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Eur J Med Chem. 2019 Jul 1;173:107-116. doi: 10.1016/j.ejmech.2019.04.014. Epub 2019 Apr 10.

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

Author information

1
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100050, PR China; Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China.
2
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China.
3
Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China.
4
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.
5
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. Electronic address: mailto:zzbcaptain@aliyun.com.

Abstract

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.

KEYWORDS:

Pulmonary hypertension; Riociguat; pyrazolo[3,4-b]pyridine-3-yl pyrimidine derivatives; sGC stimulators

PMID:
30995566
DOI:
10.1016/j.ejmech.2019.04.014
[Indexed for MEDLINE]

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