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

Table 8

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

No.	X	Y	Z	R^1	R^2	R^3	IC50 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
65	C	N	CH	H	Ph	Propyl	α: 56	β + 24	—	—	2003 [82]
66	C	N	CH	H	2-F-Ph	Propyl	α: 18	β + 24	—	—	2003 [82]
67	C	N	CH	H	3-Pyridyl	Propyl	α: 11	β + 24	—	—	2003 [82]
68	N	N	CH	—	Ph	Propyl	α: 4	β + 24	—	PDB n.p.^a	2003 [83]
69	N	CH	CH	—	Ph	Propyl	α: 7	—	—	—	2003 [83]
70	N	N	CH	—	Ph		α: 22	β + 24	—	PDB n.p.^a	2003 [83]
71	C	N	CH	Ph	H		α: 425	—	—	—	2003 [84]
72	C	N	CH	Ph-4-OMe	H		α: >5000	—	—	—	2003 [84]
73	C	N	CH	Ph-4-OH	H		α: 8	α + 23	—	PDB n.p.^a	2003 [84, 85]
74	C	N	CH	Ph-4-OH	Br		α: 0.8	α + 23	—	PDB n.p.^a	2003 [84, 85]
75	C	N	CH	Ph	Br		α: 75	α + 23	—	—	2003 [85]
76	C	CH	CH	5-Indolyl	H		α: 42	α + 1	—	—	2003 [85]
77	C	N	CH	2-Furyl	Br		α: 7	β + 23	—	—	2003 [85]
No.				IC50/𝐾𝑖 (nM)				Kinase panel	In vivo	X-ray	Year/lit.
78				α: 2.3; β: 2.0				α & β + 27	Yes	—	2009 [86]

^aNot published as PDB; α: GSK-3α; β: GSK-3β.