Synthesis and biological evaluation of 4-quinazolinones as Rho kinase inhibitors

被引：29

作者：

Fang, Xingang

Chen, Yen Ting ^{[1
]}

Sessions, E. Hampton

Chowdhury, Sarwat

Vojkovsky, Tomas

Yin, Yan

Pocas, Jennifer R.

Grant, Wayne

Schroeter, Thomas

Lin, Li

Ruiz, Claudia

Cameron, Michael D.

LoGrasso, Philip

Bannister, Thomas D.

Feng, Yangbo

机构：

[1] Scripps Res Inst, Translat Res Inst, Jupiter, FL 33458 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 06期

关键词：

Rho kinase; Quinazolinone; Pyrazole; ROCK inhibitor; Protein kinase A; INTRAOCULAR-PRESSURE; ROCK INHIBITORS; POTENT; DISCOVERY;

D O I：

10.1016/j.bmcl.2011.01.039

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Rho kinase ( ROCK) is an attractive therapeutic target for various diseases including glaucoma, hypertension, and spinal cord injury. Herein, we report the development of a series of ROCK-II inhibitors based on 4-quinazolinone and quinazoline scaffolds. SAR studies at three positions of the quinazoline core led to the identification of analogs with high potency against ROCK-II and good selectivity over protein kinase A (PKA). (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1844 / 1848

页数：5

共 22 条

[11] Rho GTPase/Rho kinase inhibition as a novel target for the treatment of glaucoma [J].

Rao, Vasantha P. ;

Epstein, David L. .

BIODRUGS, 2007, 21 (03) :167-177

[12] Rocks: Multifunctional kinases in cell behaviour [J].

Riento, K ;

Ridley, AJ .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (06) :446-456

[13] Design and Synthesis of Potent and Selective Azaindole-Based Rho Kinase (ROCK) Inhibitors [J].

Schirok, Hartmut ;

Kast, Raimund ;

Figueroa-Perez, Santiago ;

Bennabi, Samir ;

Gnoth, Mark J. ;

Feurer, Achim ;

Heckroth, Heike ;

Thutewohl, Michael ;

Paulsen, Holger ;

Knorr, Andreas ;

Huetter, Joachim ;

Lobell, Mario ;

Muenter, Klaus ;

Geiss, Volker ;

Ehmke, Heimo ;

Lang, Dieter ;

Radtke, Martin ;

Mittendorf, Joachim ;

Stasch, Johannes-Peter .

CHEMMEDCHEM, 2008, 3 (12) :1893-1904

[14] Detection of myosin light chain phosphorylation -: A cell-based assay for screening Rho-kinase inhibitors [J].

Schroeter, Thomas ;

Griffin, Evelyn ;

Weiser, Amiee ;

Feng, Yangbo ;

LoGrasso, Philip .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 374 (02) :356-360

[15] Benzimidazole- and benzoxazole-based inhibitors of Rho kinase [J].

Sessions, E. Hampton ;

Yin, Yan ;

Bannister, Thomas D. ;

Weiser, Amiee ;

Griffin, Evelyn ;

Pocas, Jennifer ;

Cameron, Michael D. ;

Ruiz, Claudia ;

Lin, Li ;

Schurer, Stephan C. ;

Schroter, Thomas ;

LoGrasso, Philip ;

Feng, Yangbo .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (24) :6390-6393

[16] The development of benzimidazoles as selective rho kinase inhibitors [J].

Sessions, E. Hampton ;

Smolinski, Michael ;

Wang, Bo ;

Frackowiak, Bozena ;

Chowdhury, Sarwat ;

Yin, Yan ;

Chen, Yen Ting ;

Ruiz, Claudia ;

Lin, Li ;

Pocas, Jennifer ;

Schroeter, Thomas ;

Cameron, Michael D. ;

LoGrasso, Philip ;

Feng, Yangbo ;

Bannister, Thomas D. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (06) :1939-1943

[17] Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity [J].

Stavenger, Robert A. ;

Cui, Haifeng ;

Dowdell, Sarah E. ;

Franz, Robert G. ;

Gaitanopoulos, Dimitri E. ;

Goodman, Krista B. ;

Hilfiker, Mark A. ;

Ivy, Robert L. ;

Leber, Jack D. ;

Marino, Joseph P., Jr. ;

Oh, Hye-Ja ;

Viet, Andrew Q. ;

Xu, Weiwei ;

Ye, Guosen ;

Zhang, Daohua ;

Zhao, Yongdong ;

Jolivette, Larry J. ;

Head, Martha S. ;

Semus, Simon F. ;

Elkins, Patricia A. ;

Kirkpatrick, Robert B. ;

Dul, Edward ;

Khandekar, Sanjay S. ;

Yi, Tracey ;

Jung, David K. ;

Wright, Lois L. ;

Smith, Gary K. ;

Behm, David J. ;

Doe, Christopher P. ;

Bentley, Ross ;

Chen, Zunxuan X. ;

Hu, Erding ;

Lee, Dennis .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (01) :2-5

[18] Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension [J].

Uehata, M ;

Ishizaki, T ;

Satoh, H ;

Ono, T ;

Kawahara, T ;

Morishita, T ;

Tamakawa, H ;

Yamagami, K ;

Inui, J ;

Maekawa, M ;

Narumiya, S .

NATURE, 1997, 389 (6654) :990-994

[19] Reduction of intraocular pressure by topical administration of an inhibitor of the Rho-associated protein kinase [J].

Waki, M ;

Yoshida, Y ;

Oka, T ;

Azuma, M .

CURRENT EYE RESEARCH, 2001, 22 (06) :470-474

[20] The scope and mechanism of phosphonium-mediated SNAr reactions in heterocyclic amides and ureas [J].

Wan, Zhao-Kui ;

Wacharasindhu, Surnrit ;

Levins, Christopher G. ;

Lin, Melissa ;

Tabei, Keiko ;

Mansour, Tarek S. .

JOURNAL OF ORGANIC CHEMISTRY, 2007, 72 (26) :10194-10210

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