Nonsteroidal antiinflammatory agents. Part 21: optically active stereoisomers of p-trifluoromethylphenyl- and p-thioanisyl-biphenylyl- hydroxypropionic acids.

The synthesis, diastereomeric separation, assignment to erythro- and threo-configuration by 1HNMR, and optical resolution of 3-(p-trifluoromethyl-phenyl)- and (p-thioanisyl)-2-biphenylyl-3-hydroxypropionic acids are described. The enantiomers were submitted to a preliminary assay to determine antiinflammatory activity.

Nonsteroidal antiinflammatory agents. Part 20(3): Optically active thienyl-biphenylyl-hydroxypropionic acids.

The optically active diastereometric erythro- and threo-3-thienyl-analogues 6a-d of 3-aryl-2-biphenylyl-3-hydroxy-propionic acids have been prepared. Some stereoisomers of 3-(3-thienyl)derivative 6b showed inhibition around 40% in the carrageenan-induced rat paw edema test.

HPLC determination of thioglycolic acid and other aliphatic thiols in cosmetic formulations using ethacrynic acid as precolumn derivatization reagent.

Synopsis Limits imposed on the usage of thioglycolic acid, its salts and esters in cosmetic formulations require selective and sensitive analytical methods for their determination. In this study a convenient and reliable method based on high-performance liquid chromatography (HPLC) has been developed. The method involves a precolumn reaction of the thiol compounds with ethacrynic acid to give thiol adducts which can be separated by reversed-phase liquid chromatography and detected at lambda= 273 nm. The derivatization reaction proved to be quantitative under mild conditions (20 min at pH 7.4 and room temperature) and the chromatographic conditions allowed thioglycolic acid, glyceryl monothioglycolate, thiolactic acid, and thioglycolic acid ethyl ester to be discriminated. The proposed method was successfully applied to the analysis of commercial cosmetic formulations containing thioglycolic acid and glyceryl monothioglycolate, fulfilling the requirements of a general and selective method for the analysis of aliphatic thiols in cosmetics.

Nonsteroidal antiinflammatory agents. XVIII - Stereomeric optically active halogenophenyl-biphenylyl-hydroxypropionic acids.

The optically active stereomers of some 3-(fluoro-, chloro-, bromophenyl)-2-biphenylyl-3-hydroxypropionic acids were prepared and tested for antiinflammatory activity. Surprisingly, the four bromo-isomers were the most active ones, particularly in the threo configuration.

[Nonsteroidal anti-inflammatory agents. 19. Synthesis and activity of stereomeric phenylacetic homologues]. / Nichtsteroidale Entzündungshemmer. 19. Mitteilung: Synthese und Aktivität von stereomeren Phenylessigsäure-Arylhomologen.

The authors synthesized the title compounds as analogues of previously prepared potential antiphlogistic agents. Starting from appropriate carbonyl compound and alpha-metallated phenylacetic acid the diastereomeric racemate pairs were obtained; they were separated, attributed to erythro/threo-configuration by NMR and finally resolved. The potassium salts of the enantiomers were tested for analgesic and antiinflammatory activity, as well as for acute toxicity. Their action in the carrageenan test has been found to be stereoselective, but relatively poor or of briefly lastening.

Nonsteroidal anti-inflammatory agents. Part 17: Stereomeric o-, m-tolyl- and anisyl-biphenylyl-hydroxypropionic acids.

As a part of wider research project on chiral anti-inflammatory arylacanoic acids, the 3-(o- and m-)-(methyl and methoxy)-phenyl-2-biphenylyl-3-hydroxypropionic acids 3a-d were synthesized and resolved in their optically active erythro and threo stereomers, which were submitted to the carrageenan induced rat paw edema test. With respect to the p-isomers, only the threo p-methoxy substitution enhances the anti-inflammatory activity. Some conclusions on structure-activity relationship are discussed.

Nonsteroidal antiinflammatory agents. Part 16: Stereomeric 3-aryl-biphenylyl-hydroxy-propionic acids.

As part of a wider research project on structure-activity relationships of chiral arylalkanoic acids, stereomeric aryl- biphenylyl-hydroxypropionic acids 3a-d have been prepared and their antiinflammatory activity evaluated. Diastereomeric racemic erythro- and threo-acids have been synthesized by reaction of alpha-lithiated biphenylyl-acetic acid salts with the appropriate aldehyde. They were separated, and after attribution of their relative configuration by 1H-NMR analysis, resolved. The antiinflammatory activities of the enantiomeric potassium salts were determined by the carrageenan test.

