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Several of the newly synthesized compounds, tested by binding studies, showed nanomolar affinity at the 5\u2010HT<jats:sub>1A<\/jats:sub> and 5\u2010HT<jats:sub>2C<\/jats:sub> receptors and moderate or no affinity for other relevant receptors (D<jats:sub>1<\/jats:sub>, D<jats:sub>2<\/jats:sub>, \u03b1<jats:sub>1<\/jats:sub>, and \u03b1<jats:sub>2<\/jats:sub>). Compound <jats:bold>8e<\/jats:bold> (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>\u2009=\u200921.4\u2009nM) was the most affine for the 5\u2010HT<jats:sub>2C<\/jats:sub> receptor, showing, at the same time, a high selectivity with respect to the other receptors analyzed. Compounds <jats:bold>4a<\/jats:bold> and <jats:bold>4c<\/jats:bold>, instead, showed an interesting mixed 5\u2010HT<jats:sub>1A<\/jats:sub>\/5\u2010HT<jats:sub>2C<\/jats:sub> activity with <jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> values of 21.3\/11.5 and 23.2\/6.48\u2009nM, respectively. The compounds with better affinity and selectivity binding profiles toward 5\u2010HT<jats:sub>2C<\/jats:sub> (<jats:bold>4a<\/jats:bold>, <jats:bold>4c<\/jats:bold>, <jats:bold>8b<\/jats:bold>, and <jats:bold>8e<\/jats:bold>) were selected for further in vivo assays to determine their functional activity. Finally, to rationalize the obtained results, molecular docking studies were performed. The results of the pharmacological studies showed that compounds <jats:bold>4a<\/jats:bold>, <jats:bold>8b<\/jats:bold>, and <jats:bold>8e<\/jats:bold> exerted antidepressant\u2010like effects and <jats:bold>4a<\/jats:bold> and <jats:bold>8e<\/jats:bold> revealed also significant anxiolytic properties. Among the developed derivatives, the most promising compound seems to be <jats:bold>4a<\/jats:bold>, which displayed antipsychotic\u2010, antidepressant\u2010 and anxiolytic\u2010like properties. No side effects, like catalepsy, motor\u2010impairment or ethanol\u2010potentiating effects, were observed after the injection of the tested compounds.<\/jats:p>","DOI":"10.1002\/ardp.201800373","type":"journal-article","created":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T08:48:50Z","timestamp":1556268530000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Synthesis, docking studies, and pharmacological evaluation of 5HT<sub>2C<\/sub> ligands containing the <i>N<\/i>\u2032\u2010cyanoisonicotinamidine or <i>N<\/i>\u2032\u2010cyanopicolinamidine nucleus"],"prefix":"10.1002","volume":"352","author":[{"given":"Elisa","family":"Magli","sequence":"first","affiliation":[{"name":"Dipartimento di Farmacia Universit\u00e0 di Napoli \u201cFederico II\u201d Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"K\u0119dzierska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka A.","family":"Kaczor","sequence":"additional","affiliation":[{"name":"Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Laboratory, Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin Lublin Poland"},{"name":"School of Pharmacy University of Eastern Finland Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Severino","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia Universit\u00e0 di Napoli \u201cFederico II\u201d Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Corvino","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia Universit\u00e0 di Napoli \u201cFederico II\u201d Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Perissutti","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia Universit\u00e0 di Napoli \u201cFederico II\u201d Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Frecentese","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia Universit\u00e0 di Napoli \u201cFederico II\u201d Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Saccone","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia Universit\u00e0 di Napoli \u201cFederico II\u201d Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Massarelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche, Chirurgiche e Neuroscienze Universit\u00e0 di Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Gibu\u0142a\u2010Tar\u0142owska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolanta H.","family":"Kotli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Santagada","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia Universit\u00e0 di Napoli \u201cFederico II\u201d Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Caliendo","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia Universit\u00e0 di Napoli \u201cFederico II\u201d Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7357-5751","authenticated-orcid":false,"given":"Ferdinando","family":"Fiorino","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia Universit\u00e0 di Napoli \u201cFederico II\u201d Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,26]]},"reference":[{"volume-title":"Handb. 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