Showing papers by "Roussel Uclaf published in 1981"

Differences in the biotransformation of a 17 beta-hydroxylated steroid, trenbolone acetate, in rat and cow.

Abstract: 1. The metabolism of trenbolone acetate, 17 beta-acetoxyestra-4,9,11-trien-3-one (TBA), an anabolic compound used as a growth promoter, was compared in rat and cow. 2. [6,7-3H] TBA was injected i.v. into rats and a heifer, and bile was collected for 24 h. In both species, the bile was the major route of excretion. TBA undergoes an extensive hydrolysis to 17 beta-hydroxyestra-4,9,11-trien-3-one and the unchanged compound was not detected, but subsequent major metabolic pathways are different in the two species. 3. In the rat, oxidation of the 17 beta-hydroxyl to the 17-oxo group and hydroxylation in the 16 alpha-position are the major routes. The three major metabolites are 17 beta-hydroxyestra-4,9,11-trien-3-one, 16 alpha, 17 beta-dihydroxyestra-4,9,11-trien-3-one and 16 alpha-hydroxyestra-4,9,11-trien-3, 17-dione. 4. In the heifer, 17 alpha-epimerization is the major pathway and the main metabolite is the 17 alpha-hydroxyestra-4,9,11-trien-3-one. 5. In both species, estra-4,9,11-trien-3,17-dione and the other metabolites, resulting either from hydroxylation in 1, 2, 6 beta, 16 alpha or 16 beta positions, or from aromatization of the A ring, were minor products. 6. Overall, 60% of the 3-oxotriene structures identified in the rat bile were 17 beta-hydroxylated and the remainder were 17-keto metabolites, whereas in the heifer bile 90% were 17 alpha-hydroxylated compounds. 7. Thus, in bovine species, the major pathway is similar to those of testosterone or 17 beta-estradiol which are mainly excreted as their 17 alpha-epimers. The epimerization strongly decreases the biological potency, as with the natural 17 beta-hormones, and leads to detoxication of tissue residues.

The Interaction of Indole Derivatives with the Serotonin Receptor and Non-Dopaminergic Circling Behaviour

Abstract: Circling behaviour applied to the study of dopaminergic mechanisms in the brain has been up to now a most fruitful pharmacological procedure and all its possibilities have certainly not been explored. It is however more and more evident that other neurotransmitters can also contribute to the expression of this behaviour. The recent demonstrations of the important role of GABA in the substantia nigra is one example (Scheel-Kruger et al. 1977; Waddington 1977; Oberlander et al. 1977) and the results obtained with novel series of piperidinyl indoles and tetrahydropyridinyl indoles (∆ 3,4) (Dumont et al. 1976; Nedelec et al. 1978), the general structure of which is shown in figure 1, is another. These compounds can be considered as semi-rigid serotonin analogues in which the side chain N atom is further away from the indole nucleus than it would be in the most stable conformations of serotonin itself (P. Hunt, L. Nedelec in preparation).

Novel erythromycin a derivatives

Abstract: Novel erythromycin derivatives in the syn form or anti form or mixtures of the syn and anti forms of the formula ##STR1## wherein A is a linear or branched alkylene of 1 to 6 carbon atoms, R is selected from the group consisting of optionally substituted alkoxy of 1 to 6 carbon atoms, optionally substituted alkenyloxy and alkynyloxy of 2 to 6 carbon atoms, optionally substituted alkylthio of 1 to 6 carbon atoms, optionally substituted alkenylthio and alkynylthio of 2 to 6 carbon atoms with the thio group optionally oxidized to the sulfoxide or sulfone form, optionally substituted aryloxy and arylthio, optionally substituted aralkyloxy and arylalkylthio, the thio derivatives optionally oxidized to sulfoxide or sulfone, ##STR2## optionally substituted quaternary ammonium group, halogen, optionally substituted 1,2-epoxyethyl and the group resulting from opening of the epoxy with a nucleophilic reactant, ##STR3## a free or protected formyl, --COOR', thiocyanate, --CN, acyl and carbamoyl, R1 and R2 are individually selected from the group consisting of hydrogen, and optionally substituted alkyl of 1 to 6 carbon atoms or taken together with the nitrogen atom to which they are attached form an optionally substituted, optionally unsaturated heterocycle which can contain another heteroatom, B is selected from the group consisting of optionally substituted alkyl and alkoxy of 1 to 6 carbon atoms, optionally substituted aryl and aryloxy and optionally substituted aralkyl and aralkoxy of 1 to 6 alkyl carbon atoms, R' is selected from the group consisting of hydrogen, a cation and an ester group, Ra is selected from the group consisting of hydrogen and acyl of an organic carboxylic acid of 1 to 18 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts having very good antibiotic activity and their preparation.

Oxime derivatives of 3-alkyloxy- or 3-alkylthiomethyl 7-amino-thiazolylacetamido cephalosporanic acid, their preparation, their use as medicaments and compositions containing them

