Benzothiophene containing Rho kinase inhibitors: Efficacy in an animal model of glaucoma

Robert L. Davis; Mehmet Kahraman; Thomas J. Prins; Yan Beaver; Travis G. Cook; Jessica Cramp; Charmagne S. Cayanan; Elisabeth M.M. Gardiner; Marsha A. McLaughlin; Abbot F. Clark; Mark R. Hellberg; Andrew K. Shiau; Stewart A. Noble; Allen J. Borchardt

doi:10.1016/j.bmcl.2010.04.020

Benzothiophene containing Rho kinase inhibitors: Efficacy in an animal model of glaucoma

Robert L. Davis, Mehmet Kahraman, Thomas J. Prins, Yan Beaver, Travis G. Cook, Jessica Cramp, Charmagne S. Cayanan, Elisabeth M.M. Gardiner, Marsha A. McLaughlin, Abbot F. Clark, Mark R. Hellberg, Andrew K. Shiau, Stewart A. Noble, Allen J. Borchardt

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21 Scopus citations

Abstract

We identified a new benzothiophene containing Rho kinase inhibitor scaffold in an ultra high-throughput enzymatic activity screen. SAR studies, driven by a novel label-free cellular impedance assay, were used to derive 39, which substantially reduced intraocular pressure in a monkey model of glaucoma-associated ocular hypertension.

Original language	English
Pages (from-to)	3361-3366
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2010.04.020
State	Published - 1 Jun 2010

Keywords

ATP competitive
Adhesion
Benzothiophene
Glaucoma
Impedance
Inhibitor
Kinase
ROCK
Rho

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10.1016/j.bmcl.2010.04.020

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Davis, R. L., Kahraman, M., Prins, T. J., Beaver, Y., Cook, T. G., Cramp, J., Cayanan, C. S., Gardiner, E. M. M., McLaughlin, M. A., Clark, A. F., Hellberg, M. R., Shiau, A. K., Noble, S. A., & Borchardt, A. J. (2010). Benzothiophene containing Rho kinase inhibitors: Efficacy in an animal model of glaucoma. Bioorganic and Medicinal Chemistry Letters, 20(11), 3361-3366. https://doi.org/10.1016/j.bmcl.2010.04.020

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abstract = "We identified a new benzothiophene containing Rho kinase inhibitor scaffold in an ultra high-throughput enzymatic activity screen. SAR studies, driven by a novel label-free cellular impedance assay, were used to derive 39, which substantially reduced intraocular pressure in a monkey model of glaucoma-associated ocular hypertension.",

keywords = "ATP competitive, Adhesion, Benzothiophene, Glaucoma, Impedance, Inhibitor, Kinase, ROCK, Rho",

author = "Davis, {Robert L.} and Mehmet Kahraman and Prins, {Thomas J.} and Yan Beaver and Cook, {Travis G.} and Jessica Cramp and Cayanan, {Charmagne S.} and Gardiner, {Elisabeth M.M.} and McLaughlin, {Marsha A.} and Clark, {Abbot F.} and Hellberg, {Mark R.} and Shiau, {Andrew K.} and Noble, {Stewart A.} and Borchardt, {Allen J.}",

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Davis, RL, Kahraman, M, Prins, TJ, Beaver, Y, Cook, TG, Cramp, J, Cayanan, CS, Gardiner, EMM, McLaughlin, MA, Clark, AF, Hellberg, MR, Shiau, AK, Noble, SA & Borchardt, AJ 2010, 'Benzothiophene containing Rho kinase inhibitors: Efficacy in an animal model of glaucoma', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 11, pp. 3361-3366. https://doi.org/10.1016/j.bmcl.2010.04.020

TY - JOUR

T1 - Benzothiophene containing Rho kinase inhibitors

T2 - Efficacy in an animal model of glaucoma

AU - Davis, Robert L.

AU - Kahraman, Mehmet

AU - Prins, Thomas J.

AU - Beaver, Yan

AU - Cook, Travis G.

AU - Cramp, Jessica

AU - Cayanan, Charmagne S.

AU - Gardiner, Elisabeth M.M.

AU - McLaughlin, Marsha A.

AU - Clark, Abbot F.

AU - Hellberg, Mark R.

AU - Shiau, Andrew K.

AU - Noble, Stewart A.

AU - Borchardt, Allen J.

PY - 2010/6/1

Y1 - 2010/6/1

N2 - We identified a new benzothiophene containing Rho kinase inhibitor scaffold in an ultra high-throughput enzymatic activity screen. SAR studies, driven by a novel label-free cellular impedance assay, were used to derive 39, which substantially reduced intraocular pressure in a monkey model of glaucoma-associated ocular hypertension.

AB - We identified a new benzothiophene containing Rho kinase inhibitor scaffold in an ultra high-throughput enzymatic activity screen. SAR studies, driven by a novel label-free cellular impedance assay, were used to derive 39, which substantially reduced intraocular pressure in a monkey model of glaucoma-associated ocular hypertension.

KW - ATP competitive

KW - Adhesion

KW - Benzothiophene

KW - Glaucoma

KW - Impedance

KW - Inhibitor

KW - Kinase

KW - ROCK

KW - Rho

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DO - 10.1016/j.bmcl.2010.04.020

M3 - Article

C2 - 20434334

AN - SCOPUS:77953292839

SN - 0960-894X

VL - 20

SP - 3361

EP - 3366

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 11

ER -

Benzothiophene containing Rho kinase inhibitors: Efficacy in an animal model of glaucoma

Abstract

Keywords

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