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 ...

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.

PROCESS FOR PREPARATION OF PROSTAGLANDIN F2 ALPHA ANALOGUES

A convergent synthesis of the prostaglandin F analogues, travoprost and bimatoprost, was developed employing Julia-Lythgoe olefination of the structurally advanced phenylsulfone with an enantiomerically pure aldehyde ω-chain synthon. The novel convergent strategy allows the synthesis of a whole series of prostaglandin analogues of high purity from a common and structurally advanced prostaglandin intermediate. 2. The process of claim 1 , wherein the α-sulfonyl carbanion of the formula (II) is generated by an alkali metal amide claim 1 , selected from the group comprising lithium N claim 1 ,N-bis(trimethylsilyl)amide claim 1 , sodium N claim 1 ,N-bis(trimethylsilyl)amide claim 1 , lithium diisopropylamide and sodium diisopropylamide.3. The process of claim 2 , wherein the α-sulfonyl carbanion of the formula (II) is generated by lithium diisopropylamide.4. The process of claim 1 , wherein the desulfonation of the β-hydroxysulfones of the formula (V) is performed by using sodium amalgam in the presence of NaHPObuffer.5. The process of claim 1 , wherein the R-Rgroups are removed by reacting the compound of the formula (VI) with hydrogen fluoride or tetra-n-butylammonium fluoride.6. The process of claim 1 , wherein the Rgroup of the compound of the formula (VII) is hydrolyzed in the presence of an aqueous solution of citric acid.7. The process of claim 1 , wherein the Rgroup of the compound of the formula (VIII) is hydrolyzed with an alkali metal hydroxide claim 1 , preferably with lithium hydroxide.8. The process of claim 1 , wherein the compound of formula (VIII) is alkylated with a C-alkyl halogen in the presence of a base claim 1 , preferably 1 claim 1 ,8-diazabicyclo[5.4.0]undec-7-en (DBU).9. The process of claim 1 , wherein the prostamid of the formula (IC) claim 1 , which is isopropyl ester of 16-[3-(trifluoromethoxy)phenoxy]-17 claim 1 ,18 claim 1 ,19 claim 1 ,20-tetranor-prostaglandin F (travoprost) claim 1 , is obtained in a diastereoisomeric excess greater than ...

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 A NITRIC OXIDE DONATING PROSTAGLANDIN ANALOGUE

The present invention relates to a process for preparing the hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I). 2. The process according to wherein step 1) is carried out at a temperature ranging from 0° C. to room temperature in an aprotic organic solvent.3. The process according to wherein the aprotic organic solvent is methyltertbutyl ether.4. The process according to wherein in step 1) the molar ratio of compound (II) to 6-(nitrooxy)hexanoyl chloride (IVa) is from 1:1.4 to 1:1.6 and the molar ratio of compound (II) to 4-dimethylaminopyridine preferably is from 1:2.0 to 1:2.4.5. The process according to wherein in step 4) the inorganic base is potassium hydroxide.6. The process according to wherein step 4) is carried out in a solvent selected from methanol claim 1 , ethanol or isopropanol.7. The process according to wherein the solvent is methanol.8. The process according to wherein step 5) is carried out in dichloromethane.9. The process according to wherein in step 6) the concentration of the formic acid in water (HO+HCOOH) is 0.1% w/w.10. The process according to wherein in step 6) the chromatographic fractions containing the compound (Vila) are extracted with CHCl claim 1 , dried and the solvent is evaporated.11. The process according to wherein step 7) is carried out in dichloromethane and the chlorinating agent is oxalyl chloride.12. The process according to wherein the 6-(nitrooxy)hexanoyl chloride obtained in step 7) is used without further purification.15. A pharmaceutical formulation containing hexanoic acid claim 1 , 6-(nitrooxy)- claim 1 , (1S claim 1 ,2E)-3-[(1R claim 1 ,2R claim 1 ,3S claim 1 ,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3 claim 1 ,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I) and at least a pharmaceutically acceptable excipient claim 1 , wherein hexanoic acid claim 1 , 6-( ...

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 ...

