585536-05-6Relevant articles and documents
Brain-penetrant, orally bioavailable microtubule-stabilizing small molecules are potential candidate therapeutics for Alzheimer's disease and related tauopathies
Lou, Kevin,Yao, Yuemang,Hoye, Adam T.,James, Michael J.,Cornec, Anne-Sophie,Hyde, Edward,Gay, Bryant,Lee, Virginia M.-Y.,Trojanowski, John Q.,Smith, Amos B.,Brunden, Kurt R.,Ballatore, Carlo
, p. 6116 - 6127 (2014/08/18)
Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer's disease (AD) and related tauopathies. However, thus far epothilone D has been the only brain-penetrant MT-stabilizer to be evaluated in tau transgenic mice and in AD p
Synthesis and SAR of 6-chloro-4-fluoroalkylamino-2-heteroaryl-5-(substituted)phenylpyrimidines as anti-cancer agents
Zhang, Nan,Ayral-Kaloustian, Semiramis,Nguyen, Thai,Hernandez, Richard,Lucas, Judy,Discafani, Carolyn,Beyer, Carl
experimental part, p. 111 - 118 (2011/02/25)
The synthesis and SAR of a series of 6-chloro-4-fluoroalkylamino-2-heteroaryl-5-(substituted)phenylpyrimidines as anti-cancer agents are described. This series of 2-heteroarylpyrimidines was developed by modifying a series of anti-tumor [1,2,4]triazolo[1,5-a]pyrimidines and 2-cyanoaminopyrimidines we reported earlier. For the 2-heteroaryl group, the best activity is obtained when the heteroaryl group has a nitrogen atom at the ortho-position to the pyrimidyl core. The structure-activity relationship for the rest of the molecule in this 2-heteroarylpyrimidine series mimics that of the [1,2,4]triazolo[1,5-a]pyrimidine series. Like triazolopyrimidines and 2-cyanoaminopyrimidines, the 2-heteroarylpyrimidines retain the capability to overcome multidrug resistance due to Pgp. Mechanism of action studies showed that the lead compounds behaved in the same manner as triazolopyrimidines and 2-cyanoaminopyrimidines. The lead compounds in this series are more potent than the corresponding triazolopyrimidines in vitro and in vivo. Compound 21 (PTI-868) showed tumor growth inhibition in several nude mouse xenograft models, and was selected to advance to preclinical development.