Failure of N-(2,4-dinitrophenyl)-5-methoxytryptamine (a putative melatonin antagonist) and of N-(3,5-dinitrophenyl)-5-methoxytryptamine to prevent the effects of injections of melatonin in the late afternoon on testicular activity of the golden hamster.

Daily injections of 10 micrograms melatonin in the late afternoon into male golden hamsters kept under a long photoperiod (14 h light: 10 h darkness) and at low ambient temperature 6 +/- 1 degrees C) induced a complete gonadal atrophy after 4 weeks. When administered under the same conditions at doses of 25 micrograms, neither N-(3,5-dinitrophenyl)-5-methoxytryptamine or N-(2,4-dinitrophenyl)-5-methoxytryptamine, a putative melatonin antagonist termed ML-23 in the literature, showed any effect on testicular activity. Moreover, these two drugs were also unable to prevent melatonin-induced gonadal atrophy when injected 30 min before melatonin. The results demonstrate that in the golden hamster and in the present experimental conditions, these drugs do not have the melatonin-antagonistic properties as described in the rat.

Imidazole derivatives of pyrrolidonic and piperidonic as potential inhibitors of human placental aromatase in vitro.

Inhibitory activities towards human Placental aromatase of novel pyrrolidinone and piperidinone drugs were investigated and compared with those of aminoglutethimide (AG) in vitro. All compounds showing a stronger inhibitory effect than this of AG had the following common structural feature: an imidazole side-chain in C-3 position, with a substituted or non-substituted aromatic ring in the C-2 position and an aliphatic chain (n-butyl or n-octyl) or a phenyl moiety on the nitrogen of the pyrrolidone or piperidone ring. When the C-3 side-chain did not bear any imidazole ring, no activity was observed. Respective Ki values for the competitive inhibition exerted by the more potent inhibitors 10, 11, 13 and 21 with androstenedione as substrate were 19.2, 20.3, 16.8 and 15.4 microM, respectively (Ki AG= 77.0 microM).

Dipole moments and conformational equilibrium in some substituted 1-phenyl-1-fluoro-2-halogenoethanes.

Experimental dipole moments of substituted 1-phenyl-1-fluoro-2-halogenoethanes are compared with the vectorially and the theoretically calculated values using the CNDO/2 method. Results support the existence of a conformational mixture of these compounds as solutes; gauche structures are the prevailing conformations as in the related catecholamines.

Synthesis and evaluation of benzimidazole and imidazole compounds as potential aromatase inhibitors.

Several series of benzimidazole and imidazole derivatives have been synthesized and their biological activity evaluated. Their ability to inhibit human placental aromatase activity was tested in vitro. Ten of the tested compounds are more active towards aromatase than aminoglutethimide, the reference molecule. The most active compound XI is five times more potent in the same system. Compounds bearing an aryl group substituted by one or two halogen atom(s) (fluorine or chlorine) in position 4 or 2,4 respectively have also the most interesting activity.

Synthesis and microbiological activity of some 4-butyl-2H-benzo[1,4]thiazin-3-one derivatives.

The synthesis and physicochemical properties of 4-butyl-2H-benzo[1,4]thiazin-3-one derivatives are described. These new compounds were synthesised by alkylation in 4-N position and acylation and/or alkylation of 6-NH2 by phase transfer catalysis. Acid hydrolysis of 6-alkylacylamino group yielded 6-alkylamino-4-butyl-2H-benzo[1,4]thiazin-3-ones. The antimicrobial in vitro activity was determined on five compounds.

5-benzylidene pyrrolones. IV--Synthesis and antifungal activity of some 5-benzylidene derivatives of 1,2-dimethyl-3-carbethoxy-pyrrol-4-one.

In order to investigate the antifungal activity of pyrrolones, the synthesis of derivatives of 5-benzylidene-1,2,-dimethyl-3-carbethoxy-pyrrol-4-one was achieved by a one-step reaction. The condensation reaction was applied to the above-mentioned heterocycle and seven substituted benzaldehydes were obtained providing the entitled compounds, of which six are original. They have preferential E configuration. Antifugal data against Neurospora crassa in comparison with ketoconazole showed that many of the compounds exhibit interesting antifungal activity.

Synthesis and antimicrobial activity of substituted imidazolidinediones and thioxoimidazolidinones.

Synthesis and physico-chemical properties of new 3-benzyl-4-thioxo-5-arylideneimidazolidine-2-ones and 3-benzyl-5-arylideneimidazolidine-2,4-dione are described. These compounds were synthesized by condensation reaction from aromatic aldehydes and 3-substituted imidazolidine-2,4-diones or 4-thioxoimidazolidine-2-ones. The N-alkylation of 5-benzylideneimidazolidine-2,4-dione led simultaneously to mono- and dialkylated derivatives. The nucleophilic addition of 1-methyl-3-benzylimidazolidine-2,4-dione with 2-cyano-3-(3,4-dichlorophenyl) acrylate also yielded the 3-substituted 5-arylideneimidazolidine-2,4-dione derivative. Antimicrobial in vitro activity was determined on some compounds.

Substituted thiazolidinediones and thio-imidazolidinones: synthesis, structural study and pharmacological activity.

Synthesis and physico-chemical properties of six 3-(4-bromophenacyl)-5-arylidene-thiazolidine-2,4-diones and eight 3-(4-chlorobenzyl)-5-arylidene-4-thio-imidazolidine-2-ones are described. These products were synthesized by an aldolisation-crotonisation reaction from aromatic aldehydes and 3-substituted thiazolidine-2,4-diones or 4-thio-imidazolidine-2-ones. Hypoglycemic and peripheral antinociceptive activities were investigated for these compounds.

[Synthesis and antimicrobial activity of chlorobenzyl benzylidene imidazolidinedione derivatives and substituted thiazolidinediones]. / Synthèse et activité antimicrobienne de dérivès chlorobenzyl benzylidène imidazolidinediones et thiazolidinediones substituées.

The synthesis of five chlorobenzyl benzylidene imidazolidinediones and four fluorobenzyl benzylidene thiazolidinediones is described. In order to investigate their antimicrobial activity they are evaluated against microorganism such as Candida albicans, Neurospora crassa, Staphylococcus aureus, Mycobacterium smegmatis and Escherichia coli.

[Synthesis of new fluorogenic substrates derivated of 7-amino-4-trifluoromethylcoumarin. Detection of gram-negative bacteria, Streptococci group A and Enterococci]. / Synthèse de nouveaux substrats fluorogéniques dérivés de la 7-amino 4-trifluorométhyl coumarine. Détection des bactéries Gram négatif, des Streptocoques groupe A et des Entérocoques.

The synthesis of substrates having 7-amino 4-trifluoromethyl coumarin as fluorogenic reagent is described. The first group is performed from L-alanine derivative in order to investigate L-alanine aminopeptidase activity for the detection of Gram-negative bacteria. The second group is synthesized from the L-pyrrolidon carboxylic acid. It allows us to detect the PYRase activity of group A Streptococci and Enterococci. These substrates are evaluated with the N-protected form and the amino free one.

[Contribution of parachor to the study of structure-activity relationship. Aromatase inhibitor activity of androstenediones]. / Contribution du parachor à l'étude de corrélations structure-activité. Activité inhibitrice d'aromatase des androstènediones.

Parachor has been used extensively in physical organic chemistry for structure determination, but rarely in quantitative correlation of structure and biological activity. The purpose of this study is the contribution of the parachor in the QSAR of androstenediones derivatives and their inhibition of aromatase enzyme. Good correlations were obtained for two classes of steroids inhibitors of oestrogens biosynthesis.

[Quantitative anti-inflammatory and analgesic structure-activity relationship of 2-amino-3-ethoxycarbonyl thiophene derivatives]. / Relations quantitatives structure-activité anti-inflammatoire et analgésique des dérivés du 2-amino 3-éthoxycarbonyl thiophène.

Quantitative structure activity relationships of 2-amino-3-carboxylic acid ethyl ester thiophene derivatives are described. These compounds exhibit a weak anti-edema activity and a more significant analgesic activity relative to acetylsalicylic acid and oxyphenylbutazone. The application of statistical analysis has shown that for analgesic activity, lipophilic parameters and molar refractivity seem to be the parameters giving the best explanations of variances of biological data for eight compounds, the lipophilicity exhibits a degree of correlation of 81.9% regarding anti-inflammatory activity.

[5-Fluoro (3H) pyrimidine-4-ones: synthesis, reactivity and pharmacological properties]. / 5-Fluoro (3H) pyrimidine-4-ones: synthèse, réactivité et propriétés pharmacologiques.

Fourteen fluoro pyrimidine-4-ones, four fluoro bispyrimidine-4-ones and two fluoro pyrimidine-4-ones with fused ring have been prepared. The reactivity of the carbonyl group of two pyrimidine-4-ones phosphorus oxychloride was studied. The 4-chloro pyrimidines reacted with ammonia or morpholine giving 4-substituted pyrimidines. Eight compounds are evaluated for their anti-inflammatory and anti-convulsivant properties: they were found to be weakly active against oedema and three of them protected rats form tonic convulsions.

