Synthesis of 7-amino-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazole derivatives displaying combined alpha2-adrenoceptor antagonistic and 5-HT reuptake inhibiting activities.
Following a program searching for dual 5-HT reuptake inhibitors and alpha(2)-adrenoceptor antagonists started at Johnson & Johnson Pharmaceutical Research & Development, we now report on the synthesis of a series of 7-amino-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazole derivatives, some of which proved to be the most potent alpha(2)-adrenoceptor blockers within this chemical class of tricyclic isoxazolines, while keeping potent 5-HT reuptake inhibiting activity.
Johnson & Johnson Pharmaceutical Research and Development, Division of Janssen-Cilag, Medicinal Chemistry Department, Toledo, Spain. iandres@prdes.jnj.com
J Ignacio
JI
Andrés
Jesús
J
Alcázar
José M
JM
Alonso
Ana I
AI
De Lucas
Laura
L
Iturrino
Ilse
I
Biesmans
Anton A
AA
Megens
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D007555:Isoxazoles / Q000737:chemistry*; D008297:Male; D011714:Pyrans / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007555:Isoxazoles; D011714:Pyrans; D017367:Selective Serotonin Reuptake Inhibitors; C512496:7-amino-3a,4-dihydro-3H-(1)benzopyrano(4,3-c)isoxazole