Small-Molecule Inhibitors of GSK-3: Structural Insights and Their Application to Alzheimer's Disease Models

Table 7

Examples of paullone inhibitors with biological activity against GSK-3, selectivity, X-ray, and reference.

No.	X	Y	R^1	R^2	R^3	IC50 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
51	CH	CH	H	H	H	β: 620	α/β + 2	—	—	1999, 2000 [76, 77]
52	CH	CH	H	H	Cl	β: 24	α/β + 2	—	—	1999, 2000 [76, 77]
53	CH	CH	H	H	Br	β: 23	α/β + 2	—	—	1999, 2000 [76, 77]
54	CH	CH	H	H	CN	β: 10	α/β + 2	—	—	1999, 2000 [76, 77]
55	CH	CH	H	H	NO2	α: 4; β: 4	α & β + 23	Yes	1Q3W	1999, 2000, 2003, 2007 [31, 34, 76, 77]
56	CH	CH		H	Br	β: 30	β + 2	—	—	2002 [78]
57	CH	CH	H		Br	β: 40	β + 2	—	—	2002 [78]
58	CH	N	H	H	Br	β: 18	β + 2	—	—	2004 [79]
59	N	CH	H	H	Br	β: 6000	β + 2	—	—	2004 [79]
60	CH	CH	H		NO2	β: 6	β + 2	—	—	2005 [80]
61	CH	CH	H		NO2	β: 2.5	β + 2	—	—	2005 [80]
62	CH	CH	H		NO2	β: 6.5	β + 2	—	—	2005 [80]
63	CH	CH	H		NO2	β: 34	β + 2	—	—	2005 [80]
64	CH	CH	H		NO2	β: 0.8	β + 21	—	—	2005 [80]

α: GSK-3α; β: GSK-3β.