Showing papers by "Roussel Uclaf published in 1985"

Pharmacological Profile of RU 486 in Animals

Abstract: RU 486 is an original multifaceted antihormone. It appears to be a potent progestin and glucocorticoid antagonist while exhibiting no agonistic effect, even at very high doses. Thus, according to the bioassay used, RU 486 administered orally at doses between 3 and 20 mg/kg completely inhibits the effect of exogenous progesterone on the endometrial proliferation in rabbits, on the volume density of uterine gland cell mitochondria, on the deciduomata formation and on the maintenance of pregnancy in ovariectomized rats. Furthermore, it proves to be antinidatory and abortive in rats and mice. In cycling monkeys it induces menstruation when administered during the mid-luteal phase.

Effects of different dietary intake of essential fatty acids on C20∶3ω6 and C20∶4ω6 serum levels in human adults

Abstract: Four diets which differed in fatty acid composition were provided for five months each to a group of 24 healthy nun volunteers The diets contained 54% carbohydrates, 16% proteins and 30% lipids One-third of the lipid part remained unchanged during the whole study, and two-thirds were modified during each period For this latter portion, one of the following dietary fats was used: sunflower oil, peanut oil, low erucic acid rapeseed (LEAR) oil or milk fats This procedure allowed an evaluation of the effects of various amounts of dietary linoleic acid (C18:2 omega 6) and alpha-linolenic acid (C18:3 omega 3) on the serum level of their metabolites A diet providing a large amount of linoleic acid (14% of the total caloric intake) resulted in low levels of dihomo-gamma-linolenic acid (C20:3 omega 6) and arachidonic acid (C20:4 omega 6) in serum phospholipids and cholesteryl esters A diet providing a small amount of linoleic acid (06% to 13% of the total caloric intake) induced high levels of omega 6 fatty acid derivatives Intermediate serum levels of C20:3 omega 6 and C20:4 omega 6 were found with a linoleic acid supply of about 65% of the total caloric intake Serum levels of omega 6 metabolites were not different after two diets providing a similar supply of C18:2 omega 6 (45% to 65% of the total caloric intake), although in one of them the supply of C18:3 omega 3 was higher (15% for LEAR oil versus 013% for peanut oil)(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical Profile of RU 486

Abstract: The binding characteristics of RU 486 with the glucocorticoid receptor (GR) and the progestin receptor (PR) were studied in order to explain the potent antiglucocorticoid and antiprogestin activities of the compound. In vitro, (3H)RU 486 bound to the same cytosol receptors as (3H) dexamethasone (GR) and (3H)R 5020 (PR); the sedimentation coefficients, number of binding sites and specificity were similar. However, the affinity of (3H)RU 486 for these receptors was higher than that of the potent agonists, as indicated by the high affinity constant determined from Scatchard plots and by the slow dissociation rates from the GR and PR. With the cytosol receptor under heat activation, the agonists were able to give rise to more stable complexes, but (3H)RU 486 dissociated faster from the activated than from the non-activated GR. This impeded activation of the (3H)RU 486-GR complex was confirmed by observations of its lower affinity than that of (3H)dexamethasone-GR complex for DNA-cellulose and by a low retention in the nucleus that may be related to RU 486’s lack of glucocorticoid activity. Conversely, the uterine (3H)RU 486-PR complex did not undergo an acceleration of dissociation rate under heat activation, and its affinity for DNA-cellulose was similar to that of the activated (3H)R 5020-PR complex. This led to a high level of nuclear retention unrelated to the lack of progestin activity of RU 486. In contrast to in vitro interaction, high in vivo doses of RU 486 were needed to interact with the cytosol receptors in the rat; this cannot be explained by a binding to rat plasma protein.

Pharmacokinetics of RU 486.

Abstract: The pharmacokinetics of RU 486 have been studied in man, rats and cynomolgus monkeys. Single pharmacological doses were given (from 1.3 mg/kg−1 in man (oral) to 3−5 mg/kg−1 in animal species), using a tritiated compound. Radiometric assay and, in some cases, RIA were used. Absorption was satisfactory in all species, but the compound underwent a presystemic effect that reduced its bioavailability to 40% in man and rats and 15% in monkeys. Extravascular diffusion was much greater in animal species than in man; the apparent initial volume of distribution was equivalent to the body weight in rats and twice the body weight in monkeys. However, it accounted for only 10% of the body weight in man.

Novel 11 beta-substituted-19-nor-steroids

Abstract: Novel 19-nor-steroids of the formula ##STR1## wherein R 1 is an organic group of 1 to 18 carbon atoms optionally containing at least one heteroatom with the atom immediately adjacent the 11-carbon atom being carbon, R 2 is a hydrocarbon of 1 to 8 carbon atoms, X is the remainder of a pentagonal or hexagonal ring optionally substituted and optionally containing one unsaturated--bond, the A and B rings are selected from the group consisting of ##STR2## R' and R" are individually selected from the group consisting of hydrogen, --CN and alkyl of 1 to 4 carbon atoms with at least one being other than hydrogen, R x is selected from the group consisting of hydrogen and OR e , R e is selected from the group consisting of hydrogen, optionally substituted alkyl of 1 to 6 carbon atoms and acyl, R a may be in the E or Z positions as indicated by the wavy line and is selected from the group consisting of ##STR3## and acyloxy, R a ' and R a " are alkyl of 1 to 4 carbon atoms or taken together with the nitrogen atom form a heterocycle of 5 to 6 chain members optionally containing another heteroatom with the proviso that when A and B are ##STR4## R 1 contains at least one nitrogen, phosphorus or silicium atom and when A and B are ##STR5## R 1 is not a linear alkyl and their non-toxic, pharmaceutically acceptable acid addition salts having a remarkable antigluococorticoid activity, their preparation and novel intermediates.

Antibacterial activity of ofloxacin and other 4-quinolone derivatives: in-vitro and in-vivo comparison

Abstract: Ofloxacin (DL8280, RU43280) is a newly introduced oxazine quinolone derivative with broad and potent antibacterial activity. Ofloxacin showed excellent in-vitro activity against Enterobacteriaceae while most strains of Pseudomonas aeruginosa were inhibited by less than 2 mg/l. The compound was significantly more potent than norfloxacin against Acinetobacter spp. and Staphylococcus spp. Ofloxacin and norfloxacin behaved similarly with respect to inoculum size, effect of urine and serum, bactericidal properties and frequency of spontaneous resistant mutants. Ofloxacin displayed an in-vivo antibacterial activity up to five times greater than that of pefloxacin and norfloxacin, probably due to the conjunction of favourable pharmacokinetics, excellent bacterial susceptibility and good stability towards metabolic degradation.

Analogues of RU 486 for the Mapping of the Progestin Receptor: Synthetic and Structural Aspects

Abstract: The synthesis of 11s-substituted 19-norsteroids, including RU 486 and analogues, is briefly discussed. Relative binding affinities for the rabbit progestin receptor of a series of these compounds, varying either by the 11s-substituent or D-ring substitution, are reported, leading to preliminary structure-affinity relationships. It was found that rather large substituents, both in position 11-s and 17-alpha of the steroid nucleus, can be accomodated by the receptor, suggesting the existence of two unusually large hydrophobic pockets in the receptor protein in addition to the main hydrophobic site that binds the steroid framework. A computer-drawn mapping of these hydrophobic pockets has been attempted, based on crystal structures and calculated molecular conformations. The results obtained so far suggest that anti-hormones of the RU 486 type interfere with the activation of the steroid-receptor complex.

Effects of the Antiprogesterone Agent RU 486 on the Natural Cycle and Gestation in Intact Cynomolgus Monkeys

Abstract: This paper demonstrates that RU 486 is equally potent in inducing abortion and parturition in macaque monkeys at three stages of gestation (days 30, 80 and 140). The results suggest that progesterone probably plays a supportive role up to the end of gestation. However, erratic results were obtained when RU 486 was given orally, suggesting poor bioavailability of the compound when given by this route.

