title: N,N-Dialkylated monophenolic trans-2-phenylcyclopropylamines: novel central 5-hydroxytryptamine receptor agonists.
abstract: N,N-Dialkylated monophenolic derivatives of trans-2-phenylcyclopropylamine were synthesized and tested for central 5-hydroxytryptamine (5-HT) and dopamine (DA) receptor stimulating activity by use of a biochemical test method in rats. A hydroxy substituent in the 2- or 3-position of the phenyl ring was required for 5-HT-receptor stimulation. N,N-Diethyl or N,N-di-n-propyl substitution gave the most potent 5-HT-receptor agonists. The 4-hydroxy and 3,4-dihydroxy derivatives of trans-2-phenyl-N,N-di-n-propylcyclopropylamine were inactive at central DA and 5-HT receptors. In contrast, the corresponding 3-hydroxy derivative 18 and some of its derivatives weakly affected both DA and NE synthesis. Two of the most potent 5-HT-receptor agonists, trans-2-(2-hydroxyphenyl)-N,N-di-n-propylcyclopropylamine (8) and the 3-hydroxy isomer 18 were resolved into the enantiomers. The 1R,2S enantiomers of 8 and 18 displayed 5-HT activity, while the 1S,2R enantiomers were inactive. Compound (1R,2S)-18, but not (1R,2S)-8, weakly affected rat brain DA and NE synthesis.
authors.affiliation: Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Center, University of Uppsala, Sweden.
authors.forename: L E
authors.initials: LE
authors.lastname: Arvidsson
authors.forename: A M
authors.initials: AM
authors.lastname: Johansson
authors.forename: U
authors.initials: U
authors.lastname: Hacksell
authors.forename: J L
authors.initials: JL
authors.lastname: Nilsson
authors.forename: K
authors.initials: K
authors.lastname: Svensson
authors.forename: S
authors.initials: S
authors.lastname: Hjorth
authors.forename: T
authors.initials: T
authors.lastname: Magnusson
authors.forename: A
authors.initials: A
authors.lastname: Carlsson
authors.forename: P
authors.initials: P
authors.lastname: Lindberg
authors.forename: B
authors.initials: B
authors.lastname: Andersson
mesh_terms: D000478:Alkylation; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008968:Molecular Conformation; D010636:Phenols / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014191:Tranylcypromine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D010636:Phenols; D011985:Receptors, Serotonin; D014191:Tranylcypromine