On the antimicrobial activity of some new poly[2,6-bis(methyleneaminomethyl)-4-methyl]phenols and their N-iodoethylated salts.

The in vitro antimicrobial activity of the title polymers is described. Iodoethylation leads to a sensible improvement of activity only when the amino groups present in the main backbone of the polymers are connected by a long aliphatic chain.

[Nonsteroidal anti-inflammatory agents. XIII. 4-Cyclohexylphenylhydroxyalkanoic acids]. / Antiinfiammatori non steroidei. Nota XIII - Acidi 4-cicloesilfenilidrossialcanoici.

The preparation of some homologues of 2-(4-cyclohexylphenyl)-3-hydroxypropionic acid, the separation of the diastereomeric race-mates, their attribution to erythro and threo series, and the optical resolution of the enantiomers are described. The optical antipodes were screened for acute toxicity, as well as for antiinflammatory and analgesic activity.

Potential antitumor agents IX: synthesis and antitumor activity of two analogues of ketocaine.

The reaction between o-hydroxybutyrophenone and tris(2-chloroethyl)amine gave two analogues (II, V) of the well-known local anesthetic ketocaine (I). Compounds II and V showed interesting antitumor activity in mice implanted with Ehrlich ascites tumor cells (% T/C = 149 at 5 mg/kg and 171 at 50 mg/kg, respectively). Further studies on the pharmacological behavior of these new compounds are in progress.

[Non-steroidal anti-inflammatory agents. Stereoisomers of homologues of 2-(4-biphenylyl)-3-hydroxypropionic acid. XII]. / Antiinflammatori non steroidei. Stereoisomeri di omologhi dell'acido 2-(4-bifenilil)-3-ossipropionico. Nota XII.

The synthesis of some homologues of 2-(4-biphenylyl)-3-hydroxypropionic acid, the separation of related diastereoisomers, their attribution to erythro and threo series, and resolution of the optical antipodes are described. The antiinflammatory activity--initially tested by carrageenin assay--proves generally influenced by steric configuration and is interesting for the isohexanoic derivative.

[5H-Pyrimidothiazines. I. Synthesis 6- or 7-carboxyalkyl derivatives of 5H-pyrimido[4,5b][1,4]thiazine]. / Ricerche sulle 5 H-pirimidotiazine. Nota I - Sintesi di derivati 6 o 7 carbossialchil della 5H-pirimido [4,5-b][1,4]tiazina.

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.

[Preparation of 1-(5'-nitrofurfuryl)-5-halouracils]. / Preparazione di 1-(5'-nitrofurfuril)-5-alogenouracili.

Some 1-(5'-nitrofurfuryl)-5-halouracils were synthetized and tested in vitro for antimicrobial activity. N.M.R. spectra of the compounds proved 1-substitution on uracil.

[Non-steroid anti-inflammatory agents. Stereoisomers of 2-(-4-biphenylyl)-3-oxybutyric acid]. / Antiinfiammatori non steroidei. Nota I - Stereoisomeri dell'acido 2-(4-bifenilil)-3-ossibutirrico

The synthesis, diastereoisomeric separation, attribution to erythro and threo series, and resolution of the enantiomers of 2-(4-biphenylyl)-3-oxybutyric acid are described. The four isomers were tested for anti-inflammatory activity: the preliminary results are interesting, particular those for the (--) erythro enantiomer.

[Research on substances with antiviral activity. III. Structure of the monosubstituted derivatives of 1 H-benzo-[e] indene-1,3(2H)-dione]. / Ricerche su sostanze ad attivitá antivirale. III - Struttura dei derivati di monosostituzione dell'1H-benzo[e]indene-1,3(2H)-dione

The N.M.R. spectra of 1H-benz[e]indene-1,3(2H)-dione (I), 1H-benz[e]indene-2,3-dihydro-1-one (II), 7-methyl-3H-benz[e]indene-1,2-dihydro-3-one (III) and of their oximes, phenylhydrazones and 4-methylthiosemicarbazones show the preferential substitution at 3 position for monoderivatives of (I). This is very interesting in correlation with the structure-activity relationship of derivatives of (I) and (II), some of which have shown in vitro antiviral action in previous research.

[Synthesis of 2,3-diazaphenothiazine. IX. Derivatives of 1- and 4-alkylamine, triazole and N-10-dialkylaminoalky 2,3-diazaphenothiazine]. / Sintesi di 2,3-diazafenotiazine. Nota IX - Derivati 1- e 4-alchilaminici, triazolici ed N-10-dialchilamino-alchilici della 2,3-diazafenotiazina

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.