Hypercalciuria during experimental vitamin K deficiency in the rat.

Abstract: Vitamin K promotes the formation of gamma-carboxylated glutamate (GLA) in several protein species GLA residues have a high affinity for the Ca ion In the present study we tested the hypothesis that experimental vitamin K deficiency in rats could induce changes in Ca metabolism Vitamin K depletion, which was associated with a reduction in urinary GLA excretion, induced within 7 days a significant increase in cumulative urinary Ca excretion that persisted throughout the 21 days of study The hypercalciuria of vitamin K-deficient rats was corrected on vitamin K supplementation No concomitant changes were observed in intestinal Ca absorption determined by a balance technic or of skeletal resorption and apposition rates determined by bone histomorphometry Plasma Ca, but not total protein concentration, of vitamin K-depleted rats showed a transient decrease at day 15 that disappeared at day 21 Plasma sodium, phosphate and 1,25 (OH)2 vitamin D concentration, and urinary phosphate, sodium, and creatinine excretion remained unchanged In conclusion, vitamin K deficiency in the rat induces hypercalciuria that could be of renal origin Its possible relationship to vitamin K-dependent renal GLA protein remains to be clarified

Toxicological Study on RU 486

Abstract: RU 486 showed no toxic effects after acute oral administration to mice and rats. Six-month toxicological studies were performed, using rats (15, 25, and 125 mg/kg) and cynomolgus monkeys (5, 15, and 45 mg/kg). Most of the modifications induced by the high doses are due to antihormonal properties of the compound such as: antiprogesterone activity in females (frequent estrus and mammary-gland development in rats, suppression of menstruation and a decrease in serum progesterone in monkeys); antiglucocorticoid activity (increase in kidney and adrenal weights, and, in monkeys, increase in serum ACTH and cortisol); and antiandrogenic activity in male rats (decrease in prostate and seminal vesicle weights). RU 486 showed no mutagenic effect either in vitro or in vivo and provoked no teratogenic effect at usable doses, that is to say non-abortive doses (0.5 mg/kg in rats and 1 mg/kg in rabbits). Studies were performed on albino mice (Swiss — SPF) and albino rats (Sprague-Dawley — SPF), on cynomolgus monkeys (Macaca fascicularis) and on rabbits (HY). RU 486 was administered orally suspended in water containing 0.25 to 1% of carboxymethylcellulose with or without polysorbate 80 (0.20%).

Radioimmunoassay of RU 486

Abstract: A rapid and sensitive radioimmunoassay for RU 486 has been developed. The straightforward assay procedure is described in detail.

Histopharmacology of RU 486

Abstract: Histological studies were done by light and electron microscopy to improve biological tests used to evaluate the pharmacological properties of RU 486. The compound prevented the progesterone-induced appearance of giant mitochondria in uterine glandular cells in ovariectomized rats and did not show any progestogen-mimetic effect. Its antiprogestational activity was demonstrated by abortion in rats where RU 486-induced changes in the deciduoma cells could be observed, even prior to the changes caused by ovariectomy. The hypertrophic effect of RU 486 on the uterus of immature animals was distinguished from the hyperplastic effect of estradiol.

Assessment of the antimineralocorticoid effect of RU 28318 in healthy men with induced exogenous and endogenous hypermineralocorticism.

Abstract: The antimineralocorticoid effect of a single dose of RU 28318, has been assessed in healthy men with exogenous or endogenous hypermineralocorticism For exogenous hypermineralocorticism induced by ingestion of 9α-fluorohydrocortisone (9α-FHC) and aldosterone infusion, RU 28318 100 mg (9α-FHC ingestion) or 200 mg (aldosterone infusion) was administered, and its effect compared with identical doses of spironolactone or a placebo For endogenous hypermineralocorticism induced by ingestion of furosemide, RU 28318 100 and 300 mg was tested in comparison with 100 mg spironolactone or placebo In all 3 studies, both RU 28318 and spironolactone significantly raised the urinary Na/K ratio when compared to placebo administration No significant difference was apparent between RU 28318 and spironolactone Thus, a single dose of RU 28318 in man has an antimineralocorticoid effect identical to those produced by the identical molar dose of spironolactone In addition, the results show that furosemide-induced hyperaldosteronism constitutes a simple and reproducible test for assessing the antimineralocorticoid effect of a drug

A fully automatic apparatus for chemical reactions on the laboratory scale.

Abstract: It is also useful for the preparation of a given quantity of products simply by repeating the same reaction when scaling up is too difficult, or time-consuming. Moreover, the physical presence ofthe chemist near the apparatus is not necessary, which is helpful when hazardous reactions have to be studied. Furthermore, the strict control of many parameters, and the possibility of sampling the reaction medium during the course of the operation, means that information about the kinetics of the reaction

Novel 10-substituted steroids and their use in the induction of aldosterone antagonistic activity

Abstract: Novel 10-substituted steroids of the formula ##STR1## wherein R is selected from the group consisting of hydrogen, alkyl and substituted alkyl of 1 to 8 carbon atoms, alkenyl, substituted alkenyl, alkynyl and substituted alkynyl of 2 to 8 carbon atoms, aryl and substituted aryl, aralkyl and substituted aralkyl, protected hydroxy, optionally esterified carboxy, --NH 2 , protected amino, mono and di-alkyl amino of 1 to 4 alkyl carbon atoms, halogen and trialkylsilyl, R 2 is methyl or ethyl, R 6 and R 7 together with the carbon atoms to which they are attached form cyclopropyl or R 6 is hydrogen and R 7 is R 1 , R 1 is selected from the group consisting of hydrogen, alkyl and substituted alkyl of 1 to 6 carbon atoms, acetylthio and alkenyl, substituted alkenyl, alkynyl and substituted alkynyl of 2 to 6 carbon atoms, X is optionally acylated or etherified hydroxyl and Y is selected from the group consisting of hydrogen, R 4 , --CH 2 --CH 2 COOM and --CH 2 --CH 2 --CH 2 OH, M is hydrogen, alkali metal or --NH 4 or X and Y together form a member of the group consisting of ##STR2## or X is --OH and Y is ##STR3## R 4 is selected from the group consisting of alkyl of 1 to 6 carbon atoms and alkenyl and alkynyl of 2 to 6 carbon atoms, Alk is alkyl of 1 to 8 carbon atoms, the dotted lines in the 1(2) and 6(7) indicate the optional presence of a second carbon-carbon bond with the proviso that when R 6 and R 7 form cyclopropyl, there is no 6(7) second bond, the dotted line in 10-substituent indicates the optional presence of a third carbon-carbon bond, the wavy lines at R 6 and R 7 indicate the possible α- or β-position with the proviso that R is not hydrogen when R 6 and R 7 are hydrogen R 2 is methyl, X is hydroxy or acetoxy and Y is hydrogen, the dotted lines at 1(2) and 6(7) do not represent a second bond and the dotted line in the 10-substituent is a third carbon-carbon bond useful as aldosterone antagonists and for increasing hydrosodium diuresis while preserving organic potassium with reduced hormonal side effects.

