| abstract |
Compounds of formula (I) or enantiomers thereof, and pharmaceutically acceptable salts thereof, methods of preparation thereof, pharmaceutical compositions and therapies containing them, in particular their use for the treatment of diseases associated with reduced nicotine delivery are disclosed. Compounds of the invention enhance the efficacy of agonists at nicotine receptors.n n n <Formula I>n n n n n n n n Wherein R 1 and R 3 independently represent hydrogen or C 1 -C 4 alkyl; R 2 represents hydrogen, C 1 -C 4 alkyl or CH 2 CN; R 4 is hydrogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, CH 2 C (W) = CH 2 , (CH 2 ) n Ar, CH 2 CH = CHAr , CH 2 COPh, CH 2 CONHAr, C (U) NH (CH 2 ) m Ar, or (CH 2 ) d Y (CH 2 ) e Ar; U represents oxygen or sulfur; W represents halogen; X and Y independently represent O, S or NR 5 ; R 5 represents hydrogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, or R 3 and R 5 together form a ring; n and m are independently 0 to 4; d is 1 to 3; e is 0 to 1; Ar represents a 5- or 6-membered heterocyclic ring containing phenyl, naphthyl, or 0-4 nitrogen, 0-1 sulfur and 0-1 oxygen; Ar is optionally selected from hydrogen, halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, CN, NO 2 , CF 3 , OR 6 , NR 7 R 8 and COOR 9 Substituted with one or more substituents; R 6 , R 7 , and R 8 independently represent hydrogen, C 1 -C 4 alkyl, aryl, heteroaryl, C (O) R 10 , C (O) NHR 11 , SO 2 R 12 ; Or R 7 and R 8 together can represent (CH 2 ) j Q (CH 2 ) k , wherein Q represents O, S, NR 13 , or a bond; j is 2 to 4; k is 0 to 2; R 9 , R 10 , R 11 , R 12 and R 13 independently represent hydrogen, C 1 -C 4 alkyl, aryl or heteroaryl. |