Abstract: 1. Claims for Contracting States : BE CH DE GB IT LI LU NL SE Products of general formula (I') : see diagramm : EP0104671,P40,F2 syn isomers in which R, A, X', R'a, n have the following significances either A] R represents, either a linear or branched alkyl, alkenyl, alkynyl or cycloalkyl radical having at most 6 carbon atoms, or an acetyl, propionyl, butyryl, valeryl, hexanoyl, acryloyl, crotonyl, benzoyl or carbamoyl radical, each of these radicals being optionally substituted by one or more radicals chosen from the following radicals ; carboxy optionally salified or esterified, methoxy, carboxyl, ethoxy carbonyl, carbamoyl, amino dimethylcarbamoyl, methylamino, dimethylamino, halogen, methoxy, ethoxy, propyloxy, methylthio, phenyl ethylthio, tetrazolyl, phenylthio, tetrazolylthio or thiadiazolylthio optionally substituted by methyl, or R represents a methoxycarbonyl or ethoxycarbonyl radical, A represents a hydrogen atom, an equivalent of an alkali metal, of an alkaline earth metal, of magnesium, of ammonium or of an aminated organic base, or A represents the remainder of an easily cleavable ester group, R'a represents an alkyl radical optionally interrupted by a heteroatom, linear or branched alkenyl or alkynyl radical having at most 6 carbon atoms, or a benzyl or phenylethyl radical optionally substituted by a carboxy, amino or dimethylaminoethyl radical, n is equal to 0, 1 or 2, X' represents a sulphur atom optionally oxidised in the form of the sulphoxide or sulphone, or an oxygen atom, it being understood that R does not represent an alkenyl or alkynyl radical having at most 6 carbon atoms or a linear or branched alkyl radical having at most 6 carbon atoms optionally substituted by one or more radicals chosen from the following, carboxy optionally salified or esterified, alkoxycarbonyl, amino, alkylamino, dialkylamino or heterocyclic aryl, when the radical -X'-R'a represents an alkoxy, alkylthio or alkenylthio radical ; or B] n is equal to 0, A represents a hydrogen atom and either R represents a -CH2 -CH2 -NH2 , -CH2 CO2 H or -C(CH3 )2 CO2 H radical, X' represents a sulphur or oxygen atom and R'a represents a methyl or ethyl radical or R represents a see diagramm : EP0104671,P41,F1 radical, X' represents an oxygen or sulphur atom and R'a represents a methyl radical as well as the salts of products of formula (I') with mineral or organic acids. 1. Claims for Contracting State : AT Preparation process for products of general formula (I') see diagramm : EP0104671,P45,F1 syn isomers in which R, A, X', R'a, n have the following significances either A] R represents, either a linear or branched alkyl radical, an alkenyl, alkynyl or cycloalkyl radical having at most 6 carbon atoms, carbamoyl each of these radicals being optionally substituted by one or more of the following radicals, carboxy optionally salified or esterified, methoxy carboxyl, ethoxy carbonyl, carbamoyl, amino-dimethylcarbamoyl, methylamino, dimethylamino, halogen, methoxy, ethoxy, propyloxy, methylthio, phenyl ethylthio, tetrazolyl, phenylthio, tetrazolylthio or thiadiazolylthio optionally substituted by methyl, or R represents a methoxycarbonyl or ethoxycarbonyl radical, A represents a hydrogen atom, an equivalent of an alkali metal, of an alkaline earth metal, of magnesium, of ammonium or of an aminated organic base, or A represents the remainder of an easily cleavable ester group, R'a represents an alkyl radical optionally interrupted by a heteroatom, linear or branched alkenyl or alkynyl radical having at most 6 carbon atoms, or a benzyl or phenylethyl radical optionally substituted by a carboxy, amino or dimethylaminoethyl radical, n is equal to 0, 1 or 2, X' represents a sulphur atom optionally oxidised in the form of the sulphoxide or sulphone, or an oxygen atom, it being understood that R does not represent an alkenyl or alkynyl radical having at most 6 carbon atoms or a linear or branched alkyl radical having at most 6 carbon atoms optionally substituted by one or more of the following carboxy optionally salified or esterified, alkoxycarbonyl, amino, alkylamino, dialkylamino or heterocyclic aryl, when the -X'-R'a radical represents an alkoxy, alkylthio or alkenylthio radical ; or B] n is equal to 0, A represents a hydrogen atom and either R represents a CH2 -CH2 -NH2 , -CH2 CO2 H or -C(CH3 )2 CO2 H radical, X' represents a sulphur or oxygen atom and R'a represents a methyl or ethyl radical or R represents a see diagramm : EP0104671,P45,F2 radical, X' represents an oxygen or sulphur atom and R'a represents a methyl radical as well as the salts of products of formula (I') with mineral or organic acids characterised in that a product of formula (II) see diagramm : EP0104671,P46,F1 in which n, X' and R'a have the significance indicated previously and A' represents a hydrogen atom or the remainder of an easily cleavable ester group, is treated by a product of formula (III) : see diagramm : EP0104671,P46,F2 or a functional derivative of this acid, formula (III) in which R1 represents a hydrogen atom or a protector group of the amino radical and either R' represents a linear or branched alkyl radical, an alkenyl, alkynyl or cycloalkyl radical having at most 6 carbon atoms, or R' represents one of the following radicals, acetyl, propionyl, butyryl, valeryl, hexanoyl, acryloyl, crotonoyl, benzoyl, carbamoyl or alkoxycarbonyl, each of these radicals being optionally substituted, to obtain a product of formula (IV) : see diagramm : EP0104671,P46,F3 in which R1 , R', A', R'a, X' and n have the previous significance, which product, if desired, in the case where n is equal to 0 and X' represents a sulphur or oxygen atom, is treated with an oxidation agent, to obtain a product of formula (IV) in which n is equal to 1 or 2 and X' represents a sulphur atom oxidised in the form of the sulphoxide or sulphone or an oxygen atom and, which product of formula IV, if necessary or if desired, is subjected to one or more of the following reactions, in any order : a) detachment by hydrolysis, hydrogenolysis or by the action of thiourea of all or part of the ester groups or the protector groups of the amino radical or radicals, b) esterification or salification of the carboxylic radical or radicals by a base, c) salification of the amino radical or radicals by an acid.

