1282606-75-0Relevant academic research and scientific papers
Discovery of triazolone derivatives as novel, potent stearoyl-CoA desaturase-1 (SCD1) inhibitors
Sun, Shaoyi,Zhang, Zaihui,Pokrovskaia, Natalia,Chowdhury, Sultan,Jia, Qi,Chang, Elaine,Khakh, Kuldip,Kwan, Rainbow,McLaren, David G.,Radomski, Chris C.,Ratkay, Leslie G.,Fu, Jianmin,Dales, Natalie A.,Winther, Michael D.
, p. 455 - 465 (2015/01/30)
Stearoyl-CoA desaturase-1 (SCD1) plays an important role in lipid metabolism. Inhibition of SCD1 activity represents a potential novel approach for the treatment of metabolic diseases such as obesity, type 2 diabetes and dyslipidemia, as well as skin diseases, acne and cancer. Herein, we report the synthesis and structure-activity relationships (SAR) of a series of novel triazolone derivatives, culminating in the identification of pyrazolyltriazolone 17a, a potent SCD1 inhibitor, which reduced plasma C16:1/C16:0 triglycerides desaturation index (DI) in an acute Lewis rat model in a dose dependent manner, with an ED50 of 4.6 mg/kg. In preliminary safety studies, compound 17a did not demonstrate adverse effects related to SCD1 inhibition after repeat dosing at 100 mg/kg. Together, these data suggest that sufficient safety margins can be achieved with certain SCD1 inhibitors, thus allowing exploration of clinical utility in metabolic disease settings.
PYRAZOLE DERIVATIVES WHICH MODULATE STEAROYL-COA DESATURASE
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Page/Page column 75, (2011/04/25)
The present invention provides heterocyclic derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivative
