Novel 6-amino-1,3,5-triazine derivatives as potent BTK inhibitors: structure-activity relationship (SAR) analysis and preliminary mechanism investigation

Autor:	Maoxu Xiao, Meiqi Zhu, Shuangjie Wu, Luyu Ma, Lin Qi, Si Ha, Shuangshuang Xiong, Mingqi Chen, Deying Chen, Guoshun Luo, Hua Xiang
Rok vydání:	2022
Předmět:	ErbB Receptors Structure-Activity Relationship Molecular Structure Dose-Response Relationship Drug Triazines Organic Chemistry Drug Discovery Agammaglobulinaemia Tyrosine Kinase Molecular Biology Biochemistry Protein Kinase Inhibitors
Zdroj:	Bioorganic chemistry. 130
ISSN:	1090-2120
Popis:	Bruton's tyrosine kinase (BTK) is a promising drug target for the treatment of B-cell related malignancies. Irreversible inhibition of BTK by a covalent inhibitor has been proved to be a clinically effective therapy. However, most irreversible BTK inhibitors also inhibit other kinases including JAK3 and EGFR, leading to some adverse events. Herein, we reported the structure-based design and optimization of a series of irreversible BTK inhibitors bearing the 6-amino-1,3,5-triazine scaffold. Most of the synthesized compounds demonstrated considerable BTK inhibition and improved anti-proliferative activity against Raji and Ramos cells. Among them, compound C11 exhibited potent BTK inhibition (BTK IC
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ce6fc8452461da81b77023c17271822 https://pubmed.ncbi.nlm.nih.gov/36375350 Zobrazit plný text záznamu Full Text from ScienceDirect