Amino-caprolactam γ-secretase inhibitors showing potential for the treatment of Alzheimer’s disease

Neitzel, Martin L.; Aubele, Danielle L.; Marugg, Jennifer L.; Jagodziński, Jacek; Konradi, Andrei W.; Pleiss, Michael A.; Szőke, Balázs; Zmolek, Wes; Goldbach, Erich; Quinn, Kevin P.; Sauer, John‐Michael; Brigham, Elizabeth F.; Wallace, William H.; Bova, Michael P.; Hemphill, Susanna S.; Basi, Guriqbal S.

doi:10.1016/j.bmcl.2011.04.079

Cited by 5 publications

(5 citation statements)

References 19 publications

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“…ELN-318463 ( 63 ), MRK-560 ( 64 ), MK-0752 ( 65 ), ELN-475516 ( 43 ), cyclohexyl sulfone ( 66 ), and TSAI-1 ( 67 ) were synthesized based on the published procedures and were >95% pure as assessed by HPLC. Semagacestat, avagacestat, begacestat, DAPT, RO-4929097, PF-3084014, L-685,458, LY411575, compound 34, and DAPT analog were purchased from commercial providers and were >95% pure as assessed by HPLC.…”

Section: Methodsmentioning

confidence: 99%

Selective inhibitors of the PSEN1–gamma-secretase complex

Serneels

Narlawar

Pérez‐Benito

et al. 2023

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

Selective inhibitors of the PSEN1–gamma-secretase complex

Serneels

Narlawar

Pérez‐Benito

et al. 2023

Journal of Biological Chemistry

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“…Caprolactam derivatives have been reported as χsecretase inhibitors, which are involved in Alzheimer's disease. 82 Furthermore, their heterocyclic structure is present in compounds that show potent angiotensin-converting enzyme (ACE) inhibition activity. The authors carried out the photolysis in a continuous-flow reactor, demonstrating its potential usefulness to perform this type of photochemical reaction on a larger scale.…”

Section: Organic Process Research and Developmentmentioning

confidence: 99%

“… Alternatively to Schmidt and Beckmann’s rearrangements, prochiral ketones can be converted to chiral oxaziridines, which undergo a stereoselective photolytic rearrangement to produce the chiral lactam. Caprolactam derivatives have been reported as χ-secretase inhibitors, which are involved in Alzheimer’s disease . Furthermore, their heterocyclic structure is present in compounds that show potent angiotensin-converting enzyme (ACE) inhibition activity.…”

Section: Flow Photochemistrymentioning

confidence: 99%

Light on the Horizon: Current Research and Future Perspectives in Flow Photochemistry

Politano

Oksdath‐Mansilla

2018

Org. Process Res. Dev.

152

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The research area of synthetic organic photochemistry is a powerful tool for creating both natural products and molecules with high structural complexity, in a simple way and under mild conditions. However, because of the challenges in scaling-up, it has been difficult to apply a photochemical reaction in an industrial process. Flow chemistry provides an opportunity for better control over the conditions of the reaction and, additionally, improved reaction selectivity and enhanced reproducibility. Taking into account that significant interest has focused on the use of flow photochemistry as a method for the synthesis of heterocycles and its applications in target-oriented synthesis over the last few years, the aim of this review is to highlight the recent efforts to apply flow photochemistry methodology to diverse reactions as a greener and more scalable process for the pharmaceutical and fine chemical industries. Additionally, the review highlights future perspectives in the development of scale-up strategies, combining photochemical reactions in the continuous flow multistep synthesis of organic molecules, being of interest for scientists and engineers alike.

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“…25,26 In another report, amino caprolactam derivatives were shown to exhibit λ-secretase inhibitors which can be a potent drug for Alzheimer's disease. 27 In our earlier report, Keggin-based POMs, such as phosphotungstic acid and phosphomolybdic acid produced hybrid salts with ε-caprolactam (CL). 28 As a continuation to our work, we have tried to entrap POMs in caprolactam matrix.…”

Section: Introductionmentioning

confidence: 99%

Polyoxometalate entrapped caprolactam gels and their cytotoxicity study

et al. 2018

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Polyoxometalate (POM) based gels are synthesized by reacting POMs with an excess of caprolactam. These POM-entrapped caprolactam gels are thermoreversible and possess good mechanical strength. The gelation of POMs in caprolactam matrix brought the gel acidity similar to the physiological pH. The cytotoxicity studies on SCC 131 cell lines using these gels show 50% of cell death in the range of 2 to 6 mM concentration in 48 h. The supramolecular caprolactam matrix with active protons and the redox property of POMs are responsible for the cytotoxicity effect.

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Amino-caprolactam γ-secretase inhibitors showing potential for the treatment of Alzheimer’s disease

Cited by 5 publications

References 19 publications

Selective inhibitors of the PSEN1–gamma-secretase complex

Selective inhibitors of the PSEN1–gamma-secretase complex

Light on the Horizon: Current Research and Future Perspectives in Flow Photochemistry

Polyoxometalate entrapped caprolactam gels and their cytotoxicity study

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