Esters of cyclopropane-carboxylic acids related to pyrethric acid, their preparation and use as insecticides

Abstract: 1. Claims (for the Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE) In all possible isomeric forms, or in the form of a mixture of isomers, the compounds with the formula I see diagramm : EP0050534,P45,F2 in which the cyclopropane acid copula is of 1R cis structure and the geometry of the double bond is E and in which R represents either a linear, branched or cyclic alkyl radical, saturated or unsaturated, containing from 1 to 8 carbon atoms, possibly substituted by one or more functional groups, identical or different, or an aryl group containing from 6 to 14 carbon atoms, possibly substituted by one or more functional groups, identical or different, or a heterocyclic radical possibly substituted by one or more functional groups, identical or different, X represents a halogen atom and B represents either a benzyl radical possibly substituted by one or more radicals chosen from the group composed of alkyl radicals including from 1 to 4 carbon atoms, alkenyl radicals including from 2 to 6 carbon atoms, alkenyloxy radicals including from 2 to 6 carbon atoms, alkadienyl radicals including from 4 to 8 carbon atoms, the methylene dioxy radical and halogen atoms, or a see diagramm : EP0050534,P46,F1 group in which the substituent R1 represents a hydrogen atom or a methyl radical and the substituent R2 represents a monocyclic aryl or a -CH2 -C=-CH group and in particular a 5-benzyl-3-furyl methyl group, or a see diagramm : EP0050534,P46,F2 group in which a represents a hydrogen atom or a methyl radical and R3 represents an organic aliphatic radical including from 2 to 6 carbon atoms and one or more carbon-carbon unsaturations and in particular the -CH2 -CH=CH2 , -CH2 -CH=CH-CH3 , -CH2 -CH=CH-CH=CH2 , -CH2 -CH=CH-CH2 -CH3 radical, or a see diagramm : EP0050534,P46,F3 group, in which a represents a hydrogen atom or a methyl radical, R3 retains the same significance as before, each of R'1 and R'2 , identical or different, represents a hydrogen atom, a halogen atom, an alkyl radical including from 1 to 6 carbon atoms, an aryl radical including from 6 to 10 carbon atoms, an alkyloxycarbonyl group including from 2 to 5 carbon atoms, or a cyano group, or a see diagramm : EP0050534,P46,F4 group, in which B' represents an oxygen or sulphur atom, a see diagramm : EP0050534,P46,F5 or -CH2 - group or a sulphoxide group or a sulphone group and R4 represents a hydrogen atom, a -C=-CN radical, a methyl radical, a -CONH2 radical, a -CSNH2 radical or a -C=-CH radical, R5 represents a halogen atom or a methyl radical and n represents a numeral, 0, 1 or 2, and in particular the 3-phenoxybenzyl, alpha-cyano-3-phenoxybenzyl, alpha-ethynyl-3-phenoxybenzyl, 3-benzoylbenzyl, 1-(3-phenoxyphenyl) ethyl or alpha-thioamido-3-phenoxybenzyl group, or a see diagramm : EP0050534,P47,F1 group, or a see diagramm : EP0050534,P47,F2 group, in which the substituents R6 , R7 , R8 , R9 represent a hydrogen atom, a chlorine atom, or a methyl radical and in which S/l symbolises an aromatic ring or an analogous dihydro or tetrahydro ring, or a see diagramm : EP0050534,P47,F3 group or a see diagramm : EP0050534,P47,F4 group, in which R10 represents a hydrogen atom or a CN radical, R12 represents a -CH2 -radical or an oxygen atom, R11 represents a thiazolyl or a thiadiazolyl radical, whose bond with see diagramm : EP0050534,P47,F5 can be found at any one of the available positions, R12 being linked to R11 by the carbon atom contained between the sulphur atom and a nitrogen atom, or a see diagramm : EP0050534,P48,F1 group 1. a see diagramm : EP0050534,P48,F1 group or a see diagramm : EP0050534,P48,F2 group in which R13 represents a hydrogen atom or a CN radical, or a see diagramm : EP0050534,P48,F3 group in which R13 is defined as above, and the benzoyl radical is at position 3 or 4, or a see diagramm : EP0050534,P48,F4 group in which R14 represents a hydrogen atom, a methyl, ethynyl or cyano radical and each of R15 and R16 being different, represents a hydrogen, fluorine or bromine atom, or a see diagramm : EP0050534,P48,F5 group in which R14 is defined as above, each of the R17 'S represents independently an alkyl group containing from 1 to 4 carbon atoms, an alkoxy group containing from 1 to 4 carbon atoms, an alkylthio group containing from 1 to 4 carbon atoms, an alkyl sulphonyl group containing from 1 to 4 carbon atoms, a trifluoromethyl group, a 3,4-methylene dioxy group, or a chloro, fluoro or bromo group, p represents a numeral 0, 1 or 2 and B" represents an oxygen atom or a sulphur atom. 1. Claims (for the Contracting State AT) Process for preparing, in all possible isomeric forms, or in the form of a mixture of isomers, the compounds with the formula I : see diagramm : EP0050534,P52,F3 in which R represents either a linear, branched or cyclic alkyl radical, saturated or unsaturated, containing from 1 to 8 carbon atoms, possibly substituted by one or more functional groups, identical or different, or an aryl group containing from 6 to 14 carbon atoms, possibly substituted by one or more functional groups, identical or different, or a heterocyclic radical possibly substituted by one or more functional groups, identical or different, B represents either a linear, branched or cyclic alkyl radical, saturated or unsaturated, containing from 1 to 18 carbon atoms, or the residue of an alcohol used in the synthesis of esters of the pyrethrinoid series and X represents a halogen atom, the ethylene double bond having the geometry Z or E, characterized in that an acid with the formula II : see diagramm : EP0050534,P52,F4 in which X and R retain the same significance as previously, this acid being in the form of mixtures of E or Z isomers or in the form of an E or Z isomer, the substituted cyclopropane ring being able to be in all its possible sterio-isomeric forms, or in the form of a mixture of stereo-isomers or a functional derivative of this acid, is made to react with an alcohol with the formula III : where B retains the same significance as previously or with a functional derivative of this alcohol, so as to obtain a corresponding compound with the formula I, which if desired, is submitted to the action of a selective cleavage agent of the CO2 R group so as to obtain a compound with the formula IV : see diagramm : EP0050534,P53,F1 in which B retains the same significance as previously, then, this acid with the formula IV or a functional derivative of this acid, is submitted to the action of an alcohol with the formula R-OH in which R retains its previous significance, so as to obtain a corresponding compound with the formula I.

Cyclopropane carboxylic acid derivatives, their preparation, their use against parasites in plants and animals, their compositions and their intermediates

Abstract: 1. Claims (for the contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE) In all the possible isomer forms, the compounds with the formula (I') : see diagramm : EP0041021,P51,F1 in which the double bond has Z geometry, the cyclopropane copula is of 1R cis structure and A' represents : either an alkyl radical containing 1-18 carbon atoms, or a benzyl radical possibly substituted by one or more radicals chosen from the group constituted by alkyl radicals containing 1-4 carbon atoms, alkenyl radicals containing 2-6 carbon atoms, alkenyloxy radicals containing 2-6 carbon atoms, alkadienyl radicals containing 4-8 carbon atoms, the methylenedioxy residue, and the halogen atoms, or a see diagramm : EP0041021,P51,F2 group, in which the substituent R1 represents a hydrogen atom or a methyl radical and the substituent R2 represents a monocyclic aryl or a -CH2 -C -= CH group and notably a 5-benzyl-3-furylmethyl group, or a see diagramm : EP0041021,P51,F3 group in which R3 represents an aliphatic organic radical containing 2-6 carbon atoms and one or more carbon-carbon unsaturations and notably the radicals -CH2 -CH=CH2 , -CH2 -CH=CH-CH3 , -CH2 -CH=CH-C2 H5 , -CH2 -CH=CH-CH=CH2 , or a see diagramm : EP0041021,P51,F4 group, in which R3 retains the same significance as previously, each of R'1 and R'2 , identical or different, represents a hydrogen atom, a halogen atom, an alkyl radical containing 1-6 carbon atoms, an aryl radical containing 6-10 carbon atoms, an alkyloxycarbonyl group containing 2-5 carbon atoms, or a cyano group, or a see diagramm : EP0041021,P51,F5 group, in which B represents a CH2 group, or a C=O group, or a hetero element chosen from oxygen and sulphur, R4 represents a hydrogen atom, a methyl radical, a -CONH2 radical, a -CSNH2 radical or a -C -= CH radical R5 represents a halogen atom or a methyl radical and n represents a numeral 0, 1 or 2, and notably the 3-phenoxybenzyl, alpha-ethynyl-3-phenoxybenzyl, 3-benzoylbenzyl, 1-(3-phenoxyphenyl) ethyl or alpha-thioamido-3-phenoxybenzyl groups, or a see diagramm : EP0041021,P52,F1 group, or a see diagramm : EP0041021,P52,F2 group, in which each of the substituents R6 , R7 , R8 , R9 represents a hydrogen atom, a chlorine atom, or a methyl radical and in which S/I signifies an aromatic ring or a similar dihydro or tetrahydro ring, or a see diagramm : EP0041021,P52,F3 group, or a see diagramm : EP0041021,P52,F4 group, in which R10 represents a hydrogen atom or a CN radical, R12 represents a -CH2 - radical or an oxygen atom, R11 represents a thiazolyl or thiadiazolyl radical of which the bond with see diagramm : EP0041021,P52,F5 may be found at any one of the available positions, R12 being linked to R11 by the carbon atom situated between the sulphur atom and a nitrogen atom, or a see diagramm : EP0041021,P52,F6 group, or a see diagramm : EP0041021,P53,F1 group in which R13 represents a hydrogen atom or a CN radical, or a see diagramm : EP0041021,P53,F2 group, in which R13 is defined as above and the benzoyl radical is in position 3 or 4, or a see diagramm : EP0041021,P53,F3 group, in which R14 represents a hydrogen atom, a methyl, ethynyl or cyano radical and R15 and R16 , which are different from one another, represents a hydrogen, fluorine or bromine atom, or a see diagramm : EP0041021,P53,F4 group in which R14 is defined as above, each of the R17 's represents, independently, an alkyl group containing 1-4 carbon atoms, an alkoxy group containing 1-4 carbon atoms, an alkylthio group containing 1-4 carbon atoms, an alkylsulphonyl group containing 1-4 carbon atoms, or a trifluoromethyl, 3,4-methylenedioxy, chloro, fluoro, or bromo group, p represents a numeral 0, 1 or 2 and B' represents an oxygen atom or a sulphur atom, and R represents an alkyl radical, linear, branched or cyclic, saturated or unsaturated, containing 1-18 carbon atoms, as well as the mixtures of these isomers. 1. Claims (for the contracting State AT) Preparation process for all the possible isomer forms, of compounds with the formula (I') : see diagramm : EP0041021,P57,F2 in which the double bond has Z geometry, A' represents : either an alkyl radical containing 1-18 carbon atoms, or a benzyl radical possibly substituted by one or more radicals chosen from the group constituted by the alkyl radicals containing 1-4 carbon atoms, the alkenyl radicals containing 2-6 carbon atoms, the alkenyloxy radicals containing 2-6 carbon atoms, the alkadienyl radicals containing 4-8 carbon atoms, the methylene dioxy residue, and the halogen atoms, or a see diagramm : EP0041021,P58,F1 group, in which the substituent R1 represents a hydrogen atom or a methyl radical and the substituent R2 represents a monocyclic aryl or a -CH2 -C -= CH group and notably a 5-benzyl-3-furylmethyl group, or a see diagramm : EP0041021,P58,F2 group, in which R3 represents an aliphatic organic radical containing 2-6 carbon atoms and or more carbon-carbon unsaturations and notably the -CH2 -CH=CH2 , -CH2 CH=CH-CH3 , -CH2 CH=CH-C2 H5 , -CH2 -CH=CH-CH=CH2 radicals, or a see diagramm : EP0041021,P58,F3 group, in which R3 retains the same significance as previously, R'1 and R'2 identical or different, each represent a hydrogen atom, a halogen atom, an alkyl radical containing 1-6 carbons atoms, an aryl radical containing 6-10 carbon atoms, an alkyloxycarbonyl group containing 2-5 carbon atoms, or a cyano group, or a see diagramm : EP0041021,P58,F4 group, in which B represents a CH2 or C=O group, or a hetero element chosen from oxygen and sulphur, R4 represents a hydrogen atom, a methyl radical, a -CONH2 radical, a -CSNH2 radical or a -C -= CH radical, R5 represents a halogen atom or a methyl radical and n represents a numerical 0, 1 or 2, and notably the 3-phenoxybenzyl, alpha-ethynyl-3-phenoxybenzyl, 3-benzoylbenzyl, 1-(3-phenoxyphenyl)ethyl or alpha-thiomado-3-phenoxybenzyl group, or a see diagramm : EP0041021,P58,F5 group or a see diagramm : EP0041021,P59,F1 group, in which each of the substituents R6 , R7 , R8 , R9 , represents a hydrogen atom, a chlorine atom or a methyl radical and in which S/I signifies an aromatic ring or a similar dihydro or tetrahydro ring, or a see diagramm : EP0041021,P59,F2 group, or a see diagramm : EP0041021,P59,F3 group in which R10 represents a hydrogen atom or a CN radical, R12 represents a -CH2 - radical or an oxygen atom, R11 represents a thiazolyl or thiadiazolyl radical of which the bond with see diagramm : EP0041021,P59,F4 may be found in any of the available positions, R12 being linked to R11 by the carbon atom situated between the sulphur atom and a nitrogen atom, or a see diagramm : EP0041021,P59,F5 group, or a see diagramm : EP0041021,P59,F6 group, in which R13 represents a hydrogen atom or a CN radical, or a see diagramm : EP0041021,P60,F1 group, in which R13 is defined as above and the benzoyl radical is in position 3 or 4, or a see diagramm : EP0041021,P60,F2 group, in which R14 represents a hydrogen atom, a methyl, ethynyl or cyano radical, and each of R15 and R16 , which are different, represents a hydrogen, fluorine or bromine atom, or a see diagramm : EP0041021,P60,F3 group, in which R14 is defined as above, each of the R17 's represents, independently, an alkyl group containing 1-4 carbon atoms, an alkoxy group containing 1-4 carbon atoms, an alkylthio group containing 1-4 carbon atoms, an alkylsulphonyl group containing 1-4 carbon atoms, or a trifluoromethyl, 3,4-methylenedioxy, chloro, fluoro or bromo group, p represents a numeral 0, 1 or 2 and B' represents an oxygen atom or a sulphur atom, and R represents an alkyl radical, linear branched or cyclic, saturated or unsaturated, containing 1-18 carbon atoms, as well as the mixtures of these isomers, characterized in that an acid with the formula (II) : see diagramm : EP0041021,P60,F4 in which the double bond has Z geometry, R being defined as previously, or a functional derivative of this acid, is submitted to the action of an alcohol with the formula (III) : A'OH in which A' retains the same significance as previously, and in this way the corresponding compound with the formula (I') is obtained.

