Table 1.

In vitro GSK-3β inhibition by the piperidyl maleimides.^[a]

Compd	X	Y	R	IC50 [nm]
3a	H	H	H	67±6
3b	H	6-OMe	H	629±32
3c	H	7-OMe	H	134±5
3d	5-F	H	H	30±4
3e	5-Cl	H	H	272±27
3 f	5-Br	H	H	684±17
3g	5-F	7-OMe	H	28±4
3h	H	H	CH3	155±2
3i	H	H	CH2(2-pyridyl)	110±4
3j	H	H	CH2(4-pyridyl)	65±4
3k	H	H	CO(1-morpholinyl)	10±2
3l	H	H	CO(2-pyridyl)	6±1
3m	H	H	CO(3-pyridyl)	8±2
3n	H	H	CO(4-pyridyl)	4±1
3o	H	H	CO(2-pyrazyl)	4±1
3p	H	H	COCH2NH2	55±2
3q	H	H	CO(4-methylfurazanyl)	25±2
1	–	–	–	87±24[b]
Staurosporine				12±8
SB216763				23±1
AR-A014418				229±11

^[a]The synthesized maleimides were evaluated for their ability to inhibit phosphorylation of primed substrate (YRRAAVPPSPSLSRHSSPHQ(pS)E DEEE; 20 μm) by human GSK-3β in the presence of 10 μm ATP concentration. These compounds were tested at Reaction Biology Inc. (http://www.reactionbiology.com).

^[b]An IC₅₀ value of 7±3 nm was obtained when compound 1 was tested using the conditions reported in Ref. [13a].