A Dipolar Cycloaddition Reaction To Access 6-Methyl-4,5,6,7-tetrahydro-1H-[1,2,3]triazolo[4,5-c]pyridines Enables the Discovery Synthesis and Preclinical Profiling of a P2X7 Antagonist Clinical Candidate was written by Chrovian, Christa C.;Soyode-Johnson, Akinola;Peterson, Alexander A.;Gelin, Christine F.;Deng, Xiaohu;Dvorak, Curt A.;Carruthers, Nicholas I.;Lord, Brian;Fraser, Ian;Aluisio, Leah;Coe, Kevin J.;Scott, Brian;Koudriakova, Tatiana;Schoetens, Freddy;Sepassi, Kia;Gallacher, David J.;Bhattacharya, Anindya;Letavic, Michael A.. And the article was included in Journal of Medicinal Chemistry in 2018.COA of Formula: C5H9N3 This article mentions the following:
A single pot dipolar cycloaddition reaction/Cope elimination sequence was developed to access novel 1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridine P2X7 antagonists that contain a synthetically challenging chiral center. The structure-activity relationships of the new compounds are described. Two of these compounds, (S)-(2-fluoro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyrimidin-2-yl)-6-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone (I) and (S)-(3-fluoro-2-(trifluoromethyl)pyridin-4-yl)(1-(5-fluoropyrimidin-2-yl)-6-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone (II), were found to have robust P2X7 receptor occupancy at low doses in rat with ED50 values of 0.06 and 0.07 mg/kg, resp. Compound II had notable solubility compared to I and showed good tolerability in preclin. species. Compound II was chosen as a clin. candidate for advancement into phase I clin. trials to assess safety and tolerability in healthy human subjects prior to the initiation of proof of concept studies for the treatment of mood disorders. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-3-amine (cas: 55361-49-4COA of Formula: C5H9N3).
1-Ethyl-1H-pyrazol-3-amine (cas: 55361-49-4) belongs to pyrazole derivatives. Pyrazole has two ring nitrogen atoms in which N1 is pyrrolic and N2 is pyridine-like. The N1 nitrogen is not reactive but is deprotonated in the presence of a base-forming anion. Pyrazoles can be selectively lithiated at different carbons and subsequently react with electrophiles depending on the substitution patterns.COA of Formula: C5H9N3
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics