ABSTRACT
The synthesis and the pharmacological evaluation of some 3(2H)-pyridazinone derivatives are reported. The compounds were screened for analgesic, antiinflammatory and antipyretic activities. All tested derivatives showed a higher analgesic activity than phenylbutazone, while being devoid of ulcerogenic action.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Animals , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Behavior, Animal/drug effects , Chemical Phenomena , Chemistry , Male , Mice , Rats , Rats, Inbred Strains , Reaction Time/drug effects , Stomach Ulcer/chemically inducedABSTRACT
The synthesis of a series of dialkylaminoalkylic esters of 1-chloro-3-carboxy-4-methylisoquinoline and of 1-chloro-3-carboxy-4-phenylisoquinoline is described. The pharmacological activity of some of these compounds was studied. The morpholinoethylester of 1-chloro-3-carboxy-4-methylisoquinoline (VIIa), dimethylaminoethylester (VIIb) and diethylaminoethylester (VIIc) showed a good antispasmodic activity. 4-Phenyl-derivatives (XVa), (XVb), (XVc) were more active than analogous 4-methyl derivatives; particularly the diethylaminoethylester of 1-chloro-3-carboxy-4-phenylisoquinoline (XVc) showed an antagonist effect against spasmogens similar to that of papaverine.
Subject(s)
Isoquinolines/chemical synthesis , Parasympatholytics/chemical synthesis , Acetylcholine/antagonists & inhibitors , Analgesics/chemical synthesis , Animals , Anti-Inflammatory Agents/chemical synthesis , Barium/antagonists & inhibitors , Central Nervous System/drug effects , Chemical Phenomena , Chemistry , Guinea Pigs , Histamine Antagonists/chemical synthesis , In Vitro Techniques , Isoquinolines/pharmacology , Male , Mice , Motor Activity/drug effects , Rats , Rats, Inbred StrainsABSTRACT
The synthesis of a series of dialkylaminoalkylic amides of 1-chloro-3-carboxy-4-methylisoquinoline (VIII), of 1-methoxy-3-carboxy-4-methylisoquinoline (VI) and of 3-carboxy-2,4-dimethyl-1-oxoisoquinoline (XIII) is described. In addition a series of 1-amino-substituted 3-carboxymethyl-4-methylisoquinolines (II) was synthesized. The pharmacological activity of some of these compounds was studied. The compounds (XIIIa), (VIa) and (VIIIa) showed a clear local anaesthetic activity, a little lower than that of lidocaine; the same compounds also showed fairly good antispasmodic properties.
Subject(s)
Anesthetics, Local/chemical synthesis , Isoquinolines/chemical synthesis , Parasympatholytics/chemical synthesis , Animals , Anti-Inflammatory Agents/chemical synthesis , Behavior, Animal/drug effects , Chemical Phenomena , Chemistry , Exudates and Transudates/drug effects , Guinea Pigs , In Vitro Techniques , Male , Mice , Rats , Rats, Inbred StrainsABSTRACT
The synthesis of a series of 1-amino derivatives of 3-carboxymethyl-4-phenylisoquinoline and of dialkylaminoalkylamides of 2-methyl-3-carboxy-4-phenyl-1,2-dihydro-1-oxoisoquinoline and of 1-methoxy-3-carboxy-4-phenylisoquinoline is described. The pharmacological activity of some of these compounds was studied. 1-Morpholino-3-carboxymethyl-4-phenylisoquinoline (IV a) and 1-pyrrolidino derivatives (IV d) caused reduction in spontaneous activity and reactivity in mice whereas compounds (VIII a) and (XII b) showed good local anesthetic activity in infiltration tests.
Subject(s)
Isoquinolines/chemical synthesis , Anesthetics/chemical synthesis , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Isoquinolines/pharmacology , Mice , Motor Activity/drug effectsABSTRACT
The synthesis and chemical behaviour of pyrimidothiazine derivatives with a carboxyl group in position 7 [compounds (II) and (III)] or in position 6 [compounds (IV) and (V)] are described. It has been shown that these products, analogous with the isosteric benzothiazines, have the 5H-pyrimidothiazine structure. Compounds (II), (III) and (IV) show immunological activity, inhibiting passive cutaneous anaphyllaxis in the rat.
Subject(s)
Pyrimidines/chemical synthesis , Thiazines/chemical synthesis , Animals , Magnetic Resonance Spectroscopy , Methods , Passive Cutaneous Anaphylaxis/drug effects , Pyrimidines/pharmacology , Rats , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Thiazines/pharmacologyABSTRACT
A description is given of some 2 or 3 dialkylaminoalkyl derivatives of 8-acetylamino-2H-pyridazino[4,5-b][1,4]benzothiazin-1(10H)-one (IV a...d) and 8-acetylamino-3H-pyridazino[4,5-b][1,4]benzothiazin-4(10H)-one (VIII a...d). The derivatives were subjected to pharmacological examination.
