Discovery of 3-Quinazolin-4(3H)-on-3-yl-2,N-dimethylpropanamides as Orally Active and Selective PI3Kα Inhibitors was written by Dong, Jiaqiang;Huang, Jingjie;Zhou, Ji;Tan, Ye;Jin, Jing;Tan, Xi;Wang, Bei;Yu, Tao;Wu, Chengde;Chen, Shuhui;Wang, Tie-Lin. And the article was included in ACS Medicinal Chemistry Letters in 2020.Formula: C7H4ClF3O2S This article mentions the following:
Phosphoinositide 3-kinases (PI3Ks) mediate a series of events related to cell growth, proliferation, survival, and differentiation. Overexpression of PI3Ks can lead to the dysregulation of cell homeostasis and cause tumorigenesis. In this study, rationally designed compounds were investigated as PI3Kα-selective inhibitors. Our efforts culminated in the discovery of a series of quinazolin-4(3H)-one derivatives with 2-substituted-N-methylpropanamide substitutions as PI3Kα-selective inhibitors. The best compound, I, has PI3Kα enzymic and cellular IC50 values of 1.8 and 12.1 nM, resp. It exhibits biochem. selectivities for PI3Kα over PI3Kβ/δ/γ of 150/7.72/7.67-fold and cellular selectivities of 115/15.1/>826-fold, resp. Compound I is 59% orally bioavailable with a dose-normalized AUC of 3090 nM. These effects translated into in vivo conditions, as I significantly time- and dose-dependently inhibited phosphorylation of Akt in BT-474 s.c. xenograft mice and inhibited tumor growth. In the experiment, the researchers used many compounds, for example, 3-(Trifluoromethyl)benzene-1-sulfonyl chloride (cas: 777-44-6Formula: C7H4ClF3O2S).
3-(Trifluoromethyl)benzene-1-sulfonyl chloride (cas: 777-44-6) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators.While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available. Alkyl chlorides readily undergo attack by nucleophiles.Formula: C7H4ClF3O2S
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics