Publications

7-Azabicyclo[2.2.1]-heptane and -heptene derivs. I (R1, R4 = H, alkyl, substituted alkyl; R2 = H, alkyl, alkenyl, heterocyclyl, heterocyclylthio, amino heterocyclylamino, carbamoyl, heterocyclylcarbonyl, heterocyclylalkyl, etc.; R3, R5, R6 = H alkyl substituted alkyl, amino, halo, CO2H, alkoxycarbonyl, alkylsulfonyl, aryl, heteroaryl, arylsulfonyl, etc.; R2R3 may form a cyclic system; R7 = H, alkyl, substituted alkyl, aryl, cycloalkyl) were prepd. to treat disorders assocd. with a decrease or increase in cholinergic activity. Thus, (2-chloro-5-pyridyl)(phenylsulfonyl)acetylene was treated with N-carbomethoxypyrrole to give 7-carbomethoxy-2-(2-chloro-5-pyridyl)-3-(phenylsulfonyl)-7-azabicyclo[2.2.2]-2,5-diene, which underwent reductive dephenylsulfonylation with sodium dihydrophosphate and sodium amalgam followed by hydrogenation and decarbomethoxylation to give (±)-epibatidine and endo-epibatidine. (±)-Epibatidine was treated with formamidinate hydrochloride to give N-formamidinylepibatidine dichydrochloride. N-formamidinylepibatidine dichydrochloride at 10-7 M had 104% inhibition in binding to the acetylcholine nicotinic receptor using a std. binding assay. [on SciFinder(R)]