Optimisation of Tetrahydroisoquinoline-Based Chimeric Microtubule Disruptors was written by Dohle, Wolfgang;Leese, Mathew P.;Jourdan, Fabrice L.;Chapman, Christopher J.;Hamel, Ernest;Ferrandis, Eric;Potter, Barry V. L.. And the article was included in ChemMedChem in 2014.Computed Properties of C11H16ClNO2 This article mentions the following:
Tetrahydroisoquinoline (THIQ)-based “chimeric” microtubule disruptors were optimized through modification of the N-benzyl motif, in concert with changes at C3 and C7, resulting in the identification of compounds with improved in vitro antiproliferative activities, e.g. I with GI50 20 nM in DU-145. The broad anticancer activity of these novel structures was confirmed in the NCI 60-cell line assay, with two compounds displaying MGM values in the 40 nM region. In addition, their profiles as inhibitors of tubulin polymerization and colchicine binding to tubulin were confirmed. Compound I, for example, inhibited tubulin polymerization with an IC50 of 1.8 渭M, close to that of the clin. drug combretastatin A-4, and also proved effective at blocking colchicine binding. Only one phenol compound in the series to date was identified as showing both better in vitro antiproliferative properties than its corresponding sulfamate and excellent antitubulin data (IC50=1.6 渭M). Compound II was selected for in vivo evaluation at the NCI in the hollow fiber assay and showed very good activity and wide tissue distribution, illustrating the value of this template for further development. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Computed Properties of C11H16ClNO2).
6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline, as a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids. An oxidative C1 arylation of tetrahydroisoquinolines with aryl Grignard reagents is mediated by diethyl azodicarboxylate (DEAD). This C-H activation under metal-free conditions delivers target compounds, including some naturally occurring alkaloids, in good yields.Computed Properties of C11H16ClNO2
Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem