Synthesis and evaluation of pyrrolotriazine based molecules as PI3 kinase inhibitors. Issue 16 (15th August 2015)

• Record Type: Journal Article
• Authors: Dugar, Sundeep; Hollinger, Frank P.; Kuila, Bilash; Arora, Reena; Sen, Somdutta; Mahajan, Dinesh
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 16(2015)
• Page Start: 3142
• Page End: 3146
• Publication Date: 2015-08-15
• Subjects: PI3K/Akt/mTOR pathway -- PI3K inhibitor -- Pyrrolotriazine -- Oncology -- Kinase screening; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.06.007
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Over activation of the PI3K/Akt/mTOR pathway is found in most cancer tumor types. Controlled regulation of this pathway using PI3K inhibitors can provide therapeutic significance in cancer treatment. Herein, we report the synthesis and evaluation of pyrrolotriazine based novel small molecules as pan-PI3K inhibitors. The SAR studies based on in vitro potency along with microsomal metabolic stability screening, identified18 as a preclinical lead found to be suitable for in vivo evaluation. The identified lead was also found to be a selective inhibitor of PI3K isoforms and mTOR when screened across a panel of 23 homologous kinases.