Asymmetric total synthesis and identification of tetrahydroprotoberberine derivatives as new antipsychotic agents possessing a dopamine D1, D2 and serotonin 5-HT1A multi-action profile

2,3,9- and 2,3,11-Trisubstituted tetrahydroprotoberberines as D2 dopaminergic ligands

“…The isomeric forms selected were first chosen on the basis of previously reported results [8][9][10][11][12][13][14] and on the exploratory simulations in which the spatially preferred form for these compounds was determined (results not shown). In this context, Sun et al [23] showed that when a substituition was performed at the D ring, the S-isomers of THPBs displayed stronger affinities for the D 2 DR than their corresponding R-isomer. In addition, previous experimental findings with BTHIQs also supported this hypothesis since S forms were the preferred conformation of these compounds [13].…”

“…Indeed, coreximine, a natural tetrasubstituted THPB, and other analogues were reported as selective D 2 dopaminergic alkaloids [22]. Recently, lstepholidine analogues have been synthetized displaying a dual dopaminergic activity, partial agonism at the D 1 DR and antagonism at D 2 DR [23].…”

A method for rapid screening of interactions of pharmacologically active compounds with albumin

“…The compounds were obtained in a search for a new generation of antipsychotics following the principles of the multitarget strategy. The derivatives were designed for 5-HT 2A and D 2 receptors (the basic profile of pharmaceutical activity of atypical antipsychotics) and, additionally, for 5-HT 1A receptors [19][20][21][22][23][24][25]. With the aim of enhancing cognitive factors and memory, which might be improved by potential antipsychotics [26], the activity of the compounds was expanded to their affinity to 5-HT 1A receptors.…”

A divergent route to 9,10-oxygenated tetrahydroprotoberberine and 8-oxoprotoberberine alkaloids: synthesis of (±)-isocorypalmine and oxypalmatine

“…6,7 There have also been several reports on THPBs as central nervous system receptor (particularly dopamine receptor) ligands with potential as antipsychotic agents. 8–10 The core tetracyclic nucleus of naturally occurring THPBs is usually decorated with hydroxyl or alkoxyl substituents in the aromatic A and D rings.…”