Pharmaceutical compositions and methods for use as agonists of nicotinic cholinergic receptors

摘要

A compound having the structure represented by the formula (I) that is capable of affecting nicotinic cholinergic receptors is disclosed, wherein: Cy represents a 5 member aromatic ring; B' represents an alkylen bridging moiety; Q is (CH2)m; Q' is (CH2)p; and Q" is (CH2)q; where m is 1, 2, 3 or 4; p is 0, 1, 2 or 3; and q is 0,1 or 2; and the values of m, p and q are selected such that the azabicyclic ring shown in the structure contains 6, 7,8 or 9 members; Zj represents a non-hydrogen substituent group selected from alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, H, F, Cl, Br, or I, NR'R",.-CF3, -OH, -CN, -NO2, -C2R', -SH, -SCH3, -N3, -SO2CH3, -OR', -SR', -C(=O)NR'R'', -NR'C(=O)R', -C(=O)R', -C(=O)OR', -(CH2)xOR', -OC(=O)R', (CR'R'')xOCH2C2R', -(CR'R'')xC(=O)R', -O(CR'R'')xC(=O)R', -C2(CR'R'')xOR', (CR'R")xNR'R", -OC(=O)NR'R" and -NR'C(=O)OR' where R' and R" are individually hydrogen, C1-C5 or substituted or unsubstituted aromatic group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, and benzyl; x is an integer from 1 to 6; j is an integer from 0 to 5, Z' represent hydrogen or lower alkyl, the dotted lines in the structure signify bonds that can be either carbon-carbon single bonds or carbon-carbon double bonds subject to the provision that only one dotted line represents a carbon-carbon double bond. A wide variety of conditions and disorders, and particularly conditions and disorders associated with dysfunction of the central and autonomic nervous systems can be treated using pharmaceutical compositions incorporating compounds of formula (I) in which an aromatic ring is bridged with an ethylenic or acetylenic unit to an azabicyclic moiety.