Synthesis, cyclooxygenase inhibitory effects, and molecular modeling study of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and-2-alkylsulfonyl-1H-imidazole derivatives

被引：19

作者：

Assadieskandar, Amir ^{[1
,2
]}

Amirhamzeh, Amirali ^{[1
,2
]}

Salehi, Marjan ^{[1
,2
]}

Ozadali, Keriman ^{[3
,4
]}

Ostad, Seyed Nasser ^{[5
,6
]}

Shafiee, Abbas ^{[7
,8
]}

Amini, Mohsen ^{[1
,2
]}

机构：

[1] Univ Tehran Med Sci, Dept Med Chem, Fac Pharm, Tehran 14176, Iran

[2] Univ Tehran Med Sci, Drug Design & Dev Res Ctr, Tehran 14176, Iran

[3] Univ Alberta, Fac Pharm & Pharmaceut Sci, Katz Grp Ctr Pharm & Hlth Res 2142L, Edmonton, AB T6G 2E9, Canada

[4] Hacettepe Univ, Dept Pharmaceut Chem, Fac Pharm, TR-06100 Ankara, Turkey

[5] Univ Tehran Med Sci, Dept Pharmacol & Toxicol, Fac Pharm, Tehran, Iran

[6] Univ Tehran Med Sci, Rat Drug Use Res Ctr, Tehran, Iran

[7] Univ Tehran Med Sci, Dept Med Chem, Fac Pharm, Tehran 14176, Iran

[8] Univ Tehran Med Sci, Pharmaceut Sci Res Ctr, Tehran 14176, Iran

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 08期

关键词：

Cyclooxygenase; Human whole blood assay; Docking; Tautomerization; 2-Alkylthio-1H-imidazole; 2-Alkylsulfonyl-1H-imidazole; HYDE SCORING FUNCTION; BIOLOGICAL EVALUATION; SELECTIVE-INHIBITION; COX-2; INHIBITORS; SYNTHASE-1;

D O I：

10.1016/j.bmc.2013.01.058

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A series of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and 2-alkylsulfonyl-1H-imidazole derivatives were synthesized. All compounds were tested in human blood assay to determine COX-1 and COX-2 inhibitory potency and selectivity. Among the synthesized compounds, 2-alkylthio series were more potent and selective than 2-sulfonylalkyl derivatives. In molecular modeling, interaction of 2-sulfonylalkyl moiety with Arg120 in COX-1 and an extra hydrogen bond with Tyr341 in COX-2 increased the residence time of ligands in the active site in 2-sulfonylalkyl and 2-alkylthio analogs, respectively. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：2355 / 2362

页数：8

共 34 条

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