Interspecific recombination among aminoglycoside producing streptomycetes.

Abstract: From auxotrophic double mutants of Streptomyces rimosus forma paromomycinus and Streptomyces kanamycerticus producing little or no antibiotic, stable prototrophic recombinants were obtained with low frequencies. Most of the recombinants differed from the parents in morphology and antibiotic production. The most frequent classes of recombinants behaved as streptomycetes of the "red" series and produced a wide range of neomycin yields, in contrast to the parents which produced paromomycin and a small proportion of neomycin, or kanamycin, respectively. Hypotheses on the nature of the genetic material exchanged are discussed.

Cyclopropane-carboxylic-acid derivatives, their preparation, their use in combating vegetal parasites, animals and locations, their compositions, and intermediates

Abstract: 1. Claims for the Contracting States : BE CH DE FR GB IT LI LU NL SE In all the possible isomeric forms or in the form of mixtures, the compounds with the formula (I') see diagramm : EP0048186,P72,F1 in which the cyclopropane copula is of IR cis structure and the double bond is of Z geometry and in which A' represents either an alkyl radical containing from 1 to 18 carbon atoms or a benzyl radical possibly substituted by one or more radicals chosen from the group composed of the alkyl radicals containing from 1 to 4 carbon atoms, the alkenyl radicals containing from 2 to 6 carbon atoms, the alkenyloxy radicals containing from 2 to 6 carbon atoms, the alkadienyl radicals containing from 4 to 8 carbon atoms, the methylene dioxy radical and halogen atoms, or a group see diagramm : EP0048186,P72,F2 in which the substituent R1 represents a hydrogen atom or a methyl radical and the substituent R2 a monocyclic aryl radical or a group -CH2 -C -= CH or a group see diagramm : EP0048186,P72,F3 in which a represents a hydrogen atom or a methyl radical and R3 represents the radical -CH2 -CH=CH2 , -CH2 -CH=CH-CH3 , -CH2 -CH=CH-CH=CH2 , CH2 -CH=CH-CH2 -CH3 , or a group see diagramm : EP0048186,P72,F4 in which a represents a hydrogen atom or a methyl radical, R3 retains the same significance as previously, R'1 and R'2 , being identical or different, represent a hydrogen atom, a halogen atom, an alkyl radical containing from 1 to 6 carbon atoms, an aryl radical containing from 6 to 10 carbon atoms, an alkyloxy-carbonyl group including from 2 to 5 carbon atoms, or a cyano group, or a group see diagramm : EP0048186,P72,F5 in which B represents an oxygen or sulphur atom or a group see diagramm : EP0048186,P73,F1 or -CH2 - and R4 represents a hydrogen atom, a -C -= N radical, a methyl radical, a -CONH2 radical, a -CSNH2 radical or a -C -= CH radical, R5 represents a halogen atom or a methyl radical and n represents a number 0, 1 or 2, or a group see diagramm : EP0048186,P73,F2 or a group see diagramm : EP0048186,P73,F3 in which the substituents R6 , R7 , R8 , R9 represent a hydrogen atom, a chlorine atom, or a methyl radical and in which S/l symbolises an aromatic ring or a similar dihydro or tetrahydro ring, or a group see diagramm : EP0048186,P73,F4 or a group see diagramm : EP0048186,P73,F5 in which R10 represents a hydrogen atom or a radical CN, R12 represents a radical -CH2 - or an oxygen atom, R11 represents a thiazolyl or a thiadiazolyl radical, of which the bond with -CH-/R10 can be found at any one of the available positions R12 being attached to R11 by the carbon atom included between the sulphur atom and a nitrogen atom, or a group see diagramm : EP0048186,P73,F6 or a group see diagramm : EP0048186,P73,F7 in which R13 represents a hydrogen atom or a radical CN, or a group see diagramm : EP0048186,P74,F1 in which R13 is defined as above, and the benzoyl radical is in position 3 or 4, or a group see diagramm : EP0048186,P74,F2 in which R14 represents a hydrogen atom, a methyl, ethynyl or cyano radical and R15 and R16 , are different and represent a hydrogen, fluorine or bromine atom, or a group see diagramm : EP0048186,P74,F3 in which R14 is defined as above, each of the R17 's represents independently an alkyl group containing from 1 to 4 carbon atons, an alkoxy group containing from 1 to 4 carbon atoms, an alkylthio group containing from 1 to 4 carbon atoms, an alkylsulphonyl group containing from 1 to 4 carbon atoms, a trifluoromethyl, 3,4-methylenedioxy, chloro, fluoro or bromo group, p represents a numeral 0, 1 or 2, and B' represents an oxygen atom or a sulphur atom and R represents an alkyl radical containing from 1 to 18 carbon atoms, substituted by one or more identical or different groups chosen from the group constituted by the halogen atoms, the OH or SH groups, the OR' or SR' groups in which R' represents an alkyl radical containing from 1 to 8 carbon atoms, the groups NO2 or see diagramm : EP0048186,P74,F4 in which R" and R'", being identical or different, represent a hydrogen atom or an alkyl radical containing from 1 to 8 carbon atoms, the groups C -= N, SO3 H or PO4 H2 or the groups COalk1 , SO2 alk2 , or SO3 alk3 in which alk1 , alk2 and alk3 represent alkyl radicals containing from 1 to 18 carbon atoms or R represents an alkyl radical containing from 1 to 18 carbon atoms substituted by an aryl radical, itself possibly substituted by one or more OH, Oalk or alk groups containing from 1 to 18 carbon atoms, by one or more CF3 , OCF3 SCF3 , or by a group (G) : see diagramm : EP0048186,P74,F5 or R represents an alkyl radical containing from 1 to 18 carbon atoms, substituted on two adjacent carbons by a group (G1 ) see diagramm : EP0048186,P74,F6 or substituted by a group see diagramm : EP0048186,P75,F1 or R represents an aryl group containing from 6 to 14 carbon atoms, possibly substituted by one or more OH, Oalk or alk groups containing from 1 to 8 carbon atoms or by a CF3 , OCF3 or SCF3 group, or R represents a pyridinyl, furanyl, thiophenyl, oxazolyl or thiazolyl radical. 1. Claims for the Contracting State : AT Process for preparing in all the possible isomeric forms or in the form of mixtures, the compounds with the formula (I') see diagramm : EP0048186,P82,F3 in which the cyclopropane copula is of IR cis structure and the double bond of Z geometry and in which A' represents either an alkyl radical containing from 1 to 18 carbon atoms or a benzyl radical possibly substituted by one or more radicals chosen from the group constructed by the alkyl radicals containing from 1 to 4 carbon atoms, the alkenyl radicals containing from 2 to 6 carbon atoms, the alkenyloxy radicals containing from 2 to 6 carbon atoms, the alkadienyl radicals containing from 4 to 8 carbon atoms, the methylene dioxy radical and halogen atoms, or a group see diagramm : EP0048186,P82,F4 in which the substituent R1 represents a hydrogen atom or a methyl radical and the substituent R2 a monocyclic aryl or a -CH2 - C -= CH group, or a group see diagramm : EP0048186,P82,F5 in which a represents a hydrogen atom or a methyl radical and R3 represents the radical -CH2 -CH=CH2 , -CH2 -CH=CH-CH3 , -CH2 -CH=CH-CH=CH2 , CH2 -CH=CH-CH2 -CH3 , or a group see diagramm : EP0048186,P82,F6 in which a represents a hydrogen atom or a methyl radical, R3 retains the same significance as previously, R'1 and R'2 , being identical or different, represent a hydrogen atom, a halogen atom, an alkyl radical containing from 1 to 6 carbon atoms, an aryl radical containing from 6 to 10 carbon atoms, an alkyl-oxycarbonyl group containing from 2 to 5 carbon atoms, or a cyano group, or a group see diagramm : EP0048186,P83,F1 in which B represents an oxygen or sulphur atom or a group see diagramm : EP0048186,P83,F2 or -CH2 - and R4 represents a hydrogen atom, a -C -= N radical, a methyl radical, a -CONH2 radical, a -CSNH2 radical or a -C -= CH radical, R5 represents a halogen atom or a methyl radical and n represents a numeral 0, 1 or 2, or a group see diagramm : EP0048186,P83,F3 or a group see diagramm : EP0048186,P83,F4 in which the substituents R6 , R7 , R8 , R9 represent a hydrogen atom, a chlorine atom, or a methyl radical and in which S/l symbolises an aromatic ring or a similar dihydro or tetrahydro ring, or a group see diagramm : EP0048186,P83,F5 or a group see diagramm : EP0048186,P83,F6 in which R10 represents a hydrogen atom or a CN radical, R12 represents a -CH2 - radical or an oxygen atom, R11 represents a thiazolyl or a thiadiazolyl radical, of which the bond with -CH-/R10 can be found at any one of the available positions, R12 being attached to R11 by the carbon atom included between the sulphur atom and a nitrogen atom, or a group see diagramm : EP0048186,P84,F1 or a group see diagramm : EP0048186,P84,F2 in which R13 represents a hydrogen atom or a CN radical, or a group see diagramm : EP0048186,P84,F3 in which R13 is defined as above, and the benzoyl radical is in position 3 or 4, or a group see diagramm : EP0048186,P84,F4 in which R14 represents a hydrogen atom, a methyl, ethynyl or cyano radical and R15 and R16 , which are different, represent a hydrogen atom, a fluorine or a bromine atom, or a group see diagramm : EP0048186,P84,F5 in which R14 is defined as above, each of the R17 's represents independently an alkyl group containing from 1 to 4 carbon, an alkoxy group containing from 1 to 4 carbon atoms, an alkylthio group containing from 1 to 4 carbon atoms, an alkylsulphonyl group containing from 1 to 4 carbon atoms, a trifluoromethyl, 3,4-methylenedioxy, chloro, fluoro or bromo group, p represents a numeral 0, 1 or 2 and B' represents an oxygen atom or a sulphur atom and R represents an alkyl radical containing from 1 to 18 carbon atoms, substituted by one or more identical or different functional groups chosen from the group constituted by the halogen atoms, the OH or SH groups, the OR' or SR' groups in which R' represents an alkyl radical containing from 1 to 8 carbon atoms, the NO2 or see diagramm : EP0048186,P84,F6 groups in which R" and R'", which are identical or different, represent a hydrogen atom or an alkyl radical containing from 1 to 8 carbon atoms, the groups C -= N, SO3 H or PO4 H2 groups or the COalk1 , SO2 alk2 , or SO3 alk3 groups in which alk1 , alk2 and alk3 represent alkyl radicals containing from 1 to 18 carbon atoms, or R represents an alkyl radical containing from 1 to 18 carbon atoms substituted by an aryl radical, itself possibly substituted by one or more OH, Oalk or alk groups containing from 1 to 8 carbon atoms, by one or more CF3 , OCF3 SCF3 , or by a group (G) : see diagramm : EP0048186,P85,F1 or R represents an alkyl radical containing from 1 to 18 carbon atoms, substituted on two adjacent carbons by a group (G1 ) see diagramm : EP0048186,P85,F2 or su

