title: Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and alpha2-adrenoceptor antagonistic activities. Part 2: Further exploration on the cinnamyl moiety.
abstract: In our previous paper we have described the synthesis of a series of 3-piperazinylmethyl-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, as novel dual 5-HT reuptake inhibitors and alpha2-adrenoceptor antagonists. That investigation led to the identification of the cinnamyl fragment as the most suitable moiety for combined activity. This paper outlines a further optimisation programme, focused on the exploration of the aromatic ring present on the cinnamyl moiety of compounds 1, 2 and 3.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, Division of Janssen-Cilag, Medicinal Chemistry Department, Jarama s/n, 45007 Toledo, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Pastor
authors.forename: Jesús
authors.initials: J
authors.lastname: Alcázar
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Alvarez
authors.forename: J Ignacio
authors.initials: JI
authors.lastname: Andrés
authors.forename: José M
authors.initials: JM
authors.lastname: Cid
authors.forename: Ana I
authors.initials: AI
authors.lastname: De Lucas
authors.forename: Adolfo
authors.initials: A
authors.lastname: Díaz
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández
authors.forename: Luis M
authors.initials: LM
authors.lastname: Font
authors.forename: Laura
authors.initials: L
authors.lastname: Iturrino
authors.forename: Celia
authors.initials: C
authors.lastname: Lafuente
authors.forename: Sonia
authors.initials: S
authors.lastname: Martínez
authors.forename: Margot H
authors.initials: MH
authors.lastname: Bakker
authors.forename: Ilse
authors.initials: I
authors.lastname: Biesmans
authors.forename: Lieve I
authors.initials: LI
authors.lastname: Heylen
authors.forename: Anton A
authors.initials: AA
authors.lastname: Megens
mesh_terms: D018674:Adrenergic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists; D002934:Cinnamates / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D018674:Adrenergic Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D002934:Cinnamates; D007555:Isoxazoles; D017367:Selective Serotonin Reuptake Inhibitors