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  • Title: 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, Schlyer S, Smith JD, Turner MR, Wu F, Young ER.
    Journal: Bioorg Med Chem Lett; 2010 Sep 01; 20(17):5153-6. PubMed ID: 20678931.
    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.
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