New 5-HT(1A) receptor ligands containing a N'-cyanoisonicotinamidine nucleus: synthesis and in vitro pharmacological
Ferdinando Fiorino1, Beatrice Severino, Francesca De Angelis
1Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Via D. Montesano, 49, 80131 Napoli, Italy.
Abstract:
N'-cyanoisonicotinamidine derivatives, linked to an arylpiperazine moiety, were prepared to identify highly selective and potent 5-HT(1A) ligands as potential pharmacological tools in studies of wide spread psychiatric disorders. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to be critical in order to have affinity on 5-HT(1A) receptor and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed affinity in nanomolar and subnanomolar range at 5-HT(1A) and moderate to no affinity for other relevant receptors (5-HT(2A), 5-HT(2C), D(1), D(2), alpha(1) and alpha(2)). N'-cyano-N-(3-(4-(pyridin-2-yl)piperazin-1-yl)propyl)isonicotinamidine (4o) with K(i)=0.038 nM, was the most active and selective derivative for the 5-HT(1A) receptor with respect to other serotoninergic, dopaminergic and adrenergic receptors.
Related Concept Videos
Cholinergic Receptors: Nicotinic
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
The direct-acting...
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Drug-Receptor Interaction: Agonist
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.


