1421684-99-2

Basic information

• Product Name: 3-([1,2,4]triazolo[1,5-a]pyrimidin-6-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)-phenyl)benzamide
• Synonyms: 3-([1,2,4]triazolo[1,5-a]pyrimidin-6-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)-phenyl)benzamide
• CAS NO: 1421684-99-2
• Molecular Weight: 533.556
• Mol File: 1421684-99-2.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: 3-([1,2,4]triazolo[1,5-a]pyrimidin-6-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)-phenyl)benzamide(CAS DataBase Reference)
• NIST Chemistry Reference: 3-([1,2,4]triazolo[1,5-a]pyrimidin-6-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)-phenyl)benzamide(1421684-99-2)
• EPA Substance Registry System: 3-([1,2,4]triazolo[1,5-a]pyrimidin-6-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)-phenyl)benzamide(1421684-99-2)

Safety Data

• Hazardous Substances Data: 1421684-99-2(Hazardous Substances Data)

Upstream product

• 957147-17-0 4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-((trimethylsilyl)ethynyl)benzamide 
• 694499-26-8 4-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethylaniline 
• 90347-66-3 methyl 3-iodo-4-methylbenzoate 
• 957147-18-1 3-ethynyl-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide 
• 89167-24-8 6-bromo[1,2,4]triazolo[1,5-α]pyrazine 
• 943320-50-1 3-iodo-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl) phenyl)benzamide 

Relevant articles and documents

Identification of GZD824 as an orally bioavailable inhibitor that targets phosphorylated and nonphosphorylated breakpoint cluster region-Abelson (Bcr-Abl) kinase and overcomes clinically acquired mutation-induced resistance against imatinib

Bcr-AblT315I mutation-induced imatinib resistance remains a major challenge for clinical management of chronic myelogenous leukemia (CML). Herein, we report GZD824 (10a) as a novel orally bioavailable inhibitor against a broad spectrum of Bcr-Abl mutants including T315I. It tightly bound to Bcr-AblWT and Bcr-AblT315I with Kd values of 0.32 and 0.71 nM, respectively, and strongly inhibited the kinase functions with nanomolar IC50 values. The compound potently suppressed proliferation of Bcr-Abl-positive K562 and Ku812 human CML cells with IC 50 values of 0.2 and 0.13 nM, respectively. It also displayed good oral bioavailability (48.7%), a reasonable half-life (10.6 h), and promising in vivo antitumor efficacy. It induced tumor regression in mouse xenograft tumor models driven by Bcr-AblWT or the mutants and significantly improved the survival of mice bearing an allograft leukemia model with Ba/F3 cells harboring Bcr-AblT315I. GZD824 represents a promising lead candidate for development of Bcr-Abl inhibitors to overcome acquired imatinib resistance.