A new one step synthesis of maleimides by condensation of glyoxylate esters with acetamides

Faul, Margaret M.; Winneroski, Leonard L.; Krumrich, Christine A.

doi:10.1016/s0040-4039(98)02594-5

Cited by 66 publications

(52 citation statements)

References 11 publications

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“…The 3-(indol-3-yl)-4-(1H-indazol-3-yl)maleimide-based ligands 5-35 were prepared by condensation of the indolyl-3-glyoxylate esters 3 and the indazolyl-3-acetamides 4 [12] (Scheme 1). NAlkylation of indoles 1 with various alkyl halides in the presence of sodium hydride followed by acylation of the resulting indoles 2 with oxalyl chloride and then ester formation afforded the precursors 3.…”

Section: Introductionmentioning

confidence: 99%

Highly Potent and Specific GSK‐3β Inhibitors That Block Tau Phosphorylation and Decrease α‐Synuclein Protein Expression in a Cellular Model of Parkinson's Disease

et al. 2006

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Research by Klein and co-workers suggests that the inhibition of GSK-3beta by small molecules may offer an important strategy in the treatment of a number of central nervous system (CNS) disorders including Alzheimer's disease, Parkinson's disease, and bipolar disorders. Based on results from kinase-screening assays that identified a staurosporine analogue as a modest inhibitor of GSK-3beta, a series of 3-indolyl-4-indazolylmaleimides was prepared for study in both enzymatic and cell-based assays. Most strikingly, whereas we identified ligands having poor to high potency for GSK-3beta inhibition, only ligands with a Ki value of less than 8 nM, namely maleimides 18 and 22, were found to inhibit Tau phosphorylation at a GSK-3beta-specific site (Ser 396/404). Accordingly, maleimides 18 and 22 may protect neuronal cells against cell death by decreasing the level of alpha-Syn protein expression. We conclude that the GSK-3beta inhibitors described herein offer promise in defending cells against MPP+-induced neurotoxicity and that such compounds will be valuable to explore in animal models of Parkinson's disease as well as in other Tau-related neurodegenerative disease states.

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Section: Introductionmentioning

confidence: 99%

Highly Potent and Specific GSK‐3β Inhibitors That Block Tau Phosphorylation and Decrease α‐Synuclein Protein Expression in a Cellular Model of Parkinson's Disease

et al. 2006

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“…Treatment of the alkylated indoles 33 with ethyl chlorooxoacetate in diethyl ether afforded the glyoxalates 34 . Perkin-type condensation 30 between the glyoxalates and benzofuran-3-yl-acetamide 28 generated the desired maleimides 2–4 . Alkylation of 32a and 32b with tert -butyl (2-bromoethyl)carbamate followed by treatment of the intermediary indoles 35a and 35b with ethyl chlorooxoacetate gave the glyoxalates 36a and 36b .…”

Section: Chemistrymentioning

confidence: 99%

Characterization of Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitors as Stimulators of Steroidogenesis

et al. 2013

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Inhibition of GSK-3β has been well documented to account for the behavioral actions of the mood stabilizer lithium in various animal models of mood disorders. Recent studies have showed that genetic or pharmacological inhibition of GSK-3β resulted in anxiolytic-like and pro-social behavior. In our ongoing efforts to develop GSK-3β inhibitors for the treatment of mood disorders, SAR studies on maleimide-based compounds were undertaken. We present herein for the first time that some of these GSK-3β inhibitors, in particular analogs 1 and 9, were able to stimulate progesterone production in the MA-10 mouse tumor Leydig cell model of steroidogenesis without any significant toxicity. These two compounds were tested in the SmartCube® behavioral assay and showed anxiolytic-like signatures following daily dose administration (50 mg/kg, i.p.) for 13 days. Taken together, these results support the hypothesis that GSK-3β inhibition could influence neuroactive steroid production thereby mediating the modulation of anxiety-like behavior in vivo.

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“…Among the number of synthetic methods for preparing asymmetrical 3,4-diarylmaleimides, the method of Faul et al (1999) can be used conveniently. Among the number of synthetic methods for preparing asymmetrical 3,4-diarylmaleimides, the method of Faul et al (1999) can be used conveniently.…”

Section: Commentmentioning

confidence: 99%

4-(3-Hydroxy-4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)-2,5-dihydro-1H-pyrrole-2,5-dione

Schollmeyer

Peifer

Dannhardt³

2005

Acta Cryst E

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A new one step synthesis of maleimides by condensation of glyoxylate esters with acetamides

Cited by 66 publications

References 11 publications

Highly Potent and Specific GSK‐3β Inhibitors That Block Tau Phosphorylation and Decrease α‐Synuclein Protein Expression in a Cellular Model of Parkinson's Disease

Highly Potent and Specific GSK‐3β Inhibitors That Block Tau Phosphorylation and Decrease α‐Synuclein Protein Expression in a Cellular Model of Parkinson's Disease

Characterization of Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitors as Stimulators of Steroidogenesis

4-(3-Hydroxy-4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)-2,5-dihydro-1H-pyrrole-2,5-dione

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