Pyridinyl- and pyridazinyl-3,6-diazabicyclo[3.1.1]heptane-anilines: Novel selective ligands with subnanomolar affinity for αβ nACh receptors.

The cholinergic pathways in the central nervous system (CNS) of animals and humans are important for cognitive and behavioural functions. Until a few years ago, it was thought that the key molecules transducing the cholinergic message were the metabotropic muscarinic receptors, but it is now known that ionotropic neuronal nicotinic receptors (nAChRs) are also involved. Based on recent studies, we prepared a small library of novel 3-substituted-3,6-diazabicyclo [3.

Synthesis, Pharmacological Evaluation, and Docking Studies of Novel Pyridazinone-Based Cannabinoid Receptor Type 2 Ligands.

In recent years, cannabinoid type 2 receptors (CB R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB R are devoid of the psychoactive effects typically observed for CB R ligands. Based on our recent studies on a class of pyridazinone 4-carboxamides, further structural modifications of the pyridazinone core were made to better investigate the structure-activity relationships for this promising scaffold with the aim to develop potent CB R ligands.

Novel sulfenamides and sulfonamides based on pyridazinone and pyridazine scaffolds as CB receptor ligand antagonists.

A series of sulfenamide and sulfonamide derivatives was synthesized and evaluated for the affinity at CB and CB receptors. The N-bornyl-S-(5,6-di-p-tolylpyridazin-3-yl)-sulfenamide, compound 11, displayed good affinity and high selectivity for CB receptors (K values of 44.6 nM for CB receptors and >40 μM for CB receptors, respectively).

New pyridazinone-4-carboxamides as new cannabinoid receptor type-2 inverse agonists: Synthesis, pharmacological data and molecular docking.

In the last few years, cannabinoid type-2 receptor (CBR) selective ligands have shown a great potential as novel therapeutic drugs in several diseases. With the aim of discovering new selective cannabinoid ligands, a series of pyridazinone-4-carboxamides was designed and synthesized, and the new derivatives tested for their affinity toward the hCBR and hCBR. The 6-(4-chloro-3-methylphenyl)-2-(4-fluorobenzyl)-N-(cis-4-methylcyclohexyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (9) displayed high CB-affinity (KCB = 2.

Design of novel 3,6-diazabicyclo[3.1.1]heptane derivatives with potent and selective affinities for α4β2 neuronal nicotinic acetylcholine receptors.

New analogues (3a-l) of the previously described α4β2 selective ligand 3-(6-halopyridin-3-yl)-3,6-diazabicyclo[3.1.1]heptanes (2a,b) have been synthesized and their binding activity for neuronal acetylcholine receptor subtypes α4β2 and α7 were assayed.

Synthesis, pharmacological evaluation and docking studies of pyrrole structure-based CB2 receptor antagonists.

During the last years, there has been a continuous interest in the development of cannabinoid receptor ligands that may serve as therapeutic agents and/or as experimental tools. This prompted us to design and synthesize analogues of the CB2 receptor antagonist N-fenchyl-5-(4-chloro-3-methyl-phenyl)-1-(4-methyl-benzyl)-1H-pyrazole-3-carboxamide (SR144528). The structural modifications involved the bioisosteric replacement of the pyrazole ring by a pyrrole ring and variations on the amine carbamoyl substituents.