Phase II trial of 4-demethoxydaunorubicin in advanced colorectal carcinoma.
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Biomedical subjects
Publications and source records attributed to F Arena.
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A group of ethyl 2-methylimidazo[1,2-a]pyrimidine-3-carboxylates were prepared by reaction of ethyl 2-chloroacetoacetate with some 2-aminopyrimidines. These ethyl esters were then converted into the corresponding carboxylic acids via alkaline hydrolysis. The acids so obtained were evaluated for antiinflammatory, analgesic, antipyretic and ulcerogenic activities.
We have taken into consideration a group of 28 imidazo [1,2-a]pyridine derivatives, some of which were already known, whereas the others have been synthesized and characterized to complete the series. Antiinflammatory, analgesic, antipyretic and ulcerogenic activities of such compounds were evaluated in comparison with indomethacin. The pharmacological data demonstrated the effects exerted on activity by the presence on the heterocyclic system of methyl substituents and/or an acidic moiety.
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The synthesis of a series of 2-methylimidazo[1,2-a]pyridine-3-carboxylic acids was accomplished by reacting some 2-aminopyridines with ethyl 2-chloroacetoacetate and then hydrolyzing the resulting ethyl carboxylates. Such new carboxylic acids were evaluated for antiinflammatory, analgesic, antipyretic, and ulcerogenic activities.
Since we had previously observed the considerable anti-inflammatory activity of imidazo[1,2-a]pyrazine 2-acetic acid, we prepared a series of imidazo[1,2-a]pyrazine derivatives, bearing some substituents on the pyrazine ring and a carboxylic, acetic or alpha-methylacetic moiety on the imidazole ring. These new compounds were tested for antiinflammatory, analgesic, antipyretic and ulcerogenic activities.
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A series of imidazo[1,2-a]pyrimidine-, imidazo[1,2-c]pyrimidine- and imidazo[1,2-b]pyridazinecarboxamides and acetamides were prepared and their antiinflammatory, analgesic, antipyretic and ulcerogenic activities were evaluated.
New sulfones were synthesized; these are analogues of bis-(4-aminophenyl)sulfone (DDS) but contain, instead of one benzene nucleus, a heterocycle that is a pyrimidine, pyrazine or pyridazine nucleus. This was substituted with amine, methoxy, methyl groups or halogens in order to obtain long-acting drugs, similarly to those obtained in the field of sulfonamides. The synthesis was accomplished by reaction of sodium p-amino- or p-acetamidobenzensulfinate with the corresponding halodiazine; only the p-aminophenyl 3-aminopyridazin-6-yl sulfone was obtained by acid hydrolysis. The compounds showed good antitubercular activity in vitro.
A series of imidazo[1,2-a]pyridine-, imidazo[2,1-b]thiazole- and imidazo[2,1-b]benzothiazole-carboxamides and -acetamides were synthesized and their antiinflammatory, analgesic, antipyretic and ulcerogenic activities were evaluated.
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Pseudouridylate synthetase from Salmonella typhimurium has been purified 1,000 fold and is about 90% pure. The enzyme has a molecular weight of 50,000 daltons. In the presence of tRNA there is a change in molecular weight from 50.000 to 100.000. This change does not seem to be due to the formation of a tRNA-enzyme complex but rather to a tRNA induced dimerization. Other properties of the enzyme are described.
2-Hydroxyiminomethyl-4-alkylpyridine methiodides were prepared and tested for their in vitro reactivating potency on phosphorylated electric eel cholinesterase. They were also tested as in vivo protecting agents: only one of the compounds, 4-methyl-2-hydroxyiminopyridine, offered a greater protection from DFP than 2-PAM, the others had little to no effect.
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The preparation of a group of imidazo[1,2-b]pyridazin-2-carboxylic and -2-acetic acids is reported. The ethyl esters of these acids were prepared by reaction of some 3-aminopyridazines with ethyl bromopyruvate or 4-bromoacetoacetate. The acids were obtained by hydrolysis of the corresponding esters, and their anti-inflammatory activity was tested.
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