| Autor: |
Goodman KB; Department of Medicinal Chemistry, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. krista.b.goodman@gsk.com, Cui H, Dowdell SE, Gaitanopoulos DE, Ivy RL, Sehon CA, Stavenger RA, Wang GZ, Viet AQ, Xu W, Ye G, Semus SF, Evans C, Fries HE, Jolivette LJ, Kirkpatrick RB, Dul E, Khandekar SS, Yi T, Jung DK, Wright LL, Smith GK, Behm DJ, Bentley R, Doe CP, Hu E, Lee D |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2007 Jan 11; Vol. 50 (1), pp. 6-9. |
| DOI: |
10.1021/jm0609014 |
| Abstrakt: |
Rho kinase (ROCK1) mediates vascular smooth muscle contraction and is a potential target for the treatment of hypertension and related disorders. Indazole amide 3 was identified as a potent and selective ROCK1 inhibitor but possessed poor oral bioavailability. Optimization of this lead resulted in the discovery of a series of dihydropyridones, exemplified by 13, with improved pharmacokinetic parameters relative to the initial lead. Indazole substitution played a critical role in decreasing clearance and improving oral bioavailability. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
