Arylalkylamine-, β-carboline-, quinolizine- and azecine-derived compounds and their in vitro interaction with the ionotropic 5-HT3 receptor: search for new lead structures

Abstract

Specific serotonin receptor agonists and antagonists are marketed with respect to various diseases, most prominently severe emesis. To identify new chemical classes with affinity for the serotonin 5-HT3 channel, several compounds were synthesized which can be structurally classified as arylalkylamines, azecines, quinolizines and beta-carbolines. These were tested in three models: (1) direct effect on ileum (overall model for contracting or relaxant effect), (2) antiserotoninergic effects on rat ileum (crude serotonin model), (3) inhibitory effect on the 5-HT, receptor channel complex expressed in N1E-115 cells (serotonin-induced [14C]guanidinium influx (specific model)). Key findings and conclusion: Several azecine-type compounds exhibit 5-HT3 receptor channel antagonistic properties at concentrations close to that of tropisetron (used as a positive control) and might serve as potential lead structures for the development of further 5-HT3 channel receptor antagonists.

Atom-Economical Construction of a Rare 6,7-Dihydropyrido[3′,2′:4,5]imidazo[1,2-d][1,4]benzodiazepine Scaffold

“…1 The 2-aminoethyl side chain in 2 (derived from the imidazoline bismethylene moiety in 1) means that these compounds may be considered as analogues of tryptamine. 2 We reasoned that the primary amine functionality could be viewed not only as a site for introducing additional side-chain diversity (e.g., via reductive amination) but also as providing an opportunity for linking the imidazo [4,5-b]pyridine moiety to the 2-aryl substituent (via intramolecular aryl halide amination) and thus forming a tetracyclic scaffold 3 (Scheme 1). A preliminary review of the literature related to 3 revealed its novelty.…”

One-Pot Organocatalytic Enantioselective Domino Double-Michael Reaction and Pictet-Spengler–Lactamization Reaction. A Facile Entry to the “Inside Yohimbane” System with Five Contiguous Stereogenic Centers

“…Examples of natural and synthetic compounds bearing the dodecahydrobenz[ a ]indolo[3,2- h ]quinolizine skeleton have shown various biological activities (Figure ). Manadomanzamine A and manadomanzamine B have anti HIV, antifungal, antimycobacterial, and cytotoxic activities; 21a-homo-14-nor-yohimba-15,17,19-triene has high affinity for the α1 adrenergic receptors; 2,3,4,4aβ,5,6,7,8,13,13bβ-decahydro-1 H -6a,13-diazaindeno[1,2- c ]phenanthren-13cβ-ol has high affinity for the α2C-adrenoceptor; pentacyclic benzindoloquinolizine has been reported to have antiserotoninergic effects . The inside α-yohimbine intermediates have been prepared following the method for the total synthesis of reserpine and α-yohimbane .…”