NOVEL PROCESSES FOR THE PREPARATION OF PROSTAGLANDIN AMIDES

NOVEL PROCESSES FOR THE PREPARATION OF PROSTAGLANDIN AMIDES

The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, - where in the formula the bonds marked with dotted lines may be single or double bonds, in the case of double bounds at positions 5,6 and 13,14 they may be in cis or in trans orientation, Q stands for a hydroxyl-group and Z stands for a hydroxyl- or oxo-group, R1 and R2 independently represent hydrogen atom or a straight or branched C1-10 alkyl- or aralkyl- group, optionally substituted with -ONO2 group, or an aralkyl- or aryl- group, which contains heteroatom, R3 represents a straight or branched, saturated or unsaturated C4-6 hydrocarbon group, or a C4-10 alkylcycloalkyl- or cycloalkyl- group, or an optionally with alkyl group or halogen atom substituted phenyl-, C7-10 alkylaryl- or hetaryl- group, Y represents (CH2)n group or 0 atom or S atom, and where n=0-3.

NOVEL PROCESSES FOR THE PREPARATION OF PROSTAGLANDIN AMIDES

The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, where in the formula the bonds marked with dotted lines may be single or double bonds, in the case of double bounds at positions 5,6 and 13,14 they may be in cis or in trans orientation, Q stands for a hydroxyl-group and Z stands for a hydroxyl- or oxo-group, Rand Rindependently represent hydrogen atom or a straight or branched Calkyl- or aralkyl- group, optionally substituted with —ONOgroup, or an aralkyl- or aryl- group, which contains heteroatom, Rrepresents a straight or branched, saturated or unsaturated Chydrocarbon group, or a Calkylcycloalkyl- or cycloalkyl- group, or an optionally with alkyl group or halogen atom substituted phenyl-, Calkylaryl- or hetaryl- group, Y represents (CH), group or 0 atom or S atom, and where n=0-3. 4. Process according to method i.) of claim 1 , characterized in that the compound suitable to introduce the group R claim 1 , is 1 claim 1 ,1′-carbonyldiimidazole or 1 claim 1 ,1′-thiocarbonyldiimidazole.5. Process according to method ii.) of claim 1 , characterized in that for the introduction of group R claim 1 , N-hydroxysuccinimide claim 1 , N-hydroxyphthalimide claim 1 , N-hydroxy-5-norben-endo-2 claim 1 ,3-dicarboxamide claim 1 , 1-hydroxybenzotriazole claim 1 , (benzotriazol-1-yloxy)tris(dimethylamino)-phosphonium hexafluorophosphate claim 1 , N claim 1 ,N′-disuccinimidyl carbonate or N claim 1 ,N′-disuccinimidyl oxalate are used claim 1 , in a given case in the presence of an activating agent.6. Process according to claim 5 , characterized in that the applied activating agent is N claim 5 ,N′-diisopropylcarbodiimide claim 5 , N claim 5 ,N′-dicyclohexylcarbodiimide or 2-chloro-1 claim 5 ,3-dimethylimidazolinium chloride.7. Process according to claim 1 , characterized in that the reaction is carried out in an ether-type claim 1 , or aromatic claim 1 , or polar-aprotic solvent claim 1 , or in the mixture of them.8. ...

PREPARATION OF LATANOPROSTENE BUNOD OF DESIRED, PRE-DEFINED QUALITY BY GRAVITY CHROMATOGRAPHY

The subject of the invention is a process for the preparation of Latanoprostene bunod of formula (I) with a purity higher than 95% where chromatography is used applying normal phase gravity silica gel column chromatography where the used silica gel is irregular silica gel or spherical silica gel an as eluent and eluent mixture consisting of an apolar and a polar solvent is used and if desired, contamination of the purified compound of formula I arising from the solvents are removed by silica gel filtration chromatography. 2. Process a.) or b.) as defined in claim 1 , characterized in that claim 1 , the eluent mixture contains as apolar solvent straight- or branched-chain aliphatic claim 1 , cyclic or aromatic hydrocarbons claim 1 , halogenated aliphatic hydrocarbons or ether-type solvents.3. Process as defined in claim 2 , characterized in that claim 2 , as apolar solvent pentane claim 2 , hexane claim 2 , heptane claim 2 , cyclohexane claim 2 , dichloromethane or diisopropyl ether claim 2 , preferably hexane is applied.4. Process a.) or b.) as defined in claim 1 , characterized in that claim 1 , as polar solvent an alcohol- claim 1 , ester- or ketone-type solvent containing straight- or branched-chain alkyl group is applied.5. Process as defined in claim 4 , characterized in that claim 4 , as polar solvent a C1-5 alcohol claim 4 , preferably ethyl alcohol or isopropyl alcohol is applied.6. Process as defined in claim 3 , characterized in that claim 3 , the eluent mixture is a gradient mixture containing hexane and ethyl alcohol in 6:1-8:1 volume ratios.7. Process as defined in claim 4 , characterized in that claim 4 , as polar solvent a ketone-type solvent claim 4 , preferably acetone is applied.8. Process as defined in claim 3 , characterized in that claim 3 , the eluent mixture contains hexane and acetone in 2:1 volume ratio.9. Filtration chromatography process as defined in claim 1 , characterized in that claim 1 , the eluent mixture contains an apolar and a ...

NEW PROCESS FOR THE PREPARATION OF HIGH PURITY PROSTAGLANDINS

The subject of the invention is a process for the preparation of high purity prostaglandin acid of the general formula II wherein the bonds marked with dotted lines represent single or double bonds wherein the double bonds may be cis- or trans oriented, Y represents 0 or CH, and Rstands for a phenyl group which is optionally substituted with CF, wherein the crude prostaglandin acid of the general formula II is purified by normal phase silicagel chromatography. 2. The process as defined in claim 1 , wherein chromatography is carried out by normal phase gravitational claim 1 , medium- or high pressure silica gel chromatography.3. The process as defined in claim 1 , wherein the applied silica gel is a spherical silica gel having average particle size in a range of 10-150 micrometer.4. The process as defined in claim 1 , wherein a multicomponent eluent mixture is applied as eluent.5. The process as defined in claim 4 , wherein the eluent mixture contains one or more apolar solvents claim 4 , one or more polar solvents and solvent of acidic character claim 4 , in a ratio of (91-73%):(24-8.7%):(0.1-4.3%).6. The process as defined in claim 5 , wherein the apolar component of the eluent mixture is straight or branched open-chain or cyclic or aromatic hydrocarbon claim 5 , optionally containing one or more substituents.7. The process as defined in claim 6 , wherein the substituent is halogen atom.8. The process as defined in claim 6 , wherein as apolar solvent aliphatic hydrocarbon is applied.9. The process as defined in claim 5 , wherein as polar solvent an alcohol- claim 5 , ether- claim 5 , ester- or ketone-type solvent is applied which contains straight or branched open-chain alkyl claim 5 , alkenyl or cyclic or cycloalkyl group.10. The process as defined in claim 9 , wherein as polar solvent Calcohol is applied.11. The process as defined in claim 10 , wherein as polar solvent isopropyl alcohol is applied.12. The process as defined in claim 5 , wherein the solvent of ...

PROCESS FOR THE PREPARATION OF POLYMORPH FORM B OF TREPROSTINIL DIETHANOLAMINE SALT

The invention relates to a robust and reproducible process for the preparation of polymorph form B of treprostinil diethanolamine salt, comprising the following steps: a. treprostinil is dissolved in methanol, b. to the solution of step a) diethanolamine or its methanol solution is added, c. the reaction mixture of step b) is agitated till dissolution, d. when salt formation is completed in step c), first portion of an aprotic solvent is added to the solution, e. the solution of step d) is filtered to remove insoluble impurities, f. the filtrate of step e) is seeded with polymorph form B of treprostinil diethanolamine salt, g. to the crystal suspension obtained in step f) a second portion of the aprotic solvent is added, h. the suspension of step g) is agitated until crystallisation is completed, i. the crystals are separated, washed and dried. 1. Robust , reproducible , one-step process for the preparation of polymorph form B of treprostinil diethanolamine salt comprising the following steps:a. treprostinil is dissolved in methanol,b. to the solution of step a) diethanolamine or its solution in methanol is added,c. the reaction mixture of step b) is agitated till dissolution,d. after completion of salt formation in step c) a first portion of aprotic solvent is added to the solution,e. the solution of step d) is filtered,f. the filtrate of step e) is seeded with polymorph form B of treprostinil diethanolamine salt,g. to the crystal suspension obtained in step f), a second portion of the aprotic solvent is added,h. the suspension of step g) is agitated until crystallisation is completed,i. the crystals are separated, washed and dried.2. Process according claim 1 , characterized in that dissolution of treprostinil and diethanolamine is carried out at 25-50° C.3. Process according to claim 2 , characterized in that dissolution of treprostinil and diethanolamine is carried out at 30-40° C.4. Process according to claim 1 , characterized in that ethers claim 1 , such as ...

Process for the preparation of optically active beraprost

The invention provides a new process for the preparation of optically active Beraprost of formula (I) starting from racemic Beraprost alkyl ester through hydrolysis, enantiomer esterification, preparation of diacyl-Beraprost ester diastereomers and their separation and hydrolysis.

