Showing papers by "Roussel Uclaf published in 1983"

New approach in the treatment of prostate cancer: Complete instead of partial withdrawal of androgens

Abstract: To completely eliminate androgens of both testicular and adrenal origin, 37 previously untreated patients with advanced (stages C or D) prostatic cancer received the combination therapy using an LHRH agonist (HOE-766) and a pure antiandrogen (RU-23908). The response criteria developed by the National Prostatic Cancer Project were used. A positive response (assessed by bone scan and/or serum prostatic acid phosphatase measured by radioimunoassay was observed in 29 of the 30 cases who could be evaluated by these objective criteria (97%). The objective response was parallel to a rapid and marked improvement of the clinical signs and symptoms related to prostate cancer (prostatism, bone pain, and general well being). In marked contrast, the same combination therapy applied to patients previously treated with high doses of diethylstilbestrol (13 patients) showed a positive objective response in only 55% of cases. In 23 previously castrated patients showing relapse, an objective response was seen in only 25% of cases after neutralization of adrenal androgens by the antiandrogen. Previous treatment with chlorotrianisene (TACE) had no detectable effect on prostatic cancer and patients having previously received such treatment had a rate of positive response similar to previously untreated patients (five of five). In the previously untreated patients receiving the combination therapy, a 60% fall in serum prostatic acid phosphatase was observed as early as five days after starting treatment, at a time when the serum androgen concentration was 100% to 200% above control. Combined treatment with the pure antiandrogen completely prevents flare-up of the disease, a complication previously found in a significant proportion of patients treated with an LHRH agonist alone. The present data show that complete withdrawal of androgens by combined hormonal therapy with the LHRH agonist (or castration) and a pure antiandrogen leads to a positive objective response in more than 95% of cases as opposed to 60%-70% as reported by many groups using the previous partial hormonal therapy (castration or high doses of estrogens). Adrenal androgens are most likely responsible for this difference. The present study also shows that the proportion of androgen-sensitive cells decreases from more than 95% in untreated patients to 25% to 55% after previous partial hormonal therapy. Such data clearly indicate that the previous partial hormonal therapy exclusively aimed at neutralizing testicular androgens left 25% to 55% of cancer cells having a relatively low sensitivity to adrogens in a hormonal milieu compatible with their continuous growth. No clinical or biochemical side effect could be detected except those related to reduced serum androgen levels. Due to the ease of its application and the lack of secondary effects other than those related to hypoandrogenicity, the present data clearly suggest that complete (instead of partial) androgen withdrawal should be performed as early as possible after diagnosis, at least in advanced prostatic cancer, to reduce the development of androgen-insensitive cell clones and to facilitate the adjuvant treatment with chemotherapeutic agents and/or radiotherapy of androgen-insensitive tumors in the appropriate cases.

Steroid hormone receptors in human meningiomas, gliomas and brain metastases

Abstract: Progestin, estrogen, androgen, glucocorticoid as well as mineralocorticoid receptors (PR, ER, AR, GR and MR, respectively) were all evaluated with specific synthetic radioligands (biochemical assays) in 25 meningiomas, 9 gliomas and 4 brain metastases. In meningiomas the main steroid hormone receptors appeared to be the progestin receptor, present in 24/25 cases (mean level: 7 105 fmol/ gT) and the androgen receptor, present in 23/25 cases (mean level: 2 265 fmol/ gT). Progestin receptor levels were found to be significantly lower in meningiomas of the fibroblastic subtype whereas none of the steroid hormone receptors were detected in the anaplastic case. On the other hand, glucocorticoid receptor levels were related to the preoperative glucocorticoid therapy. In gliomas only estrogen receptors (2/9 cases) and especially androgen receptors (8/9 cases) were noticeable: the latter seemed to be related to the histological types and to the sex of patients. No receptors were found in any of the four studied metastases, including one from breast cancer. The biochemical characterization of the receptors as well as their relevance to tumor biology and to the physiology of the normal tissues where tumors arise, were discussed, and biochemical data were compared with those previously reported.

New fluorinated erythromycins obtained by mutasynthesis

Abstract: Following the previously described semisynthetic preparation of new aglycones (8S)-8-fluoroerythronolide A (I), (8S)-8-fluoroerythronolide B (II) and the monoglycoside 3-O-mycarosyl-(8S)-8-fluoroerythronolide B (III), their conversion into new fluoroerythromycins was attempted by mutational biosynthesis. The strain Streptomyces erythraeus ATCC 31772, a mutant blocked in the biosynthesis of erythromycin, was employed in the present investigation. Four new antibiotics, (8S )-8-fluoroerythromycin A (IV), (8S)-8-fluoroerythromycin B (V), (8S)-8-fluoroerythromycin C (VI) and (8S)-8-fluoroerythromycin D (VII) were successfully derived by such an approach. The result is also discussed in terms of the substrate specificity of the enzymes involved in the biosynthesis of erythromycins. The new antibiotics exhibited promising biological properties.

Triglycerides, dietetic and therapeutical applications and compositions containing them

Abstract: The present invention concerns new triglycerides of Formula I: ##STR1## wherein R represents an acyl fragment of a polyunsaturated fatty acid containing 18 to 22 carbon atoms, the acyl fragment being capable of being oxidized, however, R cannot represent the acyl fragment of eicosatetrayn-5, 8, 11, 14-oic acid, and wherein n represents an integer varying from 2 to 16; a process for their preparation, their dietetic and therapeutic applications and compositions containing them.

19-nor steroids substituted at position 11 and optionally at position 2, their preparation, their utilization as medicaments, compositions containing them and intermediates obtained

Abstract: L'invention a pour objet les produits de formule (I) The invention has for its object the products of formula (I) dans laquelle : in which : R 1 = radical organique C 1-18 comportant eventuellement R 1 = C 1-18 organic radical comprising optionally un ou plusieurs heteroatomes; one or more heteroatoms; R 2 = radical hydrocarbone C 1-8 ; R 2 = C 1-8 hydrocarbon radical; X = cycle pentagonal ou hexagonal; X = pentagonal or hexagonal ring; les cycles A et B representent les groupements : the rings A and B represent the groups: R' et R" = H, CN ou Alkyle C 1-4 ; Rx = H ou ORe; Re = H, alkyle C 1-8 ou acyle; R 'and R "= H, CN or C 1-4 alkyl; Rx = H or OR e; Re = H, C 1-8 alkyl or acyl; R'a et R"a = Alk C 1-4 soit R'a et R"a forment un heterocycle ou Ra = acyloxy; R'a and R "a = Alk is C 1-4 R'a and R" a form a heterocycle or Ra = acyloxy; leur procede de preparation, leur application comme medi- caments, les compositions les renfermant et les nouveaux intermediaires obtenus. process for their preparation, their application as mediclean caments, compositions containing them and new intermediates obtained.

Insecticidal cyclopropane carboxylic acid derivatives with 3-unsaturated-side chain

Abstract: Novel isomers and mixtures thereof of cyclopropane carboxylic acid derivatives with a 3-unsaturated side chain of the formula ##STR1## The double bond having Z or E geometry and having insecticidal and nematocidal activity as well as plant and animal acaricidal activity.

Novel 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,1-j-k][1]-benzazepin-2-(1H)-one

Abstract: Novel 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,l-j-k][1]-benzazepin-2-(1H)-one derivatives of the formula ##STR1## wherein R is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms optionally substituted with a hydroxyl, aryl and aryloxy of 6 to 10 carbon atoms, cycloalkyl of 3 to 7 carbon atoms optionally interrupted with a heteroatom optionally substituted with alkyl of 1 to 4 carbon atoms and the wavy lines indicates that the 7-OH and 6-amino have the trans configuration and their non-toxic, pharmaceutically acceptable acid addition salts having remarkable anti-hypertensive and hypotensive activity and vasodilatatory activity and their preparation.

1-3-dihydro 4-(1-hydroxy-2-amino-ethyl)-2h-indol-2-one derivatives, their salts, process for their preparation, their use as medicines and compositions containing them

