Aporphines. 11. Synthesis and dopaminergic activity of monohydroxyaporphines. Total synthesis of (+-)-11-hydroxyaporphine, (+-)-11-hydroxynoraporphine, and (+-)-11-hydroxy-N-propylnoraporphine

Advances Towards the Synthesis of Aporphine Alkaloids: C‐Ring Formation via Approaches Based on One‐ and Two‐Bond Disconnections

“…employing similar routes to that presented in Scheme 8, which were subjected to pharmacological evaluation in order to determine their emetic, dopaminergic, and antinociceptive activities. [74][75][76][77][78][79] Neumeyer and Granchelli published a communication in 1970 [80] and a full paper in 1974 [81] addressing the synthesis of (�)-7-hydroxyaporphine ((�)-43), (�)-7-hydroxynoraporphine ((�)-44), and 6a,7-dehydronoraporphine (45) involving the simultaneous protection of the labile hydroxyl group and secondary amino group via the formation of an oxazolonecontaining intermediate. 1-(2-Nitrobenzyl)isoquinoline (35) was oxidized to give ketone 37, which was then reduced to alcohol 38.…”

Synthesis, functional and binding profile of (R)-apomorphine based homobivalent ligands targeting the dopamine D2 receptor

“…(a) tolerated in binding assays at DA receptors; 18 and, (b) shown to retain agonism at DA receptors in vivo. 19 A variety of spacer groups have been reported in the literature, varying from polymethylene, polyamide, polyethyleneglycol, polyproline, and piperazine containing spacer portions, all with varying degrees of exibility and lipophilicity. 5 The spacer portion of the homobivalent ligands herein were designed with polymethylene chains linked via amide bonds to the respective pharmacophores.…”

Further SAR study on 11-O-substituted aporphine analogues: Identification of highly potent dopamine D3 receptor ligands

“…27 Alkylation of phenol 5 with propargyl bromide provided 11-prop-2-ynyloxy N-propylnoraporphine 4 in 97% yield (Scheme 1). Alkylation of commercially available arylpiperazines with an appropriate chloroalkyl bromide followed by axidization with NaN 3 gave corresponding azide precursors 6a-e in 52-75% overall yields.…”