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Preparation and testing of homocubyl amines as therapeutic NMDA receptor antagonists

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Abstract

Computational modeling demonstrates that the van-der-Waals surfaces of homocubyl amines are similar to that of the neuroprotector Memantine®. Utilizing readily available precursors we report the preparation of a series of homological cubylamines, namely pentacyclo[6.3.0.02,6.03,10.05,9]undecyl-4-amine (trishomocubyl-4-amine, 2), pentacyclo[5.3.0.02,5.03,9.04,8]decyl-10-amine (bishomocubyl-10-amine, 3), pentacyclo[4.3.0.02,5.03,8.04,7]nonyl-9-amine (homocubyl-9-amine, 4), and pentacyclo[4.2.0.02,5.03,8.04,7]octyl-1-amine (cubylamine, 5). The hydrochlorides of amines 2–5 show pronounced affinity for the (+)MK-801 channel binding site, and it seems likely that these compounds would act as very fast voltage-dependent NMDA receptor antagonists.

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Acknowledgments

This work was supported in part by the Ministry of Science and Education of Ukraine and Merz Pharma GmbH & Co.

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Authors and Affiliations

  1. Department of Organic Chemistry, Kiev Polytechnic Institute, 37 Pobeda Ave, Kiev, 03056, Ukraine

    Anna S. Sklyarova, Vladimir N. Rodionov & Andrey A. Fokin

  2. Merz Pharmaceuticals GmbH & Co. KGaA Zentrale, Eckenheimer Landstraße 100, 60318, Frankfurt, Germany

    Christopher G. Parsons & Günter Quack

  3. Institut für Organische Chemie der Justus-Liebig-Universität, Heinrich-Buff-Ring 58, 35392, Giessen, Germany

    Peter R. Schreiner & Andrey A. Fokin

Authors
  1. Anna S. Sklyarova
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  2. Vladimir N. Rodionov
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  3. Christopher G. Parsons
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  4. Günter Quack
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  5. Peter R. Schreiner
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  6. Andrey A. Fokin
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Correspondence to Andrey A. Fokin.

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Sklyarova, A.S., Rodionov, V.N., Parsons, C.G. et al. Preparation and testing of homocubyl amines as therapeutic NMDA receptor antagonists. Med Chem Res 22, 360–366 (2013). https://doi.org/10.1007/s00044-012-0029-7

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  • DOI: https://doi.org/10.1007/s00044-012-0029-7

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