Abstract: For the contracting states : BE CH DE FR GB IT LI LU NL SE 1. Derivatives of 1,3-dihydro-4-(1-hydroxy-2-aminoethyl)-2H-indol-2-one, as well as their salts of addition with mineral or organic acids, characterized in that they answer to the general formula I see diagramm : EP0099766,P19,F1 in which R represents a hydrogen atom or an alkyl radical containing from 1 to 6 carbon atoms or a phenyl alkyl radical containing from 7 to 10 carbon atoms, R1 and R2 represent a hydrogen atom a linear or branched alkyl radical containing from 1 to 8 carbon atoms, possibly substituted, except in the case of the methyl radical, by one or more halogen or by one more hydroxy, phenyl, or phynoxy radicals, or phenyl or phenoxy radicals substituted by one or more halogen, hydroxy, methyl or methoxy radicals, or R1 and R2 represent a cycloalkyl radical containing from 3 to 7 carbon atoms, a cycloalkyl radical containing from 4 to 7 carbon atoms or an allyl or propargyl radical. For the contracting state : AT 1. process for preparing new derivatives of 1,3-dihydro-4-(1-hydroxy-2-aminoethyl)-2H-indol-2-one, as well as their salts of addition with mineral or organic acids answering to the general formula (I) see diagramm : EP0099766,P21,F1 in which R represents a hydrogen atom or an alkyl radical containing from 1 to 6 carbon atoms or a phenyl alkyl radical containing from 7 to 10 carbon atoms, R1 and R2 represent a hydrogen atom a linear or branched alkyl radical containing from 1 to 8 carbon atoms, possibly substituted, except in the case of the methyl radical, by one or more halogen or by one more hydroxy, phenyl, or phenoxy radicals, or phenyl or phenoxy radicals substituted by one or more halogen, hydroxy, methyl or methoxy radicals, or R1 and R2 represent a cycloalkyl radical containing from 3 to 7 carbon atoms, a cycloalkyl radical containing from 4 to 7 carbon atoms or an allyl or proparglyl radical, characterized in that a product with the formula (II) : see diagramm : EP0099766,P21,F2 in which R, R1 and R2 have the significance already indicated, is submitted to the action of a halogenetion agent, so as to obtain a product with the formula III : see diagramm : EP0099766,P22,F3 in which Hal represents a halogen atom and R, R1 and R2 have the significance already indicated, which is hydrolized so as to obtain a product with the formula I : see diagramm : EP0099766,P22,F4 in which R, R1 and R2 have the signification already indicated, which is isolated and if desired, salified.

Single and repeated dose kinetics of the hypnotic agent loprazolam in healthy volunteers.

Abstract: The pharmacokinetics of loprazolam have been studied in eight healthy male volunteers after single and repeated 2 mg oral doses taken at night, for eight nights. The absorption and disposition of unchanged drug (HPLC-GC assay) and receptor active benzodiazepine-type materials (radioreceptor assay) were examined after the first and eighth dose. Maximum levels of approximately 10 ng ml−1 (range 3.6 to 15.5 ng ml−1) were reached within about 2.5 h after dosing. The post-peak levels declined in a single exponential fashion with an overall mean±SD half-life of 7.06±1.98 h and total areas under the curve ranging from 35.9 to 189.0 ng ml−1 h. There were no statistical differences between the values for the first and eighth doses. There was no evidence to suggest that significant accumulation of parent drug or receptor active benzodiazepine-type materials had occurred, and it is concluded that the kinetics of loprazolam would allow repeated daily doses of 2 mg.

4-(1H-indol-3-yl)-α-methyl-piperidine-1-ethanol derivatives

Abstract: Novel 4-(1H-indol-3-yl)-α-methyl-piperidine-1-ethanol derivatives of the formula ##STR1## wherein R is selected from the group consisting of hydrogen, halogen, alkyl and alkoxy of 1 to 5 carbon atoms, --NO 2 , --NH 2 , CF 3 -- and CH 3 S--, R 1 is selected from the group consisting of hydrogen and alkyl of 1 to 5 carbon atoms, R 2 is selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms and --OH, Ar is selected from the group consisting of optionally substituted aryl and heteroaryl, the dotted line indicates the optional presence of a double bond and their non-toxic, pharmaceutically acceptable acid addition salts having remarkable antagonistic properties toward calcium ion and antihypertensive activity and certain compounds possess α and/or β-blocking properties.

Hypnotic benzodiazepines: Relationship between sleep parameters and pharmacokinetics of loprazolam

Abstract: In the search for a relationship between subjective and electrophysiologic sleep parameters and blood levels of loprazolam during night sleep after single and repeated administration, eight normal volunteers took loprazolam, a novel imidazo-benzodiazepine, on eight consecutive evenings. The assessment of the pharmacokinetics of the drug was done by two different methods: a high-pressure liquid chromatography-gas chromatography (HPLC-GC) measuring the parent drug specifically and a radioreceptor assay (RRA) measuring both the parent drug and the metabolites binding to the benzodiazepine-receptor; the latter gave slightly higher values indicating the existence of metabolites binding to the benzodiazepine-receptor. The elimination half-life of the parent drug was about eight hr and did not significantly increase after repeated administration; the half-life when using the RRA was some-what longer since steady state was not reached until the fourth day. A relationship was looked for between pharmacokinetic data and either self-evaluated or polygraphic sleep parameters obtained from all-night recordings on the first and eighth treatment nights. No correspondence could be demonstrated, suggesting that the drug does not act directly on sleep systems and that its hypnotic effects may be indirect, secondary to anxiolytic effects or to deactivation of wake systems.