Subject(s)
Phenothiazines/chemical synthesis , Animals , Aza Compounds/chemical synthesis , Aza Compounds/pharmacology , Methods , Mice , Phenothiazines/pharmacologyABSTRACT
The synthesis and pharmacological activity of a series of dialkylaminoalkyl esters and dialkylaminoalkyl amides of 4-phenylisocoumarin-3-carboxylic acid are described. The esters show anticoagulant activity whereas the amides show marked antiarhythmic activity.
Subject(s)
Anti-Arrhythmia Agents/chemical synthesis , Anticoagulants/chemical synthesis , Carboxylic Acids/chemical synthesis , Amides/chemical synthesis , Amides/pharmacology , Animals , Carboxylic Acids/pharmacology , Esters/chemical synthesis , Esters/pharmacology , Mice , Motor Activity/drug effectsABSTRACT
Some derivatives of 7-acetylamino-2H-pyridazino [4,5-b] [1,4] benzothiazin-1 (1OH)-one (VI a...d) and of 7-acetylamino-3H-pyridazino [4,5-b] [1,4]benzothiazin-4 (1OH)-one (X a...d) substituted in the 2 and 3 positions with dialkylaminoalkyl groups are described. The compounds were subjected to pharmacological screening.
Subject(s)
Thiazines/chemical synthesis , Alkylation , Crystallization , Isomerism , Pyridazines/chemical synthesis , Pyridazines/pharmacology , Thiazines/pharmacologyABSTRACT
The alkylation with methyl iodide and methyl sulfate of 2-phenyl-10-methyl-2,3-dihydropyridazino [4,5-b] [1,4]benzothiazin-1,4(10H)-dione (A) and the corresponding 3-phenyl substituted isomer (B) has been studied. Some derivatives of (A) and (B) substituted at the O atom with dialkyaminoalkyl groups are described; these have been subjected to pharmacological testing.
Subject(s)
Benzothiadiazines/chemical synthesis , Phenothiazines/chemical synthesis , Alkylation , Indicators and ReagentsABSTRACT
The synthesis of 3-phenyl-10-methyl-2,3-dihydropyridazine[4,5-b] [1,4]benzothiazin-1,4(10H)-dione (I) and the 2 phenyl siomer-(II) is described. The compounds were prepared by the reaction of 2-methylaminothiophenol with 1,2-dihydro-20phenyl-4,5-dibromopyridazin-3,6-dione in an alkaline aqueous/alcoholic medium. The structure of the two isomers was demonstrated by transformation of (I) into 3-phenyl-10-methyl-3H-pyridazino[4,5-b] [1,4]benzothiazin-4(10H)-one (IV) reported in the literature.
Subject(s)
Phenothiazines/chemical synthesis , Pyridazines/chemical synthesis , Thiazines/chemical synthesis , Cyclization , Fibrinolytic Agents/chemical synthesis , Isomerism , MethylationABSTRACT
A description is given of the synthesis of 7- and 8-nitro-derivatives of 1-keto- and 4-keto-2,3-diazaphenothiazine, by cyclization with acids and hydrated alkaline sulfides (XIV) and (XV). Oxidation of these nitroderivatives (XI), (XII), (XVI) and (XVII) gives products corresponding to those obtained by oxidation of the heterocyclic S atom to sulfones (IV), (XIII), (VIII) and (XVIII). Nitration of 1-keto- and 4-keto-2,3-diazaphenothiazine (1) and (V) gives the 7-nitroderivatives with simultaneous oxidation of the sulfur to sulfoxide (II) and (VI); oxidation of these sulfoxides or sulfones gives the same products (IV) and (VIII) obtained by the methods described above. The same compounds are obtained also by nitration of 1-keto- and 4-keto-5,5-dihidroxy-2,3-diazaphenothiazine (III) and (VII).
Subject(s)
Phenothiazines/chemical synthesis , Aza Compounds/chemical synthesis , Cyclization , Nitro Compounds/chemical synthesis , Oxidation-ReductionABSTRACT
Methods of synthesis are described for 10H-pyridazino[4,5-b] [1,4]benzothiazine with alkylamine groups at the 1 and 4 position, triazole derivatives of the same heterocycle containing a pentadecanoic chain and derivatives with dialkylaminoalkyl groups at N-10. The results of pharmacological and microbiological examination are reported.
