2. Academic Validation
  3. Design, synthesis and biological evaluation of novel serotonin and dopamine receptor ligands being 6-bromohexyl saccharine derivatives

Design, synthesis and biological evaluation of novel serotonin and dopamine receptor ligands being 6-bromohexyl saccharine derivatives

  • Bioorg Med Chem Lett. 2019 Nov 1;29(21):126667. doi: 10.1016/j.bmcl.2019.126667.
Damian Kułaga 1,  Jolanta Jaśkowska 2,  Grzegorz Satała 3
Affiliations

Affiliations

  • 1 Faculty of Chemical Engineering and Technology, Institute of Organic Chemistry and Technology, Cracow University of Technology, ul. Warszawska 24, 31-155 Kraków, Poland. Electronic address: dkulaga@chemia.pk.edu.pl.
  • 2 Faculty of Chemical Engineering and Technology, Institute of Organic Chemistry and Technology, Cracow University of Technology, ul. Warszawska 24, 31-155 Kraków, Poland.
  • 3 Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, ul. Smętna 12, 31-343 Kraków, Poland.
PMID: 31547945 DOI: 10.1016/j.bmcl.2019.126667
Abstract

Due to numerous side effects of current antidepressants, the search for new, safer bioactive compounds is still a valid research topic in medical chemistry. In our research we decided to synthesize and determine SAR for new hexyl arylpiperazines (LACPs) derivated with saccharin moiety. High biological activity has been explained using molecular modelling methods. The compounds obtained show high affinity for the 5-HT1A (compound 18, Ki = 4 nM - antagonist mode) and D2 (compound 15, Ki = 7 nM - antagonist mode) receptor, and in some cases also 5-HT7 receptor (compound 17, Ki = 20 nM). A preliminary ADME analysis showed that the compounds exhibit CNS drugability properties. We have proved that carbon-chain lengthening may have a beneficial effect on increasing the activity towards serotonin and dopamine receptors.

Keywords

Depression; Dopamine receptors; Organic synthesis; Serotonin receptors; Solvent-free.

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