The chemical properties of alicyclic heterocycles are similar to those of the corresponding chain compounds. Compound: 4-(Bromomethyl)-1-chloro-2-fluorobenzene, is researched, Molecular C7H5BrClF, CAS is 206362-80-3, about Development of pyrazolo[3,4-d]pyrimidine-6-amine-based TRAP1 inhibitors that demonstrate in vivo anticancer activity in mouse xenograft models, the main research direction is pyrazolo pyrimidine amine derivative preparation TRAP1 Hsp90 inhibitor cancer; Anticancer; Drug; Hsp90; Mitochondria; Selectivity; TRAP1.Name: 4-(Bromomethyl)-1-chloro-2-fluorobenzene.
TNF Receptor Associated Protein 1 (TRAP1) is a mitochondrial paralog of Hsp90 related to the promotion of tumorigenesis in various cancers via maintaining mitochondrial integrity, reducing the production of reactive oxygen species, and reprogramming cellular metabolism Consequently, Hsp90 and TRAP1 have been targeted to develop cancer therapeutics. Herein, we report a series of pyrazolo[3,4-d]pyrimidine derivatives that are mitochondria-permeable TRAP1 inhibitors. Structure-based drug design guided the optimization of potency, leading to the identification of compounds 47 and 48 as potent TRAP1 and Hsp90 inhibitors with good metabolic and plasma stability as well as acceptable CYP and hERG inhibition. X-ray co-crystallization studies confirmed both 47 and 48 interact with the ATP binding pocket in the TRAP1 protein. Compounds 47 and 48 demonstrated excellent anticancer efficiency in various cancer cells, with limited toxicity over normal hepatocyte and prostate cells. Mouse PC3 xenograft studies showed 47 and 48 significantly reduced tumor growth.
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Reference:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem