Design, Synthesis, and Evaluation of Trivalent PROTACs Having a Functionalization Site with Controlled Orientation was written by Huang, Yifan;Yokoe, Hiromasa;Kaiho-Soma, Ai;Takahashi, Kazunori;Hirasawa, Yusuke;Morita, Hiroshi;Ohtake, Fumiaki;Kanoh, Naoki. And the article was included in Bioconjugate Chemistry in 2022.Related Products of 111-46-6 This article mentions the following:
Trivalent PROTACs having a functionalization site with controlled orientation were designed, synthesized, and evaluated. Based on the X-ray structure of BRD protein degrader MZ1 (1) in complex with human VHL and BRD4BD2, we expected that the 1,2-disubstituted Et group near the JQ-1 moiety in MZ1 (1) could be replaced by a planar benzene tether as a platform for further functionalization. To test this hypothesis, we first designed six divalent MZ1 derivatives, 2a-c and 3a-c, by combining three variations of substitution patterns on the benzene ring (1,2-, 1,3-, and 1,4-substitution) and two variations in the number of ethylene glycol units (2 or 1). We then tested the synthesized compounds for the BRD4 degradation activity of each. As expected, we found that 1,2D-EG2-MZ1 (2a)(I), an MZ1 derivative with 1,2-disubstituted benzene possessing two ethylene glycol units, had an activity profile similar to that of MZ1 (1). Based on the structure of 2a, we then synthesized and evaluated four isomeric trivalent MZ1 derivatives, 15a-15d, having a tert-Bu ester unit on the benzene ring as a handle for further functionalization. Among the four isomers, 1,2,5T-EG2-MZ1 (15c)(II) retained a level of BRD4 depletion activity similar to that of 2a without inducing a measurable Hook effect, and its BRD4 depletion kinetics was the same as that of MZ1 (1). Other isomers were also shown to retain BRD4 depletion activity. Thus, the trivalent PROTACs we synthesized here may serve as efficient platforms for further applications. In the experiment, the researchers used many compounds, for example, 2,2′-Oxybis(ethan-1-ol) (cas: 111-46-6Related Products of 111-46-6).
2,2′-Oxybis(ethan-1-ol) (cas: 111-46-6) belongs to alcohols. Alkyl halides are often synthesized from alcohols, in effect substituting a halogen atom for the hydroxyl group. Tertiary alcohols cannot be oxidized at all without breaking carbon-carbon bonds, whereas primary alcohols can be oxidized to aldehydes or further oxidized to carboxylic acids.Related Products of 111-46-6
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts