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

Yangbo Feng; 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

doi:10.1021/jm800986w

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

Yangbo Feng, 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

Molecular and Cellular Pharmacology

Research output: Contribution to journal › Article

67 Scopus citations

Abstract

The identification of a new class of potent and selective ROCK-II inhibitors is presented. Compound 5 (SR-3677) had an IC₅₀ of ∼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.

Original language	English (US)
Pages (from-to)	6642-6645
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	51
Issue number	21
DOIs	https://doi.org/10.1021/jm800986w
State	Published - Nov 13 2008

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm800986w

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Feng, Y., Yin, Y., Weiser, A., Griffin, E., Cameron, M. D., Lin, L., Ruiz, C., Schürer, S. C., Inoue, T., Rao, P. V., Schröter, T., & LoGrasso, P. (2008). Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. Journal of Medicinal Chemistry, 51(21), 6642-6645. https://doi.org/10.1021/jm800986w

Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. / Feng, Yangbo; Yin, Yan; Weiser, Amiee; Griffin, Evelyn; Cameron, Michael D.; Lin, Li; Ruiz, Claudia; Schürer, Stephan C.; Inoue, Toshihiro; Rao, P. Vasanth; Schröter, Thomas; LoGrasso, Philip.

In: Journal of Medicinal Chemistry, Vol. 51, No. 21, 13.11.2008, p. 6642-6645.

Research output: Contribution to journal › Article

Feng, Y, Yin, Y, Weiser, A, Griffin, E, Cameron, MD, Lin, L, Ruiz, C, Schürer, SC, Inoue, T, Rao, PV, Schröter, T & LoGrasso, P 2008, 'Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors', Journal of Medicinal Chemistry, vol. 51, no. 21, pp. 6642-6645. https://doi.org/10.1021/jm800986w

Feng, Yangbo ; Yin, Yan ; Weiser, Amiee ; Griffin, Evelyn ; Cameron, Michael D. ; Lin, Li ; Ruiz, Claudia ; Schürer, Stephan C. ; Inoue, Toshihiro ; Rao, P. Vasanth ; Schröter, Thomas ; LoGrasso, Philip. / Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 21. pp. 6642-6645.

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abstract = "The identification of a new class of potent and selective ROCK-II inhibitors is presented. Compound 5 (SR-3677) had an IC50 of ∼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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AU - Griffin, Evelyn

AU - Cameron, Michael D.

AU - Lin, Li

AU - Ruiz, Claudia

AU - Schürer, Stephan C.

AU - Inoue, Toshihiro

AU - Rao, P. Vasanth

AU - Schröter, Thomas

AU - LoGrasso, Philip

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