Literature DB >> 18834107

Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors.

Yangbo Feng1, Yan Yin, Amiee Weiser, Evelyn Griffin, Michael D Cameron, Li Lin, Claudia Ruiz, Stephan C Schürer, Toshihiro Inoue, P Vasanth Rao, Thomas Schröter, Philip Lograsso.   

Abstract

The identification of a new class of potent and selective ROCK-II inhibitors is presented. Compound 5 (SR-3677) had an IC 50 of approximately 3 nM in enzyme and cell based assays and had an off-target hit rate of 1.4% against 353 kinases, and inhibited only 3 out of 70 nonkinase enzymes and receptors. Pharmacology studies showed that 5 was efficacious in both, increasing ex vivo aqueous humor outflow in porcine eyes and inhibiting myosin light chain phosphorylation.

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Year:  2008        PMID： 18834107      PMCID： PMC3708311          DOI： 10.1021/jm800986w

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  28 in total

1.  Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors.

Authors:  Krista B Goodman; Haifeng Cui; Sarah E Dowdell; Dimitri E Gaitanopoulos; Robert L Ivy; Clark A Sehon; Robert A Stavenger; Gren Z Wang; Andrew Q Viet; Weiwei Xu; Guosen Ye; Simon F Semus; Christopher Evans; Harvey E Fries; Larry J Jolivette; Robert B Kirkpatrick; Edward Dul; Sanjay S Khandekar; Tracey Yi; David K Jung; Lois L Wright; Gary K Smith; David J Behm; Ross Bentley; Christopher P Doe; Erding Hu; Dennis Lee
Journal:  J Med Chem       Date:  2007-01-11       Impact factor: 7.446

2.  Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity.

Authors:  Robert A Stavenger; Haifeng Cui; Sarah E Dowdell; Robert G Franz; Dimitri E Gaitanopoulos; Krista B Goodman; Mark A Hilfiker; Robert L Ivy; Jack D Leber; Joseph P Marino; Hye-Ja Oh; Andrew Q Viet; Weiwei Xu; Guosen Ye; Daohua Zhang; Yongdong Zhao; Larry J Jolivette; Martha S Head; Simon F Semus; Patricia A Elkins; Robert B Kirkpatrick; Edward Dul; Sanjay S Khandekar; Tracey Yi; David K Jung; Lois L Wright; Gary K Smith; David J Behm; Christopher P Doe; Ross Bentley; Zunxuan X Chen; Erding Hu; Dennis Lee
Journal:  J Med Chem       Date:  2007-01-11       Impact factor: 7.446

Review 3.  Rho GTPase/Rho kinase inhibition as a novel target for the treatment of glaucoma.

Authors:  Vasantha P Rao; David L Epstein
Journal:  BioDrugs       Date:  2007       Impact factor: 5.807

4.  Syntheses of potent, selective, and orally bioavailable indazole-pyridine series of protein kinase B/Akt inhibitors with reduced hypotension.

Authors:  Gui-Dong Zhu; Viraj B Gandhi; Jianchun Gong; Sheela Thomas; Keith W Woods; Xiaohong Song; Tongmei Li; R Bruce Diebold; Yan Luo; Xuesong Liu; Ran Guan; Vered Klinghofer; Eric F Johnson; Jennifer Bouska; Amanda Olson; Kennan C Marsh; Vincent S Stoll; Mulugeta Mamo; James Polakowski; Thomas J Campbell; Ruth L Martin; Gary A Gintant; Thomas D Penning; Qun Li; Saul H Rosenberg; Vincent L Giranda
Journal:  J Med Chem       Date:  2007-05-25       Impact factor: 7.446

5.  Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil.

Authors:  Hiroto Yamaguchi; Miyuki Kasa; Mutsuki Amano; Kozo Kaibuchi; Toshio Hakoshima
Journal:  Structure       Date:  2006-03       Impact factor: 5.006

6.  Design and synthesis of Rho kinase inhibitors (II).

Authors:  Masayuki Iwakubo; Atsuya Takami; Yuji Okada; Takehisa Kawata; Yoshimichi Tagami; Hiroshi Ohashi; Motoko Sato; Terumi Sugiyama; Kayoko Fukushima; Hiroshi Iijima
Journal:  Bioorg Med Chem       Date:  2006-10-12       Impact factor: 3.641

7.  Effects of topical administration of y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys.

Authors:  Hideki Tokushige; Masaru Inatani; Shingo Nemoto; Hideyuki Sakaki; Koushirou Katayama; Masayoshi Uehata; Hidenobu Tanihara
Journal:  Invest Ophthalmol Vis Sci       Date:  2007-07       Impact factor: 4.799

8.  Structure-activity relationships, and drug metabolism and pharmacokinetic properties for indazole piperazine and indazole piperidine inhibitors of ROCK-II.

