2-Aryl benzimidazoles: Human SCD1-specific stearoyl coenzyme-A desaturase inhibitors

Powell, David A.; Ramtohul, Yeeman K.; Lebrun, Marie-Eve; Oballa, Renata M.; Bhat, Sathesh; Falgueyret, Jean‐Pierre; Guiral, Sébastien; Huang, Zheng; Skorey, Kathryn; Tawa, Paul; Zhang, Lei

doi:10.1016/j.bmcl.2010.09.094

Cited by 23 publications

(9 citation statements)

References 50 publications

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“…Benzimidazoles can easily interact with the biopolymers of the living systems, which are responsible for their numerous biological activities and functions. In particular, benzimidazole derivatives exhibit antimicrobial [7][8][9], antiviral [10,11], anticancer [12][13][14], anti-inflammatory [15][16][17], and antioxidant [18] activities, whereas various derivatives have been developed as therapeutic agents, such as proton pump inhibitors [2], level modulators [19], and antidiabetics (Figure 1) [20,21].…”

Section: Introductionmentioning

confidence: 99%

Selective Synthesis of Benzimidazoles from o-Phenylenediamine and Aldehydes Promoted by Supported Gold Nanoparticles

Tzani

Gabriel²,

Lykakis

2020

Nanomaterials

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We investigated the catalytic efficacy of supported gold nanoparticles (AuNPs) towards the selective reaction between o-phenylenediamine and aldehydes that yields 2-substituted benzimidazoles. Among several supported gold nanoparticle platforms, the Au/TiO2 provides a series of 2-aryl and 2-alkyl substituted benzimidazoles at ambient conditions, in the absence of additives and in high yields, using the mixture CHCl3:MeOH in ratio 3:1 as the reaction solvent. Among the AuNPs catalysts used herein, the Au/TiO2 containing small-size nanoparticles is found to be the most active towards the present catalytic methodology. The Au/TiO2 can be recovered and reused at least five times without a significant loss of its catalytic efficacy. The present catalytic synthetic protocol applies to a broad substrate scope and represents an efficient method for the formation of a C–N bond under mild reaction conditions. Notably, this catalytic methodology provides the regio-isomer of the anthelmintic drug, Thiabendazole, in a lab-scale showing its applicability in the efficient synthesis of such N-heterocyclic molecules at industrial levels.

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Section: Introductionmentioning

confidence: 99%

Selective Synthesis of Benzimidazoles from o-Phenylenediamine and Aldehydes Promoted by Supported Gold Nanoparticles

Tzani

Gabriel²,

Lykakis

2020

Nanomaterials

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“…To obtain the 5-substituted compounds 9-11, the 4-substituted or 4,5-disubstituted-1,2-phenylenediamines were mono-acylated with palmitoyl chloride and the monoamides 40-42 were cyclised by the action of 4 N HCl. The benzimidazoles 43-45 were methylated with methyl iodide in the presence of Cs 2 CO 3 (46)(47)(48) and, finally, quaternised at r.t. with excess of methyl iodide (Scheme 2). The intermediates 40, 41, 46 and 47 (Scheme 2) could be a mixture of two regioisomers, however we did not succeed in separating them, but it is not important for the structures of the final compounds 9-11.…”

Section: Synthesismentioning

confidence: 99%

“…On the other hand, some 2-aryl-5-substituted benzimidazoles, devoid of basic chain, have been shown to inhibit the stearoyl coenzyme A desaturase (SCD1), blocking the formation of oleic and palmitoleic triglycerides, cholesterol esters and phospholipids 46 . The SCD1, besides being investigated for the treatment of dislipidemic diseases and body weight control, has been found to participate, together with other desaturase enzymes, in the de novo synthesis of mono-and poly-unsaturated fatty acids (C18-C22 PUFA) of parasitic membrane.…”

Section: Compdmentioning

confidence: 99%

Benzimidazole derivatives endowed with potent antileishmanial activity

Tonelli

Gabriele

Piazza

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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Two sets of benzimidazole derivatives were synthesised and tested in vitro for activity against promastigotes of Leishmania tropica and L. infantum. Most of the tested compounds resulted active against both Leishmania species, with IC values in the low micromolar/sub-micromolar range. Among the set of 2-(long chain)alkyl benzimidazoles, whose heterocyclic head was quaternised, compound 8 resulted about 100-/200-fold more potent than miltefosine, even if the selectivity index (SI) versus HMEC-1 cells was only moderately improved. In the set of 2-benzyl and 2-phenyl benzimidazoles, bearing a basic side chain in position 1, compound 28 (2-(4-chlorobenzyl)-1-lupinyl-5-trifluoromethylbenzimidazole) was 12-/7-fold more potent than miltefosine, but exhibited a further improved SI. Therefore, compounds 8 and 28 represent interesting hit compounds, susceptible of structural modification to improve their safety profiles.

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“…72 Benzimidazoles were identified from a HTS campaign and later confirmed in a selectivity assay against hSCD1 and hSCD2. The compound 28 appeared to be the more interesting one with IC 50 values of 65 nM versus rSCD1, 27 nM versus hSCD1, and .20 mM versus hSCD2.…”

Section: Scd1 Selective Inhibitorsmentioning

confidence: 99%

Chapter 9. Stearoyl-CoA Desaturase 1 (SCD1) Inhibitors: Bench to Bedside Must Only Go Through Liver

Liu¹

2012

Drug Discovery

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2-Aryl benzimidazoles: Human SCD1-specific stearoyl coenzyme-A desaturase inhibitors

Cited by 23 publications

References 50 publications

Selective Synthesis of Benzimidazoles from o-Phenylenediamine and Aldehydes Promoted by Supported Gold Nanoparticles

Selective Synthesis of Benzimidazoles from o-Phenylenediamine and Aldehydes Promoted by Supported Gold Nanoparticles

Benzimidazole derivatives endowed with potent antileishmanial activity

Chapter 9. Stearoyl-CoA Desaturase 1 (SCD1) Inhibitors: Bench to Bedside Must Only Go Through Liver

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