title: 8-Amino-5-nitro-6-phenoxyquinolines: potential non-peptidic neuropeptide Y receptor ligands.
abstract: The synthesis and pharmacological evaluation of analogues of PD 160170, a neuropeptide Y1 (NPY) receptor antagonist are reported. Phamacomodulation of this 8-amino-5-nitro-6-phenylsulfonylquinoline was carried out by replacing the sulfone moiety by oxygen. The corresponding ethers 11-16 were obtained by nucleophilic substitution of 8-acetamido-6-chloro-5-nitroquinoline 4 with phenols, followed by acidic hydrolysis of the intermediary amides 5-10. The test compounds 11-16 exerted no appreciable Y1 activity and they were also inactive in terms of Y5 receptor binding; their IC50 values were >1 microM and 10 microM, respectively. The dramatic decrease in potency resulting from replacement of the sulfone function by an ether was confirmed by IP administration of 16 to ob/ob mice; after a 4-day administration, no decrease in food consumption or weight was observed.
authors.affiliation: Laboratoire de Chimie Thérapeutique et de Chimie Organique, UPRES EA 1155, Faculté de Pharmacie, 1 rue Gaston Veil-F44035 Nantes cedex 01, France. gaetane.wielgosz-collin@isomer.univ-nantes.fr
authors.forename: Gaetane
authors.initials: G
authors.lastname: Wielgosz-Collin
authors.forename: Muriel
authors.initials: M
authors.lastname: Duflos
authors.forename: Patricia
authors.initials: P
authors.lastname: Pinson
authors.forename: Guillaume
authors.initials: G
authors.lastname: Le Baut
authors.forename: Pierre
authors.initials: P
authors.lastname: Renard
authors.forename: Caroline
authors.initials: C
authors.lastname: Bennejean
authors.forename: Jean
authors.initials: J
authors.lastname: Boutin
authors.forename: Michele
authors.initials: M
authors.lastname: Boulanger
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000737:chemistry / Q000494:pharmacology; D001835:Body Weight; D004353:Drug Evaluation, Preclinical; D005247:Feeding Behavior / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008024:Ligands; D051379:Mice; D008820:Mice, Obese; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry
chemical_list: D001067:Appetite Depressants; D008024:Ligands; D011804:Quinolines; D017476:Receptors, Neuropeptide Y; D013450:Sulfones