[Methionine derivatives with liver protecting activity]. / Derivati della metionina ad attività epatoprotettrice.

Some methionine derivatives with the amine group acylated with an aliphatic group bearing a free, esterified or etherified thiol group in the omega position were prepared and tested for protection against CCl4, paracetamol, ethyl alcohol and ethionine intoxication. Acid (XIV) (MG 28013) (Table I) and some of its alkyl derivatives (XVIII) (MG 28228) and (XIX) (MG 28226) proved to have significant activity in these tests. A more in-depth study on MG 28226 however indicated a slight intolerance when subacute toxicity was examined (90 gg).

[Synthesis and pharmacologic study of new esters of naproxen with derivatives of N-oxyethylpiperazine]. / Sintesi e studio farmacologico di nuovi esteri del naproxen con derivati dell'N-ossietilpiperazina.

The preparation of naproxen esters with N,N'-dioxyethylpiperazine and derivatives of N-oxyethylpiperazine with various substituents on the nitrogen is described. Study of analgesic-antiinflammatory properties in comparison with a reference compounds has shown that in most of the new compounds analgesic activity (phenylquinone) is preserved whereas antiinflammatory activity (carrageenin) is generally reduced. The diester with N,N'-dioxyethylpiperazine (MG 28136) proved most interesting, showing clear pharmacological activity and very low toxicity.

Pantetheine and pantethine esters with hypolipidemic nicotinic acid derivatives.

We prepared several esters of pantetheine and pantethine, respectively, with 3-pyridineacetic acid and with 3-(3-pyridinemethoxycarbonyl)propionic acid, and we tested these products for their capacity to lower serum non-esterified fatty acids and triglycerides in normal animals. Among the products thus tested, the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid (MG 28362) displayed marked hypolipidemic activity, the action being of uncommonly long duration.

[Heterocyclic compounds with potential anti-inflammatory activity containing a 4-aminophenylalkanoic acid residue. V. Derivatives of 2,4-dihydro-3H-pyrazole-3-one]. / Composti eterociclici a potenziale attività antiinfiammatoria contenenti il residuo di un acido 4-amminofenilalcanoico. Nota V. Derivati del 2,4-diidro-3H-pirazol-3-one.

The synthesis and pharmacological study of some derivatives of 2,4-dihydro-3H-pyrazol-3-one of general formula (I) are described. The compound in which R = C6H5 and R' = CH3 [2-(4- carboxymethylphenyl )-4-phenyl-5-methyl-2,4- dihydropyrazol -3-one] (MG 18949) proved to have antipyretic activity equal to that of ibuprofen and aminopyrine.

[Heterocyclic compounds containing the residue of a 4-aminophenylalkanoic acid with potential anti-inflammatory activity. IV. Derivatives of 2-phenyl-2H-indazole]. / Composti eterociclici contenenti il residuo di un acido 4-amminofenilalcanoico a potenziale attività antiinfiammatoria. Nota IV - Derivati del 2-fenil-2H-indazolo.

Numerous derivatives of 2-phenyl-2H-indazole were prepared. The compounds were of general formula I: where R is an acid, neutral or basic radical and R1, R2, R3 represent various functional groups, hydrogen atom or chlorine. The compounds were examined for analgesic-antiinflammatory properties and in some cases as inhibitors of platelets aggregation. Among the compounds where R is an alkanoic acid residue, the only compound showing interesting activity was M.G. 18755 [R = CH(CH3) COOH; R1, R2, R3 = H] and its lysine salt (M.G. 18334), which in various tests showed activity greater than that of ibuprofen. The homologous butyric derivative (M.G. 18860) showed a good anti-aggregatin activity.

[Heterocyclic compounds containing a 4-aminophenylalkanoic acid group with potential antiinflammatory activity. II. 2-Substituted morpholine derivatives]. / Composti eterociclici contenenti il residuo di un acido 4-amminofenilalcanoico a presunta attività antiinfiammatoria. Nota II--Derivati morfolinici 2-sostituiti.

Derivatives of 4-aminophenylalkanoic acids where the amino groups is part of a 3-morpholinone or a 2-morpholine ring, substituted in position 2 with a methyl, phenyl, 2-thienyl or (2-cyclohexyl)phenoxymethyl residue are described. Pharmacological evaluation aimed at evidencing analgesic and anti-inflammatory activity gave no noteworthy results.

[2-(2-Thienyl)morpholines with CNS activity]. / 2-(2-Teinil)morfoline attive sul S.N.C.

The synthesis and pharmacological investigation of 2-(2-thienyl)morpholine and some of its derivatives substituted on the nitrogen are described. The non-substituted compound showed interesting antidepressive properties with a pharmacological profile similar to that of imipramine.

[Cyclohexylphenoxymorpholines with antidepressive activity]. / Cicloesilfenossimorfoline ad attività antidepressiva.

A report is given of the synthesis and pharmacological investigation of some cyclohexylphenoxymethylmorpholines of general formula: Formula: (see text). The compound in which R = H and bearing the cyclohexyl group at the ortho position showed a pharmacological profile typical of drugs with antidepressant activity and was studied in detail in comparison with viloxazine and imipramine.

Cyclohexylphenoxy amidoximes and imidazolines with antidepressive and alpha-adrenergic activity.

The effect of variation of the cycloaliphatic residue position on pharmacological activity was studied in two series of cyclohexylphenoxy derivatives (A and B). (Formula: See text) The ortho derivatives generally exhibit remarkably strong activity; (A) has an imipramine-like pharmacological profile; (B) with Y = H is more active than naphazoline and xylomethazoline as vasoconstrictor. The meta and para substituted derivatives and all (B) derivatives with R = CH3 exhibited no definite or interesting pharmacological activities.

[Lidoflazine derivatives with cycloaliphatic residues of coronary dilator activity]. / Derivati della lidoflazina con residui cicloalifatici ad attività coronarodilatatrice.

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.

[Synthesis of quinazolinic and benzoxazinonic acids and study of their anti-inflammatory activity]. / Sintesi di acidi chinazolinonici e benzossazinonici e studio delle loro proprieta antiinfiammatorie

The preparation of some phenylalkonic acids where the phenylalkanoic moiety is introduced into the position 3 of derivatives of 4(3H)quinazolinone, 2,3-dihydro-4(1H)quinazolinone or of 2,3-dihydro-4H-1,3-benzoxain-4-one is described. The products were tested for antinflammatory activity but proved to be devoid of significant activity.

Basic ethers of cyclohexylphenols with beta-blocking activity: synthesis and pharmacological study of exaprolol.

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.

Synthesis and pharmacological study of diphenylalkylamines with cycloaliphatic residues. New coronary vasodilators.

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.