D’Angelo, Noel D.; Kim, Tae-Seong; Andrews, Kristin; Booker, Shon K.; Caenepeel, Sean; Chen, Kui; Freeman, Dan; Jiang, Jian; McCarter, John D.; San Miguel, Tisha; Mullady, Erin L.; Schrag, Michael; Subramanian, Raju; Tang, Jin; Wahl, Robert C.; Wang, Ling; Whittington, Douglas A.; Wu, Tian; Xi, Ning; Xu, Yang; Yakowec, Peter; Zalameda, Leeanne P.; Zhang, Nancy; Hughes, Paul; Norman, Mark H. published the artcile< Discovery and Optimization of a Series of Benzothiazole Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors>, Electric Literature of 1524-40-9, the main research area is benzothiazole derivative preparation SAR mTOR PI3K inhibitor antitumor bioavailability.
Phosphoinositide 3-kinase α (PI3Kα) is a lipid kinase that plays a key regulatory role in several cellular processes. The mutation or amplification of this kinase in humans has been implicated in the growth of multiple tumor types. Consequently, PI3Kα has become a target of intense research for drug discovery. Our studies began with the identification of benzothiazole compound 1 from a high throughput screen. Extensive SAR studies led to the discovery of sulfonamide 45 as an early lead, based on its in vitro cellular potency. Subsequent modifications of the central pyrimidine ring dramatically improved enzyme and cellular potency and led to the identification of chloropyridine 70. Further arylsulfonamide SAR studies optimized in vitro clearance and led to the identification of 82 as a potent dual inhibitor of PI3K and mTOR. This mol. exhibited potent enzyme and cell activity, low clearance, and high oral bioavailability. In addition, compound 82 demonstrated tumor growth inhibition in U-87 MG, A549, and HCT116 tumor xenograft models.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 1524-40-9 belongs to class amides-buliding-blocks, and the molecular formula is C6H6FNO2S, Electric Literature of 1524-40-9.
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics