Structure-Based Design of Benzimidazole Sugar Conjugates: Synthesis, SAR and In Vivo Anti-inflammatory and Analgesic Activities

被引：19

作者：

El-Nezhawy, Ahmed O. H. ^{[1
]}

Gaballah, Samir T. ^{[2
]}

Radwan, Mohamed A. A. ^{[3
]}

Baiuomy, Ayman R. ^{[4
]}

Abdel-Salam, Omar M. E. ^{[4
]}

机构：

[1] Natl Res Ctr, Chem Nat & Microbial Prod Dept, Cairo, Egypt

[2] Natl Res Ctr, Photochem Dept, Cairo, Egypt

[3] Natl Res Ctr, Appl Organ Chem Dept, Cairo, Egypt

[4] Natl Res Ctr, Dept Pharmacol, Cairo, Egypt

来源：

MEDICINAL CHEMISTRY | 2009年 / 5卷 / 06期

关键词：

Benzimidazole; trichloroacetimidate; imidomethylation; anti-inflammatory; analgesic; STEREOSELECTIVE SYNTHESIS; ANTIBACTERIAL ACTIVITY; AGENTS; INHIBITORS; DERIVATIVES; (+)-LENTIGINOSINE; VIRUS;

D O I：

10.2174/157340609790170461

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 2-methyl-N-substituted-benzimidazoles, bearing hydroxypyrrolidinon-5-yl or hydroxypyrrolidin-2-yl, 2,3: 5,6-di-O-isopropylidene-alpha-D-mannofuranoside, 2,3,5,6-tetrahydroxy-alpha-D-mannofuranoside, 1:2,5:6-di-O-isopropylidene-alpha-D-gluco-furanose, 3-O-benzyl-6,7-dideoxy-1: 2-O-isopropylidene-alpha-D-xylo-heptofuranos-5-ulose, 3-O-benzyl-6,7- dideoxy-1,2-dihydroxy-alpha-D-xylo-heptofuranos-5-ulose, 1,2,5,6-tetrahydroxy-alpha-D-glucofuranose sugar moieties, were obtained in good yields from 2-methyl N-(trichloroacetamidomethyl) benzimidazole as a donor and carbohydrate residues as acceptor precursors in the presence of catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as Lewis acid. Compounds 6, 7, 10, 13, 15, and 16 showed significant anti-inflammatory and analgesic activities.

引用

页码：558 / 569

页数：12

共 38 条

[1] Stereoselective synthesis of pseudoglycal C-glycosides via trichloroacetimidate activation of glycals [J].

Abdel-Rahman, AAH ;

Takhi, M ;

El Ashry, EH ;

Schmidt, RR .

JOURNAL OF CARBOHYDRATE CHEMISTRY, 2002, 21 (1-2) :113-122

[2] Protection of hydroxy groups with diphenylmethyl and 9-fluorenyl trichloroacetimidates - Effect on anomeric stereocontrol [J].

Ali, IAI ;

El Ashr, ESH ;

Schmidt, RR .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2003, 2003 (21) :4121-4131

[3] Novel dual-targeting benzimidazole urea inhibitors of DNA gyrase and topoisomerase IV possessing potent antibacterial activity: Intelligent design and evolution through the judicious use of structure-guided design and stucture-activity relationships [J].

Charifson, Paul S. ;

Grillot, Anne-Laure ;

Grossman, Trudy H. ;

Parsons, Jonathan D. ;

Badia, Michael ;

Bellon, Steve ;

Deininger, David D. ;

Drumm, Joseph E. ;

Gross, Christian H. ;

LeTiran, Arnaud ;

Liao, Yusheng ;

Mani, Nagraj ;

Nicolau, David P. ;

Perola, Emanuele ;

Ronkin, Steven ;

Shannon, Dean ;

Swenson, Lora L. ;

Tang, Qina ;

Tessier, Pamela R. ;

Tian, Ski-Kai ;

Trudeau, Martin ;

Wang, Tiansheng ;

Wei, Yunyi ;

Zhang, Hong ;

Stamos, Dean .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (17) :5243-5263

[4] ANTIOXIDANT PROPERTIES OF BENZIMIDAZOLES [J].

COLE, ER ;

CRANK, G ;

SALAMSHE.A .

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 1974, 22 (05) :918-918

[5]

de Belder A N, 1965, Adv Carbohydr Chem Biochem, V20, P219

[6]

De Belder A.N., 1977, ADV CARBOHYD CHEM BI, V34, P179

[7] SYNTHESIS AND ANTIINFLAMMATORY ACTIVITY OF SOME 2-SUBSTITUTED ALPHA-METHYL-5-BENZIMIDAZOLEACETIC ACIDS [J].

DUNWELL, DW ;

EVANS, D ;

SMITH, CE ;

WILLIAMSON, WRN .

JOURNAL OF MEDICINAL CHEMISTRY, 1975, 18 (07) :692-694

[8]

El-Nezhawy AOH, 2002, EUR J ORG CHEM, V2002, P4137

[9] Synthesis and biological evaluation of nonclassical 2,4-diamino-5-methylpyrido[2,3-d]pyrimidines with novel side chain substituents as potential inhibitors of dihydrofolate reductases [J].

Gangjee, A ;

Vasudevan, A ;

Queener, SF .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (04) :479-485

[10]

Grimmett M.R., 1996, COMPREHENSIVE HETERO, V3, P77

← 1 2 3 4 →