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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish
Pages (from-to)3361-3366
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number11
DOIs
StatePublished - 1 Jun 2010

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rho-Associated Kinases
Ocular Hypertension
Electric Impedance
Intraocular Pressure
Scaffolds
Glaucoma
Haplorhini
Labels
Assays
Animals
Animal Models
Throughput
benzothiophene

Keywords

  • ATP competitive
  • Adhesion
  • Benzothiophene
  • Glaucoma
  • Impedance
  • Inhibitor
  • Kinase
  • ROCK
  • Rho

Cite this

Davis, R. L., Kahraman, M., Prins, T. J., Beaver, Y., Cook, T. G., Cramp, J., ... 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
Davis, Robert L. ; Kahraman, Mehmet ; Prins, Thomas J. ; Beaver, Yan ; Cook, Travis G. ; Cramp, Jessica ; Cayanan, Charmagne S. ; Gardiner, Elisabeth M.M. ; McLaughlin, Marsha A. ; Clark, Abbot F. ; Hellberg, Mark R. ; Shiau, Andrew K. ; Noble, Stewart A. ; Borchardt, Allen J. / Benzothiophene containing Rho kinase inhibitors : Efficacy in an animal model of glaucoma. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 11. pp. 3361-3366.
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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

Benzothiophene containing Rho kinase inhibitors : Efficacy in an animal model of glaucoma. / Davis, Robert L.; Kahraman, Mehmet; Prins, Thomas J.; Beaver, Yan; Cook, Travis G.; Cramp, Jessica; Cayanan, Charmagne S.; Gardiner, Elisabeth M.M.; McLaughlin, Marsha A.; Clark, Abbot F.; Hellberg, Mark R.; Shiau, Andrew K.; Noble, Stewart A.; Borchardt, Allen J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 11, 01.06.2010, p. 3361-3366.

Research output: Contribution to journalArticle

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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

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KW - ATP competitive

KW - Adhesion

KW - Benzothiophene

KW - Glaucoma

KW - Impedance

KW - Inhibitor

KW - Kinase

KW - ROCK

KW - Rho

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M3 - Article

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