Christopher P. Doe
GlaxoSmithKline
8 Papers
126 Citations
Christopher P. Doe is an academic researcher from GlaxoSmithKline. The author has contributed to research in topics: Receptor & Vasoconstriction. The author has an hindex of 7, co-authored 8 publications.
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Papers
Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors.
Krista B. Goodman,Haifeng Cui,Sarah E. Dowdell,Dimitri E. Gaitanopoulos,Robert L. Ivy,Clark A. Sehon,Robert A. Stavenger,Gren Z. Wang,Andrew Q. Viet,Weiwei Xu,Guosen Ye,Simon Semus,Christopher P. Evans,Harvey E. Fries,Larry J. Jolivette,Robert B. Kirkpatrick,Edward Dul,Sanjay S. Khandekar,Tracey Yi,David Kendallc Jung,Lois L Wright,Gary K Smith,David J. Behm,Ross Bentley,Christopher P. Doe,Erding Hu,Dennis Lee +26 more
TL;DR: Indazole substitution played a critical role in decreasing clearance and improving oral bioavailability and a series of dihydropyridones were discovered, exemplified by 13, with improved pharmacokinetic parameters relative to the initial lead.
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Deletion of the UT receptor gene results in the selective loss of urotensin‐II contractile activity in aortae isolated from UT receptor knockout mice
David J. Behm,Stephen M. Harrison,Zhaohui Ao,Kristeen Maniscalco,Susan J. Pickering,Evelyn Grau,Tina N Woods,Robert W. Coatney,Christopher P. Doe,Robert N. Willette,Douglas G. Johns,Stephen A. Douglas +11 more
TL;DR: The present study is the first to directly link hU‐II‐induced vasoconstriction with the UT receptor, and the contribution that h U‐II and its receptor make to basal systemic haemodynamics appears to be negligible in this species.
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Urotensin-II: a novel systemic hypertensive factor in the cat
David J. Behm,Christopher P. Doe,Douglas G. Johns,Kristeen Maniscalco,Gerald Stankus,Alexandra Wibberley,Robert N. Willette,Stephen A. Douglas +7 more
TL;DR: The cat could be suitable for determining the effects of urotensin-II receptor antagonism on cardiovascular homeostasis in both normal and diseased states since it effectively doubles both mean blood pressure and systemic vascular resistance in the anaesthetized cat.
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The peptidic urotensin-II receptor ligand GSK248451 possesses less intrinsic activity than the low-efficacy partial agonists SB-710411 and urantide in native mammalian tissues and recombinant cell systems
David J. Behm,Gerald Stankus,Christopher P. Doe,Robert N. Willette,Henry M. Sarau,James J. Foley,Dulcie B. Schmidt,Parvathi Nuthulaganti,James A. Fornwald,Robert S. Ames,David G. Lambert,Girolamo Calo,Valeria Camarda,Valeria Camarda,Nambi Aiyar,Stephen A. Douglas +15 more
TL;DR: It is demonstrated that the use of high signal transduction/coupling efficiency isolated blood vessel assays (primate>cat arteries) is required in order to characterize UT receptor antagonism thoroughly, and GSK248451 represents a suitable peptidic tool antagonist for delineating the role of U‐II in the aetiology of mammalian cardiometabolic diseases.
Optimization of orally bioavailable alkyl amine renin inhibitors
Zhenrong Xu,Salvacion Cacatian,Jing Yuan,Robert D. Simpson,Lanqi Jia,Wei Zhao,Colin M. Tice,Patrick T. Flaherty,Joan Guo,Ishchenko Alexey,Suresh B. Singh,Zhongren Wu,Brian M. McKeever,Boyd B. Scott,Yuri Bukhtiyarov,Jennifer Berbaum,Jennifer M. Mason,Reshma Panemangalore,Maria Grazia Cappiello,Ross Bentley,Christopher P. Doe,Richard K. Harrison,Gerard McGeehan,Lawrence W. Dillard,Baldwin John J,David A. Claremon +25 more
TL;DR: Lead compound 21a, has an IC(50) of 0.83nM for the inhibition of human renin in plasma (PRA), and oral administration of 21a at 10mg/kg resulted in >20h reduction of blood pressure in a double transgenic rat model of hypertension.
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