1378287-83-2

Upstream product

• 151266-23-8 4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidine 
• 862730-04-9 3-iodo-1-(propan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 
• 54060-30-9 3-acetylenephenylamine 

Relevant academic research and scientific papers

Development of Alkyne-Containing Pyrazolopyrimidines to Overcome Drug Resistance of Bcr-Abl Kinase

Despite the success of imatinib at inhibiting Bcr-Abl and treating chronic myelogenous leukemia (CML), resistance to the therapy occurs over time in patients. In particular, the resistance to imatinib caused by the gatekeeper mutation T315I in Bcr-Abl remains a challenge in the clinic. Inspired by the successful development of ponatinib to curb drug resistance, we hypothesize that the incorporation of an alkyne linker in other heterocyclic scaffolds can also achieve potent inhibition of Bcr-AblT315I by allowing for simultaneous occupancy of both the active site and the allosteric pocket in the Abl kinase domain. Herein, we describe the design, synthesis, and characterization of a series of alkyne-containing pyrazolopyrimidines as Bcr-Abl inhibitors. Our results demonstrate that some alkyne-containing pyrazolopyrimidines potently inhibit not only AblT315I in vitro but also Bcr-AblT315I in cells. These pyrazolopyrimidines can serve as lead compounds for future development of novel targeted therapy to overcome drug resistance of CML.

Preparation of 3-substituted-1-isopropyl-1 H-pyrazolo[3,4-d]pyrimidin-4- amines as RET kinase inhibitors

A series of 3-substituted-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines have been designed, synthesized, and evaluated as RET protein kinase inhibitors. On the basis of docking results, a small library of pyrazolopyrimidine compounds with an extended hydrophobic side arm was synthesized. The most promising of the compounds (7a) displayed efficient inhibition in vitro and good selectivity when tested on a panel of kinases. Furthermore, 7a inhibited GDNF-induced RET phosphorylation of ERK1/2 in MCF-7 breast cancer cells at concentrations as low as 100 nM.