Design, Synthesis and in Vivo Anti-inflammatory Activities of 2,4-Diaryl-5-4H-imidazolone Derivatives

被引：46

作者：

El-Araby, Moustafa ^{[1
,2
]}

Omar, Abdelsattar ^{[1
,3
]}

Hassanein, Hassanein H. ^{[4
]}

El-Helby, Abdel-Ghany H. ^{[3
]}

Abdel-Rahman, Asharf A. ^{[3
]}

机构：

[1] King Abdulaziz Univ, Dept Pharmaceut Chem, Fac Pharm, Jeddah 21589, Saudi Arabia

[2] Helwan Univ, Dept Organ Pharmaceut Chem, Fac Pharm, Cairo 11790, Egypt

[3] Al Azhar Univ, Dept Pharmaceut Chem, Fac Pharm, Cairo 11884, Egypt

[4] Cairo Univ, Dept Pharmaceut Chem, Fac Pharm, Cairo 11787, Egypt

来源：

MOLECULES | 2012年 / 17卷 / 10期

关键词：

anti-inflammatory; COX-2; inhibitors; imidazolone; oxazolone; docking; structure-based design; CYCLOOXYGENASE-2; INHIBITORS; ACID-DERIVATIVES; COX-2; OSTEOARTHRITIS; SCAFFOLD; PLASMA; DRUGS;

D O I：

10.3390/molecules171012262

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：

A series of 2,4-diaryl-5(4H)-imidazolones were prepared and evaluated for their anti-inflammatory activities. Some selected 2,4-diaryl-5(4H)-imidazolones exhibited excellent anti-inflammatory activity in the carrageenan-induced rat paw edema model. Structure Activity Relationships within the series were studied. The substitution at the N-sulfonamide moiety by a small hydrophilic acetyl group resulted in compounds with superior in vivo anti-inflammatory properties. As expected from their COX-2 selectivity, most of the active compounds lacked gastrointestinal toxicity in vivo in rats after a 3-day treatment of 25 mg/kg/day.

引用

页码：12262 / 12275

页数：14

共 26 条

[1]

[Anonymous], 2010, SYBYL X SUIT VERS SY

[2] Medicine - Lipid signals in pain control [J].

Bazan, NG ;

Flower, RJ .

NATURE, 2002, 420 (6912) :135-+

[3] Novel Ester and Acid Derivatives of the 1,5-Diarylpyrrole Scaffold as Anti-Inflammatory and Analgesic Agents. Synthesis and in Vitro and in Vivo Biological Evaluation [J].

Biava, Mariangela ;

Porretta, Giulio C. ;

Poce, Giovanna ;

Battilocchio, Claudio ;

Manetti, Fabrizio ;

Botta, Maurizio ;

Forli, Stefano ;

Sautebin, Lidia ;

Rossi, Antonietta ;

Pergola, Carlo ;

Ghelardini, Carla ;

Galeotti, Nicoletta ;

Makovec, Francesco ;

Giordani, Antonio ;

Anzellotti, Paola ;

Patrignani, Paola ;

Anzini, Maurizio .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (02) :723-733

[4] Regulator cancels registration of osteoarthritis drug [J].

Burton, Bob .

BRITISH MEDICAL JOURNAL, 2007, 335 (7616) :363-363

[5] Substituents Effect on the Erlenmeyer-Plochl Reaction: Understanding an Observed Process Reaction Time [J].

Chavez, Flavio ;

Kennedy, Nicole ;

Rawalpally, Thimma ;

Williamson, R. Thomas ;

Cleary, Thomas .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2010, 14 (03) :579-584

[6] Parecoxib (parecoxib sodium) [J].

Cheer, SM ;

Goa, KL .

DRUGS, 2001, 61 (08) :1133-1141

[7] THE ERLENMEYER REACTION WITH ALIPHATIC ALDEHYDES, 2-PHENYLOXAZOL-5-ONE BEING USED INSTEAD OF HIPPURIC ACID [J].

CRAWFORD, M ;

LITTLE, WT .

JOURNAL OF THE CHEMICAL SOCIETY, 1959, (FEB) :729-731

[8] Novel acid-type cyclooxygenase-2 inhibitors: Design, synthesis, and structure-activity relationship for anti-inflammatory drug [J].

Hayashi, Shigeo ;

Ueno, Naomi ;

Murase, Akio ;

Nakagawa, Yoko ;

Takada, Junji .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 50 :179-195

[9] 2-chloro-1,3-dimethylimidazolinium chloride. 2. Its application to the construction of heterocycles through dehydration reactions [J].

Isobe, T ;

Ishikawa, T .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (19) :6989-6992

[10] Synthesis of some novel imidazolinones as potent anticonvulsant agents [J].

Joshi, H ;

Upadhyay, P ;

Karia, D ;

Baxi, AJ .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2003, 38 (09) :837-840

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