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Your search keyword '"Ginn JD"' showing total 2 results
Start Over Author "Ginn JD" Topic protein kinase inhibitors
2 results on '"Ginn JD"'

1. Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 2, optimization for blood pressure reduction in spontaneously hypertensive rats.

Author

Ginn JD, Bosanac T, Chen R, Cywin C, Hickey E, Kashem M, Kerr S, Kugler S, Li X, Prokopowicz A 3rd, Schlyer S, Smith JD, Turner MR, Wu F, and Young ER

Subjects
Animals, Isoquinolines chemistry, Models, Molecular, Protein Kinase Inhibitors chemistry, Rats, Rats, Inbred SHR, Structure-Activity Relationship, Blood Pressure drug effects, Isoquinolines pharmacology, Protein Kinase Inhibitors pharmacology, rho-Associated Kinases antagonists & inhibitors
Abstract

Phenylglycine substituted isoquinolones 1 and 2 have previously been described as potent dual ROCK1/ROCK2 inhibitors. Here we describe the further SAR of this series to improve metabolic stability and rat oral exposure. Piperidine analog 20 which demonstrates sustained blood pressure normalization in an SHR blood pressure reduction model was identified through this effort., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Published
2010
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2. Discovery of potent and selective PKC-theta inhibitors.

Author

Cywin CL, Dahmann G, Prokopowicz AS 3rd, Young ER, Magolda RL, Cardozo MG, Cogan DA, Disalvo D, Ginn JD, Kashem MA, Wolak JP, Homon CA, Farrell TM, Grbic H, Hu H, Kaplita PV, Liu LH, Spero DM, Jeanfavre DD, O'Shea KM, White DM, Woska JR Jr, and Brown ML

Subjects
CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes enzymology, CD4-Positive T-Lymphocytes immunology, Humans, Interleukin-2 metabolism, Models, Molecular, Molecular Structure, Protein Conformation, Protein Kinase C-theta, Structure-Activity Relationship, Isoenzymes antagonists & inhibitors, Protein Kinase C antagonists & inhibitors, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors pharmacology, Pyrimidines chemistry, Pyrimidines pharmacology
Abstract

An uHTS campaign was performed to identify selective inhibitors of PKC-theta. Initial triaging of the hit set based on selectivity and historical analysis led to the identification of 2,4-diamino-5-nitropyrimidines as potent and selective PKC-theta inhibitors. A homology model and initial SAR is presented demonstrating that a 2-arylalkylamino substituent in conjunction with suitable 4-diamino substituent are essential for achieving selectivity over many kinases. Additional hit to lead profiling is presented on selected compounds.

Published
2007
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