3-(Methoxycarbonyl)thiophene Thiourea Derivatives as Potential Potent Bacterial Acetyl-CoA Carboxylase Inhibitors

Vikram, Venugopalarao; Amperayani, Karteek Rao; Umadevi, P.

doi:10.1134/s1070428021080145

Cited by 2 publications

(1 citation statement)

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“…The concept of isosterism applied to the thiophene ring was established in 1932 by Erlenmeyer, which proposed the equivalence between -CH = CH- and -S- (in benzene and thiophene, respectively) in terms of size, mass and capacity to provide an aromatic lone pair. Over time, compounds containing thiophene have been extensively investigated in medicinal chemistry, since they show a variety of pharmacological activities, such as anti-inflammatory, antioxidant, antimicrobial, antitumor, and antidepressant action [ 1 , 2 , 3 , 4 ]. Moreover, several thiophene-heterocycles-fused compounds have been approved by FDA as therapeutic agents for the treatment of osteoporosis (Raloxifene), peripheral artery disorder (Ticlopidine), psychosis (Olanzapine), anxiety and convulsion (Etizolam); see Figure 1 .…”

Section: Introductionmentioning

confidence: 99%

4,5-Dihydro-5-Oxo-Pyrazolo[1,5-a]Thieno[2,3-c]Pyrimidine: A Novel Scaffold Containing Thiophene Ring. Chemical Reactivity and In Silico Studies to Predict the Profile to GABAA Receptor Subtype

et al. 2023

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The isosteric replacement of the benzene with thiophene ring is a chemical modification widely applied in medicinal chemistry. Several drugs containing the thiophene ring are marketed for treating various pathologies (osteoporosis, peripheral artery disorder, psychosis, anxiety and convulsion). Taking into account this evidence and as a continuation of our study in the GABAA receptor modulators field, we designed and synthesized new compounds containing the thiophene ring with 4,5-dihydro-5-oxo-pyrazolo[1,5-a]thieno[2,3-c]pyrimidine and pyrazolo[1,5-a]thieno[2,3-c] pyrimidine scaffold. Moreover, these cores, never reported in the literature, are isosteres of pyrazolo[1,5-a]quinazolines (PQ), previously published by us as GABAAR subtype ligands. We introduced in the new scaffold those functions and groups (esters, ketones, alpha/beta-thiophene) that in our PQ derivatives were responsible for the activity, and at the same time, we have extensively investigated the reactivity of the new nucleus regarding the alkylation, reduction, halogenation and hydrolyses. On the six final designed compounds (12c–f, 22a,b) molecular docking and dynamic simulation studies have been performed. The analysis of dynamic simulation, applying our reported model ‘Proximity Frequencies’, collocates with high probability 12c, 22b, in the agonist class towards α1β2γ2-GABAAR.

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