POSITIVE MODULATORS OF NICOTINIC RECEPTOR AGONISTS.

摘要

A compound of Formula (I) wherein R1 and R3 independently represent hydrogen, or C1 C4 alkyl; R2 represents hydrogen, C1 C4 alkyl, or CH2CN; R4 represents hydrogen, C1 C4 alkyl, C2 C4 alkenyl, C2 C4 alkynyl, CH2C(W)=CH2, (CH2) nAr, CH2CH=CHAr, CH2COPh, CH2CONHAr, C(U)NH(CH2) mAr, or (CH2) dY(CH2) eAr; U represents O, or S; W represents halogen; X and Y independently represent O, S, or NR5; R5 represents hydrogen, C1 C4 alkyl, C2 C4 alkenyl; or together R3 and R5 form a ring; n and m independently are 0 4; d is 1 3; e is 0 1; Ar represents phenyl, naphthyl or 5 or 6 membered heterocyclic ring containing zero to four nitrogens, zero to one sulfurs and zero to one oxygens; Ar is optionally substituted with one or more substituents selected from: hydrogen, halogen, C1 C4 alkyl, C2 C4 alkenyl, C2 C4 alkynyl CN, NO2, CF3, OR6, NR7R8, COOR9; R6, R7 and R8 are independently hydrogen, C1 C4 alkyl, aryl, heteroaryl, C(O)R10, C(O)NHR11, SO2R12, or; R7 and R8 together may be (CH2)jQ(CH2) k where; Q is O, S, NR13 or a bond; j is 2 4; k is 0 2; R9, R10, R11, R12 and R13 are independently hydrogen, C1 C4 alkyl, aryl or heteroaryl; or an enantiomer thereof, and pharmaceutically acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy, especially for treatment of conditions associated with reductions in nicotinic transmission. The compounds of the invention enhance the efficacy of agonists at nicotinic receptors.