Chain-modified pyridino-N substituted nicotine compounds for use in the treatment of CNS pathologies

A compound including resolved enantiomers and diastereoisomers thereof selected from a formula consisting of formula (V) and formula (VI):

• 5
• wherein
• Q is selected from the group consisting of a straight chain or branched alkylene group having 1-3 carbon atoms, a substituted alkenylene group having 1-3 carbon atoms, C(O), O, C(S), S, S(O) and S(O)2 containing alkylene moiety, provided that any heteroatom contained in Q is separated from N by at least one carbon atom;
• R1 is selected from the group consisting of hydrogen, lower straight chain or branched alkyl, cycloalkyl, substituted cycloalkyl, aryl, aralkyl, or heterocyclic group;
• R2, Z1 and Z4 are each independently selected from the group consisting of hydrogen, lower alkyl, lower branched alkyl, lower alkenyl, and lower branched alkenyl;
• A and B are selected from nitrogen or carbon with the proviso that when A or B is nitrogen, R3 or R4 cannot be present;
• R3, R4, Z2 and Z3 are each independently selected from the group consisting of hydrogen;
• alkyl;
• substituted alkyl;
• cycloalkyl;
• substituted cycloalkyl;
• substituted alkenyl;
• substituted alkenyl;
• alkynyl;
• substituted alkynyl;
• aryl;
• substituted aryl;
• alkylaryl;
• substituted alkylaryl;
• arylalkyl;
• substituted arylalkyl;
• arylalkenyl;
• substituted arylalkenyl;
• arylalkynyl;
• substituted arylalkynyl;
• heterocyclic;
• substituted heterocyclic;
• trifluoromethyl;
• halogen;
• cyano;
• nitro;
• S(O)Y1, S(O)2Y1, S(O)2Y1 or S(O)2NHY1, wherein each Y1 is independently hydrogen, lower alkyl, alkenyl, alkynyl or aryl, with the proviso that when R3, R4 or R5 is S(O)Y1,Y1 is not hydrogen, and with the further proviso that when Y1 is alkenyl or alkynyl, the site of unsaturation is not conjugated with a heteroatom;
• C(O)Y2, wherein Y2 is selected from hydrogen, alkyl, substituted alkyl, alkoxy, alkylamino, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, aryloxy, arylamino, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, heterocyclic, substituted heterocyclic or trifluoromethyl, with the proviso that the carbonyl functionality is not conjugated with an alkenyl or alkynyl functionality;
• OY3 or N(Y3)2 wherein each Y3 is independently selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, heterocyclic, substituted heterocyclic, acyl, trifluoromethyl, alkylsulfonyl or arylsulfonyl, with the proviso that OY3 or N(Y3)2 functionality is not conjugated with an alkenyl or alkynyl functionality;
• SY4 wherein Y4 is selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, heterocyclic, substituted heterocyclic or trifluoromethyl, with the proviso that the SY4 functionality is not conjugated with an alkenyl or alkynyl functionality;
• or R3 and R4 together form a three to eight membered saturated or unsaturated ring, wherein from one to three carbon atoms of said ring may optionally and independently be replaced by a nitrogen, oxygen or sulfur atom, and wherein said rings may optionally be substituted with one or more substituents that are defined as Z3 and Z4;
• or either Z1 and Z2 or Z1 and Z3 together form a fused ring structure;
• or either Z2 and Z4 or Z3 and Z4 together form a spiro ring structure;
• R5 is selected from the group consisting of alkyl;
• substituted alkyl;
• cycloalkyl;
• substituted cycloalkyl;
• alkenyl;
• substituted alkenyl;
• alkynyl;
• substituted alkynyl;
• aryl;
• substituted aryl;
• arylalkyl;
• substituted arylalkyl;
• arylalkenyl;
• substituted arylalkenyl;
• arylalkynyl;
• substituted arylalkynyl;
• heterocyclic;
• substituted heterocyclic;
• S(O)Y1, S(O)2Y1, S(O)2OY1 or S(O)2NHY1, wherein each Y1 is independently hydrogen, lower alkyl, alkenyl, alkynyl or aryl, with the proviso that when R3, R4 or R5 is S(O)Y1, Y1 is not hydrogen, and further with the proviso that when Y1 is alkenyl or alkynyl, the site of unsaturation is not conjugated with a heteroatom;
• C(O)Y2, wherein Y2 is selected from hydrogen, alkyl, substituted alkyl, alkoxy, alkylamino, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, aryloxy, arylamino, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, heterocyclic, substituted heterocyclic or trifluoromethyl, with the proviso that the carbonyl functionality is not conjugated with an alkenyl or alkynyl functionality;
• OY3 or N(Y3)2 wherein each Y3 is independently selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, heterocyclic, substituted heterocyclic, acyl, trifluoromethyl, alkylsulfonyl or arylsulfonyl, with the proviso that the OY3 or N(Y3)2 functionality is not conjugated with an alkenyl or alkynyl functionality;
• SY4 wherein Y4 is selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, heterocyclic, substituted heterocyclic or trifluoromethyl, with the proviso that the SY4 functionality is not conjugated with an alkenyl or alkynyl functionality;
• and with the further proviso that when A and B are carbon, R5 is not N-alkyl or branched alkyl with 2-19 carbon atoms, cycloalkyl, aralkyl, N-alkenyl or alkenyl with 2-19 carbon atoms, or N-alkynyl or branched alkynyl with 2 to 19 carbon atoms;
• R6 is hydrogen;
• X is selected from the group consisting of Cl, Br, I, HSO4, ½SO2, CH3SO3, p-TsO and CF3SO3;
• and
• Y is selected from the group consisting of 2Cl, 2Br, 2I, 2HSO4, SO2, 2CH3SO3, 2p-TsO and 2CF3SO3.