Design, synthesis and bioactivities of novel diarylthiophenes:: inhibitors of tumor necrosis factor-α (TNF-α) production

被引：39

作者：

Fujita, M ^{[1
]}

Hirayama, T ^{[1
]}

Ikeda, N ^{[1
]}

机构：

[1] Nikken Chem Co Ltd, Pharmaceut Res Labs, Omiya, Saitama 3300835, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2002年 / 10卷 / 10期

关键词：

D O I：

10.1016/S0968-0896(02)00224-9

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：

The design, synthesis and SAR of novel diarylthiophene derivatives were performed. These compounds were designed by structural hybridization of TNF-alpha production inhibitors bearing 4-fluorophenyl and 4-pyridyl groups such as FR133605, FR167653 and SB210313, and 6-acetyl-3-ethoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine (1) found previously by us. As a result, several compounds were more potent in vitro than FR133605 against TNF-alpha production stimulated with lipopolysaccharide (LPS). (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：3113 / 3122

页数：10

共 26 条

[1]

BENDER PE, 1988, Patent No. 4719218

[2] 1-substituted 4-aryl-5-pyridinylimidazoles: A new class of cytokine suppressive drugs with low 5-lipoxygenase and cyclooxygenase inhibitory potency [J].

Boehm, JC ;

Smietana, JM ;

Sorenson, ME ;

Garigipati, RS ;

Gallagher, TF ;

Sheldrake, PL ;

Bradbeer, J ;

Badger, AM ;

Laydon, JT ;

Lee, JC ;

Hillegass, LM ;

Griswold, DE ;

Breton, JJ ;

ChabotFletcher, MC ;

Adams, JL .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (20) :3929-3937

[3] Matrix metalloproteinase expression during experimental autoimmune encephalomyelitis and effects of a combined matrix metalloproteinase and tumour necrosis factor-alpha inhibitor [J].

Clements, JM ;

Cossins, JA ;

Wells, GMA ;

Corkill, DJ ;

Helfrich, K ;

Wood, LM ;

Pigott, R ;

Stabler, G ;

Ward, GA ;

Gearing, AJH ;

Miller, KM .

JOURNAL OF NEUROIMMUNOLOGY, 1997, 74 (1-2) :85-94

[4]

DEZUBE BJ, 1992, J ACQ IMMUN DEF SYND, V5, P1099

[5] REPEATED THERAPY WITH MONOCLONAL-ANTIBODY TO TUMOR-NECROSIS-FACTOR-ALPHA (CA2) IN PATIENTS WITH RHEUMATOID-ARTHRITIS [J].

ELLIOTT, MJ ;

MAINI, RN ;

FELDMANN, M ;

LONGFOX, A ;

CHARLES, P ;

BIJL, H ;

WOODY, JN .

LANCET, 1994, 344 (8930) :1125-1127

[6]

ENGELBERTS I, 1991, LYMPHOKINE CYTOK RES, V10, P127

[7] Anti-TNFα therapy is useful in rheumatoid arthritis and Crohn's disease:: Analysis of the mechanism of action predicts utility in other diseases [J].

Feldman, M ;

Taylor, P ;

Paleolog, E ;

Brennan, FM ;

Maini, RN .

TRANSPLANTATION PROCEEDINGS, 1998, 30 (08) :4126-4127

[8] Anti-tumor necrosis factor-alpha therapy of rheumatoid arthritis [J].

Feldmann, M ;

Elliott, MJ ;

Woody, JN ;

Maini, RN .

ADVANCES IN IMMUNOLOGY, VOL 64, 1997, 64 :283-350

[9] Synthesis and bioactivities of novel bicyclic thiophenes and 4,5,6,7-tetrahydrothieno[2,3-c]pyridines as inhibitors of tumor necrosis factor-α (TNF-α) production [J].

Fujita, M ;

Seki, T ;

Ikeda, N .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (15) :1897-1900

[10] Synthesis and bioactivities of novel 4,5,6,7-tetrahydrothieno [2,3-c]pyridines as inhibitors of tumor necrosis factor-α (TNF-α) production [J].

Fujita, M ;

Seki, T ;

Inada, H ;

Ikeda, N .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (12) :1607-1611

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