[Synthesis and antifungal activity of chlorobenzyl benzylidene thiazolidinediones and substituted of imidazolidinediones]. / Synthèse et activité antifongique des chlorobenzyl benzylidène thiazolidinediones et imidazolidinediones substituées.

The synthesis of six benzylidene thiazolidinediones and four benzylidene imidazolidinediones is described. In order to investigate their antifungal activity, they are evaluated against microorganism such as Candida albicans, Neurospora crassa, Staphylococcus aureus and Escherichia coli.

[Substituted thio-arylidene thiazolidinones: synthesis and structural study]. / Thio-arylidène thiazolidinones substituées: synthèse et étude structurale.

The synthesis and physico-chemical properties of fourteen 4-thio-5-arylidene-thiazolidine-2-ones and eight 3-(4-bromophenacyl)-4-thio-5-arylidene-thiazolidine-2-ones are described. These products were synthetized by the aldolisation-crotonisation reaction between aromatic aldehydes and 4-thio-thiazolidine-2-one followed by N-alkylation of this substituted compounds.

[Synthesis and structure of substituted bromo and nitrobenzyl benzylidene imidazolidinediones and thiazolidinediones]. / Synthèse et structure des bromo et nitrobenzyl benzylidène imidazolidinediones et thiazolidinediones substituées.

Synthesis and physico-chemical properties of five bromobenzyl-benzylidene-imidazolidinediones and five nitrobenzyl- or benzyl-benzylidene-thiazolidinediones are described. The microbiological activity of bromobenzyl-benzylidene-imidazolidinediones against microorganisms such as Candida albicans, Neurospora crassa and Mycobacterium smegmatis are evaluated.

[Synthesis and structural study of 5-arylidene thiazolidine-2,4-diones and 3-substituted-4-thio-imidazolidine-2-ones]. / Synthèse et étude structurale des 5-arylidène thiazolidine-2, 4-diones et 4-thio-imidazolidine-2-ones-3-substituées.

The synthesis and the physico-chemical properties of four 3-(4-bromophenacyl)-5-arylidene-thiazolidine-2,4-diones, two 3-(4-bromobenzyl)-5-arylidene-thiazolidine-2,4-diones and seven 3-(4-chlorobenzyl)-5-arylidene-4-thio-imidazolidine-2-ones were described. These products were synthetized by the aldolisation-crotonisation reaction between aromatic aldehydes and substituted thiazolidinediones or thio-imidazolidinones.

[Quantitative structure-hypoglycemic activity relationships of some thiazolidine and imidazolidine-2,4-diones]. / Relations quantitatives structure-activité hypoglycémiante de quelques thiazolidine- et imidazolidine-2,4-diones.

Quantitative structure-activity relationships are described for twenty six title compounds. Five compounds exhibit a significant hypoglycemic activity like insulin used as standard. The aim of the present paper is to investigate the contribution of the different substituents in the biological activity. The application of Fujita-Ban and Hansch models has shown that lipophilic and electronic parameters seem to be the best explanation of variance of biological data.

[New substituted 4-thioxothiazolidin-2-one derivatives: synthesis and structural study]. / Synthèse et étude structurale de nouvelles 4-thioxothiazolidin-2-ones substituées.

Synthesis and physico-chemical properties of some 3-benzyl- and 3-phenacyl-4-thioxo-5-benzylidenethiazolidin-2-one derivatives are described. Fifteen new compounds were synthesized from thiazolidin-2-one by thionation of the 4-carbonyle, alkylation of the 3-N and aldolisation-crotonisation of 5-CH(2) with aromatic aldehydes. Soon, these new compounds will be tested for their bacteriostatic activity.

[Synthesis and structure of substituted arylazo-imidazolidines and arylidenethiazolidines]. / Synthèse et structure des arylazo-imidazolidines et arylidènethiazolidines substituées.

Synthesis and physico-chemical properties of four 3-benzyl or 3-(4-chlorobenzyl)-4-thioxo-5-arylazo-imidazolidin-2-ones, five 3-(4-nitrobenzyl)-5-arylidenethiazolidine-2,4-diones and three 3-(4-phenyl-phenacyl)-4-thioxo-5-arylidenethiazolidin-2-ones have been described. These new products were synthesized by an aldolisation-crotonisation reaction from aromatic aldehydes and 3-substituted thioxothiazolidin-2-ones or thiazolidine-2,4-diones. The arylazo-imidazolidine compounds were synthesized by copulation of diazonium ions with imidazolidines. Antimicrobial activity was determined for some compounds.