PMID- 10052980
OWN - NLM
STAT- MEDLINE
DCOM- 19990316
LR  - 20121115
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 42
IP  - 4
DP  - 1999 Feb 25
TI  - Synthesis of retinoid X receptor-specific ligands that are potent inducers of 
      adipogenesis in 3T3-L1 cells.
PG  - 742-50
AB  - A novel series of oxime ligands has been synthesized that displays potent, 
      specific activation of the retinoid X receptors (RXRs). The oximes of 
      3-substituted (tetramethyltetrahydronaphthyl)carbonylbenzoic acids are readily 
      available by condensation with hydroxyl- or methoxylamine; alkylation of the 
      hydroxyl oxime provides a variety of analogues. Oximes and variously substituted 
      oxime derivatives demonstrate high binding affinity for the RXRs and specific RXR 
      activation and, hence, are called rexinoids. These oxime rexinoids are activators 
      of the RXR:PPARgamma heterodimer and are potent inducers of differentiation of 
      3T3-L1 preadipocytes to adipocytes. We have recently reported that ligands which 
      activate the RXR:PPARgamma heterodimer in this manner are effective in the 
      treatment of type II diabetes (non-insulin-dependent diabetes mellitus, NIDDM). 
      Thus, these new oxime rexinoids are potential therapeutic agents for the 
      treatment of metabolic disorders, such as obesity and diabetes.
FAU - Canan Koch, S S
AU  - Canan Koch SS
AD  - Departments of Medicinal Chemistry, Retinoid Research, and New Leads Discovery, 
      Ligand Pharmaceuticals, Incorporated, 10255 Science Center Drive, San Diego, 
      California 92121, USA.
FAU - Dardashti, L J
AU  - Dardashti LJ
FAU - Cesario, R M
AU  - Cesario RM
FAU - Croston, G E
AU  - Croston GE
FAU - Boehm, M F
AU  - Boehm MF
FAU - Heyman, R A
AU  - Heyman RA
FAU - Nadzan, A M
AU  - Nadzan AM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (4-((3,5,5,8,8-pentamethyl--5,6,7,8-tetrahydro-2-naphthyl)carbonyl)benzoic acid 
      O-methyloxime)
RN  - 0 (4-((3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl)benzoic acid 
      oxime)
RN  - 0 (Benzoates)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Ligands)
RN  - 0 (Oximes)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 0 (Triglycerides)
SB  - IM
MH  - 3T3 Cells
MH  - Adipocytes/*drug effects/metabolism/physiology
MH  - Animals
MH  - Benzoates/*chemical synthesis/chemistry/metabolism/pharmacology
MH  - Binding, Competitive
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Crystallography, X-Ray
MH  - DNA-Binding Proteins/*metabolism
MH  - Ligands
MH  - Mice
MH  - Oximes/*chemical synthesis/chemistry/metabolism/pharmacology
MH  - Receptors, Cytoplasmic and Nuclear/agonists/biosynthesis
MH  - Receptors, Retinoic Acid/*agonists/biosynthesis/metabolism
MH  - Recombinant Proteins/agonists/biosynthesis/metabolism
MH  - Retinoid X Receptors
MH  - Transcription Factors/*agonists/biosynthesis/metabolism
MH  - Transfection
MH  - Triglycerides/metabolism
EDAT- 1999/03/03 00:00
MHDA- 1999/03/03 00:01
CRDT- 1999/03/03 00:00
PHST- 1999/03/03 00:00 [pubmed]
PHST- 1999/03/03 00:01 [medline]
PHST- 1999/03/03 00:00 [entrez]
AID - jm980621r [pii]
AID - 10.1021/jm980621r [doi]
PST - ppublish
SO  - J Med Chem. 1999 Feb 25;42(4):742-50. doi: 10.1021/jm980621r.