Interactions between hydralazine, propildazine and purines on arterial smooth muscle

Abstract: 1 The interaction of hydralazine (Hyd) and propildazine (Pyd) with purine compounds was studied in the isolated tail artery from normotensive Wistar (NW) rats. 2 Exogenously added purines inhibit non competitively the antispasmogenic response to Hyd in denervated NW segments. The order of potency is 2-Cl-adenosine > adenosine > adenosine 5′-triphosphate (ATP) > inosine. Pyd action is modified only by the most active purine 2-Cl-adenosine, which displaces the dose-response curves to the right. Hyd and Pyd seem to act on the same site, since their maximal effects are not additive. 3 Theophylline (Theo) 50 μM induces the appearance of the antispasmogenic effect of Hyd in the usually poorly responsive innervated proximal NW arterial segments. The potentiating action of Theo is identical to the enhancement of the Hyd response observed after 6-hydroxydopamine denervation. This result suggests that the release of endogenous purines from sympathetic nerves is sufficient to block the smooth muscle responses to Hyd, under our experimental conditions. A similar potentiating effect is obtained with propranolol (5 μM). 4 The spontaneous release of 3H, after loading with [3H]-noradrenaline, was considered as an indirect indication of purine leakage from nerve terminals. There is an inverse relationship between the rate of 3H release, under these conditions, and the magnitude of the relaxant response to Hyd, i.e., 3H leakage is higher in proximal NW segments. 5 The most satisfactory explanation for the interaction of Hyd and Pyd with exogenous purines, and for the modulating actions of sympathetic nerve terminals, is that both antihypertensives act on a common receptor, sensitive to endogenous ATP and adenosine.