Novel pyrrole derivatives

Abstract: Novel pyrrole derivatives of the formula ##STR1## wherein one of R 2 and R 3 is ##STR2## and the other of R 2 and R 3 as well as R 4 and R 5 are individually selected from the group consisting of hydrogen, halogen, alkyl of 1 to 18 carbon atoms, aryl of 6 to 14 carbon atoms, aralkyl of 7 to 18 carbon atoms, --CN, --CF 3 , --NO 2 , --COOAlk and Alk is alkyl of 1 to 8 carbon atoms, alkoxy of 1 to 8 carbon atoms, ##STR3## n is 0, 1 or 2, R', R 1 ' and R 2 ' are alkyl of 1 to 8 carbon atoms and R 4 and R 5 taken together with the carbon atoms to which they are attached may form an optionally further unsaturated carbon homocycle of up to 8 carbon atoms, Z is selected from the group consisting of hydrogen, --CN, --C.tbd.CH, --CF 3 and alkyl of 1 to 3 carbon atoms, A is the residue of a pyrethrinoid acid, R 1 is selected from the group consisting of ##STR4## X', X, Y, Y' and Y" are individually selected from the group consisting of hydrogen, halogen, alkyl of 1 to 8 carbon atoms and aryl of 6 to 14 carbon atoms, the dotted line indicating an optional double bond, r' is selected from the group consisting of hydrogen, alkyl of 1 to 18 carbon atoms, aryl of 6 to 14 carbon atoms, aralkyl of 7 to 18 carbon atoms, --CF 3 , --COOAlk and alkoxy of 1 to 8 carbon atoms and Alk has the above definition, R" and R'" are individually selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, aryl of 6 to 14 carbon atoms, aralkyl of 6 to 18 carbon atoms, --CF 3 ' --COOAlk' and alkoxy of 1 to 8 carbon atoms and Alk' is alkyl of 1 to 8 carbon atoms having pesticidal properties and novel intermediates.

Product containing an antiprogestomimetic and a uterotonic substance

Abstract: The product comprises at least one substance possessing antiprogestomimetic properties and at least one substance possessing uterotonic properties.

Novel 23-dihydro-oxazolyl steroids

Abstract: Novel 23-dihydro-oxazolyl steroids of the formula ##STR1## wherein R1 is selected from the group consisting of hydrogen and methyl, R2 is selected from the group consisting of methyl and ethyl, R3 and R4 are individually selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, the A, B, C and D rings may contain 1 to 3 double bonds and may be optionally substituted with one or more members of the group consisting of --OH, protected hydroxyl, ═0, protected keto, halogen alkyl or alkoxy of 1 to 4 carbon atoms and alkenyl and alkynyl of 2 to 4 carbon atoms and the dotted line indicates the optional presence of a second bond useful for the preparation of 20-keto-pregnanes and novel intermediates.

Derivatives of omega-mercaptopropanamide and their salts, their preparation, their use as medicines and compositions containing them

