Discovery and optimization of a novel CNS penetrant series of mGlu4 PAMs based on a 1,4-thiazepane core with in vivo efficacy in a preclinical Parkinsonian model was written by Kent, Caitlin N.;Fulton, Mark G.;Stillwell, Kaylee J.;Dickerson, Jonathan W.;Loch, Matthew T.;Rodriguez, Alice L.;Blobaum, Anna L.;Boutaud, Olivier;Rook, Jerri L.;Niswender, Colleen M.;Conn, P. Jeffrey;Lindsley, Craig W.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2021.Safety of 3-Bromo-5-chlorophenylamine This article mentions the following:
A high throughput screen (HTS) identified a novel, but weak (EC50 = 6.2μM, 97% Glu Max) mGlu4 PAM chemotype based on a 1,4-thiazepane core, VU0544412. Reaction development and chem. optimization delivered a potent mGlu4 PAM VU6022296 (EC50 = 32.8 nM, 108% Glu Max) with good CNS penetration (Kp = 0.45, Kp,uu = 0.70) and enantiopreference. Finally, VU6022296 displayed robust, dose-dependent efficacy in reversing Haloperidol-Induced Catalepsy (HIC), a rodent preclin. Parkinson’s disease model. In the experiment, the researchers used many compounds, for example, 3-Bromo-5-chlorophenylamine (cas: 96558-78-0Safety of 3-Bromo-5-chlorophenylamine).
3-Bromo-5-chlorophenylamine (cas: 96558-78-0) belongs to organobromine compounds. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents. Bromine-containing agents predominate because not only are they more efficient than similar chlorine-containing species, but also the high atomic weight of bromine ensures that it is present in a high mass fraction within most organobromine compounds.Safety of 3-Bromo-5-chlorophenylamine
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary