Phenylpropanoic acid derivatives bearing a benzothiazole ring as PPARδ-selective agonists

被引：16

作者：

Fujieda, Hiroki

Usui, Shinya

Suzuki, Takayoshi

Nakagawa, Hidehiko

Ogura, Michitaka

Makishima, Makoto

Miyata, Naoki

机构：

[1] Nagoya City Univ, Grad Sch Pharmaceut Sci, Mizuho Ku, Nagoya, Aichi 4678603, Japan

[2] Nihon Univ, Sch Med, Itabashi Ku, Tokyo 1738610, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 15期

关键词：

PPAR delta; agonist; drug design; nuclear receptor; metabolic syndrome;

D O I：

10.1016/j.bmcl.2007.05.017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To find novel PPAR delta-selective agonists, we designed and synthesized phenylpropanoic acid derivatives bearing 6-substituted benzothiazoles. Optimization of this series led to the identification of a potent and selective PPAR delta agonist 17. Molecular modeling suggested that compound 17 occupies the Y-shaped pocket of PPAR6 appropriately. (c) 2007 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4351 / 4357

页数：7

相关论文

共 26 条

[1] The heck reaction as a sharpening stone of palladium catalysis [J].

Beletskaya, IP ;

Cheprakov, AV .

CHEMICAL REVIEWS, 2000, 100 (08) :3009-3066

[2] [[OMEGA-(HETEROCYCLYLAMINO)ALKOXY]BENZYL]-2,4-THIAZOLIDINEDIONES AS POTENT ANTIHYPERGLYCEMIC AGENTS [J].

CANTELLO, BCC ;

CAWTHORNE, MA ;

COTTAM, GP ;

DUFF, PT ;

HAIGH, D ;

KINDLEY, RM ;

LISTER, CA ;

SMITH, SA ;

THURLBY, PL .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (23) :3977-3985

[3] 1,3,5-Trisubstituted aryls as highly selective PPARδ agonists [J].

Epple, R ;

Azimioara, M ;

Russo, R ;

Bursulaya, B ;

Tian, SS ;

Gerken, A ;

Iskandar, M .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (11) :2969-2973

[4] Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta [J].

Forman, BM ;

Chen, J ;

Evans, RM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (09) :4312-4317

[5] Sulfonylurea agents exhibit peroxisome proliferator-activated receptor γ agonistic activity [J].

Fukuen, S ;

Iwaki, M ;

Yasui, A ;

Makishima, M ;

Matsuda, M ;

Shimomura, I .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (25) :23653-23659

[6] 2,4-dinitrobenzenesulfonamides: A simple and practical method for the preparation of a variety of secondary amines and diamines. [J].

Fukuyama, T ;

Cheung, M ;

Jow, CK ;

Hidai, Y ;

Kan, T .

TETRAHEDRON LETTERS, 1997, 38 (33) :5831-5834

[7] 2-NITROBENZENESULFONAMIDES AND 4-NITROBENZENESULFONAMIDES - EXCEPTIONALLY VERSATILE MEANS FOR PREPARATION OF SECONDARY-AMINES AND PROTECTION OF AMINES [J].

FUKUYAMA, T ;

JOW, CK ;

CHEUNG, M .

TETRAHEDRON LETTERS, 1995, 36 (36) :6373-6374

[8] Asymmetry in the PPARγ/RXRα crystal structure reveals the molecular basis of heterodimerization among nuclear receptors [J].

Gampe, RT ;

Montana, VG ;

Lambert, MH ;

Miller, AB ;

Bledsoe, RK ;

Milburn, MV ;

Kliewer, SA ;

Willson, TM ;

Xu, HE .

MOLECULAR CELL, 2000, 5 (03) :545-555

[9] The PPARδ agonist GW0742X reduces atherosclerosis in LDLR-/- mice [J].

Graham, TL ;

Mookherjee, C ;

Suckling, KE ;

Palmer, CNA ;

Patel, L .

ATHEROSCLEROSIS, 2005, 181 (01) :29-37

[10] Transcriptional repression of atherogenic inflammation:: Modulation by PPARδ [J].

Lee, CH ;

Chawla, A ;

Urbiztondo, N ;

Liao, D ;

Boisvert, WA ;

Evans, RM .

SCIENCE, 2003, 302 (5644) :453-457