ABSTRACT
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.
Subject(s)
Central Nervous System Agents/chemical synthesis , Central Nervous System Agents/pharmacology , Oxazines/chemical synthesis , Oxazines/pharmacology , Pyrimidinones/chemical synthesis , Pyrimidinones/pharmacology , Quinolines/chemical synthesis , Quinolines/pharmacology , Animals , Computer Simulation , Drug Evaluation, Preclinical/methods , Female , Indicators and Reagents , Lethal Dose 50 , Magnetic Resonance Spectroscopy , Male , Mice , Quinolines/toxicity , Rats , Rats, Wistar , Structure-Activity RelationshipABSTRACT
A series of new 2,4-dioxo-1,2,3,4-tetrahydropyrimido[5,4-c]cinnolines and their 3-substituted derivatives were prepared. These compounds were obtained by cyclocondensation of the appropriate substituted 4-amino-3-cinnolinecarboxylic acid with urea or 4-amino-3-cinnolinecarboxamides with N,N'-carbonyldiimidazole (DCl), oxalyl chloride or diethyl carbonate. Most of these compounds showed a high sedative action in low doses.
Subject(s)
Carboxylic Acids/chemical synthesis , Hypnotics and Sedatives/chemical synthesis , Analgesics, Non-Narcotic/pharmacology , Animals , Body Temperature/drug effects , Carboxylic Acids/pharmacology , Chemical Phenomena , Chemistry, Physical , Female , Helplessness, Learned , Hypnotics and Sedatives/pharmacology , Male , Mice , Motor Activity/drug effects , Motor Activity/physiology , Pain Measurement/drug effects , Rats , Rats, Wistar , Serotonin Antagonists/pharmacologyABSTRACT
6,7,8-Substituted 4-amino-3-cinnolinecarboxylic acids 1 were condensed with amines to the corresponding 4-amino-3-cinnolinecarboxamides 7, 8. A variety of pharmacological tests showed a significant CNS activity of some new amides. Decarboxylation of 4-amino-3-cinnolinecarboxylic acids 1 yielded the corresponding 4-aminocinnolines 4 and alkaline hydrolysis of 1 gave 4-oxo-3-cinnolinecarboxylic acids 2. The acids 1 were converted into pyrimido[5,4-c]cinnolines 6 on two ways of synthesis.
Subject(s)
Carboxylic Acids/chemical synthesis , Central Nervous System Agents/chemical synthesis , Amphetamine/pharmacology , Animals , Anticonvulsants/chemical synthesis , Anticonvulsants/pharmacology , Carboxylic Acids/pharmacology , Carboxylic Acids/toxicity , Central Nervous System Agents/pharmacology , Central Nervous System Agents/toxicity , Central Nervous System Stimulants/pharmacology , Chemical Phenomena , Chemistry, Physical , Drug Interactions , Female , Lethal Dose 50 , Magnetic Resonance Spectroscopy , Male , Mice , Motor Activity/drug effects , Pentylenetetrazole , Rats , Rats, Wistar , Seizures/chemically induced , Seizures/prevention & control , Spectrophotometry, Infrared , Stereotyped Behavior/drug effects , Structure-Activity RelationshipABSTRACT
The method of preparation of N1-substituted 4-hydroxycinnolines is described, by alkylation with methyl bromopropionate of the corresponding 4-hydroxycinnolines. The obtained esters were further converted into amides and hydrazides. The effect of several synthesized derivatives on central nervous system was studied. The structure of some of them was confirmed by the X-ray analysis.
Subject(s)
Central Nervous System Agents/chemical synthesis , Animals , Central Nervous System Agents/pharmacology , Crystallography , Female , Male , Mice , Motor Activity/drug effects , Rats , Rats, WistarABSTRACT
This work describes the synthesis of 4-amino-3-cinnolinecarboxamides, which were then hydrolyzed to corresponding 4-amino-3-cinnolinecarboxylic acids. Several compounds were tested for their antibacterial and antifungal activity, and for the central nervous system effect.