PROCESS FOR THE PREPARATION OF EPOPROSTENOL SODIUM OF ENHANCED STABILITY

The invention provides a stable epoprostenol sodium and a process for the preparation this pharmaceutically active ingredient. 1. Stable epoprostenol sodium drug substance which can be stored in deep freezer (−20±5° C.) for at least 3 years , characterized by that the lyophilized drug substance contains epoprostenol sodium salt and , related to the amount of the epoprostenol sodium salt , it contains in 3-7.5 mass % inorganic base or basic-hydrolyzing inorganic salt.2. Drug substance as defined in claim 1 , wherein the lyophilized drug substance contains epoprostenol sodium salt and claim 1 , related to the amount of the epoprostenol sodium salt claim 1 , it contains in 4 mass % inorganic base or basic-hydrolyzing inorganic salt.3. Drug substance as defined in claim 1 , wherein the lyophilized drug substance contains epoprostenol sodium salt and claim 1 , related to the amount of the epoprostenol sodium salt claim 1 , it contains in 5 mass % inorganic base or basic-hydrolyzing inorganic salt.4. Drug substance as defined in claim 1 , wherein the lyophilized drug substance contains epoprostenol sodium salt and claim 1 , related to the amount of the epoprostenol sodium salt claim 1 , it contains in 6 mass % inorganic base or basic-hydrolyzing inorganic salt.5. Drug substance as defined in claim 1 , wherein as inorganic base it contains sodium hydroxide.6. Process for the preparation of stable epoprostenol sodium which can be stored in deep freezer (−20±5° C.) for at least 3 years claim 1 , characterized by that the aqueous solution of the epoprostenol sodium salt is lyophilized in the presence of such an amount of inorganic base or basic-hydrolyzing inorganic salt ensuring a pH>11 medium claim 1 , that the lyophilisate contains 3-7.5 mass % claim 1 , preferably 4-6 mass % of excess sodium hydroxide claim 1 , related to the amount of the epoprostenol sodium salt.7. Process as defined in claim 6 , wherein as inorganic base or basic-hydrolyzing inorganic salt claim 6 , a ...

PROCESS FOR THE PREPARATION OF TRIPLE-BOND-CONTAINING OPTICALLY ACTIVE CARBOXYLIC ACIDS, CARBOXYLATE SALTS AND CARBOXYLIC ACID DERIVATIVES

The invention provides a new enzimatic process for the preparation of chiral carboxylic acids, their salts and acid derivatives of the general formula (I) by enzymatic hydrolysis of racemic carboxylic acid ester of the general formula (II) and optionally subsequent esterification or acylation. 2. Process as defined in claim 1 , wherein the enzymatic hydrolysis is carried out with hydrolase enzyme.3Candida rugosa, Pseudomonas fluorescens, Candida antarctica A, Candida antarctica B, Burkholderia cepacia, Rhizopus arrhizus, Rhizomucor miehei, Pseudomonas cepacia lipase. Process as defined in claim 2 , wherein as hydrolase enzyme lipase enzyme claim 2 , such as or pig pancrease lipase claim 2 , calf pancrease lipase are applied.4Candida rugosa. Process as defined in claim 3 , wherein as lipase enzyme enzyme is applied.5. Process as defined in claim 1 , wherein the hydrolysis is carried out in the presence of solvent.6. Process as defined in claim 5 , wherein as solvent ethers claim 5 , hydrocarbon-type and aromatic solvents claim 5 , such as diisopropyl ether claim 5 , methyl tert.-butyl ether claim 5 , n-hexane claim 5 , toluene are applied.7. Process as defined in claim 6 , wherein as solvent methyl tert.-butyl ether is applied.8. Process as defined in claim 1 , wherein depending on the amount and activity of the enzyme claim 1 , the reaction time is 2-48 hours.9. Process as defined in claim 1 , wherein the reaction is performed at 20-40° C.10. Process as defined in claim 2 , wherein the hydrolysis is carried out in the presence of solvent.11. Process as defined in claim 3 , wherein the hydrolysis is carried out in the presence of solvent.12. Process as defined in claim 4 , wherein the hydrolysis is carried out in the presence of solvent.13. Process as defined in claim 2 , wherein depending on the amount and activity of the enzyme claim 2 , the reaction time is 2-48 hours.14. Process as defined in claim 3 , wherein depending on the amount and activity of the enzyme ...

NOVEL PROCESSES FOR THE PREPARATION OF PROSTAGLANDIN AMIDES

The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, 3. Process according to claim 2 , characterized in that dimethyl ether claim 2 , diethyl ether claim 2 , diisopropyl ether are used as ether-type solvents.4. Process according to claim 2 , characterized in that ethyl-acetate claim 2 , methyl-acetate claim 2 , isopropyl-acetate are used as ester-type solvents.5. Process according to claim 2 , characterized in that crystallisation is performed between (−)30° C. and 30° C.6. Process according to claim 2 , characterized in that the suspension of crystals is stirred 1-24 hours.7. Process according to claim 2 , characterized by that the crystal suspension is filtered and washed with ether type solvent.8. Process according to claim 2 , characterized in that the filtered crystals are dried under vacuum between 25-50° C.9. Process according to claim 2 , characterized in that diethyl-ether and diisopropyl ether are used as ether-type solvents.10. Process according to claim 2 , characterized in that isopropyl-acetate are used as ester-type solvents.11. Process according to claim 2 , characterized in that crystallisation is performed between 0-25° C.12. Process according to claim 2 , characterized in that the suspension of crystals is stirred 8 hours.13. Process according to claim 2 , characterized by that the crystal suspension is filtered and washed with diisopropyl ether.14. Process according to claim 2 , characterized in that the filtered crystals are dried under vacuum between 35-40° C. This application is a Divisional of copending application Ser. No. 14/123,497, filed on Jan. 29, 2014, which was filed as PCT International Application No. PCT/HU2012/000045 on May 25, 2012, which claims the benefit under 35 U.S.C. §119(a) to Patent Application No. P11 00291, filed in Hungary on Jun. 2, 2011 and Patent Application No. P11 00292, filed in Hungary on Jun. 2, 2011, all of which are hereby expressly incorporated by ...

PROCESS FOR THE PREPARATION OF TRAVOPROST

The crystalline compound of formula (III) 1. The crystalline compound of formula (III)having the melting point of 129.5-134.5° C. This application is a Divisional of copending application Ser. No. 14/367,317, filed on Jun. 20, 2014, which was filed as PCT International Application No. PCT/HU2012/000132 on Dec. 10, 2012, which claims the benefit under 35 U.S.C. §119(a) to Patent Application No. P1100701, filed in Hungary on Dec. 21, 2011, all of which are hereby expressly incorporated by reference into the present application.The subject of our invention is a novel process for the preparation of travoprost.Travoprost of Formula (I)is a known prostaglandin derivative used for the treatment of glaucoma and high eye pressure (U.S. Pat. No. 5,510,383).Processes for the preparation of travoprost are disclosed for example in EP 2143712, WO 2011/046569, WO 2011/055377.The process according to EP 2143 712 is shown on .Stereoselectivity of the enone→enol reduction is 88.7% (Example 10.).According to the process disclosed in WO 2011/046569 the 15-epi impurity is removed by protection of the OH-groups of the diol with tert-butyl-dimethylsilyl group (TBDMS) and crystallization of the thus obtained protected diol.In the process according to WO 2011/055377 the enone→enol transformation is carried out with N,N-diethylaniline-borane complex as reducing agent, in the presence of Corey catalyst (CBS-oxazaborolidine). The product is purified by preparative HPLC.The overall yield is 7%.We aimed to work out a process with higher stereoselectivity and better yield.The subject of our invention is the preparation of travoprost of formula (I)by stereoselective reduction of the compound of formula (II),reduction of the lactone group of the resulting compound of formula (III),removal of the p-phenylbenzoyl protecting group of the thus obtained compound of formula (IV),transformation of the resulting triol of formula (V) by Wittig reactioninto the acid of formula (VI)which is then esterified. ...

NOVEL PROCESSES FOR THE PREPARATION OF PROSTAGLANDIN AMIDES

The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, 2. Crystal form II. prepared by the process according to claim 1 , characterized in that its melting point is between 72-78° C.3. Crystal form II. prepared by the process according to claim 1 , characterized in that on the basis of DSC investigation the endothermic peak is between 72-79° C. and its melting heat is higher than 75 J/g.4. Process according to claim 1 , characterized in that 20-60 mass % amount of protic solvent is applied.5. Process according to claim 1 , characterized in that alcohols and/or water are used as protic solvents.6. Process according to claim 5 , characterized in that methanol or ethanol is used as alcohol.7. Process according to claim 5 , characterized in that water is used as protic solvent.8. Process according to claim 1 , characterized in that 2000-8000 mass % amount of ether-type solvent is applied.9. Process according to claim 1 , characterized in that dimethyl ether claim 1 , diethyl ether claim 1 , diisopropyl ether are used as ether-type solvents.10. Process according to claim 1 , characterized in that stirring or scratching claim 1 , or both are applied as mechanical effect.11. Process according to claim 1 , characterized in that the added solvent is removed by drying.12. Process according to claim 4 , characterized in that drying is performed in vacuum claim 4 , at a temperature between (−) 60° C. and 70° C.13. Process according to claim 8 , characterized in that drying is performed at a temperature between 0-(−)50° C. by passing through nitrogen gas.14. Process according to claim 1 , characterized in that 35 mass % amount of protic solvent is applied. This application is a Divisional of copending application Ser. No. 14/123,497, filed on Jan. 29, 2014, which was filed as PCT International Application No. PCT/HU2012/000045 on May 25, 2012, which claims the benefit under 35 U.S.C. §119(a) to Patent Application No. P11 ...

