Synthesis and nicotinic binding of novel phenyl derivatives of UB-165. Identifying factors associated with α7 selectivity

Central Nicotinic Receptors: Structure, Function, Ligands, and Therapeutic Potential

“…Karig et al have synthesized analogues of 26 a with general formula 26 carrying a phenyl ring on the pyridine moiety: the introduction of a phenyl ring in the 2', 5', and 6'-position reduced affinity for the a4b2* and the a3b4 subtypes, but the 4'-phenyl analogue showed a three-fold increased affinity for the a7* subtype compared to 26 a, suggesting a possible area of structural modification to improve affinity/selectivity for this subtype. [83] It would be interesting to determine the functional properties of these analogues as it is known that the introduction of a phenyl moiety on the pyridine ring on epibatidine (postiton 3') or on 2 a (position 5') gave high affinity compounds endowed with antagonistic properties. [84,85] Compounds 27 and 28 are deschloro-epibatidine analogues in which the azanorbornane and the pyridine rings are connected through an isoxazolidine moiety.…”

The Chemistry and Pharmacology of Anatoxin-a and Related Homotropanes with respect to Nicotinic Acetylcholine Receptors

“…A third generation of UB-165 analogues was reported in 2003 and these were based on retaining core 3′-substituted pyridyl unit but allowing additional (phenyl) substitution on the heteroaryl component [ 78 ]. Locating an additional phenyl residue at all four possible positions was only possible because of the flexibility associated with the synthetic chemistry that had been developed in the course of developing methodology for UB-165.…”

Synthesis of New Functionally Substituted 9-Azabicyclo[4.2.1]nona-2,4,7-trienes by Cobalt(I)-Catalyzed [6π + 2π]-Cycloaddition of N-Carbocholesteroxyazepine to Alkynes

“…Although some 9-azabicyclo[4.2.1]nonane derivatives were described for the first time back in the 1970s [ 1 , 2 , 3 , 4 , 5 ], they are still attracting the attention of synthetic chemists [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ], largely related to their pronounced biological activity and high pharmacological potential [ 14 ]. The 9-azabicyclo[4.2.1]nonane cage is a key structural component of several important natural and synthetic alkaloids (anatoxin-a [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ], pinnamine [ 13 , 16 , 17 ], bis-homoepibatidine [ 18 , 19 ], and UB-165 [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]), possessing properties of nicotinic acetylcholine receptor agonists in the central and vegetative nervous systems ( Figure 1 ). Therefore, various analogues containing the 9-azabicyclo[4.2.1]nonane cage are actively being studied by pharmaceutical scientists as potential medicinal agents for the treatment of severe neurological disorders such as Parkinson’s and Alzheimer’s diseases, schizophrenia, and depression [ 21 , 22 , 23 , 24 , 25 , 26 ,…”