molecules in transfected mouse cells have been studied to evidence the efficiency of the chemical structure on the TRPV1 receptor. 9,10 In this work the synthesis of new coumarins is reported, which incorporate both greater conformational restriction in B region of Capsaicin (Figure 2, VI) and hydrophobic units in the coumarin structure.…”

Synthesis and Antiviral Activity of Novel 1,4-Pentadien-3-one Derivatives Containing a 1,3,4-Thiadiazole Moiety

“…1,3,4-Thiadiazole is a potent multi-targeting pharmacological scaffold in heterocyclic chemistry [ 23 ]. 1,3,4-Thiadiazole derivatives have various biological activities, such as antimicrobial [ 24 ], antitubercular [ 25 ], anticonvulsants [ 26 ], antibacterial [ 27 ], anti-inflammatory [ 28 , 29 ], anticancer [ 30 , 31 ], antinociceptive [ 32 ], enzyme inhibitory [ 33 ], antidepressant and anxiolytic [ 34 ] effects. In our previous work, a number of 5-(4-chlorophenyl)-1,3,4-thiadiazole sulfonamides were designed and synthesized, and these compounds showed moderate anti-TMV activities [ 35 ].…”