AN
2004:256580 BIOSIS
DN
PREV200400256670
TI
Carbazates as potent inhibitors of hormone-sensitive lipase.
AU
de Jong, Johannes C.; Sorensen, Lotte G.; Tornqvist, Hans; Jacobsen, Poul [Reprint Author]
CS
Medicinal Chemistry, Novo Nordisk A/S, Novo Nordisk Park, 2760, Maaloev, Denmark pjac@novonordisk.com
SO
Bioorganic & Medicinal Chemistry Letters, (5 April 2004) Vol. 14, No. 7, pp. 1741-1744. print. CODEN: BMCLE8. ISSN: 0960-894X.
DT
Article
LA
English
ED
Entered STN: 12 May 2004 Last Updated on STN: 12 May 2004
AB
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.
CC
Biochemistry studies - General 10060 Biochemistry studies - Lipids 10066 Enzymes - General and comparative studies: coenzymes 10802 Pathology - Therapy 12512 Metabolism - General metabolism and metabolic pathways 13002 Metabolism - Metabolic disorders 13020 Endocrine - Pancreas 17008 Pharmacology - General 22002
IT
Major Concepts Enzymology (Biochemistry and Molecular Biophysics); Pharmacology
IT
Parts, Structures, & Systems of Organisms adipose tissue
IT
Diseases diabetes: endocrine disease/pancreas, metabolic disease, drug therapy Diabetes Mellitus (MeSH)
IT
Diseases obesity: nutritional disease Obesity (MeSH)
IT
Chemicals & Biochemicals 1,2,3,4-tetrahydroisoquinoline; carbazates: enzyme inhibitor-drug; fatty acid: metabolism; hormone-sensitive lipase: inhibition; morphine
IT
Miscellaneous Descriptors peripheral insulin resistance
RN
91-21-4 (1,2,3,4-tetrahydroisoquinoline) 9001-62-1 (hormone-sensitive lipase) 57-27-2 (morphine)