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Identification of pyrazolopyridine derivatives as novel spleen tyrosine kinase inhibitors
Author(s) -
Huang Yahui,
Li Yu,
Dong Guoqiang,
Zhang Wannian,
Liu Na,
Sheng Chunquan
Publication year - 2018
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800083
Subject(s) - syk , indazole , chemistry , rheumatoid arthritis , pharmacology , tyrosine kinase , virtual screening , structure–activity relationship , quinazolinone , cancer research , biochemistry , drug discovery , combinatorial chemistry , immunology , medicine , stereochemistry , signal transduction , in vitro
Inhibition of spleen tyrosine kinase (Syk) is a promising strategy for the treatment of various allergic and autoimmune disorders such as asthma, rheumatoid arthritis, and allergic rhinitis. Previously, a Syk inhibitor with novel indazole scaffold was discovered by structure‐based virtual screening. Herein, the structure–activity relationship of the indazole Syk inhibitors was investigated. Several new inhibitors demonstrated potent activity against Syk. In particular, compound 18c showed good Syk inhibitory activity (IC 50 = 1.2 µM), representing a good lead compound for further optimization.