Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH) was written by Tully, David C.;Rucker, Paul V.;Chianelli, Donatella;Williams, Jennifer;Vidal, Agnes;Alper, Phil B.;Mutnick, Daniel;Bursulaya, Badry;Schmeits, James;Wu, Xiangdong;Bao, Dingjiu;Zoll, Jocelyn;Kim, Young;Groessl, Todd;McNamara, Peter;Seidel, H. Martin;Molteni, Valentina;Liu, Bo;Phimister, Andrew;Joseph, Sean B.;Laffitte, Bryan. And the article was included in Journal of Medicinal Chemistry in 2017.HPLC of Formula: 225525-63-3 The following contents are mentioned in the article:
The farnesoid X receptor (FXR) is a nuclear receptor that acts as a master regulator of bile acid metabolism and signaling. Activation of FXR inhibits bile acid synthesis and increases bile acid conjugation, transport, and excretion, thereby protecting the liver from the harmful effects of bile accumulation, leading to considerable interest in FXR as a therapeutic target for the treatment of cholestasis and nonalcoholic steatohepatitis. We identified a novel series of highly potent non-bile acid FXR agonists that introduce a bicyclic nortropine-substituted benzothiazole carboxylic acid moiety onto a trisubstituted isoxazole scaffold. Herein, we report the discovery of 1 (tropifexor, LJN452), a novel and highly potent agonist of FXR. Potent in vivo activity was demonstrated in rodent PD models by measuring the induction of FXR target genes in various tissues. Tropifexor has advanced into phase 2 human clin. trials in patients with NASH and PBC. This study involved multiple reactions and reactants, such as Methyl 2-amino-4-methylbenzo[d]thiazole-6-carboxylate (cas: 225525-63-3HPLC of Formula: 225525-63-3).
Methyl 2-amino-4-methylbenzo[d]thiazole-6-carboxylate (cas: 225525-63-3) belongs to thiazole derivatives. The higher aromaticity of thiazole is due to delocalization of a lone pair of sulfur electrons across the ring, which is evidenced by chemical shifts of ring hydrogen at δ 7.27 and 8.77 ppm (C2 and C4), indicating diamagnetic ring current. Various laboratory methods exist for the organic synthesis of thiazoles. Prominent is the Hantzsch thiazole synthesis is a reaction between haloketones and thioamides.HPLC of Formula: 225525-63-3
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica