Comparison of pharmacophore cinnoline and quinoline systems on the basis of computer calculation and pharmacological screening of their condensed systems.
A series of new pyrimido[5,4-c]quinoline derivatives were prepared to compare the pharmacophore systems of cinnoline and quinoline. These compounds were obtained by the cyclocondensation of appropriately substituted 4-amino-3-quinolinecarboxylic acids 3 with acetic anhydride to the respective 2-methyl-1,3-oxazino[5,4-c]quinolin-4(3 H)-ones 4. These derivatives reacted with amines and gave N-3 substituted 2-methylpyrimido[5,4-c]quinolin-4(3 H)-ones 6. 4-Amino-3-quinolinecarboxamide 2 reacted with diethyl carbonate to give 1,2,3,4-tetrahydropyrimido[5,4-c]quinolin-2,4-diones 5. The SAR parameters of the derivatives obtained were analysed with the HyperChem 5.1/ChemPlus 2.0 computer program. The compounds synthesized were screened for their effect on the CNS.
Stańczak
A
A
Department of Pharmaceutical Chemistry and Drug Analysis, Medical University of Łódź, Poland.
Pakulska
W
W
Pietrzak
B
B
Lewgowd
W
W
D000818:Animals; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D007202:Indicators and Reagents; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D002491:Central Nervous System Agents; D007202:Indicators and Reagents; D010078:Oxazines; D011744:Pyrimidinones; D011804:Quinolines