PROCESS FOR THE PREPARATION OF TREPROSTINIL

Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anhydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. 2. Process as defined in for the preparation of the salts of treprostinil of formula I given with bases claim 1 , wherein as polar solvent Copen-chain or branched organic alcohol claim 1 , is applied.3. Process as defined in for the preparation of the salts of treprostinil of formula I given with bases claim 1 , wherein as for base claim 1 , the solventless organic or inorganic base which contains the cation of the desired salt is applied.4. Process as defined in for the preparation of the salts of treprostinil of formula I given with bases claim 3 , wherein as for base claim 3 , an organic or inorganic base containing alkali metal or alkali earth-metal cation is applied.5. Process as defined in for the preparation of the salts of treprostinil of formula I given with bases claim 4 , wherein as for base sodium carbonate monohydrate claim 4 , sodium hydrogen carbonate claim 4 , sodium methylate claim 4 , or sodium carbonate hydrate is applied.6. Process as defined in for the preparation of the salts of treprostinil of formula I given with bases claim 1 , wherein the reaction mixture is agitated in an inert atmosphere until salt formation proceeds.7. Process as defined in for the preparation of the salts of treprostinil of formula I given with bases claim 1 , wherein as the organic solvent of the crystallisation an ether claim 1 , ester claim 1 , or ketone solvent is applied.8. Process as defined in for the preparation of the salts of ...

PROCESS FOR THE PREPARATION OF TREPROSTINIL

The invention provides a new process for the preparation of treprostinil of formula (I) and its salts using several new intermediates during the building of the ring system. 2. The method as defined in claim 1 , characterized in that as Rprotective group methoxymethyl- claim 1 , methoxyethoxymethyl- or tetrahydropyranyl-group claim 1 , as Rprotective group methyl group claim 1 , as Rprotective group a protective group containing silicium atom claim 1 , preferably tert-butyldimethylsilyl group claim 1 , as Rprotective group p-phenylbenzoyl group is applied.3. Process as defined in claim 1 , wherein in a1) in that as Grignard reagent methyl- claim 1 , ethyl- claim 1 , propyl- claim 1 , butyl- claim 1 , cyclohexyl-magnesium bromide claim 1 , preferably methylmagnesium bromide is applied.4. Process as defined in claim 1 , wherein in a1) the oxidation of the compound of formula XV is carried out with pyridinium chlorochromate.5. Process as defined in claim 1 , wherein in a1) the oxidation of the compound of formula XV is carried out by Swern oxidation.6. Process as defined in claim 1 , wherein in a1) the reduction is carried out with borane compound claim 1 , in the presence of chiral oxazaborolidine catalyst.7. Process as defined in claim 6 , characterized in that as borane compound borane-dimethyl sulfide complex claim 6 , catecholborane or borane-diethylaniline complex claim 6 , preferably borane-dimethyl sulfide complex is applied.8. Process as defined in claim 1 , wherein in a2) as chiral base chiral aminoalcohols or diamines claim 1 , preferably (+)-N-methylephedrine are applied.9. Process as defined in claim 1 , wherein in a2) as zinc salt claim 1 , zinc triflate is applied.10. Process as defined in claim 1 , wherein in 1b) the intramolecular cyclisation is carried out by Pauson-Khand cyclisation method.11. Process as defined in claim 10 , characterized in that the Pauson-Khand cyclisation is carried out by using dicobalt octacarbonyl.12. Process as defined in ...

PROCESS FOR THE PREPARATION OF CARBOPROST AND ITS TROMETHAMINE SALT

The subject of the invention is a novel process for the preparation of Carboprost tromethamine salt where alkylation the enone of the general formula (II) is carried out in the presence of a chiral auxiliary in aprotic solvent with a Grignard reagent. The methyl ester epimers of formula (VII) are separated by gravity silicagel chromatography and the salt formation is carried out by using solid tromethamine base. 2. Process as defined in claim 1 , comprising that as Grignard reagent methylmagnesium chloride or methylmagnesium bromide claim 1 , preferably methylmagnesium bromide is applied.3. Process as defined in claim 2 , comprising that methylmagnesium bromide is applied in 3-4 molar equivalent claim 2 , preferably 3.5 molar equivalent amount.4. Process as defined in claim 1 , comprising that as chiral auxiliary a complex-forming chiral auxiliary material is used.5. Process as defined in claim 4 , comprising that as complex-forming chiral auxiliary material (S)-Taddol is applied.6. Process as defined in claim 5 , comprising that (S)-Taddol is used in 1 molar equivalent amount.7. Process as defined in claim 1 , comprising that as R protecting group ether- claim 1 , silyl ether- claim 1 , benzyl- claim 1 , substituted benzyl- claim 1 , or acyl-groups are applied.8. Process as defined in claim 7 , comprising that as R protecting group -p-phenylbenzoyl group is applied.9. Process as defined in claim 1 , comprising that as aprotic organic solvent ethers claim 1 , as diethyl ether claim 1 , methyl tertiary-butyl ether claim 1 , diisopropyl ether claim 1 , tetrahydrofuran claim 1 , methyltetrahydrofuran claim 1 , dimethoxyethane; aromatic hydrocarbons claim 1 , as benzene claim 1 , toluene claim 1 , xylene; halogenated solvents claim 1 , as dichloromethane claim 1 , or the mixture of these solvents are applied.10. Process as defined in claim 9 , comprising that as solvent claim 9 , toluene is applied.11. Process as defined in claim 1 , comprising that methylation is ...

Prostaglandins

The invention relates to a novel process for the preparation of 13,14-dihydro-15(R)-17-phenyl-18,19,20-trinor-PGF2α isopropyl ester of formula (I), wherein R stands for saturated or unsaturated straight, branched or cyclic C1-7 alkyl or phenyl or benzyl group. The process of the invention comprises reducing the oxo group on the side chain of the compound of formula (VII), transforming the obtained 3,3a,4,5,6,6a-hexahydro-2-oxo-4-[5'-phenyl-3'(R)-hydroxypent-1'-enil]-5-(4'-phenylbenzoxyloxy)-2H-cyclopenta[b]furan of formula (VI) by hydrogenation to 3,3a,4,5,6,6a-hexahydro-2-oxo-4-[5'-phenyl-3'(R)-hydroxy-1'-pentyl]-5-(4'-phenylbenzoyloxy)-2H-cyclopenta[b]furan of formula (V) reducing the compound of formula (V) to 3,3a,4,5,6,6a-hexahydro-2-hydroxy-4-[5'-phenyl-3'(R)-hydroxy-1'-pentyl]-5-(4'-phenylbenzoyloxy)-2H-cyclopenta[b]furan of formula (IV), removing the protective group from the compound of formula (IV) to obtain 3,3a,4,5,6,6a-hexahydro-2,5-dihydroxy-4-[5'-phenyl-3'(R)-hydroxy-1'-pentyl]-2H-cyclopenta[b]furan of formula (III) then transforming the compound of formula (III) obtained to 13,14-dihydro-15(R)-17-phenyl-18,19,20-trinor-PGF2α of formula (II) by using 4-carboxybutyl-triphenylphosphonium halide and finally, transforming the compound of formula (II) with a compound of the general formula R-X- wherein R has the same meaning as stated above, X is halogen sulphate, mesyl, tosyl or any suitable group to 13,14-dihydro-15(R)-17-phenyl-18,19,20-trinor-PGF2α esters of general formula (I).

钯催化剂、其制备方法及其用途

本发明涉及式(I)的钯(0)-四{三-[3,5-二(三氟甲基)-苯基]-膦}配合物,以及其制备和用途。该化合物非常稳定，可用作催化剂，具有优异的结果。

Diphenkylpropylamines for the therapy of heart disease

The invention relates to novel diphenylpropylamine derivatives of the general formula (I). ##STR1## R 1 stands for hydrogen or a methyl group; R 2 stands for hydrogen, a methyl or n-decyl group; Z means a phenyl group substituted by R 3 , R 4 and R 5 , wherein R 3 means hydrogen, fluorine, chlorine or bromine, or a nitro, C 1-12 alkyl, C 1-4 alkoxy, phenoxy or benzyloxy group; R 4 and R 5 represent hydrogen, chlorine or a hydroxy, alkoxy, benzyloxy, acetamino or carboxy group; or R 4 and R 5 together form a methylendioxy group; or Z may stand for a 4-methoxynaphtyl or 4-ethoxy-naphthyl group; and R 6 stands for hydrogen or fluorine, with the proviso that each of R 1 , R 2 , R 3 , R 4 and R 6 cannot simultaneously stand for hydrogen, as well as their physiologically acceptable acid addition salts. The invention also relates to a process for the preparation of these compounds and to the pharmaceutical compositions containing these compounds. The compounds of the general formula (I) can preferably be used for the treatment of cardiovascular diseases.

new palladium catalyst, method for its preparation and use

N-aralkyl-1, 1-diphenyl-propylamine derivatives

New salt preparation method

本发明涉及结构式I的新的7-氧代-PGl2麻黄碱盐(其中A代表-(CH 2 ) 2 -，顺或反式CH-CH-或-C≡C-；B代表一化学键，-CH 2 -或CR 2 R 3 ；R 2 和R 3 均代表低级烷基或氢；X是一化学键，-O-或-CH 2 -；R 4 代表C 1-6 烷基、C 4-7 环烷基、C 1-6 氟烷基、C 2-6 链烯基、C 2-6 炔基、苯基、被取代的苯基或杂芳基)。结构式I之化合物表现有与PG-I2钠盐相同的药理作用，可抑制血小板聚集和胃酸的分泌，用于预防心绞痛发作。

Novel 5*66dihydroimidazo*5*11a* isoquinoline derivative

Method for preparing carboprost and tromethamine salt thereof

本发明的主题是制备卡前列素氨丁三醇盐的新方法，其中通式II的烯酮的烷基化在手性助剂存在下在非质子溶剂中用格氏试剂进行。通过重力硅胶色谱分离式VII的甲酯差向异构体并通过使用固体氨丁三醇碱进行盐的形成。

Dibenzo[b,d]pyran derivatives and their cyclodextrin inclusion complexes, process for the preparation thereof and pharmaceutical products containing these compounds

The invention relates to dibenzo[b,d]pyran derivatives of the general formula <IMAGE> R<1> = OH, C1-4-acyloxy, R<2> = C1-12-alkyl, C1-12-O-alkyl, O-aralkyl, <IMAGE> R<11> = C1-4-alkyl, R<12> = H or C1-4-alkyl, m = 0, p and r = 1-4, R<3> = H, C1-4-alkyl, R<4> = H, C1-4-alkyl or together with R<3> an oxo group X = -O-, -NH- R<5> = C1-4-alkyl, when R<8>, R<9> and R<10> = H and R<6> together with R<7> another chemical bond, or OH and R<6>, R<7>, R<8>, R<9>, R<10> = H or together with R<6> an oxo group when i) R<7>, R<8>, R<9> and R<10> = H or ii) R<8> and R<10> = H and R<7> together with R<9> a chemical bond or iii) R<7> and R<8> = H and R<9> together with R<10> a chemical bond or together with R<6> = -O-(CH2)2-O- when R<7> and R<8> = H and R<9> together with R<10> a chemical bond, the salts thereof, the inclusion complexes, formed with 2,6-di-O-methyl- beta -cyclodextrin, of the compounds of the general formula (I) and the salts thereof, the preparation thereof and pharmaceutical products containing these compounds.

New process for preparing high purity prostaglandins

Prostaglandins.

Nouveau procédé de préparation de l'ester de 13,14-dihydro-15(R)-17-phényl-18,19,20-trinor-PGF2alpha isopropyle répondant à la formule (I), dans laquelle R représente un groupe alkyle ou phényle ou benzyle C1-7 droit, ramifié ou cyclique et saturé ou insaturé. Le procédé consiste à réduire le groupe oxo sur la chaîne latérale du composé répondant à la formule (VII); à transformer par hydrogénation le composé ainsi obtenu, c'est-à-dire le 3,3a,4,5,6,6a-hexahydro-2-oxo-4-[5'-phényl-3'(R)-hydroxypent-1'-ényl]-5-(4'-phényl-benzoxyloxy)-2H-cyclopenta[b]furane répondant à la formule (VI), de manière à obtenir le 3,3a,4,5,6,6a-hexahydro-2-oxo-4-[5'-phényl-3'(R)-hydroxy-1'-pentyl]-5-(4'-phénylbenzoyloxy)-2H-cyclopenta[b]furane répondant à la formule (V); à reduire le composé de la formule (V) en 3,3a,4,5,6,6a-hexahydro-2-hydroxy-4-[5'-phényl-3'(R)-hydroxy-1'-pentyl]-5-(4'-phénylbenzoyloxy)-2H-cyclopenta[b]furane répondant à la formule (IV); à enlever le groupe protecteur du composé de la formule (IV) de manière à obtenir un 3,3a,4,5,6,6a-hexahydro-2,5-dihydroxy-4-[5'-phényl-3'(R)-hydroxy-1'-pentyl]-2H-cyclopenta[b]furane répondant à la formule (III); puis à transformer le composé ainsi obtenu répondant à la formule (III) en 13,14-dihydro-15(R)-17-phényl-18,19,20-trinor-PGF2alpha répondant à la formule (II), à l'aide d'un halogénure de 4-carboxybutyl-triphénylphosphonium; et enfin à transformer le composé de la formule (II) à l'aide d'un composé répondant à la formule générale R-X-, dans laquelle R a la même notation que ci-dessus, et X représente sulfate d'halogène, mésyle, tosyle ou tout groupe approprié, de manière à obtenir des esters de 13,14-dihydro-15(R)-17-phényl-18,19,20-trinor-PGF2alpha répondant à la formule générale (I). New process for the preparation of the 13,14-dihydro-15 (R) -17-phenyl-18,19,20-trinor-PGF2alpha isopropyl ester corresponding to formula (I), in which R ...

Process for the preparation of 13,14-dihydro-15(R)-17-phenyl-18,19,20-trinor-PGF2α isopropyl ester

The invention relates to a novel process for the preparation of 13,14-dihydro-15 (R)-17-phenyl-18,19,20-trinor-PGF 2 α isopropyl ester of the formula (I)--wherein R stands for saturated or unsaturated straight, branched or cyclic C 1-7 alkyl or phenyl or benzyl group-- ##STR1##

Chemical process

Process for preparing 13, 14-dihydro-15(R)-17-phenyl-18'19'20-trinor-PGF 2 alpha esters

本发明涉及一种用于制备通式为(I)的13，14-二氢-15(R)-17-苯基-18，19，20，-三降-PGF 2 α异丙基酯的新方法。

Prostaglandins

Prostaglandins.

PROSTAGLANDINAS.

LA INVENCION SE REFIERE A UN NUEVO PROCESO PARA LA PREPARACION DE UN ESTER DE 13, 14-DIHIDRO-15(R)-17-FENIL-18, 19, 10-TRINORPGF2(ALFA) ISOPROPIL DE LA FORMULA (I), EN DONDE R REPRESENTA UN GRUPO DE ALQUIL O FENIL C1-C7 SATURADO O INSATURADO, RECTO, RAMIFICADO O CICLICO. EL PROCESO DE LA INVENCION COMPRENDE LA REDUCCION DEL GRUPO OXO DE LA CADENA LATERAL DEL COMPUESTO DE LA FORMULA (VII), TRANSFORMANDO EL 3,3A,4,5,6,6A-HEXAHIDRO-2-OXO-4-[5''-FENIL-3''(R)HIDROXIPENT-1''-ENIL]-5-(4''-FENILBENZOXILOXIDO)-2H-CICLOPENTA[B] FURAN OBTENIDO DE LA FORMULA (VI) MEDIANTE SU HIDROGENACION EN 3,3A, 4,5,6,6A-HEXAHIDRO-2-OXO-4-[5''-FENIL-3''(R)-HIDROXI-1''PENTIL]-5-(4''-FENILBENZILOXIDO)-2H-CICLOPENTA[B]FURAN OBTENIDA DE LA FORMULA (V) REDUCIENDO EL COMPUESTO DE LA FORMULA (V) EN 3,3A,4,5,6,6A-HEXAHIDRO-2-HIDROXI-4-[5''-FENIL-3''(R)-HIDROXI-1''PENTIL]-5-(4''-FENILBENZILOXI)-2H-CICLOPENTA[B]FURAN DE LA FORMULA (IV), SEPARANDO EL GRUPO PROTECTOR DE LA FORMULA (IV) PARA OBTENER 3,3A,4,5,6,6A,HEXAHIDRO-2,5-DIHIUDROXI-4-[5''-FENIL-3''(R)HIDROXI-1''-PENTIL]-2H-CICLOPENTA[B]FURAN DE LA FORMULA (III) Y ENTONCES TRANSFORAMANDO EL COMPUESTO DE LA FORMULA (III) OBTENIDO EN 13,14-DIHIDRO-15(R)-17-FENIL-18, 19, 20-TRINOR-PGF2(ALFA) DE LA FORMULA (II) USANDO ALURO DE 4-CARBOXIBUTIL-TRIFENILFOSFONIO Y FINALMENTE, TRANSFORMANDO EL COMPUESTO DE LA FORMULA (II) CON UN COMPUESTO DE LA FORMULA GENERAL R-X O, X ES SULFATO DE HALOGENO, MESIL, TOSIL O CUALQUIER GRUPO ADECUADO PARA LOS ESTERES DE 13,14DIHIDRO.15(R)-17-FENIL-18, 19, 20-TRINOR-PGF2(ALFA) DE LA FORMULA (I). THE INVENTION REFERS TO A NEW PROCESS FOR THE PREPARATION OF A 13, 14-DIHYDRO-15 (R) -17-PHENYL-18, 19, 10-TRINORPGF2 (ALPHA) ISOPROPIL OF THE FORMULA (I), WHERE R REPRESENTS A GROUP OF RENT OR PHENYL C1-C7 SATURATED OR UNSATURATED, STRAIGHT, BRANCHED OR CYCLIC. THE PROCESS OF THE INVENTION INCLUDES THE REDUCTION OF THE ...

Novel process for the preparation of travoprost

Novel process for preparing travoprost

Prostaglandins.

Prostaglandins

The invention relates to a novel process for the preparation of 13,14-dihydro-15 (R)-17-phenyl-18,19,20-trinor-PGF2 alpha isopropyl ester of the formula (I)-wherein R stands for saturated or unsaturated straight, branched or cyclic C1-7 alkyl or phenyl or benzyl group- <IMAGE> (I)

The preparation 13,14-dihydro-15 (R)-17-phenyl-18,19,20-three just-PGF 2The method of α ester

本发明涉及一种用于制备通式为(I)的13，14- 二氢-15(R)-17-苯基-18，19，20，-三正-PCF 2 α异 丙基酯的新方法。

Novel process for preparing high purity prostaglandins

本申请主题是用于制备高纯度通式II的前列腺素酸的方法，其中以虚线标示的键表示单键或双键，其中所述双键可为顺式或反式取向，Y表示氧原子或CH 2 ，及R 3 表示苯基，其任选地以CF 3 取代，其中粗制的通式II的前列腺素酸以正相硅胶色谱法纯化。

Process for the preparation of iloprost

The present invention relates to a process for the preparation of iloprost of formula I through new intermediates, isolation of iloprost of formula I in solid form, as well as preparation of the 16(S)-iloprost and 16(R)-iloprost isomers of formulae (S)-I and (R)-I and isolation of iloprost of formula I and 16(S)-iloprost of formula (S)-I in solid, crystalline form.

Sulfurrcontaining isoquinoline derivative

5,6-dihydropyrimidin-4(3h)one derivatives, and antiedema compositions and methods employing them

An antiedema compound of the formula: ##STR1## in which R 1 is methyl, ethyl, cyclohexyl, phenyl, m-tolyl, p-tolyl, p-tert-butylphenyl, m-trifluoromethylphenyl, m-fluorophenyl, p-fluorophenyl, m-chlorophenyl, p-chlorophenyl, m-bromophenyl, p-bromophenyl, o-hydroxyphenyl, p-methoxyphenyl, p-nitrophenyl, benzyl, p-chlorobenzyl, m,p-dimethoxybenzyl, and o-pyridyl; R 2 is hydrogen, p-tolyl, p-ethoxyphenyl, m-pyridyl, methyl or phenyl; and n is 1, 2 or 3 And a process for the preparation thereof are disclosed.

Process for preparation of diphenylpropylamine derivatives and their salts

本发明涉及一种制备通式(I)的新型二苯基丙胺衍生物及其生理上可接受的酸加成盐的方法。 式中R 1 、R 2 、R 6 的定义见说明书。 通式(I)的化合物最好用于心血管疾病的治疗。

Process for the preparation of benzimidazole thiols

Novev amines

Derivative and preparation method thereof, and the pharmaceutical preparation 2-amino-tetrahydrochysene-different quinoline woods that contains this derivative

通式I化合物、及其作为有效成分的药用组合物及其制法。式I中各符号定义见说明书。通式I化合物具有利尿、降血压和促尿食盐排泄的作用。

Patent FR2190820B1

PROCESS FOR THE PRODUCTION OF CARBAMATE AND UREA DERIVATIVES

Quinoline carboxylic acid boric acid anhydrides and process for the preparation thereof

A B S T R A C T The invention relates to new quinoline-3-carboxylic acid anhydrides of the general Formula I /I/ /wherein R stands for cyclopropyl, a group of the general Formula -CH2CR5R6R7 /wherein R5, R6 and R7 stand for hydrogen or halogen/7 or phenyl optionally substituted by 1 or 2 halogen, R1 and R2 stand for halogen, or an aliphatic acyloxy group containing 2 to 6 carbon atoms optionally substituted by halogen, or an aromatic acyloxy group containing 7 to 11 carbon atoms, R3 stands for chlorine or fluorine and R4 stands for hydrogen or fluorine/ and to the process for the preparation thereof which comprises reacting a compound of the general Formula II /II/ [wherein R, R3 and R4 are the same as stated above, R8 stands for hydrogen or alkyl containing 1 to 4 carbon atoms] with a compound of the Formula III HBF4 [III] or a borone derivative of the general Formula BX3 [IV] [wherein X stands for fluorine, chlorine or bromine] or an ether complex thereof, or a triacyloxy borate derivative of the general Formula V -B(OCOR9)3 [V] [wherein R9 stands for alkyl containing 1 to 5 carbon atoms optionally substituted by halogen, or aryl containing 6 to 10 carbon atoms]. The compounds of the general Formula I are new inter-mediates for the preparation of known quinoline-3-carboxylic acids showing antibacterial activity.

Cyclodextrinn indomethacine inclusion complex

Manufacture of dichloropentadiene

A sulphamoyl-benzothiadiazine derivative and preparation thereof

The invention comprises 6-chloro-7-sulphamoyl-2, 4-iminodimethylene-benzo-dihydro-1,2, 4-thiadiazine-1, 1-dioxide of the formula: <FORM:0955522/C2/1> and its preparation by treating 6-chloro-7-sulphamoyl - 2, 4 - methylenediiminodimethylene - benzo-dihydro-1, 2, 4-thiadiazine-1, 1-dioxide (obtainable by reaction of 5-chloro-2, 4-disulphamoyl-aniline with hexamethylene tetramine) with water under neutral or alkaline conditions at 0-110 DEG C. Specification 888,647 is referred to.ALSO:Pharmaceutical preparations having diuretic and saliuretic activity comprise 6-chloro-7-sulphamoyl - 2,4 - iminodimethylene - benzodihydro - 1,2,4 - thiadiazone - 1,1-dioxide and a carrier or excipient. The preparations suitably take the form of tablets, dragees, capsules, solutions suspensions or suppositories and may contain additional active compounds such as hypotensive agents. Specification 888,647 is referred to.

Patent FR2068471B1

Patent FR2223368A1

CYCLODEXTRIN POLYVINYL ALCOHOL POLYMERS AND PROCESS FOR THEIR PREPARATION IN THE FORM OF PEARLS, SHEETS, FIBERS OR BLOCKS

L'invention concerne de nouveaux polymères. Il s'agit d'un polymère cyclodextrine-alcool polyvinylique. Ce polymère est susceptible de former des complexes d'inclusion. The invention relates to novel polymers. It is a cyclodextrin-polyvinyl alcohol polymer. This polymer is capable of forming inclusion complexes.

Patent FR2190441A1

Process for preparing quaternary compounds

Low calorie foods - by swelling natural food with aqs. cellulose ether and drying

Low calorie foods are made by allowing natural foods contg. edible carbohydrate to swell with a cellulose ether in the presence of water, and drying and opt. comminuting the resulting gel. The foods treated may be cereals, peas, beans and other leguminous vegetables, tubers such as potatoes, root vegetables such as carrots, etc. The food may be treated prior to the above e.g. by grinding (of cereals into flour) or by boiling or steaming (e.g. of potatoes). The food and the cellulose ether are e.g. kneaded together with water at 20-40 degrees C o give a swollen paste which is then dried e.g. by baking and then e.g. comminuted by grinding into a flour which can be used in soups, biscuits, cakes, puddings, etc. The treated prods. are useful for diabetics and in diets requiring a reduced calorie intake.

Patent FR2221134A1

NITROGENED BRIDGE-HEAD COMPOUNDS USEFUL IN PARTICULAR AS MEDICINAL PRODUCTS AND PROCESS FOR THE PREPARATION

LA PRESENTE INVENTION CONCERNE DES COMPOSES CHIMIQUES NOUVEAUX ET UN PROCEDE POUR LEUR PREPARATION. IL S'AGIT DE COMPOSES A TETE DE PONT D'AZOTE REPONDANT A LA FORMULE: (CF DESSIN DANS BOPI) ET DES SELS DE CES COMPOSES. CES COMPOSES SONT UTILES NOTAMMENT COMME MEDICAMENT. THE PRESENT INVENTION CONCERNS NEW CHEMICAL COMPOUNDS AND A PROCESS FOR THEIR PREPARATION. THESE ARE NITROGEN BRIDGE-HEAD COMPOUNDS RESPONDING TO THE FORMULA: (CF DRAWING IN BOPI) AND THE SALTS OF THESE COMPOUNDS. THESE COMPOUNDS ARE USEFUL IN PARTICULAR AS A MEDICINAL PRODUCT.

