Nicotinic acetylcholine receptor ligands

A compound having low P-glycoprotein-mediated efflux according to formula I:

• wherein:
• D represents oxygen or sulfur;
• E represents a single bond, oxygen, sulfur, or NR1;
• Ar1 is selected from an ortho-substituted 5- or 6-membered aromatic or heteroaromatic ring having 0, 1 or 2 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or 1 sulfur atoms, or selected from an ortho-substituted 8-, 9- or 10-membered fused aromatic or heteroaromatic ring system having 0, 1, 2 or 3 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or 1 sulfur atoms, said aromatic or heteroaromatic rings or ring systems having ortho-substituents selected from —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, halogen, —CN, —NO2, —CF3, —S(O)nR2, —NR2R3, —CH2NR2R3, —OR2, —CH2OR2 or —CO2R4;
• Ar2 is selected from a 5- or 6-membered aromatic or heteroaromatic ring having 0, 1 or 2 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or 1 sulfur atoms;
• where Ar2 is unsubstituted or has 1, 2 or 3 substituents independently selected from —R2, —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, halogen, —CN, —NO2, —CF3, —S(O)nR2, —NR2R3, —CH2NR2R3, —OR2, —CH2OR2 or —CO2R4;
• R2 and R3 are independently selected at each occurrence from hydrogen, —C1-C4alkyl, aryl, heteroaryl, —C(O)R4, —C(O)NHR4, —CO2R4 or —SO2R4, or
• R2 and R3 in combination is —(CH2)jG(CH2)k—wherein G is oxygen, sulfur, NR4, or a bond;
• j is 2, 3 or 4;
• k is 0, 1 or 2;
• n is 0, 1 or 2, and
• R4 is independently selected at each occurrence from hydrogen, —C1-C4alkyl, aryl, or heteroaryl, and
• stereoisomers, enantiomers, in vivo-hydrolysable precursors and pharmaceutically-acceptable salts thereof.