Methods of making lubiprostone and intermediates thereof

There is provided processes for preparing Lubiprostone and intermediates thereof. Also provided are compounds, including intermediates for preparing Lubiprostone as well compositions comprising Lubiprostone and other compounds, including intermediates for preparing Lubiprostone and other compounds. (I)

PROSTAGLANDIN SYNTHESIS AND INTERMEDIATES FOR USE THEREIN

Fused cyclopentane—4-substituted 3,5-dioxalane lactone compounds useful as an intermediate in the synthesis of prostaglandin analogs are provided. The compounds have the formula A: 2. Compound A according to wherein R represents a substituted phenyl group.3. Compound A according to wherein R represents p-methoxyphenyl5. Compound B according to wherein R′ represents p-methoxybenzyl. This invention relates to prostaglandin analogs and their synthesis. More particularly, it relates to a novel, simplified synthesis of prostaglandin analogs, and novel chemical compounds useful as intermediates in such synthesis.Prostaglandins (PGs) are organic carboxylic acids, namely cyclopentanes carrying two side chain substituents, typically linear C6-C8 side chains, bonded to adjacent positions on the cyclopentane nucleus. One of the side chains, the α-side chain, carries a terminal carboxylic acid group. Many are natural products found in mammalian organs and tissues (primary PGs), and exhibit a variety of physiological activities. Primary PGs generally have a prostanoic acid skeleton, which forms the basis of the nomenclature:A significant number of synthetic PG analogs have been made and found to have useful pharmacological properties. These may have modified skeletons, and substituted and unsaturated side chains. PGs are characterized by a hydroxyl (or ketone) substituent on the cyclopentane nucleus, position 9.Prostaglandin analogs are difficult to synthesize. Complications arise because of the requirements of the end products to have several functional groups and two side chains of significant size and complexity. Stereospecificity is commonly required, for substituent groups and for bonds in the core. Since the products are intended for pharmaceutical use, the range of industrially acceptable reagents, solvents, catalysts, etc. which can be used in their synthesis is limited to those having pharmaceutical industry acceptability.A common starting material for PG analog ...

USE OF MEXIPROSTIL IN THE TREATMENT OF INFLAMMATORY BOWEL DISEASE AND/OR OF IRRITABLE BOWEL SYNDROME

The invention relates to the use of mexiprostil in the treatment and/or prevention of inflammatory bowel disease and of irritable bowel syndrome, to the combinations of mexiprostil with other drugs, and also to a novel method for the synthesis of mexiprostil. 1. A method of treatment and/or prevention of inflammatory bowel disease (IBD) and/or of irritable bowel syndrome (IBS) comprising administering an effective amount of mexiprostil to patient in need thereof.2. The method according to claim 1 , for the treatment and/or prevention of ulcerative colitis.3. The method according to claim 1 , for the treatment and/or prevention of Crohn's disease.4. A method of treatment and/or prevention of the constipation (IBS-C) claim 1 , diarrhoeal (IBS-D) or alternating (IBS-A) variants of irritable bowel syndrome (IBS) comprising administering an effective amount of mexiprostil to patient in need thereof.5. The method according to claim 1 , wherein mexiprostil is administered at a rate of from 0.25 to 2.5 mg per day.6. The method according to claim 1 , wherein mexiprostil is administered in dosage units comprising from 0.5 to 1.5 mg of mexiprostil claim 1 , one or more times per day.7. The method according to claim 1 , wherein mexiprostil is formulated in gastroresistant and controlled-release compositions.8. The method according to claim 1 , wherein mexiprostil is formulated in compositions which comprise:a) a matrix which is composed of lipophilic compounds having a melting point of less than 90° C. and optionally of amphiphilic compounds in which the active ingredient is at least partially incorporated;b) optionally an amphiphilic matrix;c) an outer hydrophilic matrix in which the lipophilic matrix and the optional amphiphilic matrix are dispersed;d) optionally other excipients.9. The method according to claim 8 , characterized in that the composition comprises a gastroresistant coating.10. The method according to claim 1 , wherein mexiprostil is administered in combination ...

Process for the preparation of lubiprostone

Processes for preparing and purifying lubiprostone are disclosed. Intermediates and preparation thereof are also disclosed.

Ester Derivatives of Bimatoprost Compositions and Methods

Provided herein, inter alia, are prodrugs of bimatoprost, methods of using the same and compositions including the same. 2. The compound of claim 1 , wherein R claim 1 , Rand Rare independently substituted or unsubstituted C-Calkyl.3. The compound of claim 2 , wherein R claim 2 , Rand Rare independently substituted or unsubstituted C-Calkyl.4. The compound of claim 3 , wherein R claim 3 , Rand Rare independently substituted or unsubstituted Calkyl.5. The compound of claim 4 , wherein R claim 4 , Rand Rare independently methyl.6. The compound of claim 1 , wherein R claim 1 , Rand Rare independently substituted or unsubstituted C-Ccycloalkyl.7. The compound of claim 6 , wherein R claim 6 , Rand Rare independently unsubstituted C-Ccycloalkyl.8. The compound of claim 1 , wherein R claim 1 , Rand Rare independently substituted or unsubstituted aryl.9. The compound of claim 8 , wherein R claim 8 , Rand Rare independently aryl.10. The compound of claim 1 , wherein R claim 1 , Rand Rare independently phenyl.11. The compound of claim 1 , wherein Ris substituted or unsubstituted C-Calkyl claim 1 , or substituted or unsubstituted C-Ccycloalkyl.12. The compound of claim 11 , wherein Ris substituted or unsubstituted C-Calkyl.13. The compound of claim 12 , wherein Ris substituted or unsubstituted C-Calkyl.14. The compound of claim 13 , wherein Ris substituted or unsubstituted Calkyl.15. The compound of claim 14 , wherein Ris ethyl.16. The compound of claim 11 , wherein Ris substituted or unsubstituted C-Ccycloalkyl.17. The compound of claim 1 , wherein Ris hydrogen.22. The method of claim 21 , wherein said subject suffers from alopecia.23. The method of claim 21 , wherein said subject is in need of hair growth of the cilia claim 21 , the supercilia claim 21 , scalp pili claim 21 , or body pili.24. The method of claim 21 , wherein said administering is topical administering.25. The method of claim 24 , wherein said administering is topical epidermal administering. This application ...

Prostaglandin synthesis and intermediates for use therein

Fused cyclopentane—4-substituted 3,5-dioxalane lactone compounds useful as an intermediate in the synthesis of prostaglandin analogs are provided. The compounds have the formula A: wherein R represents an aryl group such as p-methoxyphenyl. This compound can be reacted with a lower alkyl aluminum compound to open the dioxalane ring and reduce the lactone to lactol, without over-reducing to diol. The resulting compound can be functionalized to insert chemical side groups of target prostaglandins, adding the required α-side chain and then the required ω-side chain sequentially and independently of each other. The compounds and process are particularly suitable for preparing lubiprostone.

METHOD FOR TREATING SCHIZOPHRENIA

The present invention provides a novel fatty acid derivative. The present invention also provides a method for treating schizophrenia in a mammalian subject, which comprises administering to the subject in need thereof an effective amount of a fatty acid derivative. 2. The method as described in claim 1 , wherein Z is C═O.3. The method as described in claim 1 , wherein B is —CH—CH—.4. The method as described in claim 1 , wherein B is —CH—CH— and Z is C═O.5. The method as described in claim 1 , wherein L is hydroxy or oxo claim 1 , M is hydrogen or hydroxy claim 1 , N is hydrogen claim 1 , B is —CH—CH— and Z is C═O.6. A compound of 7-[2-(4 claim 1 ,4-difluoro-3-oxooctyl)-5-oxocyclopentyl]hept-2-enoic acid or functional derivative thereof.7. A compound of 7-[2-(4 claim 1 ,4-difluoro-3-oxooctyl)-5-oxocyclopentyl]hept-2-enoic acid. This is a continuation of application Ser. No. 13/566,353 filed Aug. 3, 2012, which claims benefit of Provisional Application No. 61/515,418 filed Aug. 5, 2011; the above noted prior applications are all hereby incorporated by reference.The present invention relates to a method for treating schizophrenia.Schizophrenia is a chronic, severe, and disabling brain disorder that has affected people throughout history. About 1 percent of Americans have this illness.People with the disorder may hear voices other people don't hear. They may believe other people are reading their minds, controlling their thoughts, or plotting to harm them. This can terrify people with the illness and make them withdrawn or extremely agitated.People with schizophrenia may not make sense when they talk. They may sit for hours without moving or talking. Sometimes people with schizophrenia seem perfectly fine until they talk about what they are really thinking.Families and society are affected by schizophrenia too. Many people with schizophrenia have difficulty holding a job or caring for themselves, so they rely on others for help. Treatment helps relieve many symptoms of ...

CATALYTIC CONVERSION OF CELLULOSE TO LIQUID HYDROCARBON FUELS BY PROGRESSIVE REMOVAL OF OXYGEN TO FACILITATE SEPARATION PROCESSES AND ACHIEVE HIGH SELECTIVITIES

Described is a method to make liquid chemicals. The method includes deconstructing cellulose to yield a product mixture comprising levulinic acid and formic acid, converting the levulinic acid to γ-valerolactone, and converting the γ-valerolactone to pentanoic acid. Alternatively, the γ-valerolactone can be converted to a mixture of n-butenes. The pentanoic acid can be decarboxylated yield 1-butene or ketonized to yield 5-nonanone. The 5-nonanone can be hydrodeoxygenated to yield nonane, or 5-nonanone can be reduced to yield 5-nonanol. The 5-nonanol can be dehydrated to yield nonene, which can be dimerized to yield a mixture of Cand Colefins, which can be hydrogenated to yield a mixture of alkanes. 1. A method for converting glucose to γ-valerolactone , the method comprising:(a) hydrolyzing glucose derived from any source in an aqueous, acid-catalyzed reaction to yield a product mixture comprising levulinic acid and formic acid; then{'sub': 2', '2, '(b) converting at least a portion of the formic acid present in the product mixture to Hand COwithout separating the levulinic acid and formic acid present in the product mixture; and'}{'sub': '2', '(c) reducing at least a portion of the levulinic acid present in the product mixture to γ-valerolactone using the Hproduced in step (b).'}2. The method of claim 1 , wherein step (a) comprises hydrolyzing the glucose by reacting it with an acid.3. The method of claim 2 , wherein step (a) comprises hydrolyzing the glucose by reacting it with a mineral acid selected from the group consisting of sulfuric acid claim 2 , hydrochloric acid claim 2 , nitric acid claim 2 , phosphoric acid claim 2 , boric acid claim 2 , hydrofluoric acid claim 2 , hydrobromic acid claim 2 , oxalic acid claim 2 , acetic acid claim 2 , acetic anhydride claim 2 , and combinations thereof.4. The method of claim 1 , wherein step (b) comprises converting the converting the formic acid present in the product mixture to Hand COby contacting the product mixture ...

Ester derivatives of bimatoprost compositions and methods

Provided herein, inter alia, are prodrugs of bimatoprost, methods of using the same and compositions including the same.

Amine salts of prostaglandin analogs

The present application relates to amine salts of prostaglandin analogs and their uses for the preparation of substantially pure prostaglandin analogs. Specific embodiments relate to amine salts of tafluprost and their uses for the preparation of substantially pure tafluprost.

Salts of Prostaglandin Analog Intermediates

The present invention relates to crystalline 1-adamantanamine salts, and polymorphic forms thereof, of prostaglandin analog intermediates of formula 3a, 4a and 6a, useful in the preparation of Tafluprost and Lubiprostone and processes for their preparation. The process includes combining 1-adamantanamine, water, an organic solvent, and a compound of Formula 3 or 6, thereby obtaining a suspension. The process also includes isolating the solid salt of Formula 3a or 6a from the suspension. 2. The crystalline salt of having the Formula 3a.3. The crystalline salt of claim 2 , wherein the salt is characterized by a Powder X-Ray Diffraction (PXRD) diffractogram comprising a peak claim 2 , expressed in degrees two-theta claim 2 , at 11.0+/−0.2 claim 2 , and at least four peaks claim 2 , expressed in degrees two-theta claim 2 , selected from the group consisting of: 3.7+/−0.2 claim 2 , 7.5+/−0.2 claim 2 , 8.1+/−0.2 claim 2 , 9.5+/−0.2 claim 2 , 12.9+/−0.2 claim 2 , 13.6+/−0.2 claim 2 , 15.1+/−0.2 claim 2 , 15.7+/−0.2 claim 2 , 17.0+/−0.2 claim 2 , and 20.5+/−0.2.4. The crystalline salt of claim 3 , wherein the PXRD diffractogram comprises peaks claim 3 , expressed in degrees two-theta claim 3 , at: 3.7+/−0.2 claim 3 , 7.5+/−0.2 claim 3 , 8.1+/−0.2 claim 3 , 9.5+/−0.2 claim 3 , 11.0+/−0.2 claim 3 , 12.9+/−0.2 claim 3 , 13.6+/−0.2 claim 3 , 15.1+/−0.2 claim 3 , 15.7+/−0.2 claim 3 , 17.0+/−0.2 and 20.5+/−0.2.5. The crystalline salt of claim 3 , wherein the salt is characterized by a Differential Scanning Calorimetry (DSC) thermogram comprising an endothermic peak having a peak onset at approximately 78° C.6. The crystalline salt of having the Formula 4a.702. The crystalline salt of claim 6 , wherein the salt is Form APO-I characterized by a Powder X-Ray Diffraction (PXRD) diffractogram comprising a peak claim 6 , expressed in degrees two-theta claim 6 , at approximately 5.6+/−. claim 6 , and at least four peaks claim 6 , expressed in degrees two-theta claim 6 , selected from ...

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 ...

METHOD FOR PRODUCING TETRAHYDROPYRANYL ESTERS

The present invention relates to a method for preparing tetrahydropyranyl esters from the corresponding 4-hydroxytetrahydropyran compounds by reaction with a ketene compound. 112.-. (canceled)14. The method according to claim 13 , where Ris a straight-chain or branched C-C-alkyl claim 13 , straight-chain or branched C-C-alkenyl or phenyl.15. The method according to claim 13 , where Ris methyl claim 13 , ethyl claim 13 , n-propyl claim 13 , isopropyl claim 13 , n-butyl claim 13 , isobutyl claim 13 , n-pentyl claim 13 , n-hexyl or phenyl.16. The method according to claim 13 , where Ris n-propyl or isobutyl.17. The method according to claim 13 , where R claim 13 , Rand Rare all hydrogen.18. The method according to claim 13 , where Ris methyl.19. The method according to claim 13 , where Ris ethyl.20. The method according to claim 13 , where Rand Rare both hydrogen.21. The method according to claim 13 , wherein the compound of the general formula (II) is subjected to a reaction with a ketene (III) at a temperature in the range of 0 to 150° C.22. The method according to claim 13 , wherein the compound of the general formula (II) is subjected to a reaction with a ketene (III) at a temperature in the range of 10 to 120° C.23. The method according to claim 13 , wherein the compound of the general formula (II) is subjected to a reaction with a ketene (III) in the absence of an added catalyst.24. The method according to claim 13 , wherein the compound of the general formula (II) is subjected to a reaction with a ketene (III) in the presence of a catalyst.25. The method according to claim 13 , wherein the compound of the general formula (II) is subjected to a reaction with a ketene (III) in the presence of a catalyst selected from zinc salts.26. The method according to claim 13 , wherein the compound of the general formula (II) is subjected to a reaction with a ketene (III) in the presence of a catalyst selected from zinc salts of carboxylic acids.27. The method according to ...

PROCESSES AND INTERMEDIATES FOR THE PREPARATIONS OF ISOMER FREE PROSTAGLANDINS

Novel processes for the preparation of a compound of Formula I-2 substantially free of the 5,6-trans isomer: 2. A compound according to wherein Ris methyl claim 1 , phenyl claim 1 , or p-phenylphenyl. This application is a Divisional of U.S. patent application Ser. No. 14/802,026 filed Jul. 17, 2015, which is a divisional of U.S. patent application Ser. No. 13/967,473 filed Aug. 15, 2013 (now U.S. Pat. No. 9,115,109 issued Aug. 25, 2015), the contents of which are incorporated herein by reference.The present invention relates to novel processes and intermediates for the preparations of isomer free Prostaglandins and the derivatives thereof.Prostaglandin ester analogues of the following Formula I-2whereinis a single or double bond; Ris a single bond or a C-alkylene or —CHO—; and Ris a C-alkyl or an aryl or an aralkyl, each of which is unsubstituted or substituted by a C-alkyl, a halogen or a trihalomethyl; and Ris C-alkyl, such as, Latanoprost, Isoproyl unoprostone, Isoproyl cloprostenol, Travoprost and Tafluprost have been used in the management of open-angle glaucoma. The Prostaglandin ester analogues of Formula I-2 have been shown to have significantly greater hypotensive potency than the parent compound, presumably as a result of their more effective penetration through the cornea. They reduce intra-ocular pressure by enhancing uveoscleral outflow, and may also have some effect on trabecular meshwork as well.As shown in the following Scheme A:most of the Prostaglandin ester analogues of Formula I-2 disclosed in the prior art, such as in WO02096898, EP1886992, EP2143712, JP2012246301, U.S. Pat. No. 6,720,438, US2008033176, WO2010097672, and U.S. Pat. No. 7,582,779 were obtained by first synthesizing a Lactone VIII, whereinor is a protective group of carbonyl group; Pand Pare protective groups for the hydroxyl groups; is a single or double bond; Ris a single bond or a C-alkylene or —CHO—; and Ris a C-alkyl or an aryl or an aralkyl, each of which is unsubstituted or ...

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. ...

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.

NONIONIC SURFACTANT AND METHOD FOR PRODUCING NONIONIC SURFACTANT

The nonionic surfactant of the present invention has a structure represented by formula (1): 7. The method for producing the nonionic surfactant according to claim 6 ,wherein the addition reaction is a reaction in which dihydropyran is added to each hydroxy group in the presence of an acid catalyst. The present invention relates to a nonionic surfactant and a method for producing the nonionic surfactant.Nonionic surfactants are widely used as materials of detergent compositions for kitchens, bathrooms, and commercial cooking facilities. Examples of nonionic surfactants include higher alcohol EO adducts in which a large number of oxyethylene groups (hereinafter also referred to as EO) are added to a higher alcohol residue.Detergent compositions may contain a chlorine agent for bleaching stain. Examples of the chlorine agent include salts of acids such as dichloroisocyanuric acid (examples also includes aqueous solutions of these salts) which can generate hypochlorous acid or chlorous acid.It is known that coexistence of a nonionic surfactant and a chlorine agent in a detergent composition causes deactivation of both the nonionic surfactant and the chlorine agent as a result of a reaction of a terminal hydroxy group of the nonionic surfactant with chlorine of the chlorine agent.Patent Literature 1 discloses a nonionic surfactant of an end-capped polyalkylene oxide block copolymer which does not bear functional groups that are easily oxidized by a chlorine agent (hypochlorite bleach).Technical ProblemPatent Literature 1 discloses a nonionic surfactant in which an alkylene oxide is end-capped with a methyl group, resulting in the structure not having a terminal hydroxyl group. According to Patent Literature 1, this nonionic surfactant is more stable in the presence of a chlorine bleach than an uncapped parent molecule.Patent Literature 1 also discloses a method for methylation of a terminal hydroxyl group at an end of an alkylene oxide moiety by a reaction of a ...

COMPOUND FOR TREATING CARTILAGE DISORDERS

The present invention provides a compound of which active |form| is represented by a formula (A). and which can be injected into a joint cavity which is an affected part of disorders and can be accumulated in the joint cavity to exert the pharmacological effect thereof in a sustained manner, for the purpose of ameliorating cartilage disorders without developing any side effect. A compound according to the present invention, which is represented by a formula (I): 3. The compound according to claim 1 , which is selected from a group consisting of 3-{[(5Z)-7-{(1R claim 1 ,2R claim 1 ,3R claim 1 ,5R)-5-chloro-2-[(1E claim 1 ,4S)-4-(1-ethylcyclobutyl)-4-hydroxy-1-buten-1-yl]-3-hydroxycyclopentyl}-5-heptenoyl]oxy}propyl 3-(pentadecyloxy)benzoate claim 1 , 2-{[(5Z)-7-{(1R claim 1 ,2R claim 1 ,3R claim 1 ,5R)-5-chloro-2-[(1E claim 1 ,4S)-4-(1-ethylcyclobutyl)-4-hydroxy-1-buten-1-yl]-3-hydroxycyclopentyl}-5-heptenoyl]oxy}ethyl 3-(pentadecyloxy)benzoate claim 1 , 4-{[(5Z)-7-{(1R claim 1 ,2R claim 1 ,3R claim 1 ,5R)-5-chloro-2-[(1E claim 1 ,4S)-4-(1-ethylcyclobutyl)-4-hydroxy-1-buten-1-yl]-3-hydroxycyclopentyl}-5-heptenoyl]oxy}butyl 3-(pentadecyloxy)benzoate claim 1 , 2-{[(5Z)-7-{(1R claim 1 ,2R claim 1 ,3R claim 1 ,5R)-5-chloro-2-[(1E claim 1 ,4S)-4-(1-ethylcyclobutyl)-4-hydroxy-1-buten-1-yl]-3-hydroxycyclopentyl}-5-heptenoyl]oxy}ethyl 3-(dodecyloxy)benzoate claim 1 , 2-{[(5Z)-7-{(1R claim 1 ,2R claim 1 ,3R claim 1 ,5R)-5-chloro-2-[(1E claim 1 ,4S)-4-(1-ethylcyclobutyl)-4-hydroxy-1-buten-1-yl]-3-hydroxycyclopentyl}-5-heptenoyl]oxy}ethyl 3-(tetradecyloxy)benzoate claim 1 , 2-{[(5Z)-7-{(1R claim 1 ,2R claim 1 ,3R claim 1 ,5R)-5-chloro-2-[(1E claim 1 ,4S)-4-(1-ethylcyclobutyl)-4-hydroxy-1-buten-1-yl]-3-hydroxycyclopentyl}-5-heptenoyl]oxy}ethyl 3-(hexadecyloxy)benzoate claim 1 , 2-{[(5Z)-7-{(1R claim 1 ,2R claim 1 ,3R claim 1 ,5R)-5-chloro-2-[(1E claim 1 ,4S)-4-(1-ethylcyclobutyl)-4-hydroxy-1-buten-1-yl]-3-hydroxycyclopentyl}-5-heptenoyl]oxy}ethyl 3-(octadecyloxy)benzoate claim 1 ...

Method for producing pkrostaglandin

The present invention provides a method for producing a compound represented by Formula (1a), (1b), or (1c), comprising a step of reducing a compound represented by Formula (3) in the presence of a metal complex represented by Formula (5), an inorganic base, and a solvent under a hydrogen atmosphere to obtain a compound represented by Formula (4). In the formula, Ar 1 is an aryl group, each Are is independently a phenyl group or the like, W is a biphenyl group or the like, Z is an ethylene group that is substituted with a phenyl group or the like, and L is a chlorine atom or if Z has a phenyl group or a C 1-3 alkoxyphenyl group, L is one of carbon atoms constituting the phenyl group or the C 1-3 alkoxyphenyl group.

METHOD FOR THE PURIFICATION OF PROSTAGLANDINS

The present invention provides a method for the purification of a prostaglandin by supercritical fluid chromatography, said method comprising the use of a stationary phase and a mobile phase comprising carbon dioxide, provided that when the stationary phase is unmodified silica gel, the prostaglandin is not luprostiol. The invention also provides prostaglandins obtainable by the method. 1. A latanoprost composition comprising C11-beta isomer of latanoprost in an amount greater than 0% and less than 0.03% , and containing less than 0.03% C15R-Trans isomer of latanoprost , less than 0.05% C15S-Trans isomer of latanoprost , and less than 0.03% C15S-Cis isomer of latanoprost.2. A latanoprost composition comprising C11-beta isomer of latanoprost in an amount greater than 0% and less than 0.03% , and containing less than 0.03% C15R-Trans isomer of latanoprost , less than 0.05% C15S-Trans isomer of latanoprost , and less than 0.03% C15S-Cis isomer of latanoprost , after 11 months storage at freezer temperature.3. C11-beta isomer of latanoprost.4. A latanoprost composition comprising C11-beta isomer of latanoprost in an amount greater than 0% and less than 0.03%.5. A latanoprost composition comprising at C11-beta isomer of latanoprost in an amount greater than 0% and less than 0.03% , after 11 months storage at freezer temperature.6. A composition according to claim 1 , wherein the latanopost composition is at least 99% chemically pure.7. A composition according to claim 1 , wherein the latanopost composition is at least 99.5% chemically pure.8. A composition according to claim 1 , wherein the latanopost composition is at least 99.8% chemically pure.9. A composition according to claim 1 , wherein the latanopost composition is at least 99% isometrically pure.10. A composition according to claim 1 , wherein the latanopost composition is at least 99.5% isometrically pure.11. A composition according to claim 1 , wherein the latanopost composition is at least 99.8% isometrically ...

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 ...

Compound And Method

A compound of formula (I): (I) wherein Y is, Z is OR, NRRSR, S(0)RS0R, Ris H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, CO—R, or a protecting group, and Ris optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, or alkoxyl; a process for making a compound of formula (I); and a process for making a prostaglandin or a prostaglandin analogue using a compound of formula (I). 4. (canceled)6. The process according to claim 5 , wherein the acidic co-catalyst is added to the reaction mixture after the chiral secondary amine catalyst has been added.7. (canceled)11. The process according to claim 5 , wherein the acidic co-catalyst has the structure [α][β] wherein [α] is a cation selected from [BnNH] claim 5 , [BnNH] claim 5 , [pyridinium] claim 5 , [2 claim 5 ,2′-bipyridinium] claim 5 , [2 claim 5 ,2′:6′ claim 5 ,2″-terpyridinium] claim 5 , [morpholinium] and [thiomorpholinium] claim 5 , and [β] is an anion selected from [F] claim 5 , [Cl] claim 5 , [Br] claim 5 , [I] claim 5 , [OCOCF] claim 5 , [BF] claim 5 , [OCOCHCl] claim 5 , and [O—CH-2 claim 5 ,4-(NO)].12. The process according to claim 11 , wherein the acidic co-catalyst comprises [BnNH][OCOCF].14. (canceled)16. A process for making a prostaglandin or a prostaglandin analogue claim 1 , which uses a compound of formula (I) as defined in as a reactant. The present invention relates to a compound of formula (I) as defined below, a process for making a compound of formula (I), and a process for making a prostaglandin or a prostaglandin analogue using a compound of formula (I).Prostaglandins are hormone-like chemical messengers that regulate a host of physiological ...

ANTI-CONSTIPATION COMPOSITION

An object of the present invention is to provide an anti-constipation composition containing a halogenated-bi-cyclic compound as an active ingredient in a ratio of bi-cyclic/mono-cyclic structure of at least 1:1. The halogenated-bi-cyclic compound is represented by Formula (I): 2. The pharmaceutical composition according to claim 1 , further comprising a compound which is a mono-cyclic tautomer of formula (I) claim 1 ,wherein in the composition a ratio of bi-cyclic to mono-cyclic structure is at least 1:1.3. The pharmaceutical composition according to claim 1 , further comprising a compound which is a mono-cyclic tautomer of formula (I) claim 1 ,wherein in the composition a ratio of bi-cyclic/mono-cyclic structure is at least 20:1.5. The pharmaceutical composition according to claim 4 , further comprising a compound which is a mono-cyclic tautomer of formula (I) claim 4 ,wherein in the composition a ratio of bi-cyclic/monocyclic structure is at least 1:1.6. The pharmaceutical composition according to claim 5 , wherein the ratio of bi-cyclic/mono-cyclic structure is at least 20:1.7. The pharmaceutical composition of according to claim 1 , wherein Z is a sulfur atom or a nitrogen atom.8. The pharmaceutical composition according to claim 4 , wherein Z is a sulfur atom or a nitrogen atom.9. The pharmaceutical composition according to claim 4 , wherein the medium chain fatty acid triglyceride is present in an amount of 1-1 claim 4 ,000 claim 4 ,000 parts by weight based on one part by weight of the bi-cyclic structure.10. The pharmaceutical composition according to claim 9 , wherein the medium chain fatty acid triglyceride is present in an amount of 5-500 claim 9 ,000 parts by weight based on one part by weight of the bi-cyclic structure.11. The pharmaceutical composition according to claim 9 , wherein the medium chain fatty acid triglyceride is present in an amount of 10-200 claim 9 ,000 parts by weight based on one part by weight of the bi-cyclic structure.12. The ...

PYRAN DERIVATIVES AND THEIR PREPARATION

A compound of formula (I) 2. The compound according to claim 1 , wherein said compound is selected from the group consisting of 2-(1-ethyl-propyl)-4-methyl-tetrahydro-2H-pyran-4-ol claim 1 , 2-(1-ethyl-propyl)-4-methyl-tetrahydro-2H-pyran-4-yl acetate claim 1 , propionic acid 2-(1-ethyl-propyl)-4-methyl-tetrahydro-2H-pyran-4-yl ester claim 1 , but-2-enoic acid 2-(1-ethyl-propyl)-4-methyl-tetrahydro-2H-pyran-4-yl ester claim 1 , but-3-enoic acid 2-(1-ethyl-propyl)-4-methyl-tetrahydro-2H-pyran-4-yl ester claim 1 , and 4-methyl-2-(1-pentyl)-tetrahydro-2H-pyran-4-yl acetate.3. A fragrant agent or a flavoring agent comprising the compound of and an acceptable fragrant agent or flavoring agent carrier.4. A masking agent of odors and/or flavors comprising the compound of and an acceptable masking agent carrier.5. A pharmaceutical claim 1 , cosmetic claim 1 , or food composition comprising the compound according to in combination with perfuming ingredients claim 1 , flavoring ingredients claim 1 , solvents claim 1 , additives claim 1 , or fixatives. This application is a divisional application of U.S. Ser. No. 12/988,704, having a filing date of Jan. 3, 2011, and issued on Mar. 14, 2017, as U.S. Pat. No. 9,593,092, which was a 371 application of International application PCT/EP2009/054691, filed Apr. 21, 2009, which claimed the benefit of European Patent application EP 08305118.5, filed Apr. 22, 2008, all of said applications incorporated herein by reference.The present invention relates to the field of fragrances and flavours. More particularly, the invention relates to new pyran derivatives, their method of preparation, and their use in the fields of perfumery and flavouring.Tetrahydropyrans and dihydropyrans belong to an important class of fragrant ingredients and much work has already been done to prepare known compounds, such as Rose Oxide and similar derivatives, from linear or branched alkyl and alkenyl aldehydes as described in U.S. Pat. No. 3,681,263 and WO 04/ ...

METHOD FOR PREPARING LATANOPROSTENE BUNOD, AND INTERMEDIATE THEREFOR

The present invention relates to a process for preparing latanoprostene bunod and an intermediate therefor. In accordance with the preparation process of the present invention, latanoprostene bunod can be efficiently and cost-effectively prepared while reducing side reactions. 2. The process according to claim 1 , wherein the esterification of step (i) is carried out in the presence of a base.3. The process according to claim 2 , wherein the base is potassium carbonate.4. The process according to claim 1 , wherein the nitration of step (ii) is carried out using silver nitrate (AgNO).6. The process according to claim 5 , wherein the hydrolysis is carried out using lithium hydroxide monohydrate. The present invention relates to a process for preparing latanoprostene bunod and an intermediate therefor. More particularly, the present invention relates to a cost-effective and efficient process for preparing latanoprostene bunod, and an intermediate therefor.Latanoprostene bunod of the following formula (1) (4-(nitrooxy)butyl (Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((R)-3-hydroxy-5-phenylpentyl)cyclopentyl)hept-5-enoate) is an active pharmaceutical ingredient (API) of Vesneo® which is a medicine for glaucoma.U.S. Pat. No. 7,273,946 discloses a process for preparing latanoprostene bunod by preparing 4-bromobutyl nitrate using tetrahydrofuran as a starting material and subjecting it to combination reaction with latanoprost acid, as shown in the following reaction scheme 1. However, the preparation process has the danger of using strong acids in the synthesis of 4-bromobutyl nitrate, and the risk of explosion due to rapid heat generation in dropwise addition of sulfuric acid into nitric acid solution. Further, the bromide produced by the combination reaction reacts with the nitrate of latanoprostene bunod, which causes the problem of producing a large amount of by-products.It is an object of the present invention to provide an efficient and cost-effective process for preparing ...

N-HYDROXYLSULFONAMIDE DERIVATIVES AS NEW PHYSIOLOGICALLY USEFUL NITROXYL DONORS

The invention relates to N-hydroxysulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and/or preventing the onset and/or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia/reperfusion injury. Novel N-hydroxysulfonamide derivatives release NHO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxysulfonamide derivatives. 120-. (canceled) This application claims priority to U.S. Provisional Patent Application Ser. No. 60/783,556, filed Mar. 17, 2006 and entitled “N-Hydroxylsulfonamide Derivatives as New Physiologically Useful Nitroxyl Doners,” which is incorporated herein by reference in its entirety.This invention was made in part with government support under Grant No. CHE-0518406 from the National Science Foundation. The government may have certain rights in this invention.Congestive heart failure (CHF) is a generally progressive, life threatening condition in which myocardial contractility is depressed such that the heart is unable to adequately pump the blood returning to it, also referred to as decompensation. Symptoms include breathlessness, fatigue, weakness, leg swelling, and exercise intolerance. On physical examination, patients with heart failure often have elevated heart and respiratory rates (an indication of fluid in the lungs), edema, jugular venous distension, and enlarged hearts. The most common cause of CHF is atherosclerosis, which causes blockages in the coronary arteries that provide blood flow to the heart muscle. Ultimately, such blockages may cause myocardial infarction with subsequent decline in heart function and resultant heart failure. Other causes of CHF include valvular heart disease, hypertension, viral infections of the heart, alcohol consumption, and diabetes. Some cases of CHF occur without clear ...

Preservative-free Treprostinil Devices

Embodiments include a system including a sealed prefilled drug-reservoir. The drug-reservoir may include a unit dosage of treprostinil in a sterile fluid composition. The composition may not include an antimicrobial preservative. The treprostinil may be present at a dosage of between 0.1 mg/mL and 25 mg/mL. In addition, the treprostinil may be treprostinil sodium Furthermore, the composition may include sodium chloride. The composition may also include a sodium ion from sodium chloride in a concentration from 3000 to 4500 ppm. The composition may not include metacresol.

Processes and intermediates for the preparations of isomer free prostaglandins

Novel processes for the preparation of a compound of Formula I-2 substantially free of the 5,6-trans isomer: wherein R 2 , R 3 and R 4 are as defined in the specification are provided. Novel intermediates for the preparations of isomer free Prostaglandins and derivatives thereof are also provided.

SYNTHESIS OF DELTA 12-PGJ3 AND RELATED COMPOUNDS

In one aspect, the present invention provides novel derivatives of Δ-PGJand modular synthetic pathways to obtaining Δ-PGJand derivatives thereof. In some aspects, the present derivatives of Δ-PGJare useful as chemotherapeutic agents. The present disclosure also describes compositions of these derivatives as well as methods of use of the derivatives thereof. 46.-. (canceled)7. The compound of claim 1 , wherein Yis O.8. The compound of claim 1 , wherein Yis N—OH or N—OMe.9. The compound of claim 8 , wherein Yis N—OMe.1095.-. (canceled)97. The compound of claim 96 , wherein Ais alkenediyl.98. (canceled)99. The compound of claim 96 , wherein z is 1 claim 96 , 2 claim 96 , 3 claim 96 , or 4.100101.-. (canceled)102. The compound of claim 96 , wherein Xis O.103. The compound of claim 96 , wherein Xis alkenyl.104. (canceled)107. A pharmaceutical composition comprising a compound of and an excipient.108. (canceled)109. The pharmaceutical composition of claim 107 , wherein the composition is formulated for oral claim 107 , topical claim 107 , intraarterial claim 107 , intraperitoneal claim 107 , or intravenous administration.110114-. (canceled)115. A method of treating a disease or disorder in a patient in need thereof comprising administering to the patient a pharmaceutically effective amount of a compound or composition of or a pharmaceutically acceptable salt or optical isomer thereof.116. The method of claim 115 , wherein the disease is cancer.117118.-. (canceled)119. The method of claim 116 , wherein the cancer is leukemia.120130.-. (canceled)132293.-. (canceled)295434.-. (canceled) This application claims the benefit of U.S. Provisional Application 61/882,093, filed on Sep. 25, 2013, U.S. Provisional Application 61/897,681, filed on Oct. 30, 2013, U.S. Provisional Application 61/920,302, filed on Dec. 23, 2013, U.S. Provisional Application 61/954,295, filed on Mar. 17, 2014, and U.S. Provisional Application 61/979,276, filed on Apr. 14, 2014, the entire contents of each ...

TROMETHAMINE SALT OF BIMATOPROST ACID IN CRYSTALLINE FORM 1, METHODS FOR PREPARATION, AND METHODS FOR USE THEREOF

The present invention provides tromethamine salt of (Z)-7-[3,5-Dihydroxy-2-((E)-3-hydroxy-5-phenyl-pent-1-enyl)-cyclopentyl]-hept-5-enoic acid in crystalline Form 1 and amorphous form. This compound is may also be referred to as “tromethamine salt of bimatoprost acid.” The invention crystalline form is useful for solid ocular implant or topical formulations, utilized in the treatment of various ocular conditions, such as, for example, ocular hypertension. 2. The crystalline Form 1 of having the X-ray powder diffraction pattern as shown in .3. The crystalline form of having a melting enthalpy from about 103.6 J/g to about 119.9 J/g.4. The crystalline form of having a melting temperature within the range of about 104-110° C.5. The crystalline form of having a melting temperature of about 105° C.6. The crystalline form of having a melting temperature of about 105.6° C.7. A pharmaceutical composition comprising a therapeutically effective amount of tromethamine salt of bimatoprost acid in crystalline Form 1.8. The pharmaceutical composition of wherein the tromethamine salt of bimatoprost acid in crystalline Form 1 is in a pharmaceutically acceptable carrier.9. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition is a suspension claim 7 , solution claim 7 , foam claim 7 , gel claim 7 , cream claim 7 , ointment claim 7 , emulsion claim 7 , or lotion.10. The pharmaceutical composition of claim 9 , wherein the suspension is a gel suspension claim 9 , a gel-based micro-suspension claim 9 , or a nano-suspension.11. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition is a solid dosage form.12. The pharmaceutical composition of for the treatment of elevated intraocular pressure claim 7 , glaucoma claim 7 , or localized fat reduction claim 7 , or for promotion of hair growth.13. A method for treating ocular hypertension comprising administering to a subject in need thereof a therapeutically effective amount of ...

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).

Production of cyclopentenylheptanoic acid derivatives

Cyclopentenyl heptanoic acid derivatives having the formula: wherein R is hydrogen or C, to C 4 alkyl and -(A)-is: wherein M is hydrogen or triorganosilyl, are prepared by reacting a compound having the formula: wherein X is halogen, with a compound having the formula: The derivatives belong to the pharmacologically -active class of compounds called "prostagfandins".

Microbiological reduction of PGA2 and 15-epi PGA2

Reduction of 7(2-[(3R and 3S)-3-hydroxy-1-octenyl]-5-oxo-3-cyclopenten-1-yl)-5-heptenoic acid by microorganisms of the genera Streptomyces, Pseudomonas and Corynebacterium is disclosed. The products 7-(2-[(3R)-3-hydroxy-1-octenyl]-5-oxo-cyclopentyl)-5-heptenoic acid(11-deoxy-15-epi-PGE 2 ), which is novel, and 7-(2-[(3S)-3-hydroxy-1-octenyl]-5-oxo-3-cyclopentyl)-5-heptenoic acid(11-deoxy-PGE 2 ), respectively, are useful as intermediates for the synthesis of other physiologically active ingredients.

Use of certain prostaglandin analogues to treat glaucoma and ocular hypertension

Certain D series prostaglandin analogues are effective in lowering intra ocular pressure and are useful in the treatment of glaucoma and ocular hypertension. Also disclosed are opthalmic, pharmaceutical compositions comprising such prostaglandin analogues and their use.

Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support

Methods, compositions, and devices for synthesis of therapeutically useful compounds. The invention provides a rapid approach for combinatorial synthesis and screening of libraries of derivatives of therapeutically important classes of compounds such as benzodiazepines, prostaglandins and β-turn mimetics. In order to expediently synthesize a combinatorial library of derivatives based upon these core structures, general methodology for the solid phase synthesis of these derivatives is also provided. This disclosure thus also describes an important extension of solid phase synthesis methods to nonpolymeric organic compounds.

13,14-Didehydro-PG analogs

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

7-THIAPROSTAGLANDINE AND METHOD FOR THE PRODUCTION THEREOF

New process for preparing high purity prostaglandins

Sett att framstella nya 11-desoxi-prostaglandin-f?712-derivat

Process for the preparation of 16-fluoro-16,17-didehydro prostanoids

ANALOGS OF PROSTANIC ACIDS AND THE PROCESS FOR THEIR PRODUCTION

Process of preparing derivatives of prostacycline or their epimers

1. Способ получени  производных простдциклина обшей формулы ,iH А-С-В или их эпимеров, где R -водород, щелочной металл или низший алкил; 1 -водород или метил ; --СН -СН--, транс-СН СНА у-, транс-1-н сн- ; 1((СКл},-СУ( или --С(Р В цикле гюгексил; 1 и R - одинаковые или разные, водород или этил, о т л И ч а ю щ и и с   тем, что соединение общей формулы ОН -J . ) и R2имеют указанные знагде А, В У и одинаковые или разчени , R ные, водород или защитна  группа тетрагидропйранил или триметилсилил, подвергают взаимодействию, в среде органического растворител  в инертной атмосфере при lO-ЗОс в присутствии сильного основани  с 1-6-кратным мол рным количеством соединени  общей формулы . {СбН5)зР-Ш2-О 1 ,в Hai 41 I-Ч41ЛПТ 6 JOOR где в - водород, метил или этил; Hal - бром или иод, 6 и затем, когда К водоррд, -этерифицируют диазометаном при 0-30°С, а когда R и R 5 - защитна  группа, последние отщепл ют с получением соедиО ) нени  общей формулы ОН а S но соов А-С-В КО R2 где R ,. А и В имеют указанные значени / R - метил или. этил, которое :бромируют или иодируют в присутствии инертного растворител  и при необходимости в присутствии акцептора кислоты при 0-30 с и ииклизуют в соединение общей формулы .где t, Я , А и В имеют указанные значени  ; X - бром или иод, и от полученного соединени  фбрмулы У при 0-90°С отщепл ют галоид-водо 1. A process for the preparation of prostadcycline derivatives of the general formula iH A-C-B or their epimers, where R is hydrogen, alkali metal or lower alkyl; 1 is hydrogen or methyl; --CH -CH--, trans-CHA CHA y-, trans-1-nn-; 1 ((CKl}, - SU (or –C (P in the hegexyl cycle; 1 and R are the same or different, hydrogen or ethyl), and with the fact that the compound of the general formula OH is J.) and R2 have the indicated values where A, B Y and the same or different, R are hydrogen, or the protective group of tetrahydropyranyl or trimethylsilyl, is reacted in an organic solvent medium in an inert atmosphere at 0-30 ° C in the ...

用于制备无异构体的前列腺素的方法和中间体

本申请涉及用于制备无异构体的前列腺素的方法和中间体。本发明提供用于制备实质上不含5,6‑反式异构体的式I‑2化合物的新颖方法： 其中 R 2 、R 3 和R 4 如说明书中所定义。本发明还提供用于制备无异构体的前列腺素和其衍生物的新颖中间体。

Process for preparing heterocyclic compounds and isomers thereof

Heterocyclic compds. of formula (I) are new, where R1 is H, an alcohol residue in the form up on ester, or a pharmaceutically compatible cation; R2 is H or methyl; A is -CH2-CH2- or trans-CH=CH-; and B is C5-7 alkyl of formula -CR3R4-(CH2)3-CH3 (where R3 and R4 are H or (m)ethyl or cyclohexyl opt. 4-substd. by (m)ethyl. (I) have good thrombocyte aggregation inhibiting activity in humans and also in external circulatory systems.

