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.
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.
Pastor
Joaquín
J
Johnson & Johnson Pharmaceutical Research & Development, Division of Janssen-Cilag, Medicinal Chemistry Department, Jarama s/n, 45007 Toledo, Spain.
Alcázar
Jesús
J
Alvarez
Rosa M
RM
Andrés
J Ignacio
JI
Cid
José M
JM
De Lucas
Ana I
AI
Díaz
Adolfo
A
Fernández
Javier
J
Font
Luis M
LM
Iturrino
Laura
L
Lafuente
Celia
C
Martínez
Sonia
S
Bakker
Margot H
MH
Biesmans
Ilse
I
Heylen
Lieve I
LI
Megens
Anton A
AA
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
D018674:Adrenergic Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D002934:Cinnamates; D007555:Isoxazoles; D017367:Selective Serotonin Reuptake Inhibitors