Synthesis and multiparametric evaluation of thiadiazoles and oxadiazoles as diacylglycerol acyltransferase type 1 inhibitors

Mougenot, Patrick; Namane, Claudie; Fett, E. R.; Goumy, Florence; Dadji-Faïhun, Rommel; Langot, Gwladys; Monseau, Catherine; Onofri, Bénédicte; Pacquet, François; Pascal, Cécile; Crespin, Olivier; Ben-Hassine, Majdi; Ragot, Jean-Luc; Van-Pham, Thao; Philippo, Christophe; Chatelain-Egger, Florence; Péron, Philippe; Bail, Jean-Christophe Le; Guillot, Etienne; Chamiot-Clerc, Philippe; Chabanaud, Marie-Aude; Pruniaux, Marie-Pierre; Ménégotto, J.; Schmidt, Friedemann; Venier, Olivier; Viviani, Fabrice; Nicolaï, Eric

doi:10.1016/j.bmcl.2015.11.046

Cited by 5 publications

(3 citation statements)

References 12 publications

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“…Oxadiazoles and thiadiazoles are privileged structure class compounds that demonstrate widespread pharmacological activities, such as anticancer, antiviral, anti-inflammatory, antimicrobial, anticonvulsant, cardiovascular, antimalarial, antidiabetic, and antitubercular activity, against Alzheimer’s disease, obesity, and so forth . Moreover, oxadiazoles and thiadiazoles are also attractive scaffolds because of their bioisosteric abilities to replace carboxylic acids, esters and carboxamides, and other structural motifs.…”

Section: Introductionmentioning

confidence: 99%

Current Parallel Solid-Phase Synthesis of Drug-like Oxadiazole and Thiadiazole Derivatives for Combinatorial Chemistry

Abdildinova

Gong

2018

ACS Comb. Sci.

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Solid-phase organic synthesis is a powerful tool in the synthesis of small organic molecules and building of libraries of compounds for drug discovery. Heterocyclic compounds are important components of the drug discovery field as well and serve as a core for hundreds of marketed drugs. In particular, oxadiazole and thiadiazole cores are compounds of great interest due to their comprehensive biological activities and structural features. Therefore, a plethora of oxadiazole and thiadiazole synthesis methodologies have been reported to date, including solution and solid-phase synthesis methodologies. In this review, we concentrate on and summarize solid-phase synthetic approaches of the oxadiazole and thiadiazole derivatives.

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Section: Introductionmentioning

confidence: 99%

Current Parallel Solid-Phase Synthesis of Drug-like Oxadiazole and Thiadiazole Derivatives for Combinatorial Chemistry

Abdildinova

Gong

2018

ACS Comb. Sci.

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“…因此, 开发活性优于 TCPTP 的选择性 PTP1B 抑制剂仍是一个挑战 [6,7] . 近年来, 1,3,4-噻二唑酰胺类化合物已引起了人们的关注, 因为此类化合物具有抗糖尿病 [8,9] 、抗癌 [10,11] 、改善认知障碍 [12] 、EP3 受体拮抗剂 [13] 、抗氧化 [14] 、杀虫 [15] 等多种生物活性. 咔唑(Cz)和苯并咪唑(BZM)是两种重要的含氮杂环化合物.…”

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Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity

李英俊¹,

赵月²,

靳焜³

et al. 2019

Chin. J. Org. Chem.

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A series of novel 2,5-disubstituted-1,3,4-thiadiazolamide derivatives containing carbazole/benzimidazole moity were synthesized. Their structures were characterized by IR, 1 H NMR, 13 C NMR spectra and elemental analysis. All synthesized target compounds were evaluated for the inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and T-cell protein tyrosine phosphatase (TCPTP). The structure-activity relationship was discussed. The results showed that most of compounds had good inhibitory activity against PTP1B over the highly homologous TCPTP, and 2-(9-carbazolylmethylene)-5-(3-chlorobenzoylamino)-1,3,4-thiadiazole (5c) displayed the highest inhibitory activity against PTP1B [IC 50 ＝(2.43±0.43) μg/mL]. The inhibitory activities of 2-(9-carbazolylmethylene)-5-(4-methylbenzoylamino)-1,3,4-thiadiazole (5b) and 5c against PTP1B were higher than that of positive control oleanolic acid. Molecular docking and density functional theory (DFT) calculations of the target compound 5c were performed. The docking result showed that compound 5c and PTP1B enzyme formed a stable complex by hydrogen bonds, hydrophobic and - interactions.

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“…The “flask” synthesis of amidoximes from nitriles and hydroxylammonium chloride (NH 2 OH·HCl) has been conducted in methanol or ethanol in the presence of a base, − that is, NaOH, Na 2 CO 3 , K 2 CO 3 , and triethylamine (TEA). We chose ethanol for the amidoxime generation as this solvent supported mild heating to achieve efficient conversion of the reagents and could help remove water by azeotropic distillation.…”

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confidence: 99%

Expanding Synthesizable Space of Disubstituted 1,2,4-Oxadiazoles

et al. 2016

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One-pot synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from carboxylic acids and nitriles was optimized to parallel chemistry. The method was validated on a 141 member library; the desired products were recovered with a high success rate and in moderate yields. Practical application of the approach was demonstrated in the synthesis of bioactive compound pifexole and agonists of free fatty acid receptor 1. A library of 4 948 100 synthesizable drug-like 3,5-disubstituted 1,2,4-oxadiazoles was enumerated based on the method and available validated reagents.

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Synthesis and multiparametric evaluation of thiadiazoles and oxadiazoles as diacylglycerol acyltransferase type 1 inhibitors

Cited by 5 publications

References 12 publications

Current Parallel Solid-Phase Synthesis of Drug-like Oxadiazole and Thiadiazole Derivatives for Combinatorial Chemistry

Current Parallel Solid-Phase Synthesis of Drug-like Oxadiazole and Thiadiazole Derivatives for Combinatorial Chemistry

Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity

Expanding Synthesizable Space of Disubstituted 1,2,4-Oxadiazoles

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