ABSTRACT
A series of substituted 3-aminopyrimido[5,4-c]cinnolines 3, 7 was prepared. 6,7-Substituted 4-amino-3-cinnolinecarboxylic acid 1 were condensed with acetic anhydride to give the respective 1,3-oxazino[5,4-c]cinnolines 2. The obtained derivatives reacted with hydrazines and gave 3-aminopyrimido[5,4-c]cinnolines. Reaction of the esters 5 with hydrazines produced hydrazides 6, which upon treatment with N,N-dimethylformamide dimethyl acetal gave 3-aminopyrimido[5,4-c]cinnolines 7. Treatment of 6b with bromocyan produced 2-amino-3,4-dihydro-3,10-dimethyl-5 H-1,3,4-triazepino[7,6-c]cinnolin-5-on (8b). Some of the synthesized compounds were screened for their effect on the CNS.
Subject(s)
Azepines/chemical synthesis , Central Nervous System Depressants/chemical synthesis , Pyridazines/chemical synthesis , Pyrimidines/chemical synthesis , Animals , Azepines/pharmacology , Azepines/toxicity , Blepharoptosis/chemically induced , Body Temperature/drug effects , Central Nervous System Depressants/pharmacology , Central Nervous System Depressants/toxicity , Drug Interactions , Female , Hypothermia/chemically induced , Lethal Dose 50 , Magnetic Resonance Spectroscopy , Male , Mice , Motor Activity/drug effects , Pyridazines/pharmacology , Pyridazines/toxicity , Pyrimidines/pharmacology , Pyrimidines/toxicity , Rats , Rats, Wistar , Spectrophotometry, Infrared , Stereotyped Behavior/drug effectsABSTRACT
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.