Abstract: For for the Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE 1. Compounds with the formula (I) : see diagramm : EP0159254,P17,F1 in which R1 represents a hydrogen atom or a see diagramm : EP0159254,P17,F2 radical, R'1 being an alkyl radical containing from 1 to 5 carbon atoms or an aryl radical possibly substituted by a hydroxy radical, an alkyl radical containing from 1 to 5 carbon atoms, an alkoxy radical containing form 1 to 5 carbon atoms, the nitro radical or a halogen atom, n represents a whole number variable from 1 to 5, R2 , represents a hydrogen atom, an alkyl radical containing from 1 to 5 carbon atoms, an aryl or arylalkyl radical containing from 6 to 15 carbon atoms, possibly substituted by an alkyl radical containing from 1 to 5 carbon atoms, an alkoxyl radical containing from 1 to 5 carbon atoms, a hydroxyl radical, a halogen atom or a trifluoromethyl radical, m represents a whole number variable from 0 to 5, R3 represents : - either a saturated cyclic radical containing from 3 to 12 carbon atoms, which can be fused to a phenyl radical, R3 however not being able to represent a cyclohexyl radical when R2 and R1 represent at the same time a hydrogen atom and n=1 and m=O ; - or a phenyl radical possibly substituted by one or more radicals chosen from the following radicals : alkyl containing 1 to 5 carbon atoms, alkoxy containing from 1 to 5 carbon atoms, hydroxyl, nitro, halogeno, trifluoromethyl and see diagramm : EP0159254,P17,F3 X and X' representing a hydrogen atom or an alkyl radical containing form 1 to 5 carbon atoms or a phenyl radical to which a saturated cyclic radical containing from 5 to 9 carbon atoms is fused ; or a heterocyclic radical chosen from the following radicals : thiazolyl, 4-5-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl, tetrazolyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, possibly substituted by an alkyl radical containing from 1 to 5 carbon atoms, or a piperidinyl radical substituted by an aralkyl radical containing from 7 to 15 carbon atoms, provided that when R3 represents a phenyl radical possibly substituted by at least one of the radicals previously quoted or when R3 represents one of the heterocyclic radicals mentioned above, possibly substituted by an alkyl radical containing from 1 to 5 cabon atoms, m cannot represent the value 0 and provided that : a) when n=1 or 2, m=1, 2 or 3 and R1 =R2 =H, R3 is not a phenyl radical possibly substituted by one or two alkyl radicals containing form 1 to 5 carbon atoms, b) when m=n=1 and see diagramm : EP0159254,P17,F4 and R2 =CH3 R3 is not a phenyl radical, as well as their addition salts with acids. For the Contracting State : AT 1. Process for preparing compounds with the formula (I) : see diagramm : EP0159254,P18,F1 in which R1 represents a hydrogen atom or a see diagramm : EP0159254,P18,F2 radical, R'1 being an alkyl radical containing from 1 to 5 carbon atoms or an aryl radical possibly substituted a hydroxyl radical, an alkyl radical containing from 1 to 5 carbon atoms, an alkoxy radical containing from 1 to 5 carbon atoms, a nitro radical or a halogen atom, n represents a whole number variable from 1 to 5, R2 represent ts a hydrogen atom, an alkyl radical containing from 1 to 5 carbon atoms, an aryl or arylalkyl radical containing from 6 to 15 carbon atoms, possibly substituted by an alkyl radical containing from 1 to 5 carbom atoms, an alkoxy radical containing from 1 to 5 carbon atoms, a hydroxyl radical, a halogen atom or a trifluoromethyl radical, m represents a whole number variable from 0 to 5, R3 represents : - either a saturated cyclic radical containing from 3 to 12 carbon atoms, which can be fused to a phenyl radical, R3 howerer not being able to represent a cyclohexyl radical when R2 and R1 represent at the same time a hydrogen atom and n=1 and m=0 ; - or a phenyl radical possibly substituted by one or more radicals chosen from the following radicals : alkyl containing 1 to carbon atoms, alkoxy containing from 1 to 5 carbon atoms, hydroxyl, nitro, halogeno, trifluoromethyl and see diagramm : EP0159254,P18,F3 X and X' representing a hydrogen atom or an alkyl radical containing from 1 to 5 carbon atoms or a phenyl radical to which a saturated cyclic radical containing from 5 to 9 carbon atoms is fused ; or a heterocyclic radical chosen from the following radicals : thiazolyl, 4-5-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl, tetrazolyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, possibly substituted by an alkyl radical containing from 1 to 5 carbon atoms, or a piperidinyl radical substituted by an aralkyl radical containing from 7 to 15 carbon atoms, provided that when R3 represents a phenyl radical possibly substituted by at least one of the radicals previously quoted or when R3 represents one of the heterocyclic radicals mentioned above, possibly substituted by an alkyl radical containing from 1 to 5 carbon atoms, m cannot represent the value 0 and provided that : a) when n=1 or 2, m=1, 2 or 3 and R1 =R2 =H, R3 is not a phenyl radical possibly substituted by one or two alkyl radicals containing from 1 to 5 carbon atoms, b) when m=n=1 and see diagramm : EP0159254,P19,F4 and R2 =CH3 R3 is not a phenyl radical, as well as their addition salts with acids, characterized in that - to prepare compounds with the formula (I) in which R1 , R2 and R3 and m have the previously given significance and in which n=1 as well as their addition salts with acids, an acid with the formula (II) : see diagramm : EP0159254,P19,F5 in which R'1 and R2 have the significances already indicated, or a functional derivative of this acid, is submitted to the action of a product with the formula (III) : H2 N-(CH2 )m -R3 in which R3 and m have the significances already indicated, so as to obtain a product with the formula (I), in which R1 = see diagramm : EP0159254,P19,F6 as well as R2 , R3 and m having the significances already indicated and in which n=1, which products with the formula (I) are saponified, if necessary or desired, so as to obtain a product with the formula (I) in which R1 represents a hydrogen atom and which products with the formula (I) are salified, if necessary or desired, by the action of an acid in order to form the salts, - to prepare the compounds with the formula (I) in which R1 , R2 and R3 and m have the previously given significance and in which n represents a whole number variable from 1 to 3, an acid with the formula (IV) : see diagramm : EP0159254,P19,F7 in which X is a halogen atom, and in which n and R2 have the significances given above, or a functional derivative of this acid, is submitted to the action of a product with the formula (III) H2 N(CH2 )m R3 as defined previously, so as to obtain a product with the formula (V) : see diagramm : EP0159254,P19,F8 in which X, n, m, R2 and R3 have the previous significances, which is submitted to the action of the anion of a thioacid with the formula (VI) : see diagramm : EP0159254,P19,F9 in which R'1 is defined as previously, so as to obtain a product with the formula (I) in which see diagramm : EP0159254,P19,F10 R'1 , R2 , R3 n and m having the significances given above, which product with the formula (I) is saponified, if necessary or desired, so as to obtain a product with the formula (I) in which R1 represents a hydrogen atom and which products with the formula (I) are salified, if necessary or desired, by the action of an acid so as to form the salts.

