Synthesis and biological evaluation of pyrazolo[3,4-b]pyridine-3-yl pyrimidine derivatives as sGC stimulators for the treatment of pulmonary hypertension.

Authors:
Liang Li
Liang Li
University of Alberta
Canada
Wenpeng Zhang
Wenpeng Zhang
The Ohio State University
United States
Feng Lin
Feng Lin
Shanghai Jiao Tong University
China
Xinqiang Lu
Xinqiang Lu
Beijing Institute of Pharmacology and Toxicology
China
Wei Chen
Wei Chen
State Key Laboratory of Food Science and Technology
Nanchang Shi | China
XingZhou Li
XingZhou Li
Beijing Institute of Pharmacology and Toxicology
China
Xinbo Zhou
Xinbo Zhou
Beijing Institute of Pharmacology and Toxicology
China
Ruibin Su
Ruibin Su
Beijing Institute of Pharmacology and Toxicology
China

Eur J Med Chem 2019 Jul 10;173:107-116. Epub 2019 Apr 10.

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China; Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China.

A series of new pyrazolo[3,4-b]pyridin-3-yl pyrimidine derivatives were synthesized and evaluated for the activation of sGC. Compared with riociguat, compound 13a exhibited equivalent in vitro activity on preconstricted rat thoracic aorta rings and in Rat heart Langendorff preparation. Compound 13a also showed acceptable PK profiles, which might become a promising candidate for the treatment of pulmonary hypertension.

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http://dx.doi.org/10.1016/j.ejmech.2019.04.014DOI Listing
July 2019
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