(+)-3-[2-(Benzo[ b ]thiophen-2-yl)-2-oxoethyl]-1-azabicyclo[2.2.2]octane as potent agonists for the α7 nicotinic acetylcholine receptor

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

“…As an example, the (+)-(2-benzothienyl)-2-oxoethyl derivative 46 a (X = CH 2 CO, Ar = 2-benzothiophene) showed affinity in the nanomolar range and agonistic properties in PC12 cells higher than 44 a. [102] When the azabicyclic moiety is a quinuclidine, the spacer can be an oxazolidinone ring as in AR-R17779 (47 a, R= H), a full agonist at the a7* receptor. Whereas minor structural changes, such as N-alkylation, are reported to reduce affinity and/or selectivity, [103] the introduction of an aryl moiety on the carbamate nitrogen, to give 48, considerably improved activity: the 5'chlorothiophenyl derivative 48 a (X = Cl) shows a binding affinity 38 times higher than 47 a for a7* receptor, and high selectivity for this subtype with respect to a4b2* or the muscle-type nAChR.…”

Discovery ofN-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an Agonist of the α7 Nicotinic Acetylcholine Receptor, for the Potential Treatment of Cognitive Deficits in Schizophrenia: Synthesis and Structure−Activity Relationship

“…The glass was dissolved in 1 M hydrochloric acid in methanol (1.6 mL) and stirred for 2 h. Isopropyl alcohol (2 mL) and ether (4 mL) were added to enhance precipitation. (20). 1H-Pyrrolo[2,3-c]pyridine-5-carboxylic acid (250 mg, 1.54 mmol) was combined with diisopropylethylamine (0.80 mL, 4.6 mmol) and (R)-(3)-aminoquinuclidine dihydrochloride (309 mg, 1.55 mmol) in tetrahydrofuran (8 mL) and cooled in an ice bath.…”

Metalated Heterocycles in Organic Synthesis: Recent Applications

“…45 In addition, benzo [b]thiophene can be similarly lithiated at C-2, being used as nucleophile, for instance, in alkylations 46 and azidations, 47 as well as in reactions with Weinreb amides in the synthesis of agonists for the α7 nicotinic acetylcholine receptor. 48 Furthermore, 2-iodoseleniophenes and 2-iodotellurophenes have been obtained by direct 2-lithiation of the corresponding chalcogenophenes and subsequent reaction with iodine. 49 …”