Pyrrole derivatives, process for their preparation and their application as pesticides

Abstract: La presente invention concerne les composes (I) ou The present invention relates to compounds (I) wherein - l'un des radicaux R 2 ou R 3 represente - one of R 2 or R 3 radicals represents ou A est un reste acide pyrethrinoide et Z est H, -C=N, -C=CH, -CF 3 , alkyle;- l'autre, ainsi que R 4 et R 5 representent H, Hal, alkyle, aryle, aralkyle, -C≡N, -CF 3 , CO 2 alkyle, N0 2 , alkoxy, where A is a pyrethroid acid and Z is H, -C = N, -C = CH, -CF 3, alkyl, - the other, as well as R 4 and R 5 are H, Hal, alkyl, aryl, aralkyl , -C≡N, -CF 3, CO 2 alkyl, N0 2, alkoxy, ou NR' 1 R' 2 (n = 0, 1 ou 2) R', R' 1 et R' 2 representant un alkyle; or NR '1 R' 2 (n = 0, 1 or 2) R ', R' 1 and R '2 representing an alkyl; - R 4 et R 5 peuvent former un homocycle; - R 4 and R 5 may form a homocycle; - R 1 est - R 1 is X ou X et Y representent H, Hal, alkyle, aryle; X wherein X and Y are H, Hal, alkyl, aryl; ou Y et Y' representent l'une des valeurs de X et Y; wherein Y and Y 'represents one of X and Y values; - -CO ou r' represente l'une des valeurs de R 4 et R 5 , sauf Ha CN, NO 2 , -SR' (O) n avec n = 1 ou 2 et NR 1 R 2 - -CO wherein r represents one of the values of R 4 and R 5, except Ha CN, NO 2, -SR '(O) n with n = 1 or 2 and NR 1 R 2 dans lequel R" et R"' representent H, alkyle, aryle, aralkyle, CF 3 , CO 2 alkyle ou alkoxy. wherein R "and R" 'are H, alkyl, aryl, aralkyl, CF 3, CO 2 alkyl or alkoxy. L'invention a egalement pour object un procede et des intermediaires de preparation des composes (i,), ainsi que les compositions pesticides les renfermant. The invention also has for object a process and intermediates for preparing the compounds (i), and pesticidal compositions containing them.

Dose-response relationship of vindeburnol based on spectral analysis of posturographic recordings

Abstract: The dose-response relationship of vindeburnol has been investigated by assessing postural activity in a population of elderly patients, using posturography, an objective method for measuring balance. A controlled double blind trial was done in two periods: during the first week each patient received placebo, and during the second week either placebo or vindeburnol 30, 60 or 90 mg/d was given. Subjects underwent three posturographic recordings at weekly intervals (prior to treatment, after one week on placebo and after one week of treatment). There was no placebo effect. A significant decrease in the sagittal and lateral energies of body sway was found after vindeburnol, which indicates an improvement in balance. The improvement was proportional to the daily dose of vindeburnol.