1257229-97-2Relevant academic research and scientific papers
Discovery of HSD-621 as a potential agent for the treatment of type 2 diabetes
Wan, Zhao-Kui,Chenail, Eva,Li, Huan-Qiu,Ipek, Manus,Xiang, Jason,Suri, Vipin,Hahm, Seung,Bard, Joel,Svenson, Kristine,Xu, Xin,Tian, Xianbin,Wang, Mengmeng,Li, Xiangping,Johnson, Christian E.,Qadri, Ariful,Panza, Darrell,Perreault, Mylene,Mansour, Tarek S.,Tobin, James F.,Saiah, Eddine
, p. 118 - 123 (2013)
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive glucocorticoid cortisone to its active form, cortisol. The glucocorticoid receptor (GR) signaling pathway has been linked to the pathophysiology of diabetes and metabolic syndrome. Herein, the structure-activity relationship of a series of piperazine sulfonamide-based 11β-HSD1 inhibitors is described. (R)-3,3,3-Trifluoro-2-(5-(((R)-4-(4- fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazin-1-yl)sulfonyl)thiophen-2-yl) -2-hydroxypropanamide 18a (HSD-621) was identified as a potent and selective 11β-HSD1 inhibitor and was ultimately selected as a clinical development candidate. HSD-621 has an attractive overall pharmaceutical profile and demonstrates good oral bioavailability in mouse, rat, and dog. When orally dosed in C57/BL6 diet-induced obesity (DIO) mice, HSD-621 was efficacious and showed a significant reduction in both fed and fasting glucose and insulin levels. Furthermore, HSD-621 was well tolerated in drug safety assessment studies.
11-BETA HSD1 1NHIBITORS
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Page/Page column 72, (2010/12/29)
This invention features a chemical entity E, which is a compound of Formula I, or a salt (e.g., a pharmaceutically acceptable salt), or an N-oxide thereof (e.g., a compound of Formula I, or a pharmaceutically acceptable salt thereof). Formula I is provided below: formula (I) R1, R2, R3, R4, R5, R6, R7, R8, R9, and A can be as defined anywhere herein
