1188915-87-8Relevant articles and documents
Synthesis and biological evaluation of novel phosphatidylinositol 3-kinase inhibitors: Solubilized 4-substituted benzimidazole analogs of 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl] -1H-benzimidazole (ZSTK474)
Rewcastle, Gordon W.,Gamage, Swarna A.,Flanagan, Jack U.,Kendall, Jackie D.,Denny, William A.,Baguley, Bruce C.,Buchanan, Christina M.,Chao, Mindy,Kestell, Philip,Kolekar, Sharada,Lee, Woo-Jeong,Lill, Claire L.,Malik, Alisha,Singh, Ripudaman,Jamieson, Stephen M.F.,Shepherd, Peter R.
, p. 137 - 147 (2013)
A range of 4-substituted derivatives of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H- benzimidazole (ZSTK474) were prepared in a search for more soluble analogs. 4-Aminoalkoxy substituents provided the most potent derivatives, with the 4-O(CH2)3NMe2 analog (compound 14) being identified as displaying the best overall activity in combination with good aqueous solubility (25 mg/mL for the hydrochloride salt). This compound was tested in a U87MG xenograft model, but displayed less potency than ZSTK474 as a result of an unfavorable pharmacokinetic profile.
