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

Table 9

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

No.	R^1	R^2	R^3	R^4	IC50/𝐾𝑖 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
79				H	β: 2.5^a	—	Yes	—	2004 [91]
80				H	β: 100^a	—	Yes	1GNG^c	2001; and 2004 [28, 91]
81				H	β: 4.0^a	—	Yes	1GNG^c	2001; and 2004 [28, 91]
82			H		β: 2400^a	—	—	—	2008 [92]
83			H		β: 1700^a	—	—	—	2008 [92]
84			H		α: 1020^a; β: 960^a	—	—	—	2008 [92]
85			H		α: 1900^a; β: 760^a	—	—	—	2008 [92]
86			H		α: 350^a; β: 180^a	—	—	—	2008 [92]
87			H		α: 6700^a; β: 3500^a	—	—	—	2008 [92]
88		NO2	H		α: 270^a; β: 150^a	—	—	—	2008 [92]
89		CF3	H		α: 750^a; β: 490^a	—	—	—	2008 [92]
90			H		α: 330^a; β: 628^a	α and β + 1	—	1Q5K^c	2008 [92]
91		NO2	H		α: 74^a; β: 92^a	α and β + 1	—	—	2008 [92]
92			H		α: 9^a; β: 13^a	α and β + 1	—	—	2008 [92]
93		CF3	H		α: 61^a; β: 41^a	α and β + 1	Yes	—	2008 [92]
94	H	Me			GSK-3: 7^b	GSK-3 + 4	—	3I4B	2009 [93]
95			H		α: 10; β: 6.7^a; (9.8^b)	α and β + 20	Yes	—	2003, and 2007 [34, 94]
96			H		α: 0.65; β: 0.58^a; (0.87^b)	α and β + 20	Yes	—	2003, and 2007 [34, 94]

^a IC₅₀ value; ^b𝐾_𝑖 value; ^cdocking studies, PDB code (n.d.: not denoted); α: GSK-3α; β: GSK-3β.