Synthesis and properties of 4-substituted-1-piperazinyl-propyl derivatives of 1-phenyl-7-methylpyrimido-[4,5-d]pyrimidin-4-one.
In reactions of 1-phenyl-7-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimido[ 4,5-d]pyrimidin e (1) with 1-(3-chloropropyl)-4-methyl(phenyl, 3-chlorophenyl, 2-pyrimidynyl, 2-thiazolyl)piperazines (5), mixtures of isomeric N- and S-substituted derivatives of compound 1 (3 and 4) were obtained. Isomers were separated by fractional crystallization. The structure of novel compounds 3 and 4 was confirmed by elemental and spectral analyses. In pharmacological screening compounds 3b and 4b displayed rather strong analgesic action, inhibited amphetamine hyperactivity and abolished apomorphine stereotypy. Compounds 3e,3d and 4e attenuated m-chlorophenylpiperazine-induced hypothermia.
Department of Drug Chemistry, Medical Academy, Wrocław, Poland.
W
W
Malinka
H E
HE
Zajac
A
A
Dereń
T
T
Zawisza
M
M
Wilimowski
L
L
Kedzierska-Goździk
J
J
Barczyńska
M
M
Rutkowska
W
W
Wojewódzki
A
A
Szelag
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D000978:Antiparkinson Agents / Q000138:chemical synthesis / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors; D004597:Electroshock; D005260:Female; D007536:Isomerism; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011619:Psychotropic Drugs / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects
D000700:Analgesics; D000927:Anticonvulsants; D000928:Antidepressive Agents; D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D010879:Piperazines; D011619:Psychotropic Drugs; D011744:Pyrimidinones; D001058:Apomorphine; D003913:Dextroamphetamine