Discovery and Optimization of a Series of Sulfonamide Inverse Agonists for the Retinoic Acid Receptor-Related Orphan Receptor-a was written by Doebelin, Christelle;He, Yuanjun;Campbell, Sean;Nuhant, Philippe;Kumar, Naresh;Koenig, Marcel;Garcia-Ordonez, Ruben;Chang, Mi Ra;Roush, William R.;Lin, Li;Kahn, Susan;Cameron, Michael D.;Griffin, Patrick R.;Solt, Laura A.;Kamenecka, Theodore M.. And the article was included in Medicinal Chemistry (Sharjah, United Arab Emirates) in 2019.Electric Literature of C6H7ClN2O3S2 This article mentions the following:
Background: Despite a massive industry endeavor to develop RORalpha-modulators for autoimmune disorders, there has been no indication of efforts to target the close family member RORa for similar indications. This may be due to the misconception that RORa is redundant to RORalpha, or the inherent difficulty in cultivating tractable starting points for RORa. RORa-selective modulators would be useful tools to interrogate the biol. of this understudied orphan nuclear receptor. Objective: The goal of this research effort was to identify and optimize synthetic ligands for RORa starting from the known LXR agonist T0901317. Methods: Fourty-five analogs of the sulfonamide lead (1) were synthesized and evaluated for their ability to suppress the transcriptional activity of RORa, RORalpha, and LXRa in cell-based assays. Analogs were characterized by 1H-NMR, 13C-NMR, and LC-MS anal. The pharmacokinetic profile of the most selective RORa inverse agonist was evaluated in rats with i.p. (i.p.) and per oral (p.o.)dosing. Results: Structure-activity relationship studies led to potent dual RORa/RORalpha inverse agonists as well as RORa-selective inverse agonists (20, 28). LXR activity could be reduced by removing the sulfonamide nitrogen substituent. Attempts to improve the potency of these selective leads by varying substitution patterns throughout the mol. proved challenging. In the experiment, the researchers used many compounds, for example, 2-Acetamido-4-methylthiazole-5-sulfonyl chloride (cas: 69812-29-9Electric Literature of C6H7ClN2O3S2).
2-Acetamido-4-methylthiazole-5-sulfonyl chloride (cas: 69812-29-9) belongs to thiazole derivatives. Thiazole rings are planar and aromatic. Thiazoles are characterized by larger pi-electron delocalization than the corresponding oxazoles and have therefore greater aromaticity.Various laboratory methods exist for the organic synthesis of thiazoles. For example, 2,4-dimethylthiazole is synthesized from thioacetamide and chloroacetone.Electric Literature of C6H7ClN2O3S2
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica