Preparation and pharmacological profile of 2-trifluoromethyl-benzo(8,9)-1,3-diaza-spiro (4,6)-undeca-2,8-diene and its enantiomers as new anti-obesity agents.
Obesity affects a large population of industrialised countries in which occurrence may reach 20%. The multifactorial aspect of the pathology prompted us to develop new entities associating favourable effects on both eating behaviour and metabolic parameters. The 2-trifluoromethyl-benzocyloheptene moiety has been combined with an imidazoline ring for synthesising a new anti-obesity agent. Preparation of the already known 2-trifluoromethyl-5-H-6,7,8,9-tetrahydro-benzocyclohepten-7-one as a key intermediate has been significantly improved, and an enantioselective procedure has been developed for imidazoline construction. The syntheses and pharmacological profiles of the compounds are presented here, particularly the effects on eating behaviour and body weight, and the putative involvement of the L-enantiomer in the treatment of metabolic diseases.
Boussard
M F
MF
Division of Medicinal Chemistry, Institut de Recherches Servier, Suresnes, France.
Guette
J P
JP
Wierzbicki
M
M
Beal
P
P
Fournier
J
J
Boulanger
M
M
Della-Zuana
O
O
Duhault
J
J
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001067:Appetite Depressants / Q000138:chemical synthesis / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005464:Fluorobenzenes / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011924:Rats, Zucker; D011955:Receptors, Drug / Q000187:drug effects; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism
C420244:2-trifluoromethylbenzo(8,9)-1,3-diaza-spiro(4,6)-undeca-2,8-diene; D019440:Anti-Obesity Agents; D001067:Appetite Depressants; D015306:Biogenic Monoamines; D005464:Fluorobenzenes; D011955:Receptors, Drug; D013141:Spiro Compounds