[Synthesis and pharmacologic study of some derivatives of 2-piperazinylpyrimidine].
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Biomedical subjects
Publications and source records attributed to F Ravenna.
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The synthesis of N6,O2'-dipivaloyl-cyclic AMP is described with some pharmacological tests made in comparison with the dibutyryl homolog. The two compounds proved equally active in increasing glycemia in the rabbit whereas the dipivaloyl derivative is less effective in counteracting contractions induced by imidazole in the isolated guinea-pig trachea.
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The preparation of some derivatives of lidoflazine bearing a phenylcyclohexane residue in place of the m.xylene is described. Study of the coronary dilating activity on the isolated heart showed that this activity is markedly increased by the modification. Acute toxicity in rats is also strongly increased.
The paper describes the preparation and study of the pharmacological properties of a series of derivatives with the general formula. (see article) where R is a cyclohexyl or cyclohexenyl radical and R1 is a hydrogen, methyl or cyclohexyl. The compounds with a single cycloaliphatic radical ortho to the basic chain, and in particular the one with a cyclohexyl (exaprolol), were found to be particularly active in blocking the beta-adrenergic receptors, as antiarrhythmics and local anesthetics, while the introduction of a second radical or the shift of the cycloaliphatic radical to meta or para position caused the said pharmacological activities to disappear almost entirely, with the exception of the local anesthetic action.
The paper describes the synthesis and the pharmacological evaluation of some derivatives of prenylamine, all with a cycloaliphatic ring within or instead of the isopropylamine moiety. Their general formulas are: (C6H5)2CH-CH2-CH2-NH-CH-CH2-R CH2 (I) (C6H5)2CH-CH2-CH2-NH-R' (II) where R contains and R' is a cycloaliphatic ring. Several compounds and particularly those of formula (I), and of formula (II), where the alicyclic ring had a bulky substituent in para were more active than prenylamine as coronary vasodilators on isolated guinea-pig heart (Langendorff). The most interesting derivative was M.G. 8926 [N-(3,3-diphenylpropyl)-alpha-methyl-beta-cyclohexylethylamine], which was more active than prenylamine on Langendorff's heart and in enhancing the pressor response to catecholamines and inhibiting the isoprenaline induced hypotension. Moreover, it had almost the same effects as prenylamine as spasmolytic, local and general anesthetic, on heart rate and arterial pressure and against coronary spasm from pitressin.
Seventeen acids with diphenylyl and cyclohexylphenyl groups were esterified with the hydroxyl group at position 21 of prednisolone and triamcinolone acetonide. Some of these esters showed marked activity against carrageenin edema and Selye spots in the rat, especially on local application.
Some derivatives of oxacillin were prepared containing in place of the phenyl group a cyclohexyl, cyclohexylphenyl, phenylcyclohexyl or diphenylyl moiety. In the same compounds a methylene bridge between the carboxy group and the heterocyclic ring was inserted. The results of in vitro evaluation of antibacterial activity are given.
Some penicillins with structures similar to that of ampicillin and cyclacillin bearing the phenylcyclohexane grouping were prepared. In vitro tests of antibacterial activity showed that the introduction of this residue led to reduced activity in comparison with that of the parent compound.
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