New series of N-substituted phenyl ketone oxime ethers: synthesis and bovine beta3-adrenergic agonistic activities.
A series of ten novel phenyl ketone oxime ethers substituted on the terminal nitrogen by either 1,3 benzodioxole, alkyl, aralkyl or aryl moiety were synthesized and tested for their activity at bovine beta3-adrenoceptors. The best compound, which was the benzodioxole dicarboxylate derivative, showed potent beta3-adrenergic agonistic activities in Chinese hamster ovary cells expressing the bovine beta3-adrenoceptors with Kact and Ki values better than compound CL 316,243 used as reference (14 +/- 6 nM and 203 +/- 71 nM, respectively). In this series three compounds showed an antagonistic activity. Structure-activity relationships in these ketone oxime ethers are discussed.
El-Hadri
A
A
Départment de Pharmacochimie Moléculaire, UMR 5063, Laboratoire de Chimie Organique, UFR de Pharmacie, Université Joseph Fourier, Meylan, France.
Nicolle
E
E
Leclerc
G
G
Pietri-Rouxel
F
F
Strosberg
A D
AD
Archimbault
Ph
P
D000262:Adenylyl Cyclases / Q000378:metabolism; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D004149:Dioxoles / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004987:Ethers / Q000138:chemical synthesis* / Q000494:pharmacology*; D020120:Iodocyanopindolol / Q000378:metabolism; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004149:Dioxoles; D004987:Ethers; D010091:Oximes; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D020120:Iodocyanopindolol; D000262:Adenylyl Cyclases