Structure-activity relationship in a series of new 1-(2-pyrimidinyl)piperazine derivatives with hypnotic activity.
Preparation, biological properties and QSAR of new derivatives of 1-[4-(2-pyrimidinyl)-1-piperazinyl]-1, 3-butandione (11-13, and 15-18) and 3-[4-(2-pirimidinyl)-1-piperazinyl]-3-oxopropanoate (20-22) exhibiting hypnotic activity in mice are reported. The best therapeutic indices (TI = LD50/ED50) 4.7 and 9.4 for po and ip administration, respectively, were found for 1-[4-(2-pyrimidinyl)-1-piperazinyl]-2-n-pentyl-1,3-butandione (15). QSAR studies showed that the biological activity grows initially with an increase in lipophilicity to drop dramatically for log P > 2.5.
Chilmonczyk
Z
Z
Pharmaceutical Research Institute, Warszawa, Poland.
Bogdal
M
M
Mazgajska
M
M
Cybulski
J
J
Lewandowska
U
U
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006591:Hexobarbital / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D007928:Lethal Dose 50; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D012890:Sleep / Q000187:drug effects; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011743:Pyrimidines; D006591:Hexobarbital; D000661:Amphetamine