RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: Synthesis and biological evaluation

Lee A. McDermott; Mary Simcox; Brian Higgins; Tom Nevins; Kenneth Kolinsky; Melissa Smith; Hong Yang; Jia K. Li; Yingsi Chen; June Ke; Navita Mallalieu; Tom Egan; Stan Kolis; Aruna Railkar; Louise Gerber; Kin Chun Luk

doi:10.1016/j.bmc.2005.05.012

RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: Synthesis and biological evaluation

Lee A. McDermott
, Mary Simcox
, Brian Higgins
, Tom Nevins
, Kenneth Kolinsky
, Melissa Smith
, Hong Yang
, Jia K. Li
, Yingsi Chen
, June Ke
, Navita Mallalieu
, Tom Egan
, Stan Kolis
, Aruna Railkar
, Louise Gerber
, Kin Chun Luk

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

24 Scopus citations

Abstract

(±)-1-(anti-3-Hydroxy-cyclopentyl)-3-(4-methoxy-phenyl) -7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (RO4383596) is a potent and selective inhibitor of the pro-angiogenic receptor tyrosine kinases KDR, FGFR, and PDGFR. This agent has an excellent pharmacokinetic profile and is highly efficacious in rodent models of angiogenesis upon oral administration.

Original language	English
Pages (from-to)	4835-4841
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry
Volume	13
Issue number	16
DOIs	https://doi.org/10.1016/j.bmc.2005.05.012
State	Published - 15 Aug 2005
Externally published	Yes

Keywords

FGFR inhibitor
KDR inhibitor
PDGFR inhibitor
Pyrimidopyrimidone
RO4383596
VEGFR inhibitor

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10.1016/j.bmc.2005.05.012

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McDermott, L. A., Simcox, M., Higgins, B., Nevins, T., Kolinsky, K., Smith, M., Yang, H., Li, J. K., Chen, Y., Ke, J., Mallalieu, N., Egan, T., Kolis, S., Railkar, A., Gerber, L., & Luk, K. C. (2005). RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: Synthesis and biological evaluation. Bioorganic and Medicinal Chemistry, 13(16), 4835-4841. https://doi.org/10.1016/j.bmc.2005.05.012

@article{c003455dbe5c4d86bdade74f7637fa83,

title = "RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: Synthesis and biological evaluation",

abstract = "(±)-1-(anti-3-Hydroxy-cyclopentyl)-3-(4-methoxy-phenyl) -7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (RO4383596) is a potent and selective inhibitor of the pro-angiogenic receptor tyrosine kinases KDR, FGFR, and PDGFR. This agent has an excellent pharmacokinetic profile and is highly efficacious in rodent models of angiogenesis upon oral administration.",

keywords = "FGFR inhibitor, KDR inhibitor, PDGFR inhibitor, Pyrimidopyrimidone, RO4383596, VEGFR inhibitor",

author = "McDermott, \{Lee A.\} and Mary Simcox and Brian Higgins and Tom Nevins and Kenneth Kolinsky and Melissa Smith and Hong Yang and Li, \{Jia K.\} and Yingsi Chen and June Ke and Navita Mallalieu and Tom Egan and Stan Kolis and Aruna Railkar and Louise Gerber and Luk, \{Kin Chun\}",

year = "2005",

month = aug,

day = "15",

doi = "10.1016/j.bmc.2005.05.012",

language = "English",

volume = "13",

pages = "4835--4841",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd.",

number = "16",

}

McDermott, LA, Simcox, M, Higgins, B, Nevins, T, Kolinsky, K, Smith, M, Yang, H, Li, JK, Chen, Y, Ke, J, Mallalieu, N, Egan, T, Kolis, S, Railkar, A, Gerber, L & Luk, KC 2005, 'RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: Synthesis and biological evaluation', Bioorganic and Medicinal Chemistry, vol. 13, no. 16, pp. 4835-4841. https://doi.org/10.1016/j.bmc.2005.05.012

TY - JOUR

T1 - RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor

T2 - Synthesis and biological evaluation

AU - McDermott, Lee A.

AU - Simcox, Mary

AU - Higgins, Brian

AU - Nevins, Tom

AU - Kolinsky, Kenneth

AU - Smith, Melissa

AU - Yang, Hong

AU - Li, Jia K.

AU - Chen, Yingsi

AU - Ke, June

AU - Mallalieu, Navita

AU - Egan, Tom

AU - Kolis, Stan

AU - Railkar, Aruna

AU - Gerber, Louise

AU - Luk, Kin Chun

PY - 2005/8/15

Y1 - 2005/8/15

N2 - (±)-1-(anti-3-Hydroxy-cyclopentyl)-3-(4-methoxy-phenyl) -7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (RO4383596) is a potent and selective inhibitor of the pro-angiogenic receptor tyrosine kinases KDR, FGFR, and PDGFR. This agent has an excellent pharmacokinetic profile and is highly efficacious in rodent models of angiogenesis upon oral administration.

AB - (±)-1-(anti-3-Hydroxy-cyclopentyl)-3-(4-methoxy-phenyl) -7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (RO4383596) is a potent and selective inhibitor of the pro-angiogenic receptor tyrosine kinases KDR, FGFR, and PDGFR. This agent has an excellent pharmacokinetic profile and is highly efficacious in rodent models of angiogenesis upon oral administration.

KW - FGFR inhibitor

KW - KDR inhibitor

KW - PDGFR inhibitor

KW - Pyrimidopyrimidone

KW - RO4383596

KW - VEGFR inhibitor

UR - https://www.scopus.com/pages/publications/21744442578

U2 - 10.1016/j.bmc.2005.05.012

DO - 10.1016/j.bmc.2005.05.012

M3 - Article

C2 - 15953730

AN - SCOPUS:21744442578

SN - 0968-0896

VL - 13

SP - 4835

EP - 4841

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 16

ER -

RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: Synthesis and biological evaluation

Abstract

Keywords

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