The synthesis of 2,3,6-trisubstituted 1-oxo-1,2-dihydroisoquinolines as potent CRTh 2 antagonists

New synthetic methods were developed for the preparation of 2,3,6-trisubstituted 1-oxo-1,2-dihydroisoquinolines as CRTh antagonists. The isoquinolinone core could be constructed before the introduction of substitution groups or synthesized through a catalytic intramolecular cyclization reaction with...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2017-12, Vol.27 (23), p.5344-5348
Main Authors: Huang, Xianhai, Rao, Ashwin, Zhou, Wei, Aslanian, Robert, Nargund, Ravi, Buevich, Alexei, Zhang, Li-Kang, Qiu, Hongchen, Yang, Xiaoxin, Garlisi, Charles G, Correll, Craig, Palani, Anandan
Format: Article
Language:English
Subjects:
Dose-Response Relationship, Drug
Humans
Isoquinolines - chemical synthesis
Isoquinolines - chemistry
Isoquinolines - pharmacology
Molecular Structure
Receptors, Immunologic - antagonists & inhibitors
Receptors, Prostaglandin - antagonists & inhibitors
Structure-Activity Relationship
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Summary:New synthetic methods were developed for the preparation of 2,3,6-trisubstituted 1-oxo-1,2-dihydroisoquinolines as CRTh antagonists. The isoquinolinone core could be constructed before the introduction of substitution groups or synthesized through a catalytic intramolecular cyclization reaction with desired substitution groups properly installed. These synthetic strategies have helped to accelerate the SAR development of this series, and potent lead compounds were identified in both the CRTh receptor binding assay and the CD11b biomarker assay.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2017.07.064