Liquid phase combinatorial synthesis of 1,2,5-trisubstituted benzimidazole derivatives as human DHODH inhibitors

被引：6

作者：

Sitwala, Nikum D. ^{[1
]}

Vyas, Vivek K. ^{[1
]}

Variya, Bhavesh C. ^{[2
]}

Patel, Snehal S. ^{[2
]}

Mehta, Chirag C. ^{[3
]}

Rana, Dharmraj N. ^{[3
]}

Ghate, Manjunath D. ^{[1
]}

机构：

[1] Nirma Univ, Inst Pharm, Dept Pharmaceut Chem, Ahmadabad 382481, Gujarat, India

[2] Nirma Univ, Inst Pharm, Dept Pharmacol, Ahmadabad 382481, Gujarat, India

[3] Oxygen Healthcare Res Pvt Ltd, Plot 35,Panchratna Ind Estate, Ahmadabad, Gujarat, India

来源：

BIOORGANIC CHEMISTRY | 2017年 / 75卷

关键词：

Benzimidazole derivatives; Liquid phase combinatorial synthesis; Human dihydroorotate dehydrogenase (hDHODH) hDHODH inhibitors; HUMAN DIHYDROOROTATE DEHYDROGENASE; BIOLOGICAL EVALUATION; DESIGN; LIBRARIES; BINDING; POTENT; AGENTS; HDHODH;

D O I：

10.1016/j.bioorg.2017.08.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The synthesis of 1,2,5-trisubstituted benzimidazole derivatives was carried out using liquid phase combinatorial approach using soluble polymer assisted support (PEG5000). Synthesised compounds were characterised by FTIR, ESI-MS, H-1 NMR and C-13 NMR. The purity of compounds was confirmed with HPLC analysis. Compounds were also docked into the binding site of human dihydroorotate dehydrogenase (hDHODH). The synthesised compounds were screened for hDHODH enzyme inhibition assay using brequinar as standard compound. The synthesised compounds demonstrated comparative biological activity. Synthesised compounds 8d and 8e demonstrated IC50 value of 81 +/- 2 nM and 97 +/- 2 nM, respectively. (C) 2017 Elsevier Inc. All rights reserved.

引用

页码：118 / 126

页数：9

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