Triazine and pyrimidine based ROCK inhibitors with efficacy in spontaneous hypertensive rat model

Koc Kan Ho; James R. Beasley; Laura Belanger; Darcey Black; Jui Hsiang Chan; David Dunn; Bing Hu; Anthony Klon; Steven G. Kultgen; Michael Ohlmeyer; Susan M. Parlato; Peter C. Ray; Quynhchi Pham; Yajing Rong; Andrew L. Roughton; Tiffany L. Walker; Jane Wright; Kai Xu; Yan Xu; Limei Zhang; Maria Webb

doi:10.1016/j.bmcl.2009.09.046

Triazine and pyrimidine based ROCK inhibitors with efficacy in spontaneous hypertensive rat model

Koc Kan Ho
, James R. Beasley
, Laura Belanger
, Darcey Black
, Jui Hsiang Chan
, David Dunn
, Bing Hu
, Anthony Klon
, Steven G. Kultgen
, Michael Ohlmeyer
, Susan M. Parlato
, Peter C. Ray
, Quynhchi Pham
, Yajing Rong
, Andrew L. Roughton
, Tiffany L. Walker
, Jane Wright
, Kai Xu
, Yan Xu
, Limei Zhang

Maria Webb

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

18 Scopus citations

Abstract

The profile of a series of triazine and pyrimidine based ROCK inhibitors is described. An initial binding mode was established based on a homology model and the proposed interactions are consistent with the observed SAR. Compounds from the series are potent in a cell migration assay and possess a favorable kinase selectivity. In vivo activity was demonstrated for compound 1A in a spontaneous hypertensive rat model.

Original language	English
Pages (from-to)	6027-6031
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2009.09.046
State	Published - 1 Nov 2009
Externally published	Yes

Keywords

Homology model
Hypertension
Pyrimidine
ROCK
Triazine

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10.1016/j.bmcl.2009.09.046

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Ho, K. K., Beasley, J. R., Belanger, L., Black, D., Chan, J. H., Dunn, D., Hu, B., Klon, A., Kultgen, S. G., Ohlmeyer, M., Parlato, S. M., Ray, P. C., Pham, Q., Rong, Y., Roughton, A. L., Walker, T. L., Wright, J., Xu, K., Xu, Y., ... Webb, M. (2009). Triazine and pyrimidine based ROCK inhibitors with efficacy in spontaneous hypertensive rat model. Bioorganic and Medicinal Chemistry Letters, 19(21), 6027-6031. https://doi.org/10.1016/j.bmcl.2009.09.046

@article{6abbeb488fec472f9873e53ce3a68dde,

title = "Triazine and pyrimidine based ROCK inhibitors with efficacy in spontaneous hypertensive rat model",

abstract = "The profile of a series of triazine and pyrimidine based ROCK inhibitors is described. An initial binding mode was established based on a homology model and the proposed interactions are consistent with the observed SAR. Compounds from the series are potent in a cell migration assay and possess a favorable kinase selectivity. In vivo activity was demonstrated for compound 1A in a spontaneous hypertensive rat model.",

keywords = "Homology model, Hypertension, Pyrimidine, ROCK, Triazine",

author = "Ho, \{Koc Kan\} and Beasley, \{James R.\} and Laura Belanger and Darcey Black and Chan, \{Jui Hsiang\} and David Dunn and Bing Hu and Anthony Klon and Kultgen, \{Steven G.\} and Michael Ohlmeyer and Parlato, \{Susan M.\} and Ray, \{Peter C.\} and Quynhchi Pham and Yajing Rong and Roughton, \{Andrew L.\} and Walker, \{Tiffany L.\} and Jane Wright and Kai Xu and Yan Xu and Limei Zhang and Maria Webb",

year = "2009",

month = nov,

day = "1",

doi = "10.1016/j.bmcl.2009.09.046",

language = "English",

volume = "19",

pages = "6027--6031",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "21",

}

Ho, KK, Beasley, JR, Belanger, L, Black, D, Chan, JH, Dunn, D, Hu, B, Klon, A, Kultgen, SG, Ohlmeyer, M, Parlato, SM, Ray, PC, Pham, Q, Rong, Y, Roughton, AL, Walker, TL, Wright, J, Xu, K, Xu, Y, Zhang, L & Webb, M 2009, 'Triazine and pyrimidine based ROCK inhibitors with efficacy in spontaneous hypertensive rat model', Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 21, pp. 6027-6031. https://doi.org/10.1016/j.bmcl.2009.09.046

TY - JOUR

T1 - Triazine and pyrimidine based ROCK inhibitors with efficacy in spontaneous hypertensive rat model

AU - Ho, Koc Kan

AU - Beasley, James R.

AU - Belanger, Laura

AU - Black, Darcey

AU - Chan, Jui Hsiang

AU - Dunn, David

AU - Hu, Bing

AU - Klon, Anthony

AU - Kultgen, Steven G.

AU - Ohlmeyer, Michael

AU - Parlato, Susan M.

AU - Ray, Peter C.

AU - Pham, Quynhchi

AU - Rong, Yajing

AU - Roughton, Andrew L.

AU - Walker, Tiffany L.

AU - Wright, Jane

AU - Xu, Kai

AU - Xu, Yan

AU - Zhang, Limei

AU - Webb, Maria

PY - 2009/11/1

Y1 - 2009/11/1

N2 - The profile of a series of triazine and pyrimidine based ROCK inhibitors is described. An initial binding mode was established based on a homology model and the proposed interactions are consistent with the observed SAR. Compounds from the series are potent in a cell migration assay and possess a favorable kinase selectivity. In vivo activity was demonstrated for compound 1A in a spontaneous hypertensive rat model.

AB - The profile of a series of triazine and pyrimidine based ROCK inhibitors is described. An initial binding mode was established based on a homology model and the proposed interactions are consistent with the observed SAR. Compounds from the series are potent in a cell migration assay and possess a favorable kinase selectivity. In vivo activity was demonstrated for compound 1A in a spontaneous hypertensive rat model.

KW - Homology model

KW - Hypertension

KW - Pyrimidine

KW - ROCK

KW - Triazine

UR - https://www.scopus.com/pages/publications/71749108355

U2 - 10.1016/j.bmcl.2009.09.046

DO - 10.1016/j.bmcl.2009.09.046

M3 - Article

C2 - 19800787

AN - SCOPUS:71749108355

SN - 0960-894X

VL - 19

SP - 6027

EP - 6031

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 21

ER -

Triazine and pyrimidine based ROCK inhibitors with efficacy in spontaneous hypertensive rat model

Abstract

Keywords

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