Substituted aminoquinuclidine compounds

A compound of the Formula (Ia):

• 14
• wherein R1, R2, R3, n and Z are selected from:
• 6 R1 R2 R3 n Z Config. H H H 0 N(Et)2 — 3-OMe H H 0 N(Et)2 — 3-OH H H 0 N(Et)2 — 3-CF3 H H 0 N(Et)2 — 2-OMe H H 0 N(Et)2 — 3-Cl H H 0 N(Et)2 — 3,5-diCl H H 0 N(Et)2 — H trans-Me H 0 N(Et)2 — H cis-Me H 0 N(Et)2 — 3-SMe trans-Me H 0 N(Et)2 — H H F 0 N(Et)2 — H H Me 0 N(Et)2 — H H Cl 0 N(Et)2 — 4-OMe H H 0 1-pyrrolidinyl — H H H 0 4- — morpholinyl H H H 1 N(Et)2 — 3-Cl H H 1 N(Et)2 — 2-F H H 1 N(Et)2 — 3-F H H 1 N(Et)2 — H H H 1 N(Et)2 R H H H 1 N(Et)2 S
• and pharmaceutically acceptable enantiomers, diastereomers and salts thereof.

A method for treating a disorder modulated by the δ-opioid receptor in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of Formula (I):

• 15
• wherein:
• Ar is selected from the group consisting of aryl and heteroaryl;
• n is an integer from 0 to 2;
• R1 is one to three substituents independently selected from the group consisting of hydrogen, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, aryl(C1-8)alkyl, C1-8alkoxy, aryloxy, aryl(C1-8)alkoxy, C1-8alkylthio, trifluoro(C1-8)alkyl, trifluoro(C1-8)alkoxy, amino, —NH(C1-8)alkyl, —N[(C1-8)alkyl]2, —NH(aryl), —N(aryl)2, —NH(C1-8)alkylaryl, —N[(C1-8)alkylaryl]2, —CO2H, —CO2(C1-8)alkyl, —CO2(aryl), —C(O)NH2, C(O)NH(C1-8)alkyl, —C(O)N[(C1-8)alkyl]2, —NHC(O)(C1-8)alkyl, —SO2H, —SO2(C1-8)alkyl, —SO2NH2, —SO2NH(C1-8)alkyl, —SO2N[(C1-8)alkyl]2, —C(O)(C1-8)alkyl, —C(O)aryl, —C(O)(C1-8)alkylaryl, aryl, heteroaryl, heterocyclyl, halogen, hydroxy, cyano, and nitro;
• R2 is selected from the group consisting of hydrogen and C1-8alkyl;
• R3 is selected from the group consisting of hydrogen, C1-8alkyl, C1-8alkoxy, C1-8alkylthio, trifluoro(C1-8)alkyl, trifluoro(C1-8)alkoxy, amino, —NH(C1-8)alkyl, —N[(C1-8)alkyl]2, —CO2H, —CO2(C1-8)alkyl, —C(O)NH2, —C(O)NH(C1-8)alkyl, —C(O)N[(C1-8)alkyl]2, —NHC(O)(C1-8)alkyl, —SO2H, —SO2(C1-8)alkyl, —SO2NH2, —SO2NH(C1-8)alkyl, —SO2N[(C1-8)alkyl]2, —C(O)(C1-8)alkyl, halogen, hydroxy, cyano, and nitro;
• X is selected from the group consisting of S and O;
• Z is N(R4)(R5) or is a 5- or 6-membered saturated, monocyclic, heterocyclic ring, wherein said heterocyclic ring contains one nitrogen member which is the point of attachment, optionally contains one additional heteroatom member of oxygen, sulfur or nitrogen and optionally contains a double bond between two ring members;
• R4 and R5 are independently selected from the group consisting of hydrogen, C1-8alkyl, hydroxy(C1-8)alkyl, C2-8alkenyl, C3-8cycloalkyl, aryl and aryl(C1-8)alkyl, wherein said cycloalkyl, aryl and the aryl portion of aryl(C1-8)alkyl are optionally substituted with one to three substituents independently selected from the group consisting of C1-8alkyl, C2-8alkenyl, C1-8alkoxy, trifluoro(C1-8)alkyl, trifluoro(C1-8)alkoxy, C3-8cycloalkyl and halogen;
• and,
• the moiety —C(X)Z is attached on the phenyl at the 3 or 4 position;
• and pharmaceutically acceptable enantiomers, diastereomers and salts thereof.