Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation

Axl has emerged as an attractive target for cancer therapy due to its strong correlation with tumor growth, metastasis, poor survival, and drug resistance. Herein, we report the design, synthesis and structure-activity relationship (SAR) investigation of a series of pyrrolo[2,3-d]pyrimidine derivatives as new Axl inhibitors. Among them, the most promising compound 13b showed high enzymatic and cellular Axl potencies. Furthermore, 13b possessed preferable pharmacokinetic properties and displayed promising therapeutic effect in BaF3/TEL-Axl xenograft tumor model. Compound 13b may serve as a lead compound for new antitumor drug discovery. (C) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

Axl has become an attractive target for cancer therapy due to its correlation with tumor growth, metastasis, poor survival, and drug resistance. Compound 13b, among the new Axl inhibitors studied, showed high enzymatic and cellular potencies and promising therapeutic effects in animal models, indicating its potential as a lead compound for new antitumor drug discovery.