Amino-heterocyclic compounds

A method of inhibiting PDE9 in a mammal in need of such inhibition comprising the step of administering to the mammal PDE9-inhibiting amount of:

• a) a compound of Formula (I),
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from the group consisting of
• (i) hydrogen,
• (ii) (C1-C4)alkyl,
• (iii) (C2-C4)alkenyl,
• (iv) (C2-C4)alkynyl,
• (v) (C1-C4)alkoxy,
• (vi) (C1-C4)haloalkyl,
• (vii) (C3-C6)cycloalkyl, optionally substituted with one to three substituents, the substituents being independently selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, halo, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, cyano, carboxy, and carbamoyl,
• (viii) 4 to 10 member heterocycloalkyl, optionally substituted with one to three substituents, the substituents being independently selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, halo, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, cyano, carboxy, and carbamoyl,
• (ix) aryl, optionally substituted with one to three substituents, the substituents being independently selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, halo, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, cyano, carboxy, and carbamoyl, and
• (x) heteroaryl, optionally substituted with one to three substituents, the substituents being independently selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, halo, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, cyano, carboxy, and carbamoyl;
• R2 is selected from the group consisting of hydrogen, (C1-C4)alkyl, (C1-C4)haloalkyl, cyano, and (C3-C6)cycloalkyl;
• R3 is selected from the group consisting of (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, each of which optionally may be substituted with one to three substituents, the substituents being independently selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, halo, and (C1-C4)haloalkyl;
• n is 1 or 2;
• A is —CR4R5— or —CHRa—CHRb—;
• R4 is selected from the group consisting of
• (i) hydrogen,
• (ii) (C1-C7)alkyl,
• (iii) (C3-C8)cycloalkyl,
• (iv) 4 to 10 member heterocycloalkyl,
• (v) aryl, optionally substituted with one to three substituents, the substituents being independently selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, halo, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, (C3-C6)cycloalkyl, cyano, carboxy, and carbamoyl,
• (vi) heteroaryl, optionally substituted with one to three substituents, the substituents being independently selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, halo, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, (C3-C6)cycloalkyl, cyano, carboxy, and carbamoyl, and
• (vii) LR6, wherein:
• L is selected from the group consisting of —CH2—, —NR7—, and —O—;
• R6 is aryl, heteroaryl, (C1-C8)alkyl, (C3-C8)cycloalkyl, 4 to 10 member heterocycloalkyl, or (C1-C8)alkoxy, each of which optionally may be substituted with one to three substituents, the substituents being independently selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, halo, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, (C3-C6)cycloalkyl, cyano, carboxy, and carbamoyl;
• and
• R7 is hydrogen, methyl or ethyl;
• R5 is selected from the group consisting of hydrogen, hydroxyl, (C1-C4)alkoxy, halogen, and (C1-C6)alkyl;
• or R4 and R5, together with the carbon to which they are attached, form a cycloalkyl or heterocycloalkyl ring that optionally incorporates an oxo group and is optionally substituted with (C1-C8)alkyl, (C3-C8)cycloalkyl, halo, (C1-C8)alkoxy, or (C1-C3)haloalkyl;
• Ra is (C1-C4)alkoxy or R8—O—C(O)—, wherein R8 is (C1-C4)alkyl;
• and
• Rb is aryl, heteroaryl, or heterocycloalkyl, optionally substituted with halo, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)alkoxy, or (C1-C3)haloalkyl;
• or Ra and Rb, together with the carbons to which they are attached, form a cycloalkyl or heterocycloalkyl ring that optionally incorporates an oxo group and is optionally substituted with (C1-C8)alkyl, (C3-C8)cycloalkyl, halo, (C1-C8)alkoxy, or (C1-C3)haloalkyl, or a pharmaceutically acceptable salt thereof;
• or
• b) a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable vehicle, carrier or diluent.