Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and α2-adrenoceptor antagonistic activities. Part 2: Further exploration on the cinnamyl moiety

Efficient Catalytic Synthesis of Condensed Isoxazole Derivatives via Intramolecular Oxidative Cycloaddition of Aldoximes

“…The 1,3-dipole cycloaddition reaction is one of the most powerful methods to construct five-membered heterocycles [16][17][18][19][20][21][22][23][24][25][26]. The cycloaddition of nitrile oxides with alkenes and acetylenes is often used in the synthesis of isoxazoles and isoxazolines [27][28][29][30][31][32][33][34][35][36][37]. However, nitrile oxides are unstable species usually generated in situ from aldoximes under appropriate conditions [38][39][40].…”

Discovery of a New Series of Centrally Active Tricyclic Isoxazoles Combining Serotonin (5-HT) Reuptake Inhibition with α2-Adrenoceptor Blocking Activity

“…We identified some “cinnamyl-like” fragments that increased the activity at both or at least one of the targets, and we also identified the most potent enantiomers within this series of compounds . We have also recently described a further optimization program focused on the exploration of the aromatic ring present on the cinnamyl moiety . In this article we describe the synthetic methods used to prepare the most promising compounds in this series, as well as primary pharmacological evaluation of the most active enantiomers.…”

“…26 We have also recently described a further optimization program focused on the exploration of the aromatic ring present on the cinnamyl moiety. 27 In this article we describe the synthetic methods used to prepare the most promising compounds in this series, as well as primary pharmacological evaluation of the most active enantiomers. We also report the synthesis and primary pharmacological activity of novel 3,3a,4,5-tetrahydroquinolino [4,3-c]isoxazoles and 3,3a,4,5-tetrahydronaphthaleno [4,3-c]isoxazoles in order to determine whether the presence of a nitrogen or carbon atom at 5-position of the tricyclic core structure would play a relevant role in the biological activity profile of these derivatives.…”

Novel Approach towards the Synthesis of 3,3a,4,5-Tetrahydroquinolino[4,3-c]isoxazole Derivatives: Application to the Preparation of Previously Unattainable 3a,4-Dihydroazabenzopyrano[4,3-c]isoxazole Scaffolds

“…[1][2][3] This class of compounds presents an interesting combination of activities acting as dual a 2 -adrenoceptor antagonists and 5-HT reuptake inhibitors. Several research programs around these structures have been initiated at Johnson & Johnson Pharmaceutical Research and Development to fully explore the SAR of this family of compounds.…”