title: Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT(1A) activity. part 3.
abstract: A number of 4-aryl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine with 3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole or 2-methyl-3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole residues were synthesized for further investigation of SAR in a group of pyrido[1,2-c]pyrimidine derivatives with dual 5-HT(1A)/SERT activity. Compounds 8a-8p were found to be potent ligands for both 5-HT(1A) and SERT with K(i) ranging from 28,3 to 642 nM and 42,4 nM-1,8 μM, respectively. Moreover compounds 8a, 8b, 8c, 8d, 8e and 8g were found to be selective agonists, while 8i as an antagonist of 5-HT(1A) presynaptic receptors in the inducible hypothermia test in mice.
authors.affiliation: Department of Drug Technology, Faculty of Pharmacy, Medical University of Warsaw, ul. Banacha 1, 02-097 Warszawa, Poland. franciszek.herold@wum.edu.pl
authors.forename: Franciszek
authors.initials: F
authors.lastname: Herold
authors.forename: Andrzej
authors.initials: A
authors.lastname: Chodkowski
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Izbicki
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Turło
authors.forename: Maciej
authors.initials: M
authors.lastname: Dawidowski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kleps
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Stachowicz
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Dybała
authors.forename: Agata
authors.initials: A
authors.lastname: Siwek
authors.forename: Aleksander P
authors.initials: AP
authors.lastname: Mazurek
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mazurek
authors.forename: Franciszek
authors.initials: F
authors.lastname: Pluciński
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011743:Pyrimidines; D044282:Receptor, Serotonin, 5-HT1A; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors