840488-85-9Relevant articles and documents
Piperazine derivatives and their use as therapeutic agents
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, (2016/03/19)
Compounds for treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the compounds are of formula (I): where x y, W, V, R 2 , R 3 , R 4 , R 5 , R 6 , R 6a , R 7 , R 7a , R 8 , R 8a , R 9 and R 9a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.
Discovery of piperazin-1-ylpyridazine-based potent and selective stearoyl-CoA Desaturase-1 inhibitors for the treatment of obesity and metabolic syndrome
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.
, p. 568 - 583 (2013/04/23)
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. Particularly, compound 49 (XEN103) was highly active in vitro (mSCD1 IC50 = 14 nM and HepG2 IC50 = 12 nM) and efficacious in vivo (ED50 = 0.8 mg/kg). It also demonstrated striking reduction of weight gain in a rodent model. Our findings with small-molecule SCD1 inhibitors confirm the importance of this target in metabolic regulation, describe novel models for assessing SCD1 inhibitors for efficacy and tolerability and demonstrate an opportunity to develop a novel therapy for metabolic disease.
Heterocyclic Derivatives and Their Use as Strearoyl-Coa Desaturase Inhibitors
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Page/Page column 15, (2008/12/05)
Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): where x, y, G, J, K, L, M, W, R2, R3, R5, R5a, R6, R6a, R7, R7a, R8 and R8a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.
Pyridazine Derivatives for Inhibiting Human Stearoyl-Coa-Desaturase
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Page/Page column 14-15, (2008/12/08)
Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I) where x, y, G, J, K, L, M, Q, W, V, R2, R3, R5, R5a,
HETEROAROMATIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
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Page/Page column 34-35, (2008/06/13)
Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and
HETEROCYCLIC DERIVATIVES AND THEIR USE AS MEDIATORS OF STEAROYL-COA DESATURASE
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Page/Page column 49, (2010/10/20)
Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): Formula (I) where x, y, G, J, L, M, V, W, R2, R3, R4, R5, R5a, R6, R6a, R7, R7a, R8 and R8a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.