Cyclopropane carboxylic acid derivatives

Abstract: Novel cyclopropane carboxylic acid derivatives of the formula ##STR1## wherein A is selected from the group consisting of --O--, --CH 2 -- and ##STR2## R is selected from the group consisting of alkyl of 1 to 8 carbon atoms, alkenyl and alkynyl of 2 to 8 carbon atoms and optionally unsaturated cycloalkyl and cycloalkylalkyl of 3 to 8 carbon atoms optionally substituted with at least one alkyl group and the double bond in the 3-side chain has the Z geometry in all possible stereoisomeric forms and mixtures of stereoisomers having insecticidal, nematocidal and animal and vegetable acaricidal activities and their preparation.

Triglycerides, process for their preparation, their dietetical and therpeutical use and compositions containing them

Abstract: For the Contracting States : BE, CH, DE, GB, IT, LI, LU, NL, SE 1. Triglycerides with the general formula (I) : see diagramm : EP0120169,P9,F1 in which R represents the acyl fragment of a polyunsatured fatty acid containing from 18 to 22 carbon atoms, the said acyl fragment being able to be oxidized, R, however, not being able to represent the acyl fragment of eicosatetrayn - 5, 8, 11, 14 - oic, and in which n represents a whole number which can vary from 2 to 16. For the Contracting State : AT 1. Preparation process for triglycerides with the general formula I : see diagramm : EP0120169,P10,F1 in which R represents the acyl fragment of a polyunsatured fatty acid containing from 18 to 22 carbon atoms, the said acyl fragment being able to be oxidized, R, however, not being able to represent the acyl fragment of eicosatetrayn - 5, 8, 11, 14 - oic, and in which n represents a whole number which can vary from 2 to 16, characterized in that dihydroxy acetone is esterified with two molar equivalents of a functional derivative of an acid with the formula II : see diagramm : EP0120169,P11,F2 in which n is defined as previously, a product with the formula III : see diagramm : EP0120169,P11,F3 is obtained, which is treated by a reducing agent not causing saponification of the ester groups, a product with the formula IV : see diagramm : EP0120169,P11,F4 is obtained which is esterified with a functional derivative of a polyunsatured fatty acid, the acid acid having as its formula ROH, R having the same significance as that indicated previously ; in order to obtain a triglyceride with the formula I, which is oxidized, if the case arises, in the case where R is an oxidized acyl fragment, by the action of lipoxygenases or by simple oxidation, in order to obtain the product with the formula I in which R is an oxidized acyl fragment.

Imidazo(1,2-a)pyrimidines and their salts, process and intermediates for their preparation, their use as medicaments and compositions containing them

Abstract: L'invention a pour objet les nouvelles imidazo/1,2-a/ pyrimidines 1 : The invention relates to new imidazo / 1,2-a / pyrimidines 1: ou R est un alcoyle (1-8C), un alcenyle (2-8C), un cycloalcoyle (3-7C), un cycloalcoylalcoyle (4-12C), un aryle (6-12C), un thienyle ou pyridyle, eventuellement substitue R, et R 2 representent un hydrogene, un alcoyle (1-8C), un alcenyle (2-5C), un cycloalcoyle (3-7C), un cycloalcoylalcoyle (4-12C), un benzyle ou un phenethyle, ou R, et R 2 forment un alcoylene (3-5C), R 1 et R 2 pouvant etre substitues, X est un oxygene ou un soufre, R 3 est un alcoyle (1-5C), ainsi que leurs sels d'acides, leur procede et leurs intermediaires de preparation, leur application comme medicaments, notamment anxiolytiques et les compositions les renfermant. wherein R is alkyl (1-8C), alkenyl (2-8C), cycloalkyl (3-7C), a cycloalkylalkyl (4-12C), aryl (6-12C), thienyl or pyridyl, optionally substituted R, and R 2 represent hydrogen, alkyl (1-8C), alkenyl (2-5C), cycloalkyl (3-7C), a cycloalkylalkyl (4-12C), benzyl or phenethyl, or R and R 2 form an alkylene (3-5C), R 1 and R 2 may be substituted, X is oxygen or sulfur, R 3 is alkyl (1-5C), as well as their acid salts, their method and their preparation intermediates, their use as medicaments, especially anxiolytic and compositions containing them.

A RAL compound as an anabolic in cattle.

Abstract: Zeranol given alone has a medium level of activity in calves fed milk replacer, but a good to very good activity in bulls and steers. The effect on N retention of a combination of Zeranol (36 mg)+trenbolone acetate (140 mg) is of the level of the combination E2+TBA, which appears to be the better combination in cattle. The combination of Zeranol+trenbolone acetate seems to give more regular results in cattle of any age.

