Chen, Huifen;Volgraf, Matthew;Do, Steven;Kolesnikov, Aleksandr;Shore, Daniel G.;Verma, Vishal A.;Villemure, Elisia;Wang, Lan;Chen, Yong;Hu, Baihua;Lu, Ai-Jun;Wu, Guosheng;Xu, Xiaofeng;Yuen, Po-wai;Zhang, Yamin;Erickson, Shawn D.;Dahl, Martin;Brotherton-Pleiss, Christine;Tay, Suzanne;Ly, Justin Q.;Murray, Lesley J.;Chen, Jun;Amm, Desiree;Lange, Wienke;Hackos, David H.;Reese, Rebecca M.;Shields, Shannon D.;Lyssikatos, Joseph P.;Safina, Brian S.;Estrada, Anthony A. published 《Discovery of a Potent (4R,5S)-4-Fluoro-5-methylproline Sulfonamide Transient Receptor Potential Ankyrin 1 Antagonist and Its Methylene Phosphate Prodrug Guided by Molecular Modeling》 in 2018. The article was appeared in 《Journal of Medicinal Chemistry》. They have made some progress in their research.Electric Literature of C5H5ClN2O2 The article mentions the following:
Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed in sensory neurons where it functions as an irritant sensor for a plethora of electrophilic compounds and is implicated in pain, itch, and respiratory disease. To study its function in various disease contexts, we sought to identify novel, potent, and selective small-mol. TRPA1 antagonists. Herein we describe the evolution of an N-isopropylglycine sulfonamide lead (1) to a novel and potent (4R,5S)-4-fluoro-5-methylproline sulfonamide series of inhibitors. Mol. modeling was utilized to derive low-energy three-dimensional conformations to guide ligand design. This effort led to compound 20, which possessed a balanced combination of potency and metabolic stability but poor solubility that ultimately limited in vivo exposure. To improve solubility and in vivo exposure, we developed methylene phosphate prodrug 22, which demonstrated superior oral exposure and robust in vivo target engagement in a rat model of AITC-induced pain. The experimental procedure involved many compounds, such as 6-(Chloromethyl)pyrimidine-2,4(1H,3H)-dione (cas: 18592-13-7) .
6-(Chloromethyl)pyrimidine-2,4(1H,3H)-dione (cas: 18592-13-7 Electric Literature of C5H5ClN2O2) was used in the synthesis of: 5-bromo-6-(chloromethyl)uracil, pteridine compounds, potential anticancer agents, substituted uracil pyridinium compounds, potential inhibitors of thymidine phosphorylase.
Reference:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia