Novel benzoxazole inhibitors of mPGES-1

被引：25

作者：

Kablaoui, Natasha ^{[1
]}

Patel, Snahel ^{[2
]}

Shao, Jay ^{[1
]}

Demian, Douglas ^{[3
]}

Hoffmaster, Keith ^{[4
]}

Berlioz, Francioise ^{[5
]}

Vazquez, Michael L. ^{[6
]}

Moore, William M. ^{[7
]}

Nugent, Richard A. ^{[1
]}

机构：

[1] Pfizer Res Technol Ctr, Cambridge, MA 02139 USA

[2] Genentech Inc, San Francisco, CA 94080 USA

[3] Blue Sky Biotech Inc, Worcester, MA 01605 USA

[4] Novartis Inc, Cambridge, MA 02139 USA

[5] Vertex, Cambridge, MA 02139 USA

[6] Pfizer Global Res, Groton, CT 06340 USA

[7] Monsanto Co, St Louis, MO 63167 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 03期

关键词：

mPGES-1; Benzoxazole; Selective; PROSTAGLANDIN-E SYNTHASE-1; EXPRESSION; ARTHRITIS; CARTILAGE; PYRESIS;

D O I：

10.1016/j.bmcl.2012.10.040

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of potent benzoxazole mPGES-1 inhibitors has been derived from a hit from a high throughput screen. Compound 37 displays mPGES-1 inhibition in an enzyme assay (0.018 mu M) and PGE-2 inhibition in a cell-based assay (0.034 mu M). It demonstrates 500- and 2500-fold selectivity for mPGES-1 over COX-2 and 6-keto PGF-1 alpha, respectively. In vivo PK studies in dogs demonstrate 55% oral bioavailability and an 7 h half-life. (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：907 / 911

页数：5

共 50 条

[41] Discovery of novel microsomal prostaglandin E2 synthase 1 (mPGES-1) inhibitors by a structurally inspired virtual screening study
Olgac, Abdurrahman
Jordan, Paul M.
Kretzer, Christian
Werz, Oliver
Banoglu, Erden
JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2025, 136
[42] Sinomenine increases the methylation level at specific GCG site in mPGES-1 promoter to facilitate its specific inhibitory effect on mPGES-1
Luo, Jin-Fang
Yao, Yun-Da
Cheng, Chun-Song
Lio, Chon-Kit
Liu, Jian-Xin
Huang, Yu-Feng
He, Fan
Xie, Ying
Liu, Liang
Liu, Zhong-Qiu
Zhou, Hua
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2022, 1865 (03):
[43] Pharmacophore Modeling and Virtual Screening for Novel Acidic Inhibitors of Microsomal Prostaglandin E2 Synthase-1 (mPGES-1)
Waltenberger, Birgit
Wiechmann, Katja
Bauer, Julia
Markt, Patrick
Noha, Stefan M.
Wolber, Gerhard
Rollinger, Judith M.
Werz, Oliver
Schuster, Daniela
Stuppner, Hermann
JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (09) : 3163 - 3174
[44] Synthesis, in silico studies and cytotoxicity evaluation of novel 1,3,4-oxadiazole derivatives designed as potential mPGES-1 inhibitors
Erensoy, Gizem
Ding, Kai
Zhan, Chang-Guo
Elmezayen, Ammar
Yelekci, Kemal
Duracik, Merve
Ozakpinar, Ozlem Bingol
Kucukguzel, Ilkay
JOURNAL OF RESEARCH IN PHARMACY, 2020, 24 (04): : 436 - 451
[45] Histone deacetylase inhibitors suppress interieukin-1β induced mPGES-1 expression in human chondrocytes
Chabane, Nadir
Afif, Hassan
Zayed, Nadia
Martel-Pelletier, Johanne
Pelletier, Jean-Pierre
Fahmi, Hassan
ARTHRITIS AND RHEUMATISM, 2008, 58 (09): : S670 - S670
[46] The Effect of mPGES-1 Deletion on Platelet Function in Mice
Raouf, Joan
Mobarrez, Fariborz
Larsson, Karin
Jakobsson, Per Johan
Korotkova, Marina
ARTHRITIS & RHEUMATOLOGY, 2015, 67
[47] Targeted delivery of mPGES-1 inhibitors to macrophages via the folate receptor-β for inflammatory pain
Mazaleuskaya, Liudmila L.
Lee, Seokwoo
Meng, Hu
Winkler, Jeffrey D.
FitzGerald, Garret A.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2021, 50
[48] A novel mPGES-1/EGR1/beta-catenin signaling axis in hepatocarcinogenesis
Lu, Dongdong
Han, Chang
Wu, Tong
CANCER RESEARCH, 2011, 71
[49] MICROSOMAL PROSTAGLANDIN E SYNTHASE-1 (MPGES-1) IS A NOVEL ONCOGENE THAT PROMOTES CHOLANGIOCARCINOGENESIS
Lu, Dongdong
Han, Chang
Wu, Tong
HEPATOLOGY, 2010, 52 (04) : 937A - 937A
[50] mPGES-1, mPGES-2 and cPGES expression in human gastric ulcer tissue
Gudis, K
Tatsuguchi, A
Wada, K
Futagami, S
Nagata, K
Hiratsuka, T
Osada, Y
Shinji, Y
Miyake, K
Tsukui, T
Sakamoto, C
GASTROENTEROLOGY, 2004, 126 (04) : A47 - A47

← 1 2 3 4 5 →