Identification of benzofuran central cores for the inhibition of leukotriene A4 hydrolase

被引：13

作者：

Eccles, Wendy ^{[1
]}

Blevitt, Jonathan M. ^{[1
]}

Booker, Jamila N. ^{[1
]}

Chrovian, Christa C. ^{[1
]}

Crawford, Shelby ^{[1
]}

de Leon, Aimee Rose ^{[1
]}

Deng, Xiaohu ^{[1
]}

Fourie, Anne M. ^{[1
]}

Grice, Cheryl A. ^{[1
]}

Herman, Krystal ^{[1
]}

Karlsson, Lars ^{[1
]}

Kearney, Aaron M. ^{[1
]}

Lee-Dutra, Alice ^{[1
]}

Liang, Jimmy ^{[1
]}

Luna, Rosa ^{[1
]}

Pippel, Dan ^{[1
]}

Rao, Navin ^{[1
]}

Riley, Jason P. ^{[1
]}

Santillan, Alejandro ^{[1
]}

Savall, Brad ^{[1
]}

Tanis, Virginia M. ^{[1
]}

Xue, Xiaohua ^{[1
]}

Young, Arlene L. ^{[1
]}

机构：

[1] Janssen Res & Dev LLC, San Diego, CA 92121 USA

来源：

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

关键词：

Leukotrienes; LTA(4)H; Leukotriene A4 hydrolase; Leukotriene B4 hydrolase;

D O I：

10.1016/j.bmcl.2012.11.074

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Leukotrienes (LT's) are known to play a physiological role in inflammatory immune response. Leukotriene A(4) hydrolase (LTA(4)H) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA(4) to LTB4. LTB4 is a known pro-inflammatory mediator. This paper describes the identification and synthesis of substituted benzofurans as LTH4H inhibitors. The benzofuran series demonstrated reduced mouse and human whole blood LTB4 levels in vitro and led to the identification one analog for advanced profiling. Benzofuran 28 showed dose responsive target engagement and provides a useful tool to explore a LTA(4)H inhibitor for the treatment of inflammatory diseases, such as asthma and inflammatory bowel disease (IBD). (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：811 / 815

页数：5

共 50 条

[21] Leukotriene A4 hydrolase and the committed step in leukotriene B4 biosynthesis
Haeggström, JZ
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY, 1999, 17 (1-2) : 111 - 131
[22] Gliotoxin from Aspergillus fumigatus Abrogates Leukotriene B4 Formation through Inhibition of Leukotriene A4 Hydrolase
Koenig, Stefanie
Pace, Simona
Pein, Helmut
Heinekamp, Thorsten
Kramer, Jan
Romp, Erik
Strassburger, Maria
Troisi, Fabiana
Proschak, Anna
Dworschak, Jan
Scherlach, Kirstin
Rossi, Antonietta
Sautebin, Lidia
Haeggstrom, Jesper Z.
Hertweck, Christian
Brakhage, Axel A.
Gerstmeier, Jana
Proschak, Ewgenij
Werz, Oliver
CELL CHEMICAL BIOLOGY, 2019, 26 (04): : 524 - +
[23] Modulation of inflammatory disease by inhibitors of leukotriene A4 hydrolase
Fourie, Anne M.
CURRENT OPINION IN INVESTIGATIONAL DRUGS, 2009, 10 (11) : 1173 - 1182
[24] Effect of alpha lipoic acid on leukotriene A4 hydrolase
Jose Torres, Maria
Fierro, Angelica
David Pessoa-Mahana, C.
Romero-Parra, Javier
Cabrera, Gonzalo
Faundez, Mario
EUROPEAN JOURNAL OF PHARMACOLOGY, 2017, 799 : 41 - 47
[25] Ubiquitous localization of leukotriene A4 hydrolase in the rat nephron
Nakao, A
Watanabe, T
Ohishi, N
Toda, A
Asano, K
Taniguchi, S
Nosaka, K
Noiri, E
Suzuki, T
Sakai, T
Kurokawa, K
Shimizu, T
Kimura, S
KIDNEY INTERNATIONAL, 1999, 55 (01) : 100 - 108
[26] Development of a potent and selective inhibitor of leukotriene A4 hydrolase
Wei, JM
Tays, K
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2005, 229 : U150 - U150
[27] Role of Leukotriene A4 Hydrolase Aminopeptidase in the Pathogenesis of Emphysema
Paige, Mikell
Wang, Kan
Burdick, Marie
Park, Sunhye
Cha, Josiah
Jeffery, Erin
Sherman, Nicholas
Shim, Y. Michael
JOURNAL OF IMMUNOLOGY, 2014, 192 (11): : 5059 - 5068
[28] Leukotriene A4 hydrolase as a target for cancer prevention and therapy
Chen, X
Wang, S
Wu, N
Yang, CS
CURRENT CANCER DRUG TARGETS, 2004, 4 (03) : 267 - 283
[29] INVESTIGATION OF THE INHIBITION OF LEUKOTRIENE A(4) HYDROLASE
OLLMANN, IR
HOGG, JH
MUNOZ, B
HAEGGSTROM, JZ
SAMUELSSON, B
WONG, CH
BIOORGANIC & MEDICINAL CHEMISTRY, 1995, 3 (07) : 969 - 995
[30] Leukotriene A4 hydrolase/aminopeptidase, the gatekeeper of chemotactic leukotriene B4 biosynthesis
Haeggström, JZ
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (49) : 50639 - 50642

← 1 2 3 4 5 →