3-Keto-19-nor-Δ4,9-steroids

Abstract: Novel 3-keto-19-nor-Δ4,9 -steroids of the formula ##STR1## possessing a remarkable antiglucocorticoidal activity.

6-Amino-7-hydroxy-4,5,6,7-tetrahydroimidazo(4,5,1-j,k)(1)benzazepin-2(1H)-one derivatives, their salts, their preparation, their use as medicaments and compositions containing them

Abstract: L'invention concerne des nouveaux derives de la 6-amino 7-hydroxy 4,5,6,7-tetrahydroimidazo/4,5-1-jk//1/ benzazepin 2(1 H)-one ainsi que leurs sels d'addition avec les acides mineraux ou organiques, de formule: The invention relates to new derivatives of 6-amino-7-hydroxy 4,5,6,7-tetrahydroimidazo / 4.5 to 1-jk // 1 / benzazepin 2 (1 H) -one and salts thereof addition with mineral or organic acids of the formula: R = H alcoyle C 1 -C 8 , eventuellement substitue par hydroxy, aryle ou aryloxy, cycloalcoyle C 3 -C 7 eventuellement interrompu par un heteroatome portant eventuellement un alcoyle C 1 -C 4 , leur application a titre de medicaments et les compositions les renfermant. R = H alkyl C 1 -C 8, optionally substituted by hydroxy, aryl or aryloxy, C 3 -C 7 cycloalkyl optionally interrupted with one heteroatom optionally bearing a C 1 -C 4 alkyl, their application as medicaments and compositions containing.

19-nor steroids substituted at positions 11 and 17 and optionally at position 2, their preparation, their use as medicaments, compositions containing them and intermediates obtained

Abstract: L'invention a pour objet les produits de formule (I) The invention has for its object the products of formula (I) dans laquelle : in which : R, = radical organique C 1-18 comportant eventuellement R = C 1-18 organic radical comprising optionally un ou plusieurs heteroatomes ; one or more heteroatoms; R 2 = radical hydrocarbone C 1-8 ; R 2 = C 1-8 hydrocarbon radical; R 3 et R 4 forment ensemble le radical R 3 and R 4 together form the radical les cycles A et B representent les groupements : the rings A and B represent the groups: R' et R" = H, CN ou Alkyle C 1-4 ; Rx = H ou ORe; Re = H, alkyle C 1-6 ou acyle; R 'and R "= H, CN or C 1-4 alkyl; Rx = H or OR e; Re = H, C 1-6 alkyl or acyl; R'a et R"a = Alk C 1-4 soit R'a et R"a forment un heterocycle ou Ra = acyloxy; R'a and R "a = Alk is C 1-4 R'a and R" a form a heterocycle or Ra = acyloxy; leur procede de preparation, leur application comme medicaments, les compositions les renfermant et les nouveaux intermediaires obtenus. process for their preparation, their use as medicaments, compositions containing them and new intermediates obtained.

Nouvelles compositions pour les soins de la peau renfermant de l'huile d'onagre et des extraits tissulaires de rate

Abstract: L'INVENTION CONCERNE DE NOUVELLES COMPOSITIONS COSMETIQUES OU DERMATOLOGIQUES POUR LA PEAU, CARACTERISEES EN CE QU'ELLES RENFERMENT DE L'HUILE D'ONAGRE ASSOCIEE A DES EXTRAITS TISSULAIRES DE RATE.

Light-stable pesticidal compositions

Abstract: Novel light-stable pyrethrinoid pesticidal compositions comprising (a) at least one liquid vehicle, (b) at least one surface-active agent soluble in the said liquid vehicle, (c) at least one azodyestuff stabilizer and (d) at least one ester of the formula ##STR1## .

Nouveaux 19-nor steroides substitues en 11b et eventuellement en 2, leur procede de preparation et leur application comme medicament

Abstract: L'INVENTION A POUR OBJET LES PRODUITS DE FORMULE I: (CF DESSIN DANS BOPI) DANS LAQUELLE: R RADICAL ORGANIQUE C COMPORTANT EVENTUELLEMENT UN HETEROATOME; R RADICAL HYDROCARBONE C; X CYCLE PENTAGONAL OU HEXAGONAL. LES CYCLES A ET B REPRESENTENT LES GROUPEMENTS: (CF DESSIN DANS BOPI) R ET R H, CN OU ALKYLE C; RA -N; RA ET RA ALK C SOIT RA ET RA FORMENT UN HETEROCYCLE; OU RA ACYLOXY. LEUR PROCEDE DE PREPARATION ET LEUR APPLICATION COMME MEDICAMENTS.