Synthesis and 5-HT1A/5-HT2A receptor activity of new N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclohexanepyrrolidine-2,5-dione and 3-spiro-beta-tetralonepyrrolidine-2,5-dione.
Novel N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclo-hexanepyrrolidine-2,5-dione (5-7) and 3-spiro-beta-tetralonepyrrolidine-2,5-dione (8-10) were synthesized and their 5-HT1A and 5-HT2A receptor affinities were determined. All tested compounds exhibited moderate to low 5-HT1A receptor affinity, whereas compounds 5-7 demonstrated high 5-HT2A receptor affinity (Ki = 27, 46 and 15 nM, respectively) and features of 5-HT2A receptor antagonists. Introduction of a beta-tetralone fragment in the 3-position of pyrrolidine-2,5-dione ring (8-10) did not affect 5-HT1A but decreased 5-HT2A receptor affinity.
Department of Medicinal Chemistry, Jagiellonian University, Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
Jolanta
J
Obniska
Maciej
M
Pawłowski
Marcin
M
Kołaczkowski
Anna
A
Czopek
Beata
B
Duszyńska
Aleksandra
A
Klodzińska
Ewa
E
Tatarczyńska
Ewa
E
Chojnacka-Wójcik
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D011869:Radioligand Assay; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D018490:Serotonin Agents / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship
C488273:3-spiro-beta-tetralonepyrrolidine-2,5-dione; C488274:3-spiro-cyclo-hexanepyrrolidine-2,5-dione; D011759:Pyrrolidines; D044402:Receptor, Serotonin, 5-HT2A; D018490:Serotonin Agents; D013141:Spiro Compounds; D044282:Receptor, Serotonin, 5-HT1A