Synthetic Route of C8H15BrO2In 2018 ,《Design and synthesis of potent dual inhibitors of JAK2 and HDAC based on fusing the pharmacophores of XL019 and vorinostat》 appeared in European Journal of Medicinal Chemistry. The author of the article were Chu-Farseeva, Yu-yi; Mustafa, Nurulhuda; Poulsen, Anders; Tan, Eng Chong; Yen, Jeffrey J. Y.; Chng, Wee Joo; Dymock, Brian W.. The article conveys some information:
Specifically blocking more than one oncogenic pathway simultaneously in a cancer cell with a combination of different drugs is the mainstay of the majority of cancer treatments. Being able to do this via two targeted pathways without inducing side effects through a general mechanism, such as chemotherapy, could bring benefit to patients. In this work we describe a new dual inhibitor of the JAK-STAT and HDAC pathways through designing and developing two types of mol. based on the JAK2 selective inhibitor XL019 and the pan-HDAC inhibitor, vorinostat. Both series of compounds had examples with low nanomolar JAK2 and HDAC1/6 inhibition. In some cases good HDAC1 selectivity was achieved while retaining HDAC6 activity. The observed potency is explained through mol. docking studies of all three enzymes. One example, 69c had 16-25 fold selectivity against the three other JAK-family proteins JAK1, JAK3 and TYK2. A number of compounds had sub-micromolar potencies against a panel of 4 solid tumor cell lines and 4 hematol. cell lines with the most potent compound, 45h, having a cellular IC50 of 70 nM against the multiple myeloma cell line KMS-12-BM. Evidence of both JAK and HDAC pathway inhibition is presented in Hela cells showing that both pathways are modulated. Evidence of apoptosis with two compounds in 4 sold tumor cell lines is also presented. In the part of experimental materials, we found many familiar compounds, such as 8-Bromooctanoic acid(cas: 17696-11-6Synthetic Route of C8H15BrO2)
8-Bromooctanoic acid(cas: 17696-11-6) acid is used in the synthesis of 8-(N-Methyl-4,4′-bipyridinyl)- octanoic acid. 8-Mercaptooctanoic acid was prepared from 8-bromooctanoic acid. And 8-Bromooctanoic Acid is a useful compound for sonodynamic therapy.Synthetic Route of C8H15BrO2
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Bromide – Wikipedia,
bromide – Wiktionary