Authors:  Yangbo Feng; Michael D Cameron; Bozena Frackowiak; Evelyn Griffin; Li Lin; Claudia Ruiz; Thomas Schröter; Philip LoGrasso
Journal:  Bioorg Med Chem Lett       Date:  2006-12-21       Impact factor: 2.823

9.  Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro and in vivo.

Authors:  Limei Yin; Ken-Ichirou Morishige; Toshifumi Takahashi; Kae Hashimoto; Seiji Ogata; Seiji Tsutsumi; Keiko Takata; Tsuyoshi Ohta; Jun Kawagoe; Kazuhiro Takahashi; Hirohisa Kurachi
Journal:  Mol Cancer Ther       Date:  2007-05       Impact factor: 6.261

Review 10.  Physiological role of ROCKs in the cardiovascular system.

Authors:  Kensuke Noma; Naotsugu Oyama; James K Liao
Journal:  Am J Physiol Cell Physiol       Date:  2006-03       Impact factor: 4.249
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  32 in total

Review 1.  Discovery of Molecular Therapeutics for Glaucoma: Challenges, Successes, and Promising Directions.

Authors:  Rebecca K Donegan; Raquel L Lieberman
Journal:  J Med Chem       Date:  2015-09-25       Impact factor: 7.446

Review 2.  Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity.

Authors:  C Hahmann; T Schroeter
Journal:  Cell Mol Life Sci       Date:  2009-11-12       Impact factor: 9.261

3.  In silico prediction of ROCK II inhibitors by different classification approaches.

Authors:  Chuipu Cai; Qihui Wu; Yunxia Luo; Huili Ma; Jiangang Shen; Yongbin Zhang; Lei Yang; Yunbo Chen; Zehuai Wen; Qi Wang
Journal:  Mol Divers       Date:  2017-08-02       Impact factor: 2.943

Review 4.  Morphological and hydrodynamic correlations with increasing outflow facility by rho-kinase inhibitor Y-27632.

Authors:  Haiyan Gong; Chen-Yuan Charlie Yang
Journal:  J Ocul Pharmacol Ther       Date:  2014-01-24       Impact factor: 2.671

5.  Bis-aryl urea derivatives as potent and selective LIM kinase (Limk) inhibitors.

Authors:  Yan Yin; Ke Zheng; Nibal Eid; Shannon Howard; Ji-Hak Jeong; Fei Yi; Jia Guo; Chul Min Park; Mathieu Bibian; Weilin Wu; Pamela Hernandez; HaJeung Park; Yuntao Wu; Jun-Li Luo; Philip V LoGrasso; Yangbo Feng
Journal:  J Med Chem       Date:  2015-02-04       Impact factor: 7.446

Review 6.  Impact of the clinical use of ROCK inhibitor on the pathogenesis and treatment of glaucoma.

Authors:  Megumi Honjo; Hidenobu Tanihara
Journal:  Jpn J Ophthalmol       Date:  2018-02-14       Impact factor: 2.447

7.  Regulation of Adherens Junctions in Trabecular Meshwork Cells by Rac GTPase and their influence on Intraocular Pressure.

Authors:  Padmanabhan P Pattabiraman; David L Epstein; Ponugoti Vasantha Rao
Journal:  J Ocul Biol       Date:  2013-06-05

8.  Ca2+ sensitization pathways accessed by cholinergic neurotransmission in the murine gastric fundus.

Authors:  Bhupal P Bhetwal; Kenton M Sanders; Changlong An; Danielle M Trappanese; Robert S Moreland; Brian A Perrino
Journal:  J Physiol       Date:  2013-04-22       Impact factor: 5.182

9.  Chemical interrogation of the neuronal kinome using a primary cell-based screening assay.

Authors:  Hassan Al-Ali; Stephan C Schürer; Vance P Lemmon; John L Bixby
Journal:  ACS Chem Biol       Date:  2013-03-19       Impact factor: 5.100

Review 10.  RhoA/Rho-kinase: pathophysiologic and therapeutic implications in gastrointestinal smooth muscle tone and relaxation.

Authors:  Satish Rattan; Benjamin R Phillips; Pinckney J Maxwell
Journal:  Gastroenterology       Date:  2009-11-23       Impact factor: 22.682
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