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 ZhangMaria 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

Access to Document

10.1016/j.bmcl.2009.09.046

Cite this

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

Access to Document

Fingerprint

Cite this