Aryl-8-azabicyclo[3.2.1]octanes for the treatment of depression

A compound of formula I:

• wherein:
• A is an optional residue which combines with the carbon atoms to which it is attached to complete a cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, dioxinyl, pyrrolyl, imidazolyl, pyridinyl, pyridazynyl or pyrimidinyl group;
• X is NH or S;
• n is 0-3;
• Ar1 is phenyl or pyridyl substituted with 0-2 C1-C3 alkyl, C1-C3 alkoxy, halo, cyano, nitro, trifluoromethyl, difluoromethyl, hydroxyl, or trifluoromethoxy groups;
• and,
• Ar2 is indolyl, benzimidazolyl, naphthyl, anthracenyl, phenanthrenyl, benzofuryl, or benzothienyl, substituted with 0-2 C1-C3 alkyl, C1-C3 alkoxy, halo, cyano, nitro, trifluoromethyl, difluoromethyl, hydroxyl, or trifluoromethoxy groups,
• and all crystalline forms or a pharmaceutically acceptable salt thereof.

A compound of formula:

• wherein:
• A is a residue which combines with the carbon atoms to which it is attached to complete a cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, dioxinyl, pyrrolyl, imidazolyl, pyridinyl, pyridazynyl or pyrimidinyl group;
• X is O;
• n is 0-3;
• Ar1 is phenyl or pyridyl substituted with 0-2 C1-C3 alkyl, C1-C3 alkoxy, halo, cyano, nitro, trifluoromethyl, difluoromethyl, hydroxyl, or trifluoromethoxy groups;
• and,
• Ar2 is phenyl substituted with 0-2 C1-C3 alkyl, C1-C3 alkoxy, halo, cyano, nitro, trifluoromethyl, difluoromethyl, hydroxyl, or trifluoromethoxy groups,
• and all crystalline forms or a pharmaceutically acceptable salt thereof.

A compound of formula I:

• wherein:
• A is a residue which combines with the carbon atoms to which it is attached to complete a cyclopentyl or pyrrolyl group;
• X is O;
• n is 1 to 2;
• Ar1 is phenyl substituted with 0-2 C1-C3 alkyl, C1-C3 alkoxy, halo, cyano, nitro, trifluoromethyl, difluoromethyl, hydroxyl, or trifluoromethoxy groups;
• and,
• Ar2 is naphthyl substituted with 0-2 C1-C3 alkyl, C1-C3 alkoxy, halo, cyano, nitro, trifluoromethyl, difluoromethyl, hydroxyl, or trifluoromethoxy groups;
• and all crystalline forms or a pharmaceutically acceptable salt thereof.

A compound selected from the group consisting of:

• 4-[2-(3-Naphthalen-2-yl-8-aza-bicyclo[3.2.1]oct-2-en-8-yl)-ethoxy]-1-H-indole;
• 8-[2-(Indan-4-yloxy)-ethyl]-3-naphthalen-2-yl-8-azabicyclo[3.2.1]oct-2-ene;
• 4-{2-[3-(6-Methoxy-naphthalen-2-yl)-8-aza-bicyclo[3.2.1]oct-2-en-8-yl]-ethoxy}-1H-indole;
• 4-[2-(3-Naphthalen-2-yl-8-aza-bicyclo[3.2.1]oct-8-yl)-ethoxy]-1H-indole;
• 4-[3-(3-Naphthalen-2-yl-8-aza-bicyclo[3.2.1]oct-2-en-8-yl)-propoxy]-1H-indole;
• and all crystalline forms or pharmaceutically acceptable salts thereof.

A compound of formula I:

• wherein:
• A is a residue which combines with the carbon atoms to which it is attached to complete a pyrrolyl group;
• X is O;
• n is 1 to 2;
• Ar1 is phenyl substituted with 0-2 C1-C3 alkyl, C1-C3 alkoxy, halo, cyano, nitro, trifluoromethyl, difluoromethyl, hydroxyl, or trifluoromethoxy groups;
• and,
• Ar2 is indolyl substituted with 0-2 C1-C3 alkyl, C1-C3 alkoxy, halo, cyano, nitro, trifluoromethyl, difluoromethyl, hydroxyl, or trifluoromethoxy groups;
• and all crystalline forms or a pharmaceutically acceptable salt thereof.