1429617-97-9

Upstream product

• 705263-10-1 6-bromo-pyrazolo[1,5-α]pyrimidine 
• 1255099-13-8 methyl 3-ethynyl-4-methylbenzoate 
• 90347-66-3 methyl 3-iodo-4-methylbenzoate 

Downstream Products

• 1429618-01-8 4-methyl-3-(pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzoic acid 
• 1429617-57-1 C₁₉H₁₈N₄O 
• 1429617-58-2 C₂₀H₂₀N₄O 
• 1429617-59-3 C₂₀H₂₀N₄O 
• 1429617-60-6 C₂₂H₂₂N₄O 
• 1429617-61-7 C₂₁H₂₀N₄O 
• 1429617-62-8 C₂₂H₁₆N₄O 
• 1429617-63-9 C₂₃H₁₈N₄O 
• 1429617-64-0 C₂₃H₁₈N₄O 
• 1429617-65-1 C₂₃H₁₈N₄O 
• 1429617-66-2 C₂₂H₁₅ClN₄O 
• 1429617-67-3 C₂₂H₁₅ClN₄O 
• 1429617-68-4 C₂₂H₁₅ClN₄O 
• 1429617-69-5 C₂₃H₁₈N₄O₂ 

Relevant academic research and scientific papers

Synthesis and identification of GZD856 as an orally bioavailable Bcr-AblT315I inhibitor overcoming acquired imatinib resistance

Bcr-AblT315I induced drug resistance remains a major challenge to chronic myelogenous leukemia (CML) treatment. Herein, we reported GZD856 as a novel orally bioavailable Bcr-AblT315I inhibitor, which strongly suppressed the kinase activities of both native Bcr-Abl and the T315I mutant with IC50 values of 19.9 and 15.4 nM, and potently inhibited proliferation of corresponding K562, Ba/F3WT and Ba/F3T315I cells with IC50 values of 2.2, 0.64 and 10.8 nM. Furthermore, GZD856 potently suppressed tumor growth in mouse bearing xenograft K562 and Ba/F3 cells expressing Bcr-AblT315I. Thus, GZD856 may serve as a promising lead for the development of Bcr-Abl inhibitors overcoming acquired imatinib resistance.

Discovery and optimization of 3-(2-(Pyrazolo[1,5- a ]pyrimidin-6-yl) ethynyl)benzamides as novel selective and orally bioavailable discoidin domain receptor 1 (DDR1) inhibitors

Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh and 7rj) inhibited the enzymatic activity of DDR1, with IC50 values of 6.8 and 7.0 nM, respectively, but were significantly less potent in suppressing the kinase activities of DDR2, Bcr-Abl, and c-Kit. Further study revealed that 7rh bound with DDR1 with a Kd value of 0.6 nM, while it was significantly less potent to the other 455 kinases tested. The S(35) and S(10) selectivity scores of 7rh were 0.035 and 0.008, respectively. The compounds also potently inhibited the proliferation of cancer cells expressing high levels of DDR1 and strongly suppressed cancer cell invasion, adhesion, and tumorigenicity. Preliminary pharmacokinetic studies suggested that they possessed good PK profiles, with oral bioavailabilities of 67.4% and 56.2%, respectively.