Zhang, Hongjun; Lapointe, Blair T.; Anthony, Neville; Azevedo, Rita; Cals, Jos; Correll, Craig C.; Daniels, Matthew; Deshmukh, Sujal; van Eenenaam, Hans; Ferguson, Heidi; Hegde, Laxminarayan G.; Karstens, Willem Jan; MacLean, John; Miller, J. Richard; Moy, Lily Y.; Simov, Vladimir; Nagpal, Sunil; Oubrie, Arthur; Palte, Rachel L.; Parthasarathy, Gopal; Sciammetta, Nunzio; van der Stelt, Mario; Woodhouse, Janice D.; Trotter, B. Wesley; Barr, Kenneth published the artcile< Discovery of N-(Indazol-3-yl)piperidine-4-carboxylic Acids as RORγt Allosteric Inhibitors for Autoimmune Diseases>, Recommanded Product: (2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid, the main research area is indazolylpiperidinecarboxylic acid RORgamma allosteric inhibitor autoimmune disease.
The clin. success of anti-IL-17 monoclonal antibodies (i.e., Cosentyx and Taltz) has validated Th17 pathway modulation for the treatment of autoimmune diseases. The nuclear hormone receptor RORγt is a master regulator of Th17 cells and affects the production of a host of cytokines, including IL-17A, IL-17F, IL-22, IL-26, and GM-CSF. Substantial interest has been spurred across both academia and industry to seek small mols. suitable for RORγt inhibition. A variety of RORγt inhibitors have been reported in the past few years, the majority of which are orthosteric binders. Here the authors disclose the discovery and optimization of a class of inhibitors, which bind differently to an allosteric binding pocket. Starting from a weakly active hit 1, a tool compound 14 was quickly identified that demonstrated superior potency, selectivity, and off-target profile. Further optimization focused on improving metabolic stability. Replacing the benzoic acid moiety with piperidinyl carboxylate, modifying the 4-aza-indazole core in 14 to 4-F-indazole, and incorporating a key hydroxyl group led to the discovery of I, which possesses exquisite potency and selectivity, as well as an improved pharmacokinetic profile suitable for oral dosing.
ACS Medicinal Chemistry Letters published new progress about Autoimmune disease. 603122-80-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BClO4, Recommanded Product: (2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics