Allosteric modulators of nicotinic acetylcholine receptors

A compound having the formula I

• or a pharmaceutically acceptable salt thereof, wherein:
• p is 1 or 2,
• q is 0, 1 or 2,
• each X is independently O, S, CRaRb, or NRc, provided that when p is 2 at least one X is CRaRb;
• w is 0, 1, 2, 3 or 4;
• Z is CRd or N;
• each Ra and Rb is independently hydrogen, hydroxy, (C1-C4)alkoxy, halogen, cyano, (C1-C4)alkyl, or (C1-C4)haloalkyl;
• Rc is hydrogen, (C1-C4)alkyl, (C1-C6)haloalkyl, S(O)2(C1-C4)alkyl, or —C═O(C1-C4)alkyl;
• Rd is hydrogen, hydroxy, (C1-C4)alkoxy, halogen, cyano, (C1-C4)alkyl, or (C1-C4)haloalkyl;
• each R5 is independently halogen, (C1-C4)alkyl, cyano, or (C1-C4)haloalkyl;
• y is 0, 1, 2, or 3;
• each R3 is independently selected from halogen, hydroxy, (C1-C6)alkyl, cyano, (C1-C6)alkoxy, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, aryl, and heteroaryl, wherein said alkyl or alkoxy substituted with 0, 1, 2, 3, 4, or 5, and wherein said aryl or heteroaryl is substituted with 0, 1, 2, or 3 R6 substituents;
• each R6 is independently (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl, heterocycloalkyl, or aryl(C1-C6)alkyl, and wherein said alkyl or alkoxy is substituted with 0, 1, 2, 3, 4 or 5 fluoro;
• R4 is hydrogen or (C1-C6)alkyl;
• each R2 is hydrogen or (C1-C6)alkyl;
• R1 is independently selected from hydrogen, (C1-C6)alkoxy, (C1-C6)haloalkyl, halogen, (C1-C6)heteroalkyl, (C1-C6)alkoxy(C1-C6)alkyl, (C1-C6)alkyl, (C3-C6)cycloalkyl, heterocycloalkyl, aryl, arylC1-6alkyl, —(C═O)OC1-4alkyl, and hydroxyC1-4alkyl;
• each R1 and R together with the carbon atom to which they are attached may join together to form a ring, wherein said ring is substituted with 0, 1, 2, 3, or 4 substituents selected from:
• hydroxy, halogen, methoxy, CF3, and C1-6alkyl;
• A is aryl, heteroaryl, heterocycloalkyl, or (C1-C5)cycloalkyl, wherein A is substituted with 0, 1, 2, 3, or 4 R7 substitutents;
• each R7 is independently selected from hydrogen, halogen, hydroxy, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy(C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, aryl, heteroaryl, (C1-C6)alkyl, aryl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C4)alkyl, (C3-C6)cycloalkyl(C1-C6)alkoxy, heterocycloalkyl, heterocycloalkyl(C1-C6)alkyl, and heteroaryloxy, wherein each R7 independently is substituted with 0, 1, 2, or 3 R8;
• and
• each R8 is independently selected from halogen, (C1-C6)alkoxy(C1-C6)alkyl, (C1-C6)alkoxy, and (C1-C6)alkyl.