Spirocyclic aminoquinolones as gsk-3 inhibitors

A compound of Formula (1):

• or a pharmaceutically acceptable salt thereof, wherein
• R2 is hydrogen or lower alkyl;
• R3 is hydrogen, CN, C(O)R3a, C(NH)NHOH or 5-tetrazolyl;
• R3a is OH, alkoxy or NHR3b;
• R3b is hydrogen, NH2, OH or lower alkyl;
• R5a and R5b are each independently hydrogen, lower alkyl or aralkyl which is optionally substituted with one to three substituents, each independently selected from Q0 groups;
• where Q0 is halo, cyano, nitro, NH2, alkyl or alkoxy;
• R6 is halo;
• in each instance, independently, Ra and X3 are selected from (i) or (ii) as follows:
• (i) Ra is hydrogen or lower alkyl;
• and
• X3 is substituted or unsubstituted C1-C3 alkylene, substituted or unsubstituted 3-6 membered cycloalkylene or substituted or unsubstituted 3-6 membered heterocyclylene, wherein the substituents when present are selected from one to four Q2 groups;
• or
• (ii) Ra and X3 together with the nitrogen atom to which they are bonded, may form a 5 to 7 membered saturated or unsaturated ring optionally containing one or more O or S atoms, or one or more additional N atoms, in the ring;
• Rb is —(CHR7a)nR7, —NR7bR7, —OR7, S(O)rR7, —NR7bCOY1R7 or —Y2CONR7bR7;
• Y1 is bond, O or NR7b;
• Y2 is bond or O;
• n is 0 or 1;
• r is an integer of 0 to 2;
• R7 is alkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, fused heterocyclylaryl, or fused arylheterocyclyl, where R7 is optionally substituted with one to five substituents, each independently selected from Q1 groups;
• R7a is hydrogen, alkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, fused heterocyclylaryl, or fused arylheterocyclyl, where R7a is optionally substituted with one to five substituents, each independently selected from Q1 groups;
• R7b is hydrogen, alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, or fused heterocyclylaryl, where R7b is optionally substituted with one to five substituents, each independently selected from Q1 groups;
• wherein Q1 is halo, hydroxy, oxo, thioxo, cyano, nitro, azido, mercapto, formyl, hydroxycarbonyl, hydroxycarbonylalkyl, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, alkoxy, haloalkoxy, cycloalkoxy, heterocyclyloxy, aryloxy, heteroaryloxy, aralkyloxy, heretoaralkyloxy, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aralkyloxycarbonyl, unsubstituted or substituted aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkyloxycarbonyloxy, unsubstituted or substituted aminocarbonyloxy, unsubstituted or substituted amino, alkylthio, cycloalkylthio, arylthio, heteroarylthio, aralkylthio, heteroaralkylthio, alkylsulfinyl, cycloalkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, aralkylsulfinyl, heteroaralkylsulfinyl, alkylsulfonyl, cycloalkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aralkylsulfonyl, heteroaralkylsulfonyl, alkoxysulfonyl, aryloxysulfonyl, unsubstituted or substituted aminosulfonyl or hydroxysulfonyl;
• X1 is O;
• R8 is hydrogen or lower alkyl;
• X2 is CH2, O, NR1 or S;
• R1 is hydrogen or lower alkyl;
• A is substituted or unsubstituted C2 alkylene, wherein the substituents when present are selected from one to four Q2 groups;
• where Q2 is alkyl or haloalkyl;
• p is 0;
• and
• q is an integer of 0 to 2.