Structure-activity relationship studies of CNS agents, Part 25. 4,6-di(heteroaryl)-2-(N-methylpiperazino)pyrimidines as new, potent 5-HT2A receptor ligands: a verification of the topographic model.
A series of new 4,6-di(heteroaryl)pyrimidines containing an N-methylpiperazino group (6-13) or an ethylenediamine chain (15-20) in position 2 were synthesized and their 5-HT1A and 5-HT2A receptor affinities were determined. It was shown that the substituent effects on the 5-HT2A affinity are additive and could be described quantitatively. In a behavioral model it was also demonstrated that 6-11 are 5-HT2A receptor antagonists. The molecular modelling results suggested that the distances between the basic nitrogen atom and the two aromatic centers (d1 = 5.2-8.4 A, d2 = 5.7-8.5 A, and d3 = 4.6-7.3 A) define the molecular topography of the 5-HT2A receptor antagonists under study.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051379:Mice; D008956:Models, Chemical; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D008024:Ligands; D011743:Pyrimidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists