1428940-06-0Relevant academic research and scientific papers
Indazole-based ligands for estrogen-related receptor α as potential anti-diabetic agents
Patch, Raymond J.,Huang, Hui,Patel, Sharmila,Cheung, Wing,Xu, Guozhang,Zhao, Bao-Ping,Beauchamp, Derek A.,Rentzeperis, Dionisios,Geisler, John G.,Askari, Hossein B.,Liu, Jianying,Kasturi, Jyotsna,Towers, Meghan,Gaul, Micheal D.,Player, Mark R.
, p. 830 - 853 (2017/07/25)
Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that has been functionally implicated in the regulation of energy homeostasis. Herein is described the development of indazole-based N-alkylthiazolidenediones, which function in biochemical
Process development for scale-up of a novel 3,5-substituted thiazolidine-2,4-dione compound as a potent inhibitor for estrogen-related receptor 1
Li, Xun,Russell, Ronald K.,Spink, Jan,Ballentine, Scott,Teleha, Christopher,Branum, Shawn,Wells, Kenneth,Beauchamp, Derek,Patch, Raymond,Huang, Hui,Player, Mark,Murray, William
, p. 321 - 330 (2014/03/21)
The development of a reproducible process for multihundred gram production of (Z)-5-((1-(4-chloro-2-(trifluoromethyl)benzyl)-1H-indazol-5-yl)methylene)-3- ((3R,4R)-3-fluoro-1-methylpiperidin-4-yl)thiazolidine-2,4-dione (26), a potent and selective inhibitor of estrogen-related receptor 1 (ERR1), is described. This multihundred gram synthesis was achieved via magnesium perchlorate- catalyzed regioselective epoxide ring-opening of tert-butyl 7-oxa-3- azabicyclo[4.1.0]heptane-3-carboxylate (9) with thiazolidine-2,4-dione (6, TZD) to form a diastereomeric mixture tert-butyl 4-(2,4-dioxothiazolidin-3-yl)-3- hydroxypiperidine-1-carboxylate (17), of which the 3-hydroxyl group was functionally transformed to 3-fluoro derivative 19 after treatment with Deoxo-Fluor. Chiral separation of 19 provided the desired diastereomer (3R,4R)-21 that was converted to the secondary amine 23 TFA salt. Reductive amination of 23 produced the key intermediate N-methyl 24. Knoevenagel condensation of 24 with 1-(4-chloro-2-(trifluoromethyl)benzyl)-1H-indazole-5- carbaldehyde (5) produced the final product 26 in 10% overall yield (99.7% HPLC area% with ≥99.5% de) after a convergent eight synthetic steps with the only column purification being the chiral HPLC separation of 3R,4R-21 from 3S,4S-22.
