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Synthesis and receptor activity of 2-substituted 8-methyl-5-(2-pyridinylethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles

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Pharmaceutical Chemistry Journal Aims and scope

A series of new 2-substituted 8-methyl-5-(2-pyridinylethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles have been synthesized. Their activity profiles were studied on a broad panel of therapeutic targets including GPC-receptors, ion channels, and neurotransmitter transporters. One of the studied compounds, 2-methyl-3-{2-[8-methyl-5-(2-pyridin-2-ylethyl)-2,3,4,5-tetrahydropyridino[4,3-b]indol-2-yl]ethyl}-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one, was found to be a highly active antagonist of adrenergic α1A, α1B, α1D, and α2A receptors and serotonin 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT7 receptors. The results were considered in terms of structure—activity relationships. It was established that introduction of bulky substituents into the 2-position of the other synthesized 8-methyl-5-(2-pyridinylethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles led to an activity decrease of the corresponding derivatives as compared with that of the 2,8-dimethyl analogs.

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Authors and Affiliations

  1. Chemical Diversity Research Institute, Khimki, Moscow Oblast, 141401, Russia

    A. V. Ivachtchenko, O. D. Mitkin & V. I. Kazey

  2. ChemDiv Inc., 6605 Nancy Ridge Drive, San Diego, CA, 92121, United States

    A. V. Ivachtchenko, V. M. Kysil & I. M. Okun

Authors
  1. A. V. Ivachtchenko
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  2. O. D. Mitkin
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  3. V. M. Kysil
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  4. V. I. Kazey
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  5. I. M. Okun
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Correspondence to A. V. Ivachtchenko.

Additional information

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 47, No. 1, pp. 13–20, January, 2013.

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Ivachtchenko, A.V., Mitkin, O.D., Kysil, V.M. et al. Synthesis and receptor activity of 2-substituted 8-methyl-5-(2-pyridinylethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles. Pharm Chem J 47, 12–19 (2013). https://doi.org/10.1007/s11094-013-0887-4

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  • DOI: https://doi.org/10.1007/s11094-013-0887-4

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