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Antagonists of Serotonin 5-HT6 Receptors. VI. Substituted 3-(Phenylsulfonyl)Quinolines, Synthesis and Structure–Activity Relationships

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Pharmaceutical Chemistry Journal Aims and scope

In continuation of research and development of new high-efficacy drugs based on 5-HT6 receptor antagonists for the treatment of CNS disorders, we synthesized a series of new 3-(phenylsulfonyl)quinoline derivatives, performed their molecular docking, and studied the receptor activity spectrum. It was found that the antagonist activity of the 3-(phenylsulfonyl)quinolines with respect to 5-HT6 receptors depended on the nature of the 4- and 8-substituents of the heterocycle. It was expedient for high activity of this type to introduce a tertiary nitrogen atom (dimethylamine or piperazine fragment) in the 8-position and a secondary nitrogen (methylamine fragment) or hydrogen in the 4-position. The most promising compounds were N,N-dimethyl-3-(phenylsulfonyl) quinoline-8-amine (IV, K f i  = 0.4 nM), 4-methylamino-8-dimethylamino-3-(phenylsulfonyl)quinoline (XXII, K f i  = 0.3 nM), and N-methyl-8-(piperazin-1-yl)-3-(phenylsulfonyl)quinoline-4-amine (XXIII, K f i  = 0.9 nM). Antagonist IV exhibited the maximum selectivity; XXIII, the maximum multimodality.

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Authors and Affiliations

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

    A. V. Ivachtchenko, E. S. Golovina, M. G. Kadieva & O. D. Mitkin

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

    A. V. Ivachtchenko & I. M. Okun

  3. AllaChem LLC, 1835 E. Hallandale Beach Blvd., Hallandale Beach, FL, 33009, USA

    A. V. Ivachtchenko

Authors
  1. A. V. Ivachtchenko
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  2. E. S. Golovina
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  3. M. G. Kadieva
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  4. O. D. Mitkin
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  5. I. M. Okun
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 48, No. 10, pp. 14 – 28, October, 2014.

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Ivachtchenko, A.V., Golovina, E.S., Kadieva, M.G. et al. Antagonists of Serotonin 5-HT6 Receptors. VI. Substituted 3-(Phenylsulfonyl)Quinolines, Synthesis and Structure–Activity Relationships. Pharm Chem J 48, 646–660 (2015). https://doi.org/10.1007/s11094-015-1164-5

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  • DOI: https://doi.org/10.1007/s11094-015-1164-5

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