PROCESS FOR THE PREPARATION OF TETRAHYDRO-PYRROLO (1,2-A) PYRIMIDINES SUBSTITUTED IN POSITION 3, PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS AND NEW TETRAHYDRO-PYRROLO (1,2-A) PYRIMIDINES SUBSTITUTED IN POSITION 3

L'INVENTION CONCERNE DES DERIVES DE FORMULE GENERALE: (CF DESSIN DANS BOPI) ET (CF DESSIN DANS BOPI) AINSI QU'UN MELANGE DE TELS COMPOSES ET LEURS SELS D'ADDITION D'ACIDE ET SELS QUATERNAIRES PHARMACEUTIQUEMENT ACCEPTABLES, OU: R REPRESENTE DE L'HYDROGENE OU UN GROUPE ALCOYLE INFERIEUR. R REPRESENTE UN GROUPE ALCOYLE INFERIEUR, PHENYLE, CARBOXYLE, (ALCOXY INFERIEUR) CARBONYLE, NITRILE, CARBAMOYLE OU CARBOHYDRAZIDO. R REPRESENTE DE L'HYDROGENE OU UN GROUPE ALCOYLE INFERIEUR, AVEC LA CONDITION QUE SI, DANS LA FORMULE I, R REPRESENTE DE L'HYDROGENE, ALORS R NE PEUT PAS ETRE UN GROUPE NITRILE, ALCOXY-CARBONYLE OU PROPYLE. APPLICATION COMME MEDICAMENTS. THE INVENTION RELATES TO DERIVATIVES OF THE GENERAL FORMULA: (CF DRAWING IN BOPI) AND (CF DRAWING IN BOPI) AS WELL AS A MIXTURE OF SUCH COMPOUNDS AND THEIR ADDITIONAL SALTS OF ACID AND PHARMACEUTICALLY ACCEPTABLE QUATERNARY SALTS, OR: R REPRESENTS OF HYDROGEN OR A LOWER ALCOHYL GROUP. R REPRESENTS A LOWER ALCOYL, PHENYL, CARBOXYL, (LOWER ALCOXY) CARBONYL, NITRILE, CARBAMOYL OR CARBOHYDRAZIDO GROUP. R REPRESENTS HYDROGEN OR A LOWER ALCOHYL GROUP, PROVIDED THAT IF IN FORMULA I R REPRESENTS HYDROGEN THEN R MAY NOT BE A NITRIL, ALCOXY-CARBONYL OR PROPYL GROUP. APPLICATION AS A MEDICINAL PRODUCT.

NEW DERIVATIVES OF MALEINIMIDE AND SUCCINIMIDE USEFUL AS HERBICIDES

L'invention concerne des composés chimiques nouveaux. Il s'agit de composés de formules générales : The invention relates to novel chemical compounds. These are compounds of general formulas:

Process for preparing dicarboximides

ISOQUINOLINE DERIVATIVES CONTAINING SULFUR, PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME

L'INVENTION CONCERNE NOTAMMENT DES COMPOSES DE FORMULE: (CF DESSIN DANS BOPI) DANS LAQUELLE, R EST L'HYDROGENE, UN GROUPE HYDROXYLE OU ALCOXY; R EST L'HYDROGENE, UN GROUPE ALCOYLE, PHENYLALCOYLE, PHENYLE, HALOPHENYLE, ALCOXYPHENYLE, CYANOPHENYLE OU CARBAMOYLE-PHENYLE; R EST NOTAMMENT UN GROUPE PHENYLE, HALOGENO-, ALCOXY- OU CARBOXYL-PHENYLE OU UN GROUPE ALCOYLENE EN C A C ET LA LIGNE FORMEE DE TIRETS REPRESENTE UNE LIAISON SATUREE OU NON. LES NOUVEAUX COMPOSES SONT UTILES COMME MEDICAMENTS.

Patent FR2218882B1

PROCESS FOR THE PREPARATION OF N-CARBAMOYLBENZOIC ACID SULFIMIDE DERIVATIVES

L'INVENTION CONCERNE UN PROCEDE DE PREPARATION DE DERIVES DE SULFIMIDE D'ACIDE N-CARBAMOYLBENZOIQUE. ON PREPARE DES COMPOSES DE FORMULE (I): (CF DESSIN DANS BOPI) DANS LAQUELLE R EST UN GROUPE ALCOYLE, CYCLOALCOYLE OU ARALCOYLE, DONT L'UN QUELCONQUE PEUT ETRE SUBSTITUE PAR UN OU PLUSIEURS GROUPES ALCOYLE, ET R EST DE L'HYDROGENE OU UN HALOGENE, EN FAISANT REAGIR UN FORMAMIDE N-SUBSTITUE DE FORMULE (II): (CF DESSIN DANS BOPI) AVEC UN AGENT D'HALOGENATION ET ENSUITE AVEC UN SEL DE SULFIMIDE D'ACIDE BENZOIQUE DE FORMULE (III): (CF DESSIN DANS BOPI) FORME AVEC UNE BASE ORGANIQUE OU INORGANIQUE. UTILISATION DES PRODUITS COMME PESTICIDES EN AGRICULTURE. THE INVENTION CONCERNS A PROCESS FOR THE PREPARATION OF N-CARBAMOYLBENZOIC ACID SULFIMIDE DERIVATIVES. COMPOUNDS OF FORMULA (I): (CF DRAWING IN BOPI) ARE PREPARED IN WHICH R IS AN ALCOYL, CYCLOALCOYL OR ARALCOYL GROUP, ANY OF WHICH CAN BE SUBSTITUTED BY ONE OR MORE ALCOHOL GROUPS, AND R IS HYDROGEN OR A HALOGEN, BY REACTING AN N-SUBSTITUTE FORMAMIDE OF FORMULA (II): (CF DRAWING IN BOPI) WITH A HALOGENATION AGENT AND THEN WITH A SALT OF SULFIMIDE OF BENZOIC ACID OF FORMULA (III): (CF DRAWING IN BOPI) FORM WITH AN ORGANIC OR INORGANIC BASE. USE OF THE PRODUCTS AS PESTICIDES IN AGRICULTURE.

Process for the production of cyanocobalamin-monocarboxylic acid

Microbiological oxidation process of steroids

Patent FR2107964B1

BIFUNCTIONAL XYLITE DERIVATIVES TERMINALS USEFUL AS MEDICINAL PRODUCTS

LA PRESENTE INVENTION CONCERNE DES COMPOSES CHIMIQUES. IL S'AGIT DE COMPOSES DE LA FORMULE GENERALE: (CF DESSIN DANS BOPI) DANS LAQUELLE: R ET R SONT IDENTIQUES ET REPRESENTENT CHACUN UN HALOGENE OU UN GROUPE TOSYLOXY OU MESYLOXY, AUQUEL CAS, R ET R REPRESENTENT CHACUN UN GROUPE HYDROXY, OU R ET R AINSI QUE R ET R FORMENT ENSEMBLE UN PONT D'OXYGENE, R, INDEPENDAMMENT DE LA SIGNIFICATION DE R, R, R ET R, REPRESENTE DE L'HYDROGENE OU UN GROUPE ALCANOYLE, ARALCANOYLE OU AROYLE. CES COMPOSES SONT UTILES COMME MEDICAMENTS. THE PRESENT INVENTION CONCERNS CHEMICAL COMPOUNDS. THESE ARE COMPOUNDS OF THE GENERAL FORMULA: (CF DRAWING IN BOPI) IN WHICH: R AND R ARE THE SAME AND EACH REPRESENT A HALOGEN OR A TOSYLOXY OR MESYLOXY GROUP, IN WHICH CASE, R AND R EACH REPRESENT A HYDROXY GROUP, OR R AND R AS WELL AS R AND R FORM TOGETHER A BRIDGE OF OXYGEN, R, INDEPENDENT OF THE MEANING OF R, R, R AND R, REPRESENTS HYDROGEN OR AN ALKANOYL, ARALCANOYL OR AROYL GROUP. THESE COMPOUNDS ARE USEFUL AS A MEDICINAL PRODUCT.

PROCESS FOR THE PREPARATION OF AQUEOUS SOLUTIONS OF BIOLOGICALLY ACTIVE ORGANIC COMPOUNDS INSOLUBLE OR LITTLE SOLUBLE IN WATER

The invention relates to water-soluble inclusion complexes of biologically active organic compounds which are insoluble or have only limited solubility in water, particularly of fat-soluble vitamins, steroid hormones, prostanoids, local anaesthetics and the like, to their aqueous solutions and to their preparation, wherein the biologically active compounds are converted into an aqueous solution in the form of inclusion complexes which have been formed with dimethyl- beta -cyclodextrins having an average degree of substitution of 14, in particular with heptakis(2,6-di-O-methyl)- beta -cyclodextrin, by dissolving the organic compounds which are insoluble or have only limited solubility in water in an aqueous solution of 1 to 8 mol (calculated per 1 mol of the compound to be dissolved) of dimethyl- beta -cyclodextrin. The aqueous solutions, obtained according to the invention, of the biologically active organic compounds can be processed to give pharmaceutical products which can be administered orally or parenterally.

Patent FR2183013A1

PROCESS FOR THE PREPARATION OF FERMENTATION MEDIA ALLOWING TO PRODUCE YEAST FOR ANIMAL FEEDING AND MICROSPORES AND / OR TO PRODUCE PROTEINS FROM PLANT WASTE

La présente addition concerne un procédé de préparation de milieux de fermentation permettant de produire de la levure pour l'alimentation animale et des microspores et/ou de produire des protéines à partir de déchets végétaux. Selon ce procédé, à partir de divers déchets végétaux, constituant les principales matières premières, on obtient des hydrolysats partiellement acides permettant de produire de la levure pour l'alimentation animale, et des extraits partiellement alcalins à partir desquels on peut facilement séparer, de préférence par traitement acide, la presque totalité du contenu protéinique des produits bruts végétaux. Application à la production d'aliments pour animaux. The present addition relates to a process for preparing fermentation media making it possible to produce yeast for animal feed and microspores and / or to produce proteins from plant waste. According to this process, from various plant wastes, constituting the main raw materials, partially acid hydrolysates are obtained making it possible to produce yeast for animal feed, and partially alkaline extracts from which can easily be separated, preferably by acid treatment, almost all of the protein content of raw vegetable products. Application to the production of animal feed.

NEW POWDER POWDERS CONTAINING A BIOACTIVE SUBSTANCE AND PROCESS FOR THEIR PREPARATION

L'INVENTION CONCERNE DE NOUVELLES COMPOSITIONS DE POUDRES DE POUDRAGE CONTENANT DE LA CYCLODEXTRINE OU DES POLYMERES EN DERIVANT ET EVENTUELLEMENT UN OU PLUSIEURS COMPLEXE(S) D'INCLUSION DE LA CYCLODEXTRINE COMME VEHICULE, DILUANT OU EXCIPIENT EN QUANTITE DE 0,1 A 99,9 ET UNE OU DES SUBSTANCE(S) BIOLOGIQUEMENT ACTIVE(S) ETOU UN OU DES PARFUM(S) ETOU COLORANT(S) EN QUANTITE DE 99,9 A 0,1. LES COMPOSITIONS DE POUDRES DE POUDRAGE DE L'INVENTION PEUVENT ETRE UTILISEES THERAPEUTIQUEMENT POUR DESINFECTER, AINSI QUE POUR CALMER LES INFLAMMATIONS DE LA PEAU ET LES DOULEURS SUPERFICIELLES. THE INVENTION RELATES TO NEW COMPOSITIONS OF POWDERING POWDERS CONTAINING CYCLODEXTRIN OR POLYMERS BY DERIVATING AND POSSIBLY ONE OR MORE COMPLEX (S) INCLUDING CYCLODEXTRIN AS A VEHICLE, THINNER OR EXCIPIENT FROM 0.1 TO 99, 9 AND ONE OR MORE BIOLOGICALLY ACTIVE SUBSTANCE (S) AND OR PERFUME (S) AND OR COLOR (S) IN QUANTITY OF 99.9 TO 0.1. THE POWDERING POWDER COMPOSITIONS OF THE INVENTION CAN BE USED THERAPEUALLY TO DISINFECT, AS WELL AS TO CALM SKIN INFLAMMATIONS AND SURFACE PAIN.

Patent FR2162175A1

GEMINAL DIHALOGEN DERIVATIVES OF PYRIMIDIN-4-ONE CONDENSED, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

DERIVES DIHALOGENES GEMINAUX DE PYRIMIDINE-4-ONES CONDENSEES DE LA FORMULE GENERALE: (CF DESSIN DANS BOPI) DANS LAQUELLE: R REPRESENTE DE L'HYDROGENE OU UN GROUPE ALCOYLE INFERIEUR OU (ALCOXY INFERIEUR) CARBONYLE; R REPRESENTE DE L'HYDROGENE, UN GROUPE ALCOYLE INFERIEUR, CARBOXY, UN GROUPE ESTER OU UN DERIVE D'UN TEL GROUPE, UN GROUPE CYANO, PHENYLE OU UN HALOGENE; R REPRESENTE DE L'HYDROGENE OU UN GROUPE ALCOYLE INFERIEUR OU PHENYLE; X REPRESENTE UN HALOGENE; N EST L'UN DES NOMBRES ENTIERS 0, 1 ET 2, ET LEURS SELS ET ANTIPODES OPTIQUEMENT ACTIFS. APPLICATION COMME MEDICAMENTS. GEMINAL DIHALOGENOUS DERIVATIVES OF PYRIMIDINE-4-ONES CONDENSED OF THE GENERAL FORMULA: (CF DRAWING IN BOPI) IN WHICH: R REPRESENTS HYDROGEN OR A LOWER ALCOHYL OR (LOWER ALCOXY) CARBONYL GROUP; R REPRESENTS HYDROGEN, A LOWER ALCOHYL GROUP, CARBOXY, AN ESTER GROUP OR A DERIVATIVE OF SUCH A GROUP, A CYANO, PHENYL OR HALOGEN GROUP; R REPRESENTS HYDROGEN OR A LOWER ALCOHYL OR PHENYL GROUP; X REPRESENTS A HALOGEN; N IS ONE OF THE WHOLE NUMBERS 0, 1 AND 2, AND THEIR OPTICALLY ACTIVE SALTS AND ANTIPODES. APPLICATION AS A MEDICINAL PRODUCT.

PROCESS FOR THE PREPARATION OF 2- (3-PHENOXY-PHENYL) -PROPIONIC ACID

Procédé de préparation d'acide 2-(3-phénoxy-phényl)-propionique. Ce procédé implique d'hydrolyser et de décarboxyler partiellement un composé de formule générale : Process for preparing 2- (3-phenoxy-phenyl) -propionic acid. This process involves hydrolyzing and partially decarboxylating a compound of general formula:

NEW REAGENT DERIVATIVES OF PENICILLANIC ACID AND CEPHALOSPORANIC ACID AND PROCESS FOR THEIR PREPARATION

Patent FR2236493B1

DIBENZO (BD) PYRANE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Fungicide 1-cyano-hydroxy-imino-acetyl-3-cycloalkyl-urea derivs. - prepd. e.g. by reaction of a 1-cyanoacetyl-3-cycloalkyl:urea with alkali nitrite (PT 6.3.81)

New 1-(2-cyano-2-hydroxyimino-acetyl)- 3-cycloalkyl-urea derivs. are cpds. of the formula R1-NH-CO-NH-CO-C(CN):N-OR (I) and their salts and complexes (where R is H or Me and R1 is 5-12C cycloalkyl opt. substd. by 1-4C alkyl or 1-4C alkoxy). (I) are pesticides with strong fungitoxic activity against phytopathogenic fungi. In some cases they have curative activity. Rate of application is 0.1-5 kg/ha. In an example, a 0.2% dispersion of (I; R is Me, R1 is cyclohexyl) is sprayed on to vine plants which are kept 10 days, then artificially infected with Plasmopara viticola and kept 11 days under greenhouse conditions, only 15% of leaves show signs of fungal infection whereas in untreated controls the degree of infection is 70%.

Patent FR2024805B1

Patent FR2430954B1

Patent FR2276049B1

Process for the preparation of cyclopropane carboxylate

Compounds of formula (I> <IMAGE> wherein R<2> stands for hydrogen or -CN group R<3> stands for substituted, mono- or bicyclic group optionally containing hetero atom or alkyl having 1-4 carbon atoms, R<4> stands for hydrogen atom or alkyl having 1-4 carbon atoms, R<5> stands for hydrogen atom or alkyl having 1-4 carbon atoms, R<6> stands for substituted alkyl having 1-4 carbon atoms or <IMAGE> wherein R<1> stands for halogen atom or methyl, R<7> stands for hydrogen atom, R<6> and R<7> taken together stands for substituted or unsubstituted alkylene having 1-4 carbon atoms, are prepared by reacting a salt of the corresponding carboxylic acid or a salt of its alkyl ester with a chloroformate and eliminating carbon dioxide from the unstable mixed anhydride thus obtained. The compounds prepared according to the invention are obtained in highly pure quality and can be used as insecticides without further purification.

Patent FR2394546B1

Cyclodextrin-polyvinyl alcohol polymers and a process for the preparation thereof in a pearl, foil, fibre or block form

ABSTRACT OF THE DISCLOSURE The present invention conoerns new cyclodextrin-polyvinyl alcohol polymers capable of forming inclusion complexes. The preparation of said polymers by cross-linking a cyclodextrin, a mixture of cyclodextrins, or carbohydrate mixtures containing cyclodextrins in the presence of polyvinyl alcohol, polyvinyl acetate or a polyvinyl alcohol-polyvinyl acetate copolymer with a polyfunctional coupling reactant capable of reacting with the cyclo-dextrins and with the polymers present is also within the scope of the inven tion.

Patent FR2186269B1

NOVEL 1-SUBSTITUTED 3-CYCLOALCOYL-SULFONYL-PYRROLIDINE-2,5-DIONES DERIVATIVES, FUNGICIDAL COMPOSITIONS CONTAINING THE SAME, AND PROCESS FOR THE PREPARATION OF ACTIVE INGREDIENTS

LA PRESENTE INVENTION CONCERNE DES DERIVES 1-SUBSTITUES DE 3-CYCLOALCOYL-SULFONYL-PYRROLIDINE-2,5-DIONE DE LA FORMULE GENERALE I: (CF DESSIN DANS BOPI) DANS LAQUELLE: A REPRESENTE UN GROUPE C CYCLOALCOYLE; R REPRESENTE DE L'HYDROGENE, UN GROUPE C ALCOYLE, PHENYLE EVENTUELLEMENT SUBSTITUE PAR UN OU PLUSIEURS GROUPES CHOISIS PARMI DES SUBSTITUANTS C ALCOYLE, NITRO, HYDROXY, CARBOXY, SULFO, SULFONYLAMINO, HALOGENO, C ALCOXY, C ALYLOXY, C ALCOXYCARBONYLE, C ACYLE ET N(C ALCOXYCARBONYL)-SULFONYLAMINO; OU UN GROUPE PHENYL-(C ALCOYLE) AINSI QUE LEURS SELS. UTILISATION COMME FONGICIDE. THE PRESENT INVENTION CONCERNS 1-SUBSTITUTES OF 3-CYCLOALCOYL-SULFONYL-PYRROLIDINE-2,5-DIONE DERIVATIVES OF GENERAL FORMULA I: (CF DRAWING IN BOPI) IN WHICH: A REPRESENTS A CYCLOALCOYL GROUP C; R REPRESENTS OF HYDROGEN, A GROUP C ALCOYL, PHENYL POSSIBLY SUBSTITUTED BY ONE OR MORE GROUPS CHOSEN FROM THE SUBSTITUTES C ALCOYL, NITRO, HYDROXY, CARBOXY, SULFO, SULFONYLAMINO, C ALCOYCON HALCOYLAMINO, C ALCOYCON HALCOYLAMINO, C ALCOYCONYLAMINO, C ALXYCONY AND N (C ALCOXYCARBONYL) -SULFONYLAMINO; OR A PHENYL- (C ALCOYL) GROUP AS WELL AS THEIR SALTS. USE AS A FUNGICIDE.

Pyrethroidal composition comprising more than one active ingredients

ABSTRACT According to the present invention there is provided an insecticidal composition containing more than one active ingredients which comprises as active ingredient in an amount of 0.001-99% by weight a synthetic pyrethroid of the general Formula I

Patent FR2124107B2

CYCLODEXTRIN-CAMOMILE INCLUSION COMPLEXES, PROCESS FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING SUCH COMPLEXES

COMPLEXES D'INCLUSION DE CYCLODEXTRINE-CAMOMILLE, PROCEDE POUR LEUR PREPARATION ET COMPOSITIONS CONTENANT DE TELS COMPLEXES. L'INVENTION SE RAPPORTE EN PARTICULIER A UN COMPLEXE D'INCLUSION DE CYCLODEXTRINE-CAMOMILLE QUI COMPREND DES MOLECULES DE CYCLODEXTRINE COMME MOLECULE-HOTE, ET UN EXTRAIT OBTENU A PARTIR DE CAMOMILLE MEDICAMENTEUSE PAR DES PROCEDES CLASSIQUES COMME MOLECULES INCLUSES. APPLICATIONS AUX PREPARATIONS MEDICAMENTEUSES ETOU COSMETIQUES. CYCLODEXTRIN-CHAMOMILE INCLUSION COMPLEXES, PROCESS FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING SUCH COMPLEXES. THE INVENTION RELATES IN PARTICULAR TO A CYCLODEXTRIN-CHAMOMILE INCLUSION COMPLEX WHICH INCLUDES CYCLODEXTRIN MOLECULES AS A HOST MOLECULE, AND AN EXTRACT OBTAINED FROM MEDICINATED CHAMOMILE BY CONVENTIONAL PROCESSES SUCH AS INCLUDED MOLECULES. APPLICATIONS TO MEDICINAL AND OR COSMETIC PREPARATIONS.

Patent FR2484252B1

Patent FR2426412B1

New polypeptides.

.omega.-AMINOCARBOXYLIC ACID AMIDES AND A PROCESS FOR THE PREPARATION THEREOF

ABSTRACT OF THE DISCLOSURE The invention relates to .omega.-aminocarboxylic acid amides having the general formula (I) H2N-(CH2)m-CO-NH-(CH2)n-A wherein n and m are each independently 2 or 3 and A is a group of the formula -SO2OH or -OPO(OH)2, and pharmaceutically acceptable salts thereof. These compounds possess valuable therapeutical effects and can be applied as intermediates in the synthesis of biologically active compounds.

PROCESS FOR THE PREPARATION OF DIHALOVINYL-CYCLO-PROPANE-CARBOXYLIC ACIDS

LA PRESENTE INVENTION CONCERNE UN PROCEDE DE PREPARATION D'ACIDES DIHALOVINYL-CYCLOPROPANE-CARBOXYLIQUES. SELON L'INVENTION, ON PREPARE DES COMPOSES DE FORMULE I: (CF DESSIN DANS BOPI) OU : R EST UN ALCOYLE EN C A C ET X ET Y ONT LA MEME SIGNIFICATION QUE DEFINIE CI-DESSUS. LES ACIDES OBTENUS SONT UTILES DANS LA PREPARATION D'INSECTICIDES PYRETHROIDES. THE PRESENT INVENTION CONCERNS A PROCESS FOR PREPARING DIHALOVINYL-CYCLOPROPANE-CARBOXYLIC ACIDS. ACCORDING TO THE INVENTION, COMPOUNDS OF FORMULA I: (CF DRAWING IN BOPI) OR: R IS AN ALCOHOL IN C A C AND X AND Y HAVE THE SAME MEANING AS DEFINED ABOVE ARE PREPARED. THE ACIDS OBTAINED ARE USEFUL IN THE PREPARATION OF PYRETHROID INSECTICIDES.

PROCESS FOR THE PREPARATION OF A HIGH PURITY CHRYSANTHEMIC ACID

The invention relates to a process for the preparation of chrysanthemum-monocarboxylic acid (I) in high purity by alkaline hydrolysis of the C1-C6-alkyl ester of I (II), in the absence of organic solvents and in the presence of a phase transfer catalyst, with 100-150% by weight of the equivalent amount of alkali metal hydroxide which corresponds to the ester (II) when II is to be hydrolysed completely while maintaining the isomer ratio, or with 70-110% by weight of the equivalent amount of alkali metal hydroxide corresponding to the trans-isomer of II if II is to be hydrolysed partially or selectively while changing the ratio of the isomers. I can be used as intermediate for the synthesis of insecticidal pyrethroids.

PROCESS FOR THE PREPARATION OF DIHALOVINYL-CYCLO-PROPANE-CARBOXYLIC ACIDS

Patent FR2164676A1

New 3-amino-delta 2-pyrazolines - - for pharmaceutic -or photographic use

PROCESS FOR PREPARING OPTICAL ISOMERS OF CERTAIN CYCLOPROPANE CARBOXYLIC ACIDS

PROCEDE DE PREPARATION DES ENANTIOMERES DES ACIDES TRANS-VINYLCARBOXYLIQUES DE FORMULE GENERALE: (CF DESSIN DANS BOPI) DANS LAQUELLE LES SYMBOLES R REPRESENTENT DES GROUPES METHYLE OU DES ATOMES DE CHLORE PAR RESOLUTION DU COMPOSE TRANS-RACEMIQUE OU DU MELANGE CIS-TRANS-RACEMIQUE EN LES ANTIPODES OPTIQUES. ON UTILISE COMME AGENT SALIFIANT POUR LA SEPARATION LA ()- OU LA (-)-N-(1-FORMAMIDO-2,2,2-TRICHLORETHYL)-PIPERAZINE DANS UN SOLVANT POLAIRE, ON SEPARE DES LIQUEURS MERES LE SEL DE L'AGENT SALIFIANT (-) ET DE L'ACIDE ()-TRANS-CARBOXYLIQUE OU LE SEL DE L'AGENT SALIFIANT () ET DE L'ACIDE (-)-TRANS-CARBOXYLIQUE QUI CRISTALLISE PUIS ON ISOLE LES ENANTIOMERES PAR ACIDIFICATION DES LIQUEURS MERES OU RESPECTIVEMENT DU SEL QUI A CRISTALLISE, ET EXTRACTION PAR DES SOLVANTS ET EVAPORATION. PROCESS FOR PREPARING THE ENANTIOMERS OF TRANS-VINYLCARBOXYLIC ACIDS OF GENERAL FORMULA: (CF DRAWING IN BOPI) IN WHICH THE SYMBOLS R REPRESENT METHYL GROUPS OR CHLORINE ATOMS BY RESOLUTION OF THE TRANS-RACEMIC COMPOUND OR OF TRANS-RACEMIC-MELACEMANGE OPTICAL ANTIPODES. THE () - OR THE (-) - N- (1-FORMAMIDO-2,2,2-TRICHLORETHYL) -PIPERAZINE IN A POLAR SOLVENT IS USED AS A SALTIFYING AGENT FOR THE SEPARATION, THE SALT OF THE MOTHER IS SEPARATED FROM THE MOTHER LIQUEURS SALTING AGENT (-) AND ACID () -TRANS-CARBOXYLIC OR SALT OF SALTING AGENT () AND ACID (-) - TRANS-CARBOXYLIC WHICH CRYSTALLIZES THEN THE ENANTIOMERS ARE ISOLATED BY ACIDIFICATION OF THE MOTHER LIQUEURS OR RESPECTIVELY SALT WHICH HAS CRYSTALLIZED, AND EXTRACTION BY SOLVENTS AND EVAPORATION.