Steroid hormones—agonists and antagonists

Abstract: Steroid hormones are frequently classified into broad categories such as ‘progestins’, ‘androgens’ and ‘glucocorticoids’, but this classification is often misleading or just incomplete since it only accounts for their known primary biological activity and does not adequately describe the multiplicity of actions that many of them display. In view of the ubiquity of the receptors of different classes of steroid hormone (for instance, each of the oestrogen, progestin, androgen and glucocorticoid receptors has been identified in peripheral target tissues such as the uterus and pituitary and in central tissues such as the hypothalamus), it is of interest to be able to define the receptor binding profile of a new substance and thus extrapolate, by comparison with the natural hormones and well-established steroid drugs, the possible actions of this new compound in different organs. Furthermore, since interdependent regulatory mechanisms seem to condition many hormonal responses (for example, both progestin and androgen binding sites can be induced by oestrogens), it is useful to know whether certain potent drugs classified as agonists of one natural hormone are antagonists of another.

6"'-Deamino-6"'-hydroxy derivatives, as intermediates in the biosynthesis of neomycin and paromomycin.

Abstract: From broths of a neomycin producing Streptomyces fradiae and of a mutant of Streptomyces rimosus forma paromomycinus respectively, 6'''-deamino-6'''-hydroxyneomycin and 6'''-deamino-6'''-hydroxyparomomycin were obtained and their structures established by mass and 13C-NMR spectroscopy and by the study of hydrolytic fragments. These new compounds, which are both present as two epimers at C-5''', are suggested as intermediates in the biosynthesis of the parent antibiotics. The place and the mechanism of the 5'''-epimerisation and of the 6'''-amination are discussed.

2-substituted-4-hydroxy-3-quinolinecarboxylic acids, their preparation, their use as medicaments, compositions containing them and intermediates

Abstract: L'invention concerne les composes (1'): The invention relates to compounds (1 '): X est hydrogene, halogene, alcoyle (1 a 5 carbones), alcoxy (1 a 4 carbones), F 3 C-, F 3 CS- ou F 3 CO -, R' 1 est hydrogene, alcoyle (1 a 4 carbones) R' 2 est hydrogene ou un cycle sature ou insature contenant eventuellement 0, N ou S, eventuellement substitue par un ou plusieurs a) halogenes, b) alcoyles (1 a 4 carbones) eventuellement substitues par amino, alcoylamino, dialcoylamino (alcoyles 1 a 3 carbones) c) phenyle, d) alcoxy (1 a 4 carbones), e) hydroxy, f) F 3 Cet g) -NO 2 ou R' 1 et R' 2 forment l'un quelconque des cycles mentionnes ci-dessus, R 3 est hydrogene, halogene, alcoyle (1 a4 carbones), R 4 est hydrogene ou halogene, R s est halogene, R 3 , R 4 et R s n'etant pas en meme temps un fluor et R 6 est hydrogene, alcoyle (1 a 8 carbones), acyle (2 a 8 carbones), ainsi que leurs sels avec les acides et les bases, leur preparation, leur application comme medicaments, les compositions les renfermant et les nouveaux intermediaires obtenus. X is hydrogen, halogen, alkyl (1-5 carbons), alkoxy (1 to 4 carbons), F 3 C-, F 3 CS- or F 3 CO -, R '1 is hydrogen, alkyl (1 to 4 carbons) R '2 is hydrogen or a saturated or unsaturated ring optionally containing 0, N or S, optionally substituted by one or more of a) halo, b) alkyl (1 to 4 carbons) optionally substituted by amino, alkylamino, dialkylamino (alkyl 1 to 3 carbons) c) phenyl, d) alkoxy (1 to 4 carbons), e) hydroxy, f) F 3 This g) -NO 2, or R '1 and R' 2 form, any of the above cycles R 3 is hydrogen, halogen, alkyl (1 to4 carbons), R 4 is hydrogen or halogen, R s is halogen, R 3, R 4 and R s are not simultaneously fluorine and R 6 is hydrogen, alkyl (1 to 8 carbons), acyl (2-8 carbons), and their salts with acids and bases, their preparation, their use as medicaments, compositions containing them and new intermediates obtained. Les composes l' sont doues d'une activite analgesique avec une tres faible activite antiinflammatoire. The compounds the are endowed with analgesic activity with very little anti-inflammatory activity.

Dopaminergic activity of some simplified ergoline derivatives

Abstract: The dopamine (DA) agonist activity of new simplified ergoline derivatives (RU 27849, RU 28251, and RU 28306) was studied in comparison with bromocriptine. In contrast to bromocriptine, the three compounds were weak displacers of 3H-dihydroergocriptine or 3H-spiroperidol binding from bovine anterior pituitary or rat striatal membrane sites and weak inhibitors of prolactin secretion in anterior pituitary cells in culture. Similarly to bromocriptine, they did not induce changes in either the basal or the DA-induced stimulation of the adenylate cyclase activities. In vivo, the three derivatives, at a low dose, increased plasma prolactin levels, decreased striatal DA turnover, and increased striatal acetylcholine content, as did bromocriptine. Furthermore, in 6-OHDA-lesioned rats, these molecules, like bromocriptine, induced an intense contralateral circling behavior. From their effectiveness in these different tests, the potencies of these new ergoline derivatives can be ranked in the following order : N-propyl > N-methyl > N-H.