620-19-9Relevant articles and documents
Synthesis and evaluation of tetrahydroisoquinoline derivatives against Trypanosoma brucei rhodesiense
Cullen, Danica R.,Gallagher, Ashlee,Duncan, Caitlin L.,Pengon, Jutharat,Rattanajak, Roonglawan,Chaplin, Jason,Gunosewoyo, Hendra,Kamchonwongpaisan, Sumalee,Payne, Alan,Mocerino, Mauro
, (2021/10/07)
Human African Trypanosomiasis (HAT) is a neglected tropical disease caused by the parasitic protozoan Trypanosoma brucei (T. b.), and affects communities in sub-Saharan Africa. Previously, analogues of a tetrahydroisoquinoline scaffold were reported as having in vitro activity (IC50 = 0.25–70.5 μM) against T. b. rhodesiense. In this study the synthesis and antitrypanosomal activity of 80 compounds based around a core tetrahydroisoquinoline scaffold are reported. A detailed structure activity relationship was revealed, and five derivatives (two of which have been previously reported) with inhibition of T. b. rhodesiense growth in the sub-micromolar range were identified. Four of these (3c, 12b, 17b and 26a) were also found to have good selectivity over mammalian cells (SI > 50). Calculated logD values and preliminary ADME studies predict that these compounds are likely to have good absorption and metabolic stability, with the ability to passively permeate the blood brain barrier. This makes them excellent leads for a blood-brain barrier permeable antitrypanosomal scaffold.
Mild Aliphatic and Benzylic Hydrocarbon C-H Bond Chlorination Using Trichloroisocyanuric Acid
Combe, Sascha H.,Hosseini, Abolfazl,Parra, Alejandro,Schreiner, Peter R.
, p. 2407 - 2413 (2017/03/11)
We present the controlled monochlorination of aliphatic and benzylic hydrocarbons with only 1 equiv of substrate at 25-30 °C using N-hydroxyphthalimide (NHPI) as radical initiator and commercially available trichloroisocyanuric acid (TCCA) as the chlorine source. Catalytic amounts of CBr4 reduced the reaction times considerably due to the formation of chain-carrying ·CBr3 radicals. Benzylic C-H chlorination affords moderate to good yields for arenes carrying electron-withdrawing (50-85%) or weakly electron-donating groups (31-73%); cyclic aliphatic substrates provide low yields (24-38%). The products could be synthesized on a gram scale followed by simple purification via distillation. We report the first direct side-chain chlorination of 3-methylbenzoate affording methyl 3-(chloromethyl)benzoate, which is an important building block for the synthesis of vasodilator taprostene.
Iron catalyzed halogenation of benzylic aldehydes and ketones
Savela, Risto,W?rn?, Johan,Murzin, Dmitry Yu.,Leino, Reko
, p. 2406 - 2417 (2015/04/14)
A simple and efficient iron-catalyzed method for chlorination of aromatic carbonyl compounds is reported. By using 4-10 mol% Fe(iii) oxo acetate catalyst, prepared by solid state atmospheric oxidation of Fe(ii) acetate, in combination with triethylsilane and chlorotrimethylsilane, hydrosilylation of benzylic carbonyl compounds with subsequent chlorination is achieved within a few hours at room temperature. This new method is mild and rapid compared to the conventional two step approach involving reduction and chlorination reactions in separate stages. Development of synthetic methodology is also supplemented here by kinetic investigation of the reaction mechanism, which supports the tentative mechanisms suggested previously for similar reactions. This journal is
