Pyrimidin-4-ones as GSK-3b Inhibitors
facilities to carry out this work. The authors thank DST-
SERB, Govt. of India, for awarding research project to HH
and fellowship to IK.
17. Saitoh M., Kunitomo J., Kimura E., Hayase Y., Kobaya-
shi H., Uchiyama N. et al. (2009) Design, synthesis and
structure-activity relationships of 1,3,4-oxadiazole
derivatives as novel inhibitors of glycogen synthase
kinase-3beta. Bioorg Med Chem;17:2017–2029.
18. Saitoh M., Kunitomo J., Kimura E., Iwashita H., Uno
Y., Onishi T. et al. (2009) 2-{3-[4-(Alkylsulfinyl)phenyl]-
1-benzofuran-5-yl}-5-methyl-1,3,4-oxadiazole deriva-
tives as novel inhibitors of glycogen synthase kinase-
3beta with good brain permeability. J Med Chem;
52:6270–6286.
References
1. Sperbera B.R., Leight S., Goedert M., Lee V.M.Y.
(1995) Glycogen synthase kinase-3b phosphorylates
tau protein at multiple sites in intact cells. Neurosci
Lett;197:149–153.
2. Woodgett J. (1990) Molecular cloning and expression
of glycogen synthase kinase-3/factor A. EMBO
J;9:2431–2438.
3. Cohen P., Frame S. (2001) The renaissance of GSK3.
Nat Rev Mol Cell Biol;2:769–776.
19. Ring D.B., Johnson K.W., Henriksen E.J., Nuss J.M.,
Goff D., Kinnick T.R. et al. (2003) Selective glycogen
synthase kinase 3 inhibitors potentiate insulin activation
of glucose transport and utilization in vitro and in vivo.
Diabetes;52:588–595.
4. Palomo V., Perez D.I., Perez C., Morales-Garcia J.A.,
Soteras I., Alonso-Gil S. et al. (2012) 5-imino-1,2,4-
thiadiazoles: first small molecules as substrate competi-
tive inhibitors of glycogen synthase kinase 3. J Med
Chem;55:1645–1661.
5. Mazanetz M.P., Fischer P.M. (2007) Untangling tau
hyperphosphorylation in drug design for neurodegener-
ative diseases. Nat Rev Drug Discovery;6:464–479.
6. Blennow K., de Leon M.J., Zetterberg H. (2006) Alzhei-
mer’s disease. Lancet;368:387–403.
20. Gentile G., Merlo G., Pozzan A., Bernasconi G., Bax
B., Bamborough P. et al. (2012) 5-Aryl-4-carboxa-
mide-1,3-oxazoles: potent and selective GSK-3 inhibi-
tors. Bioorg Med Chem Lett;22:1989–1994.
21. Martinez A., Alonso M., Castro A., Perez C., Moreno
F.J. (2002) First non-ATP competitive glycogen
synthase kinase 3 beta (GSK-3beta) inhibitors: thiadia-
zolidinones (TDZD) as potential drugs for the treatment
of Alzheimer’s disease. J Med Chem;45:1292–1299.
22. Bhat R., Xue Y., Berg S., Hellberg S., Ormo M., Nils-
son Y. et al. (2003) Structural insights and biological
effects of glycogen synthase kinase 3-specific inhibitor
AR-A014418. J Biol Chem;278:45937–45945.
7. Klein P.S., Melton D.A. (1996) A molecular mechanism
for the effect of lithium on development. Proc Natl
Acad Sci USA;93:8455–8459.
8. Phiel C.J., Klein P.S. (2001) Molecular targets of lithium
action. Annu Rev Pharmacol Toxicol;41:789–813.
9. Jope R.S. (2003) Lithium and GSK-3: one inhibitor, two
inhibitory actions, multiple outcomes. Trends Pharma-
col Sci;24:441–443.
10. Chen G., Huang L.D., Jiang Y.M., Manji H.K. (1999)
The mood-stabilizing agent valproate inhibits the
activity of glycogen synthase kinase-3. J Neurochem;
72:1327–1330.
11. Li X., Bijur G.N., Jope R.S. (2002) Glycogen synthase
kinase-3b, mood stabilizers, and neuroprotection.
Bipolar Disord;4:137–144.
12. Jope R.S. (1999) Anti-bipolar therapy: mechanism of
action of lithium. Mol Psychiatry;4:117–128.
13. Jope R.S., Roh M.-S. (2006) Glycogen Synthase
Kinase-3 (GSK3) in psychiatric diseases and therapeu-
tic interventions. Curr Drug Targets;7:1421–1434.
14. Berns G.S., Nemeroff C.B., editors. (2003) The Neuro-
biology of Bipolar Disorder. American Journal of Medi-
cal Genetics Part C: Seminars in Medical Genetics.
123C: Wiley Online Library (UK); 76–84 p.
15. Li X., Zhu W., Roh M.S., Friedman A.B., Rosborough K.,
Jope R.S. (2004) In vivo regulation of glycogen synthase
kinase-3beta (GSK3beta) by serotonergic activity in
mouse brain. Neuropsychopharmacology;29:1426–1431.
16. Gould T.D., Zarate C.A., Manji H.K. (2004) Glycogen
synthase kinase-3: a target for novel bipolar disorder
treatments. J Clin Psychiatry;65:10–21.
23. Uehara F., Shoda A., Aritomo K., Fukunaga K., Watan-
abe K., Ando R. et al. (2013) 6-(4-Pyridyl)pyrimidin-4
(3H)-ones as CNS penetrant glycogen synthase kinase-
3b inhibitors. Bioorg Med Chem Lett;23:6928–6932.
24. Lee S.C., Shin D., Cho J.M., Ro S., Suh Y.G. (2012)
Structure-activity relationship of the 7-hydroxy benzimi-
dazole analogs as glycogen synthase kinase 3beta
inhibitor. Bioorg Med Chem Lett;22:1891–1894.
25. Ibrahim N., Mouawad L., Legraverend M. (2010) Novel
8-arylated purines as inhibitors of glycogen synthase
kinase. Eur J Med Chem;45:3389–3393.
26. Peat A.J., Boucheron J.A., Dickerson S.H., Garrido D.,
Mills W., Peckham J. et al. (2004) Novel pyrazolopy-
rimidine derivatives as GSK-3 inhibitors. Bioorg Med
Chem Lett;14:2121–2125.
27. Miyazaki Y., Maeda Y., Sato H., Nakano M., Mellor
G.W. (2008) Rational design of 4-amino-5,6-diaryl-furo
[2,3-d]pyrimidines as potent glycogen synthase kinase-
3 inhibitors. Bioorg Med Chem Lett;18:1967–1971.
28. Polychronopoulos P., Magiatis P., Skaltsounis A.L.,
Myrianthopoulos V., Mikros E., Tarricone A. et al.
(2004) Structural basis for the synthesis of indirubins
as potent and selective inhibitors of glycogen synthase
kinase-3 and cyclin-dependent kinases.
J
Med
Chem;47:935–946.
29. Leost M., Schultz C., Link A., Wu Y.Z., Biernat J.,
Mandelkow E.M. et al. (2000) Paullones are potent
inhibitors of glycogen synthase kinase-3beta and
Chem Biol Drug Des 2016; 87: 764–772
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