Carbazates as potent inhibitors of hormone-sensitive lipase.
The central role of adipose tissue hormone-sensitive lipase in regulating fatty acid metabolism makes it a potential pharmacological target for the prevention of peripheral insulin resistance in obese, prediabetic and diabetic individuals. The synthesis of a new series of carbazates is presented. Modification of the phenolic 4-position in a series of 1,2,3,4-tetrahydroisoquinoline and morpholine derived carbazates, yielded inhibitors of the catalytic activity of this enzyme with nanomolar potency.
de Jong
Johannes C
JC
Novo Nordisk A/S, Medicinal Chemistry, Novo Nordisk Park, 2760 Maaloev, Denmark.
Sørensen
Lotte G
LG
Tornqvist
Hans
H
Jacobsen
Poul
P
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006834:Hydrazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002787:Sterol Esterase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D006834:Hydrazines; C010877:carbazic acid; D002787:Sterol Esterase