Zhang, Mingming; Wei, Wei; Peng, Chengjun; Ma, Xiaodong; He, Xiao; Zhang, Heng; Zhou, Mingkang published their research in Bioorganic & Medicinal Chemistry Letters in 2021. The article was titled 《Discovery of novel pyrazolopyrimidine derivatives as potent mTOR/HDAC bi-functional inhibitors via pharmacophore-merging strategy》.Category: bromides-buliding-blocks The article contains the following contents:
The mTOR and HDAC dual suppression is meaningful for counteracting drug resistance resulted from kinase mutation and bypass mechanisms. Herein, we communicate our recent discovery of a novel structural series of mTOR/HDAC bi-functional inhibitors featuring the pyrazolopyrimidine core via pharmacophore-merging strategy. More than half of them exerted potent dual-target inhibitory activities. In particular, compound 50 exhibited IC50 values of 0.49 and 0.91 nM against mTOR and HDAC1, resp., along with remarkably enhanced anti-proliferative activity (IC50 = 1.74μM) against MV4-11 cell line than mTOR inhibitor MLN-0128 (IC50 = 5.84μM) and HDAC inhibitor SAHA (IC50 = 8.44μM). Its intracellular intervention of both mTOR signaling and HDAC was validated by the Western blot anal. Moreover, as the first disclosed mTOR/HDAC dual inhibitor with selectivity for some specific HDAC subtypes, it has the potential to alleviate the adverse effects resulted from pan-HDAC inhibition. Attributed to its favorable in vitro performance, compound 50 is valuable for further functional investigation as a polypharmacol. anti-cancer agent. The experimental process involved the reaction of Ethyl 5-bromovalerate(cas: 14660-52-7Category: bromides-buliding-blocks)
Ethyl 5-bromovalerate(cas: 14660-52-7) belongs to bromides. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents.Category: bromides-buliding-blocks
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary