25713-57-9Relevant articles and documents
Discovery of Novel and Orally Bioavailable Inhibitors of PI3 Kinase Based on Indazole Substituted Morpholino-Triazines
Dugar, Sundeep,Hollinger, Frank P.,Mahajan, Dinesh,Sen, Somdutta,Kuila, Bilash,Arora, Reena,Pawar, Yogesh,Shinde, Vaibhav,Rahinj, Mahesh,Kapoor, Kamal K.,Bhumkar, Rahul,Rai, Santosh,Kulkarni, Rakesh
supporting information, p. 1190 - 1194 (2015/12/23)
A new class of potent PI3Kα inhibitors is identified based on aryl substituted morpholino-triazine scaffold. The identified compounds showed not only a high level of enzymatic and cellular potency in nanomolar range but also high oral bioavailability. The three lead molecules (based on their in vitro potency) when evaluated further for in vitro metabolic stability as well as pharmacokinetic profile led to the identification of 26, as a candidate for further development. The IC50 and EC50 value of 26 is 60 and 500 nM, respectively, for PI3Kα enzyme inhibitory activity and ovarian cancer (A2780) cell line. The identified lead also showed a high level of microsomal stability and minimal inhibition activity for CYP3A4, CYP2C19, and CYP2D6 at 10 μM concentrations. The lead compound 26, demonstrated excellent oral bioavailability with an AUC of 5.2 μM at a dose of 3 mpk in mice and found to be well tolerated in mice when dosed at 30 mpk BID for 5 days.
Novel orthogonal strategy toward solid-phase synthesis of 1,3,5-substituted triazines.
Bork, Jacqueline T,Lee, Jae Wook,Khersonsky, Sonya M,Moon, Ho-Sang,Chang, Young-Tae
, p. 117 - 120 (2007/10/03)
[reaction: see text] To improve upon the previous orthogonal method for synthesis of a triazine library, an alternative strategy has been developed via oxidation-activation of the thioether to the sulfone. Through a comparison between these two methods, the sulfone strategy was demonstrated as an enhanced method in the generation of highly pure triazine library compounds.
