Discovery of piperazin-1-ylpyridazine-based potent and selective stearoyl-CoA desaturase-1 inhibitors for the treatment of obesity and metabolic syndrome

…, S Sviridov, S Chowdhury, DG McLaren…

Index: Zhang, Zaihui; Sun, Shaoyi; Kodumuru, Vishnumurthy; Hou, Duanjie; Liu, Shifeng; Chakka, Nagasree; Sviridov, Serguei; Chowdhury, Sultan; McLaren, David G.; Ratkay, Leslie G.; Khakh, Kuldip; Cheng, Xing; Gschwend, Heinz W.; Kamboj, Rajender; Fu, Jianmin; Winther, Michael D. Journal of Medicinal Chemistry, 2013 , vol. 56, # 2 p. 568 - 583

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Citation Number: 19

Abstract

Stearoyl-CoA desaturase-1 (SCD1) catalyzes de novo synthesis of monounsaturated fatty acids from saturated fatty acids. Studies have demonstrated that rodents lacking a functional SCD1 gene have an improved metabolic profile, including reduced weight gain, lower triglycerides, and improved insulin response. In this study, we discovered a series of piperazinylpyridazine-based highly potent, selective, and orally bioavailable compounds. ...