Discovery of thiophene‐containing biaryl amide derivatives as novel glucagon receptor antagonists

Abstract

A novel series of thiophene-containing biaryl amide glucagon receptor (GCGR) antagonists were designed and synthesized. Two compounds of this series, 14f and 14h, exhibited good GCGR binding (IC = 6.1 and 4.4 μm, respectively) and cAMP functional activities (IC = 4.4 and 14.4 μm, respectively). The possible binding modes of compounds 14f and 14h with GCGR were explored by molecular simulation.

Synthesis, X-ray structure, antimicrobial activity, DFT and molecular docking studies of N-(thiophen-2-ylmethyl)thiophene-2-carboxamide

“…Among five-membered heteroaromatic rings, thiophene has been widely used as a building block in drug molecules and plays an important role in various biochemical processes. Thanks to the presence of the thiophene unit and with an additional amide functional group in their structure, thiophene-based amides have been reported to possess a wide variety of biological and pharmacological activities, including antibacterial (Koparır & Parlak, 2018), antifungal (Kheder & Mabkhot, 2012;Refat & Fadda, 2013), anticancer (Archna et al, 2020) anti-inflammatory (da Cruz et al, 2021), antidepressant (Wardakhan et al, 2008), glucagon receptor (GCGR) antagonist (Li et al, 2018), allosteric enhancers for A1 adenosine receptor (Baraldi et al, 2007), in the treatment of osteoporosis (Marchais-Oberwinkler et al, 2013) and anti-HIV (Kheder & Mabkhot, 2012). Furthermore, thiophene-based molecules exhibit various other applications, e.g.…”

Regioselective Synthesis of 5-Propyl-2-((trityloxy)methyl)thiophene-3-carbaldehyde

“…Alkylated thiophene-3-carbaldehyde is a widely used building block for organic synthesis of a myriad of materials with multiple applications. It has been used as the key starting material for organic field-effect transistors [1-5], glucagon antagonist [6], inhibitors of D-amino acid oxidase [7], dopamine 1 agonist ABT-431 (Figure 1) [8,9], and water-soluble fluorescent polymers [10]. Due to their strong luminescence properties, thiophene-based compounds have also been used for dye-sensitized organic solar cells and light emitting devices [11] as well as nonlinear optical chromophores [12].…”