Design and synthesis of novel 3-sulfonylpyrazol-4-amino pyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors

[Display omitted] Anaplastic lymphoma kinase (ALK) is a highly attractive therapeutic target for the treatment of some non-small cell lung cancer patients. This Letter describes the further SAR exploration on the novel 3-sulfonylpyrazol-4-amino pyrimidine scaffold. This work identified a compound 53...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2016-04, Vol.26 (8), p.1910-1918
Hauptverfasser:	Zhang, Peilong, Dong, Jiaqiang, Zhong, Boyu, Zhang, Deyi, Yuan, Hongbin, Jin, Can, Xu, Xiangyuan, Li, Hailong, Zhou, Yong, Liang, Zhi, Ji, Minghua, Xu, Tao, Song, Guowei, Zhang, Ling, Chen, Gang, Meng, Xuejing, Sun, Desheng, Shih, Joe, Zhang, Ruihao, Hou, Guojun, Wang, Chengcheng, Jin, Ying, Yang, Qiong
Format:	Artikel
Sprache:	eng
Schlagworte:	ALK Animals Anti-tumor Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Cell Line, Tumor Cell Proliferation - drug effects Dogs Dose-Response Relationship, Drug Drug Design Drug Screening Assays, Antitumor Humans Kinase Mice Models, Molecular Molecular Structure Neoplasms, Experimental - drug therapy Neoplasms, Experimental - pathology NSCLC Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Pyrazoles - chemical synthesis Pyrazoles - chemistry Pyrazoles - pharmacology Pyrimidine Pyrimidines - chemical synthesis Pyrimidines - chemistry Pyrimidines - pharmacology Rats Receptor Protein-Tyrosine Kinases - antagonists & inhibitors Receptor Protein-Tyrosine Kinases - metabolism Structure-Activity Relationship
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Zusammenfassung:	[Display omitted] Anaplastic lymphoma kinase (ALK) is a highly attractive therapeutic target for the treatment of some non-small cell lung cancer patients. This Letter describes the further SAR exploration on the novel 3-sulfonylpyrazol-4-amino pyrimidine scaffold. This work identified a compound 53 with very good in vitro/in vivo efficacies, good DMPK properties together with better hERG tolerability and it is currently being profiled for the evaluation as a potential pre-clinical candidate.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2016.03.017