Design and synthesis of 1,3-diarylurea derivatives as selective cyclooxygenase (COX-2) inhibitors

被引：28

作者：

Zarghi, Afshin ^{[1
]}

Kakhgi, Samaneh ^{[1
]}

Hadipoor, Atefeh ^{[1
]}

Daraee, Bahram ^{[2
]}

Dadrass, Orkideh G. ^{[3
]}

Hedayati, Mehdi ^{[4
]}

机构：

[1] Shahid Beheshti Univ Med Sci, Dept Pharmaceut Chem, Sch Pharm, Tehran, Iran

[2] Tarbiat Modares Univ, Tehran, Iran

[3] Azad Univ, Sch Pharm, Tehran, Iran

[4] Shahid Beheshti Univ Med Sci, Endocrine Res Ctr, Tehran, Iran

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 04期

关键词：

1,3-diarylurea; COX-2; inhibition; SAR;

D O I：

10.1016/j.bmcl.2008.01.021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A group of 1,3-diarylurea derivatives, possessing a methylsulfonyl pharmacophore at the para-position of the N-1 phenyl ring, in conjunction with a N-3 substituted-phenyl ring (4-F, 4-Cl, 4-Me, 4-OMe), were designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1/COX-2 isozyme inhibition structure - activity studies identified 1-(4methylsulfonylphenyl)-3-(4- methoxyphenyl) urea (4e) as a potent COX-2 inhibitor (IC50 = 0.11 mu M) with a high COX-2 selectivity index ( SI = 203.6) comparable to the reference drug celecoxib (COX-2 IC50 = 0.06 mu M; COX-2 SI =405). The structure - activity data acquired indicate that the urea moiety constitutes a suitable scaffold to design new acyclic 1,3-diarylurea derivatives with selective COX-2 inhibitory activity. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1336 / 1339

页数：4

共 50 条

[31] Biochemistry of cyclooxygenase (COX)-2 inhibitors and molecular pathology of COX-2 in neoplasia
Fosslien, E
CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES, 2000, 37 (05) : 431 - 502
[32] Cyclooxygenase-2 (COX-2) enzyme inhibitors and radiotherapy
Milas, L
AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 2003, 26 (04): : S66 - S69
[33] Selective COX-2 inhibitors. Part 1: Synthesis and biological evaluation of phenylazobenzenesulfonamides
Tsai, Wei-Jern
Shiao, Young-Ji
Lin, Shwu-Jiuan
Chiou, Wen-Fei
Lin, Lie-Chwen
Yang, Tsang-Hsiung
Teng, Che-Ming
Wu, Tain-Shung
Yang, Li-Ming
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (17) : 4440 - 4443
[34] Is COX-2 a perpetrator or a protector? Selective COX-2 inhibitors remain controversial
Luo, C
He, ML
Bohlin, L
ACTA PHARMACOLOGICA SINICA, 2005, 26 (08) : 926 - 933
[35] Design, synthesis and biological evaluation of new (E)- and (Z)-1,2,3-triaryl-2-propen-1-ones as selective COX-2 inhibitors
Arfaie, Sara
Zarghi, Afshin
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2010, 45 (09) : 4013 - 4017
[36] New pyridazine derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents; design, synthesis and biological evaluation
Ahmed, Eman M.
Hassan, Marwa S. A.
El-Malah, Afaf A.
Kassab, Asmaa E.
BIOORGANIC CHEMISTRY, 2020, 95
[37] Design, synthesis and biological evaluation of pyridine acyl sulfonamide derivatives as novel COX-2 inhibitors
Lu, Xiang
Zhang, Hui
Li, Xi
Chen, Guo
Li, Qing-Shan
Luo, Yin
Ruan, Ban-Feng
Chen, Xian-Wei
Zhu, Hai-Liang
BIOORGANIC & MEDICINAL CHEMISTRY, 2011, 19 (22) : 6827 - 6832
[38] Design, synthesis of celecoxib-tolmetin drug hybrids as selective and potent COX-2 inhibitors
Abdellatif, Khaled R. A.
Abdelall, Eman K. A.
Labib, Madlen B.
Fadaly, Wael A. A.
Zidan, Taha H.
BIOORGANIC CHEMISTRY, 2019, 90
[39] Design, Synthesis, Docking Studies, Enzyme Inhibitory and Antiplatelet Aggregation Activities of New 1,3-Diphenyl-3-(Phenylthio)Propan-1-One Derivatives as Selective COX-2 Inhibitors
Bayanati, Maryam
Daraei, Bahram
Zarghi, Afshin
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2023, 23 (02) : 192 - 200
[40] Design and synthesis of new 1,2-diaryl-4,5,6,7-tetrahydro-1H-benzo[d] imidazoles as selective cyclooxygenase (COX-2) inhibitors
A. Zarghi
H. Reihanfard
S. Arfaei
B. Daraei
M. Hedayati
Medicinal Chemistry Research, 2012, 21 : 1869 - 1875

← 1 2 3 4 5 →