NOVEL PROSTAGLANDIN DERIVATIVE

The present invention relates to a novel prostaglandin derivative having an alkynyl group on ω-chain, particularly, a novel prostaglandin derivative having a double bond at the 2-position and an alkynyl group on the ω-chain and a medicament containing the compound as an active ingredient. 119-. (canceled)21: The compound or pharmaceutically acceptable salt of claim 20 , wherein Y is CH.22: The compound or pharmaceutically acceptable salt of claim 20 , wherein Ris —CH═CZ(COX).23: The compound or pharmaceutically acceptable salt of claim 20 , wherein Ris —CH—CZZ(COX).24: The compound or pharmaceutically acceptable salt of claim 20 , wherein n is 1.25: The compound or pharmaceutically acceptable salt of claim 20 , wherein A-B is a carbon-carbon double bond.26: The compound or pharmaceutically acceptable salt of claim 20 , wherein Ris a hydrogen atom and Ris an alkyl group having 1 to 3 carbon atoms.27: The compound or pharmaceutically acceptable salt of claim 20 , wherein Ris a cycloalkyl group having 3 to 5 carbon atoms.28: The compound or pharmaceutically acceptable salt of claim 20 , wherein X is OR.29: A cyclodextrin clathrate compound claim 20 , comprising the compound or pharmaceutically acceptable salt of .30: A medicament claim 20 , comprising the compound or pharmaceutically acceptable salt of .31: A method of treating a blood flow disorder claim 30 , the method comprising administering the medicament of claim 30 , as a prophylactic or therapeutic agent claim 30 , to a subject in need thereof.32: The method of claim 31 , wherein the blood flow disorder is a blood flow disorder of a nerve.33: The method of claim 32 , wherein the blood flow disorder of the nerve is a blood flow disorder associated with spinal canal stenosis.34: The method of claim 31 , wherein the blood flow disorder is a blood flow disorder of a peripheral artery claim 31 , skin or brain.35: The method of claim 34 , wherein the blood flow disorder is a blood flow disorder of a peripheral artery ...

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 ...

NOVEL PROSTAMIDES FOR THE TREATMENT OF GLAUCOMA AND RELATED DISEASES

Disclosed herein are compositions comprising an amide related to a prostaglandin and a biogenic amine. Other aspects relate to certain chemical compounds, pharmaceutical compositions, and methods of treating glaucoma. 110.-. (canceled)1420.-. (canceled) This application is continuation of U.S. application Ser. No. 14/137,000, filed Dec. 20, 2013, which is a continuation application of U.S. application Ser. No. 11/573,692, filed Jun. 12, 2007, now U.S. Pat. No. 8,648,213, issued Feb. 11, 2014, which is a national stage application under 35 U.S.C. §371 of PCT application PCT/US2005/035748, filed on Oct. 4, 2005, which claims the benefit of provisional application No. 60/616,780, filed on Oct. 6, 2004, the disclosures of which are hereby incorporated by reference in their entireties and serve as the basis of a priority and/or benefit claim for the present application.Field of the InventionThe present invention relates to novel amides related to prostaglandins as potent ocular hypotensives that are particularly suited for the management of glaucoma and related diseases.Description of Related ArtOcular hypotensive agents are useful in the treatment of a number of various ocular hypertensive conditions, such as post-surgical and post-laser trabeculectomy ocular hypertensive episodes, glaucoma, and as presurgical adjuncts.Glaucoma is a disease of the eye characterized by increased intraocular pressure. On the basis of its etiology, glaucoma has been classified as primary or secondary. For example, primary glaucoma in adults (congenital glaucoma) may be either open-angle or acute or chronic angle-closure. Secondary glaucoma results from pre-existing ocular diseases such as uveitis, intraocular tumor or an enlarged cataract.The underlying causes of primary glaucoma are not yet known. The increased intraocular tension is due to the obstruction of aqueous humor outflow. In chronic open-angle glaucoma, the anterior chamber and its anatomic structures appear normal, but drainage ...

PROSTAGLANDIN F2 ALPHA DERIVATIVES FOR DECREASING INTRAOCULAR PRESSURE

The invention relates to clinical chemistry, in particular, to new biologically active compounds amide derivatives of prostaglandin F2α. These compounds have low cytotoxicity and are capable of stimulating formation of endogenous nitrogen oxide in mammal cells. Synthesis of such compounds promotes expansion of nomenclature of biologically active derivatives of prostaglandin F2α capable of reducing intraocular pressure. 2. Compounds of claim 1 , wherein salt with pharmaceutically acceptable cations is produced in the presence of free carboxyl group.3. Compounds of claim 1 , capable of reducing intraocular pressure. The invention relates to clinical chemistry, in particular, to new biologically active compounds—amide derivatives of prostaglandin F.Prostaglandins are the family of multifunctional biologically active substances synthesized in organism from arachidonic acid by means of cyclooxygenase (COX). These oxidized fatty acids are autocrine and paracrine lipid mediators, and they are characterized by broad-spectrum of physiological activity, for example, combination of dilatator (bronchi smooth muscles), constrictor (gastrointestinal tract smooth muscles), antiaggregatory (platelets), hypo- or hypertensive activities [Nicolau A. In: Bioactive Lipids (Eds. Nicolau A., Kokotos J.) II Bridgewater: Oily Press, 2004. —197 p]. Prostaglandin Fis formed in organism as a result of arachidonic acid oxidative metabolism caused by cyclooxygenase at the first stage and by reductase—at the second stage of biosynthesis [Smith W. L., Marnett L. J., DeWitt D. L. Prostaglandin and thromboxane biosynthesis//Pharmacology & Therapeutics. 1991, V. 49(3), P. 153-179]. It is G-protein coupled receptor FP endogenous ligand, which activation results in intracellular calcium mobilization [Toh H, Ichikawa A, Narumiya S. Molecular evolution of receptors for eicosanoids.//FEBS Lett. 1995, V. 361, P. 17-21].Prostaglandins are used for treatment of hypertension, thrombosis, asthma, gastric and ...

