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

Research output: Contribution to journal › Article › peer-review

75 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
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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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 › peer-review

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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doi = "10.1021/jm800986w",

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AU - Weiser, Amiee

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

PY - 2008/11/13

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

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