Thakur, Ashish; Tawa, Gregory J.; Henderson, Mark J.; Danchik, Carina; Liu, Suiyang; Shah, Pranav; Wang, Amy Q.; Dunn, Garrett; Kabir, Md.; Padilha, Elias C.; Xu, Xin; Simeonov, Anton; Kharbanda, Surender; Stone, Richard; Grewal, Gurmit published the artcile< Design, Synthesis, and Biological Evaluation of Quinazolin-4-one-Based Hydroxamic Acids as Dual PI3K/HDAC Inhibitors>, Safety of Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is quinazolinone hydroxamic acid dual PI3K HDAC inhibitor anticancer.
A series of quinazolin-4-one based hydroxamic acids was rationally designed and synthesized as novel dual PI3K/HDAC inhibitors by incorporating an HDAC pharmacophore into a PI3K inhibitor (Idelalisib) via an optimized linker. Several of these dual inhibitors were highly potent (IC50 < 10 nM) and selective against PI3Kγ, δ and HDAC6 enzymes and exhibited good antiproliferative activity against multiple cancer cell lines. The lead compound 48c, induced necrosis in several mutant and FLT3-resistant AML cell lines and primary blasts from AML patients, while showing no cytotoxicity against normal PBMCs, NIH3T3, and HEK293 cells. Target engagement of PI3Kδ and HDAC6 by 48c was demonstrated in MV411 cells using the cellular thermal shift assay (CETSA). Compound 48c showed good pharmacokinetics properties in mice via i.p. administration and provides a means to examine the biol. effects of inhibiting these two important enzymes with a single mol., either in vitro or in vivo. Journal of Medicinal Chemistry published new progress about Antitumor agents. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Safety of Ethyl 2-chloropyrimidine-5-carboxylate.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia