Synthesis, anti-inflammatory evaluation and docking studies of some new fluorinated fused quinazolines

被引：175

作者：

Balakumar, C. ^{[3
]}

Lamba, P. ^{[1
,2
]}

Kishore, D. Pran ^{[1
,2
]}

Narayana, B. Lakshmi ^{[1
,2
]}

Rao, K. Venkat ^{[1
,2
]}

Rajwinder, K. ^{[1
,2
]}

Rao, A. Raghuram ^{[1
,2
]}

Shireesha, B. ^{[4
]}

Narsaiah, B. ^{[5
]}

机构：

[1] Panjab Univ, Pharmaceut Chem Div, Univ Inst Pharmaceut Sci, Chandigarh 160014, India

[2] Panjab Univ, UGC Ctr Adv Study Pharmaceut Sci UGC CAS, Chandigarh 160014, India

[3] Panjab Univ, Ctr Potential Excellence Biomed Sci CPEBS, Chandigarh 160014, India

[4] Vaagdevi Coll Pharm, Hanamkonda 506001, Andhra Pradesh, India

[5] Indian Inst Chem Technol, Fluoroorgan Div, Hyderabad 500007, Andhra Pradesh, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 11期

关键词：

Fluorinated quinazolines; Cyclooxygenase; Anti-inflammatory activity; Docking studies; CYCLOOXYGENASE INHIBITORS; AGENTS; CYCLO-OXYGENASE-2; DERIVATIVES; EXPRESSION; SYNTHASE-2; DISCOVERY; DRUGS; COX-2; SITE;

D O I：

10.1016/j.ejmech.2010.07.063

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines have been synthesized and evaluated in vivo (rat paw edema) for their anti-inflammatory activity and in silico (docking studies) to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The compounds, 9b and 10b, were found to have good anti-inflammatory activity [around 80% of the standard: indomethacin]. The binding mode of the title compounds has been proposed based on the docking studies. Crown Copyright (C) 2010 Published by Elsevier Masson SAS. All rights reserved.

引用

页码：4904 / 4913

页数：10

共 29 条

[1] Synthesis and pharmacological evaluation of some 3-(4-methoxyphenyl)-2-substitutedamino-quinazolin-4(3H)-ones as analgesic and anti-inflammatory agents [J].

Alagarsamy, Veerachamy ;

Murugesan, Sankaranarayanan .

CHEMICAL & PHARMACEUTICAL BULLETIN, 2007, 55 (01) :76-80

[2]

[Anonymous], 2008, GOLD VERS 4 0 1

[3] Expression of cyclo-oxygenase-2 in human airway smooth muscle is associated with profound reductions in cell growth [J].

Belvisi, MG ;

Saunders, M ;

Yacoub, M ;

Mitchell, JA .

BRITISH JOURNAL OF PHARMACOLOGY, 1998, 125 (05) :1102-1108

[4] Synthesis of novel 4,6-disubstituted quinazoline derivatives, their anti-inflammatory and anti-cancer activity (cytotoxic) against U937 leukemia cell lines [J].

Chandrika, P. Mani ;

Yakaiah, T. ;

Rao, A. Raghu Ram ;

Narsaiah, B. ;

Reddy, N. Chakra ;

Sridhar, V. ;

Rao, J. Venkateshwara .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2008, 43 (04) :846-852

[5] Substituted isoquinolines and quinazolines as potential antiinflammatory agents.: Synthesis and biological evaluation of inhibitors of tumor necrosis factor α [J].

Chao, Q ;

Deng, L ;

Shih, HC ;

Leoni, LM ;

Genini, D ;

Carson, DA ;

Cottam, HB .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (19) :3860-3873

[6] Cyclooxygenase inhibitors - current status and future prospects [J].

Dannhardt, G ;

Kiefer, W .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2001, 36 (02) :109-126

[7] New trends in dual 5-LOX/COX inhibition [J].

de Leval, X ;

Julémont, F ;

Delarge, J ;

Pirotte, B ;

Dogné, JM .

CURRENT MEDICINAL CHEMISTRY, 2002, 9 (09) :941-962

[8]

El-Kerdawy MM, 1997, SAUDI PHARM J, V5, P46

[9] Chemometric rationalization of the structural and physicochemical basis for selective cyclooxygenase-2 inhibition: Toward more specific ligands [J].

Filipponi, E ;

Cecchetti, V ;

Tabarrini, O ;

Bonelli, D ;

Fravolini, A .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2000, 14 (03) :277-291

[10] Automated docking and molecular dynamics simulations of nimesulide in the cyclooxygenase active site of human prostaglandin-endoperoxide synthase-2 (COX-2) [J].

García-Nieto, R ;

Pérez, C ;

Gago, F .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2000, 14 (02) :147-160

← 1 2 3 →