849550-72-7

Upstream product

• 214707-01-4 5,7-dihydroxy-6-(2,4,6-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidine 
• 125353-44-8 (S)-2,2,2-trifluoro-1-(methyl)ethylamine hydrochloride 
• 849550-71-6 5,7-dibromo-6-(2,4,6-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidine 

Relevant academic research and scientific papers

Synthesis and SAR of [1,2,4]triazolo[1,5-a]pyrimidines, a class of anticancer agents with a unique mechanism of tubulin inhibition

The synthesis and SAR of a series of triazolopyrimidines as anticancer agents are described. Treatment of 5-chloro-6-(trifluorophenyl)-N-fluoroalkyl[1, 2,4]triazolo[1,5-a]pyrimidin-7-amine with an alcohol, a thiol, or an alkylamine provided the corresponding final compounds. A clear SAR requirement has been established for optimal activity. A (1S)-2,2,2-trifluoro-1-methylethylamino group or an achiral 2,2,2-trifluoroethylamino group is required at the 5-position to achieve high potency. On the phenyl ring, both fluoro atoms, at the positions ortho to the triazolopyrimidine core, are needed for optimal activity. At the position para to the triazolopyrimidine core, on the phenyl ring, the best activity is achieved with an oxygen linkage followed by a three-methylene unit, and an alkylamino or a hydroxy group. The mechanism of action for this series of triazolopyrimidines was shown to be unique in that they promoted tubulin polymerization in vitro, but did not bind competitively with paclitaxel. Instead, they inhibit the binding of vincas to tubulin. Selected compounds were studied further, and it was shown that these compounds were able to overcome resistance attributed to several multidrug resistance transporter proteins. Lead compounds were shown to inhibit tumor growth in several nude mouse xenograft models, with high potency and efficacy, when dosed either orally or intravenously.

6-[(SUBSTITUTED)PHENYL]TRIAZOLOPYRIMIDINES AS ANTICANCER AGENTS

This invention relates to certain 6-[(substituted)phenyl]triazolopyrimidine compounds or pharmaceutically acceptable salts thereof, and compositions containing said compounds or pharmaceutically acceptable salts thereof, wherein said compounds are anti-cancer agents useful for the treatment of cancer in mammals. This invention further relates to a method of treating or inhibiting the growth of cancerous tumor cells and associated diseases in a mammal and further provides a method for the treatment or prevention of cancerous tumors that express multiple drug resistance (MDR) or are resistant because of MDR, in a mammal in need thereof which method comprises administering to said mammal an effective amount of said compounds or pharmaceutically acceptable salts thereof. The present invention relates to a method of treating or inhibiting the growth of cancerous tumor cells and associated diseases in a mammal in need thereof by promotion of microtubule polymerization which comprises administering to said mammal an effective amount of said compounds and pharmaceutically acceptable salts thereof.