Preparation of prostaglandin-like compounds

The method of obtaining derivatives of prostanocarboxylic acid

DERIVATIVES OF 5-THIA-ω-SUBSTITUTED PHENYLPROSTAGLANDIN E, METHODS FOR ITS PREPARING, PHARMACEUTICAL COMPOSITION

FIELD: organic chemistry, medicine, pharmacy. SUBSTANCE: invention relates to new derivatives of prostaglandins, namely, to 5-thia-ω-substituted phenylprostaglandin E of the formula (I) -ω- wherein is OH or R 1 -alkoxy-group; C 1-6 is oxygen or halogen atom; R 2 is hydrogen atom or OH; R 3 and R 4a mean independently hydrogen atom or R 4b -alkyl; C 1-4 is phenyl substituted with R 5 -alkoxy-C 1-4 -alkyl, C 1-4 -alkenyloxy-C 2-4 -alkyl, phenyloxy-C 1-4 -alkyl and others. Compounds of the formula (I) can bind tightly with C 1-4 -receptors (especially with receptors of subtype PGE 2 ). Therefore, these compounds are useful for prophylaxis and/or treatment of immunologic diseases (autoimmune diseases, such as amyotrophic lateral sclerosis, disseminated sclerosis, Sjogren's syndrome, chronic rheumoarthrosis, exanthematous (systemic) erythematosus and others, rejections after organs transplantation and others), asthma, pathology in bones formation, death of nerve cells, lung damage, liver injury, acute hepatitis, renal insufficiency, hypertension, myocardium ischemia, nephritis, general inflammatory response syndrome, burns pain, sepsis, hemophagus-syndrome, macrophages activation, Still's disease, Kawasaki's disease systemic granulomatosis, nonspecific ulcerous colitis, Crohn's disease, hypercytokinemia in dialysis, multiple organs injury, shock and others. Except for, receptor of subtype EP 4 relates to sleep disorder and blood platelet aggregation. Therefore, it is believed that proposed compounds are useful in prophylaxis and/or treatment of above indicated diseases. EFFECT: improved preparing method, valuable medicinal properties of compounds. 21 cl, 4 tbl, 5 sch, 37 ex 5 О0сСсс ПЧ сэ ")2у“” 2 220 135 (° С2 57 М” С 07С 405/00, А 61 К 31/557, 47140 РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 2001101470/04, 14.07.1999 (71) Заявитель: ОНО ФАРМАСЬЮТИКАЛ КО. ЛТД. (.Р) (24) ...

Method of producing 16-fluorine-15,17-didihydroprostanoids of general formula i

16-Fluoro-16,17-didehydro prostanoids of formula: <IMAGE> wherein R is 1)-OH or -OR', wherein R' is C1-C6 alkyl optionally substituted by phenyl, monocycloalkyl or a heteromonocylic ring; <IMAGE> wherein each of R'' and R''' is, independently, hydrogen; C1-C6 alkyl; phenyl; or a heteromonocyclic ring; or R'' and R''', together with the nitrogen atom to which they are linked, form a heteromonocyclic ring -W-(CH2)n-X where W is -O- or -NH-, n is an integer of 1 to 4 and X represents a group -OR' or a group <IMAGE> or 4) -NHSO2-R<IV>, wherein R<IV> is C1-C4 alkyl, phenyl or phenyl substituted by C1-C4 alkyl; one of R1 and R2 is hydrogen and the other is hydroxy or R1 or R2, taken together, form an oxo group; one of R3 and R4 is hydrogen and the other is hydroxy or R3 and R4 are both hydrogen or, taken together, form an oxo group; one of R5 and R6 is hydroxy and the other is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or phenyl; m is zero or an integer of 1 to 3; R7 is C1-C6 alkyl; C3-C7 monocycloalkyl; unsubstituted phenyl or phenyl substituted by one or more substituents chosen from C1-C4 alkyl; C1-C4 alkoxy, tri-halo-C1-C4-alkyl, halogen, <IMAGE> wherein each of R<V> and R<VI> is, independently, hydrogen, C1-C4 alkyl or phenyl; or R7 is a heteromonocyclic ring optionally substituted by one or more of halogen, C1-C4 alkyl, C1-C4 alkoxy, phenyl and phenoxy; A is trans -CH = CH-, -CH2-CH2- or -C IDENTICAL C-, and the symbol @ represents a single bond or a cis double bond; with the condition that R3 and R4 do not form an oxo group when R1 and R2 form an oxo group; and the pharmaceutically or veterinarily acceptable salts thereof; are useful as luteolytic, anti-ulcer and anti-neoplastic agents and can inhibit platelet aggregation.

Processes for the preparation of isomer free prostaglandins

本发明提供用于制备实质上不含5,6-反式异构体的式I-2化合物的新颖方法： 其中 R 2 、R 3 和R 4 如说明书中所定义。本发明还提供用于制备无异构体的前列腺素和其衍生物的新颖中间体。

Nitric oxide donating derivatives of prostaglandins

The present invention relates to nitrooxyderivatives of tafluprost acid, their use for the treatment of glaucoma and ocular hypertension and formulation containing nitrooxyderivatives of tafluprost acid.

Processes and intermediates for the preparations of isomer free prostaglandins

5,6-트랜스 이성질체를 실질적으로 함유하지 않는 화학식 Ⅰ-2의 화합물: 의 제조를 위한 신규한 방법이 제공되며, 상기 식에서, , R 2 , R 3 및 R 4 는 본 명세서에 정의된 바와 같다. 이성질체 무함유 프로스타글란딘 제조를 위한 신규한 중간체 및 그 유도체도 제공된다. A compound of Formula I-2 that is substantially free of the 5,6-trans isomer: A novel process is provided for the preparation of , R 2 , R 3 and R 4 are as defined herein. Novel intermediates and derivatives thereof for the preparation of isomer-free prostaglandins are also provided.

Cis-13-PGF2.sub.α analogs

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is of the cis configuration. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

Composition and method for promoting hair growth

본 발명은, 두 개의 헤테로 원자를 15 위치에 갖는 프로스타글란딘 화합물을 그 활성 성분으로 함유하는, 포유류에서의 육모 촉진용 조성물 및 방법을 제공한다.

LUMINESCENT FLUORIDE AND LUMINESCENT SCREEN FITTED WITH SUCH FLUORIDE.

Method for preparing stable prostaglandine pharma ceuticals

Methods and intermediates for producing isomer-free prostaglandins

Process for producing intermediate for 13,14-didehydroprostaglandin e

Method of obtaining pyrocatechol esters

Method of producing derivatives of 16-phenoxyprostatrienic acid in the form of their stereoisomers or a mixture of stereoisomers

This invention relates to a process for making a compound of formula I in the form of a stereoisomer or mixture thereof, wherein R is hydrogen, lower alkyl; X is hydrogen, halo, trifluoromethyl, lower alkyl or lower alkoxy, and the wavy lines represent the a or β configuration with the proviso that when one wavy line is α the other is β, or a pharmaceutically acceptable, non-toxic salt of the compound wherein R is hydrogen; novel intermediates useful for preparing these compounds; processes for making the intermediates; and a stereoisomer of the compound of formula I wherein R is methyl and X is hydrogen and a process for making same.

Stabilization of 13,14-dihydro-15-keto-prostaglandins

Process for preparing prostaglandineea and certain derivatives

Compositions and methods for using ester derivatives of bimatoprost

FIELD: medicine; pharmaceuticals. SUBSTANCE: present invention relates to a compound with structural formula (I) or its pharmaceutically acceptable salt or enantiomer; where R 1 is hydrogen or R la C(O)-; R 2 is hydrogen or a R 2a C(O)-; R 3 is hydrogen or a R 3a C(O)-; R la , R 2a and R 3a independently are unsubstituted with C 1 -C 10 alkyl; and R 4 and R 5 independently represent hydrogen or unsubstituted with C 1 -C 10 alkyl; however provided that at least one of R 1 , R 2 and R 3 is not hydrogen. EFFECT: bimatoprost derivatives are effective for treatment of such diseases or disorders, as high intraocular pressure, hair loss, inflammatory diseases and disorders of skin. 10 cl, 6 tbl, 16 dwg, 18 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 599 249 C2 (51) МПК C07C 405/00 (2006.01) A61K 31/5575 (2006.01) A61P 17/14 (2006.01) A61Q 7/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ 2013141849/04, 13.02.2012 (24) Дата начала отсчета срока действия патента: 13.02.2012 Приоритет(ы): (30) Конвенционный приоритет: (43) Дата публикации заявки: 27.03.2015 Бюл. № 9 (45) Опубликовано: 10.10.2016 Бюл. № 28 (73) Патентообладатель(и): АЛЛЕРГАН, ИНК. (US) (85) Дата начала рассмотрения заявки PCT на национальной фазе: 16.09.2013 2 5 9 9 2 4 9 (56) Список документов, цитированных в отчете о поиске: WO 2009/136281 А1, 12.11.2009;WO 2007/037849 А2, 05.04.2007;WO 2008/094675 А2, 07.08.2008;WO 03/066008 А1, 14.08.2003. RU 2252212 С2, 20.05.2005. R U 14.02.2011 US 61/442,400 (72) Автор(ы): ВУДВАРД Дэвид Ф. (US), ВАНГ Дженни В. (US), ГАРСТ Майкл Е. (US), БЕРК Роберт М. (US), ГЭК Тодд С. (US), ПОЛОСО Неил Дж. (US) (86) Заявка PCT: 2 5 9 9 2 4 9 R U C 2 C 2 US 2012/024881 (13.02.2012) (87) Публикация заявки PCT: WO 2012/112451 (23.08.2012) Адрес для переписки: 191002, Санкт-Петербург а/я 5, ООО "Ляпунов и партнеры" (54) КОМПОЗИЦИИ И СПОСОБЫ ПРИМЕНЕНИЯ СЛОЖНОЭФИРНЫХ ПРОИЗВОДНЫХ БИМАТОПРОСТА (57) Реферат: Настоящее ...

METHOD OF SYNTHESIS OF 13,14-DIHYDRO-15(R)-17-PHENYL-18,19,20-TRINOR-PGF2α ESTER

Использование в качестве лекарственных препаратов широкого спектра действия. Сущность: продукт - сложные эфиры 13,14-дигидро-15(R)-17-фенил-18,19,20-тринор PGF2 α формулы I, который получают восстановлением оксогруппы в боковой цепи соответствующего лактона формулы VII, после чего проводят гидрирование полученного продукта VI до 3,3a,4,5,6,6a-гексагидро-2-оксо-4-[5'-фенил- 3'(R)-гидрокси-1'-пентил] -5-(4'-фенилбензоилокси)-2H-циклопента [b] фурана формулы V, после чего 2-оксогруппу соединения V восстанавливают до IV, после чего после ряда стадий: снятия защитной группы, размыкания цикла и алкилирования, получают продукт I. 3 с. и 7 з. п. ф-лы. с;660с ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) (51) МПК ВИ” 2 099 325 ' 13) Сл С 07С 405/00 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 93004874/04, 23.02.1993 (30) Приоритет: 24.06.1991 НЦ 2092/91 (46) Дата публикации: 20.12.1997 (56) Ссылки: ОЕ, патент, 2234709, кл. С 07 С 405/00, 1973. \!О, патент, 9002553, кл. С 07 С 1717100, 1990. (86) Заявка РСТ: НУ 92/00025 (19.06.92) (71) Заявитель: Каби Фармациа АБ ($Е), Хиноин Дьедьсер Еш Ведьесети Термекек Дьяра РТ (НЦ) (72) Изобретатель: Йожеф Иванич[НУ], Тибор Сабо[Ну], Иштван Хермец НЦ], Дюла Далмади[НУ], Йожефней Иванич[НУ], Габорней Ковач[НУ], Ресюл Бахрам[5Е] (73) Патентообладатель: Каби Фармациа АБ (3Е), Хиноин Дьедьсер Еш Ведьесети Термекек Дьяра РТ (НЦ) (54) СПОСОБ ПОЛУЧЕНИЯ ЭФИРОВ 13,14-ДИГИДРО-15(К)-17-ФЕНИЛ-18,19,20-ТРИНОР РСЕ2 а 13,14-ДИГИДРО-15(В)-17-ФЕНИЛ-18,19,20-ТРИНОР РСЕ2о СОЕДИНЕНИЯ. (57) Реферат: Использование в качестве лекарственных препаратов широкого спектра действия. Сущность: продукт - сложные эфиры 13,14-дигидро-15(К)-1 7-фенил-18,19,20-трино р РСЕ2“ формулы | который получают восстановлением оксогруппы в боковой цепи соответствующего лактона формулы УП, после чего проводят гидрирование полученного продукта М до 3,3а,4,5,6,ба-гексагидро-2-оксо-4-[5'-фенил- 3'(В)-гидрокси-1"-пентил] -5-(4 ...

Compositions and process

Method of producing crystal (4,5,6r,8r) methyl ether 9-oxo-11 alfa,15 alfa-dihydrooxy-16-phenoxy-17,18,19,20-tetranorprosta-4,5,13(e)-triene acid

Изобретение относитс  к производному класса простагландинов, в частности к получению кристаллического (4,5,6R,8R)метилового эфира-9-ок- со-1 1 d, 15сА.-дигидрокси-16-фенокси-17, 18,19,20-тетранорпроста-4,5,13(Е)- триеновой кислоты (ЭК), обладающего способностью ингибировать кислотную желудочную секрецию. Цель - создание более активных веществ указанного класса. Получение ЭК ведут охлаждением маслообразного (4,5,6К,8К)мети- лового эфира 9-ОКСО-1 Id-, 15с1-дигид- рокси-16-фенокси-17,18,19,20-тетра- норпроста-4,5,13(Е)-триеновой кислоты до температуры от -20 до 0&amp;deg;С. Кристаллический ЭК обладает большей стабильностью (96,2%) при хранении при 45&amp;deg;С в течение 4 недель и более эффективен как ингибитор кислотной желудочной секреции при дозе 0,5 мкг/кг, 2 табл. i СО со ел О5 СП СО см The invention relates to a prostaglandin class derivative, in particular to the preparation of crystalline (4,5,6R, 8R) methyl ester-9-ox-1-1 1 d, 15cA-dihydroxy-16-phenoxy-17, 18,19,20 - tetranorprost-4,5,13 (E) - trienoic acid (EC), which has the ability to inhibit acid gastric secretion. The goal is to create more active substances of the specified class. The preparation of EC is carried out by cooling oily (4,5,6K, 8K) methyl 9-OXO-1 Id-, 15c1-dihydroxy-16-phenoxy-17,18,19,20-tetra-norprost-4, 5.13 (E) -trienoic acid to a temperature of from -20 to 0 ° C. Crystalline EC has greater stability (96.2%) when stored at 45 ° C for 4 weeks and is more effective as an inhibitor of acidic gastric secretion at a dose of 0.5 µg / kg, 2 tab. i CO co. ate O5 JV CO cm

METHOD FOR OBTAINING PROSTANEOIC ACID OR ITS ETHER AND SALTS

Prostaglandin analogs and their fat emulsions

The method of obtaining optically active compounds of the prostaglandin series

Prostacylcin and preparation thereof

(57)【要約】本公報は電子出願前の出願データであるた め要約のデータは記録されません。

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。

Method of producing (4,5,6r,8r) methyl ether of 9-oxo-11alpha,15alpha-dihydroxy-16-phenoxy-17,18,19,20-tetranor-prosta-4,5,13 (e)-trienic acid

This invention relates to a process for making a compound of formula I in the form of a stereoisomer or mixture thereof, wherein R is hydrogen, lower alkyl; X is hydrogen, halo, trifluoromethyl, lower alkyl or lower alkoxy, and the wavy lines represent the a or β configuration with the proviso that when one wavy line is α the other is β, or a pharmaceutically acceptable, non-toxic salt of the compound wherein R is hydrogen; novel intermediates useful for preparing these compounds; processes for making the intermediates; and a stereoisomer of the compound of formula I wherein R is methyl and X is hydrogen and a process for making same.

Novel process

本发明涉及制备用作药物的前列腺素化合物的新方法。

Preparation of prostaglandins E1, E2 and their analogs using furyl copper reagent

(57)【要約】 プロスタグランジンＥ 1 、Ｅ 2 およびこれらの誘導体を合成する方法を提供する。この方法は、２−フリルリチウム、シアン化銅、低級アルキルリチウム試薬、および（Ｅ）−アルケニルスタナンまたはハロゲン化物のいずれかをシクロペンテノン（II） （式中、Ａ、Ｒ 6 およびＲ 7 は明細書で定義した通りである）と混合する「ワンポット」法である。この反応は所望のプロスタグランジン生成物を８０％以上の収率で生成する。

Method of preparing optically active 11-desoxy-16-aryl-omega-tetranorprostaglandines or their racemates or their salts

11-Desoxy-16-aryl- omega -tetranorprostaglandins and various intermediates and processes employed in their preparation are disclosed. The novel prostaglandins of this invention have been found to have activity profiles comparable to the parent prostaglandins but they exhibit a greater tissue specificity of action.

New acetyleneeprostaglandin derivatives* process for manufacture thereof and prostaglandinnworking agents containing said compounds

Method of preparing derivatives of prostaglandine

Ocular hypotensive agents

The present invention relates to ocular hypotensive agents which contains 13,14-dihydro-15-keto-prostagandins, which shows no transient ocular hypertensive response that PGs usually show.

Ocular hypotensive agents

The present invention relates to ocular hypotensive agents which contains 13,14-dihydro-15-keto-prostagrandins, which shows no transient ocular hypertensive response that PGs usually show.

Ocular hypotensive agents

The present invention relates to ocular hypotensive agents which contains 13,14-dihydro-15-keto-prostagrandins, which shows no transient ocular hypertensive response that PGs usually show.

Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension

The invention relates to ophthalmological compositions for topical treatment of glaucoma or ocular hypertension comprising an effective intraocular pressure reducing amount of a prostaglandin derivative of PGA, PGB, PGD, PGE or PGF, in which the omega chain contains a ring structure, in an ophthalmologically compatible carrier. The invention further relates to the preparation of said compositions and their use for treatment of glaucoma or ocular hypertension.

Cyclopentane heptenylsulfinylalkyl and heptanylsulfinylalkyl-2-aliphatic or aryl aliphatic derivatives

The present invention relates to cyclopentane heptenylsulfinylalkyl and heptanylsulfinylalkyl-2-aliphatic or arylaliphatic derivatives. In particular, heptenylsulfinylmethyl and heptanylsulfinylmethyl 2-aliphatic or arylaliphatic derivatives, substituted at the 3 and/or 5 position of the cyclopentane ring with radicals selected from the group consisting of hydroxy, alkylcarboxy and mixtures thereof, are disclosed. These compounds are useful as ocular hypotensives.

Cyclopentane heptenylnitro and heptanylnitro-2-aliphatic or aryl aliphatic derivatives and homologues

The present invention relates to cyclopentane heptenylnitro and heptanylnitro-2-aliphatic or arylaliphatic derivatives. In particular, heptenylnitrate and heptanylnitrate 2-aliphatic or arylaliphatic derivatives, substituted at the 3 and/or 5 position of the cyclopentane ring with radicals selected from the group consisting of hydroxy, alkylcarboxy and mixtures thereof, are disclosed. These compounds are useful as ocular hypotensives.

Azido derivatives of cyclopentane heptanoic or heptenoic acid

The present invention provides novel 2-aliphatic or arylaliphatic cyclopentane heptanoic and heptenoic acid derivatives including at least one azido substituent. In particular 2-aliphatic or arylaliphatic cyclopentane heptenyloic and cyclopentane heptanoic acids and esters thereof, substituted at the 3 and/or 5 position of the cyclopentane ring with radicals selected from the group consisting of hydroxy, azido and mixtures thereof, are disclosed. These azido compounds are useful as ocular hypotensives and are intermediates for the preparation of other compounds useful as ocular hypotensives.

7-(5-substituted cyclopentyl) and (5-substituted cyclopentenyl) heptyl alcohols, heptylamines and heptanoic acid amides, and method of lowering intraocular pressure in the eye of a mammal by administration of these novel compounds

Compounds of the formula ##STR1## where the dotted line represents a bond or the absence of a bond, the wavy lines represent bonds which are either in cis or trans configuration; R 1 represents H, or CO--R 2 where R 2 is lower alkyl of 1 to 6 carbons, carbocyclic aryl or heterocyclic aryl; or carbocyclic aryl or heteroaryl substituted lower alkyl group; X represents CO--NR 3 R 4 , CH 2 OH, CH 2 OR 5 , CH 2 O--COR 6 , and CH 2 --NR 3 R 4 , where R 3 and R 4 independently are H or lower alkyl, R 5 is lower alkyl of 1 to 6 carbons, and R 6 is lower alkyl of 1 to 6 carbons, carbocyclic aryl or heterocyclic aryl; or carbocyclic aryl or heteroaryl substituted lower alkyl group, and n is an integer between 0 and 8 are capable of lowering intraocular pressure in the eye of a mammal.

1,11-diesters of prostaglandin-F2α having a polar ester group at C-1

Compounds of the formula ##STR1## where the hatched lines indicate alpha (α) configuration, a solid triangle is used to indicate beta (β) configuration, lines on both sides of a double bond indicate cis (Z) configuration, and lines on opposite sides of the double bond indicate trans (E) configuration; R 1 is alkyl of 1-10 carbons, C 1 -C 10 alkylphenyl, phenyl-C 1 -C 10 alkyl, or alkenyl of 2 to 10 carbons and having 1 to 3 double bonds; R 2 is Z--OR 3 , Z--OCOR 3 , Z--OCONHR 3 , Z--OCOOR 3 , Z--NR 4 R 5 , Z--NR 4 COR 3 , Z--NR 4 SO 2 R 3 , Z--COOR 3 , Z--CONR 4 R 5 , Z--CHO; Z is (CH 2 ) n where n is 1-6, or Z is an alkenyl group having 2 to 6 carbons and 1 or 2 double bonds, R 3 is H, alkyl of 1-6 carbons, alkenyl of 2 to 6 carbons or phenyl, R 4 and R 5 independently are H or alkyl of 1 to 6 carbons, have ocular hypotensive activity.

Cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents

The present invention provides cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compounds, which may be substituted in the 1-position with amino, amido, ether or ester groups, e.g., a 1-OH cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compound. The cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma. Moreover, the cyclopentane heptanoic, 2-(cycloalkyl or arylalkyl) compounds of this invention are smooth muscle relaxants with broad application in systemic hypertensive and pulmonary diseases; smooth muscle relaxants with application in gastrointestinal disease, reproduction, fertility, incontinence, shock, etc.

Use of certain prostaglandin analogues to treat glaucoma and ocular hypertension

Certain prostaglandin analogues are useful in the treatment of glaucoma and ocular hypertension. Also disclosed are ophthalmic, pharmaceutical compositions comprising such prostaglandin analogues.

Fluorinated prostaglandin derivatives and medicines

A fluorine-containing prostaglandin derivative of the formula (1) (or a salt thereof) and a medicine containing it, particularly, a preventive or therapeutic medicine for an eye disease: wherein A is a vinylene group, an ethylene group, an ethynylene group or the like, R 1 is an aryloxyalkyl group, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aralkyl group or the like, R 2 and R 3 are hydrogen atoms, acyl groups or the like, Z is OR 4 , -NHCOR 5 , -NHSO 2 R 6 , -SR 7 , (wherein R 4 , R 5 , R 6 and R 7 are hydrogen atoms, alkyl groups or the like) or the like, and a dual line consisting of solid and broken lines is a single bond, a cis-double bond or a trans-double bond. The medicine is an excellent medicine for an eye disease which has a high pharmacological action and little side effect.

Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension

The invention relates to ophthalmological compositions for topical treatment of glaucoma or ocular hypertension comprising an effective intraocular pressure reducing amount of a prostaglandin derivative of PGA, PGB, PGD, PGE or PGF, in which the omega chain contains a ring structure, in an ophthalmologically compatible carrier. The invention further relates to the preparation of said compositions and their use for treatment of glaucoma or ocular hypertension.

Use of cloprostenol and fluprostenol analogues to treat glaucoma and ocular hypertension

Disclosed is the use of cloprostenol and fluprostenol analogues in combination with carbonic anhydrase inhibitors for the treatment of glaucoma and ocular hypertension and ophthalmic compositions therefor.

Ocular hypotensive agents

The present invention relates to an ocular hypotensive composition and a composition for treatment of glaucoma which comprising an amount of 20-substituted-PGs or 20-substituted 15-keto-PGs effective as an ocular hypotensive agent; these compounds exhibit no or little side effect such as transient ocular hypertensive response, hyperemia of conjunctiva or of iris, dacryops, lema, closed eye and the like. The present invention relates to ocular hypotensive agents which contains 13,14-dihydro-15-keto-prostagrandins, which shows no transient ocular hypertensive response that PGs usually show.

11-deoxy-16-fluoro-PGF2α analogs as FP receptor antagonists

Methods and compositions for the antagonism of FP receptor-mediated biological responses are disclosed.

Process for purification of latanoprost, synthetic analogue of prostaglandin PGF 2alfa

The present invention refers to a process for the purification of Latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinor-PGF 2α -isopropyl ester), a synthetic analogue of the natural prostaglandin PGF 2α used for the treatment of eye pressure pathologies.

Process for the purification of latanoprost by HPLC

Disclosed are processes for the synthesis and purification of prostaglandins and analogues thereof, especially analogues of PGF 2α .

Process for the synthesis of prostaglandins and intermediates thereof

A process is disclosed for the preparation of prostaglandins of the PGF 2α -series, in particular Latanoprost, Bimatoprost and Travoprost, which are active in the treatment of ocular hypertensive conditions and glaucoma. The invention also relates to novel intermediates involved in the synthesis of these prostaglandin-PGF 2α derivatives.

Process for producing 13,14-dihydro-15(r)-17-phenyl-18,19,20-trinor-pgf2alfa-isopropylester

Use of certain 9-halo-13,14-dihydroprostaglandins to treat glaucoma and ocular hypertension

9-Halo-13,14-dihydroprostaglandins are useful in the treatment of glaucoma and ocular hypertension. Also disclosed are ophthalmic, pharmaceutical compositions comprising such prostaglandins.

Use of certain 9-haloprostaglandins to treat glaucoma and ocular hypertension

9-Haloprostaglandins are useful in the treatment of glaucoma and ocular hypertension. Also disclosed are ophthalmic, pharmaceutical compositions comprising such prostaglandins.

Thioprostaglandins and -prostaglandin-like compounds and therapeutic uses thereof

Thiosubstituted prostaglandin derivatives and related compounds having the general structure <IMAGE> useful as intraocular pressure reducing agents; pharmaceutical compositions containing such compounds; and methods of treatment using such compositions are disclosed.