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 ...

Synthesis of prostanoids

The presently disclosed subject matter provides a method of synthesizing prostaglandins and prostaglandin analogs comprising the ring closing metathesis of compounds of Formula (I). Also provided are novel compounds of Formula (I) and Formula (II). In addition to their use as synthetic intermediates in the presently disclosed methods, compounds of Formula (II) can be used as prostaglandin and/or prostaglandin analog prodrugs.

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

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。

3-hydroxybutyric acid polymers

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。

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.

Methods and intermediates for producing isomer-free prostaglandins

Process for producing intermediate for 13,14-didehydroprostaglandin e

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.

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 ...

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 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.

Method of producing derivatives of prostacycline or salts thereof

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.

Cyclopentane(ene) heptenoic or heptanoic acids and derivatives thereof useful as therapeutic agents

The invention relates to 7-[5-hydroxy-2-(hydroxyhydrocarbyl or heteroatom-substituted hydroxy hydrocarbyl)-3-hydroxycyclopentyl(enyl)] heptanoic or heptenoic acids and derivatives of said acids, wherein one or more of said hydroxy groups are replaced by an ether group. The compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma.

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.

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.

C 16 unsaturated FP-selective prostaglandins analogs

Compounds having the general structure: which are useful for the treatment of a variety of diseases and conditions, such as bone disorders.

Prostaglandins and analogues as agents for lowering intraocular pressure

The present invention relates to cyclopentane heptenoic acid-5-cis-2-(3α-hydroxy or lower alkyloxy-5-thienylpentyl)-3, 5-dihydroxy, [1α, 2β, 3α, 5α] compounds, lower alkyl, hydroxyl lower alkyl and indole lower alkyl amides and esters thereof as potent ocular hypotensives that are particularly suited for the management of glaucoma.

Positively charged water-soluble prodrugs of prostaglandins and related compounds with very high skin penetration rates

The novel positively charged pro-drugs of prostaglandins, prostacyclins and related compounds in the general formula (2) 'Structure 2' were designed and synthesized. The compounds of the general formula (2) 'Structure 2' indicated above can be prepared from protected prostaglandins, prostacyclins, and related compounds, by reaction with suitable alcohols, thiols, or amines and coupling reagents, such as N, N'-Dicyclohexylcarbodiimide, N, N'-Diisopropylcarbodiimide, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, Benzotriazol-1-yl-oxy-tris (dimethylamino)phosphonium hexafluorophosphate, et al. The positively charged amino groups of these pro-drugs not only largely increases the solubility of the drugs in water, but also bonds to the negative charge on the phosphate head group of membranes and pushes the pro-drug into the cytosol. The results suggest that the pro-drugs diffuse through human skin ˆ¼1000 times faster than do prostaglandins, prostacyclins, and related compounds. In plasma, more than 90% of these pro-drugs can change back to the parent drugs in a few minutes. The prodrugs can be used medicinally in treating any prostaglandins, prostacyclins, and related compounds-treatable conditions in humans or animals. The prodrugs can be administered transdermally for any kind of medical treatments and avoid most of the side effects of prostaglandins, prostacyclins, and related compounds. Controlled transdermal administration systems of the prodrug enable prostaglandins, prostacyclins, and related compounds to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of prostaglandins, prostacyclins, and related compounds. Another great benefit of transdermal administration of these pro-drugs is that administering medication, especially to children, will be much easier.

Amino acid salts of prostaglandins

The present invention is directed to novel amino acid prostaglandin salts and methods of making and using them.

Composition, method and kit for enhancing hair

Compositions for application and methods of application of a composition to modify hair. In one embodiment, a composition includes a compound (molecule) represented by: wherein A and B are individually selected from a hydrogen, a hydroxyl group and a halogen, with the proviso that when one of A and B is a hydroxyl group, the other of A and B is a hydrogen and when one of A and B is a halogen, the other of A and B is a halogen or a hydrogen; wherein Z is, for example, an aryl moiety; and wherein X 1 and X 2 are, for example, individually selected from a hydrogen and an alkyl moiety, wherein R 1 and R 2 are individually selected from an oxo, a hydroxyl or an ester group; wherein y is 0 or 1, x is 0 or 1 and x and y are not both 1, or a salt.

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.

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.

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 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.

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 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.

Cyclopentane(ene) heptanoic or cyclopentane(ene) heptenoic acid, 2-hydrocarbyl sulfonamidomethyl and derivatives thereof as therapeutic agents

The present invention relates to cyclopentane heptanoic or cyclopentane heptenoic acid, 2-hydrocarbyl sulfonamidomethyl, and derivatives thereof, useful as therapeutic agents. In particular, the therapeutic agents of this invention are useful as ocular hypotensives.

Cyclopentane(ene) heptenoic or heptanoic acids and derivatives thereof useful as therapeutic agents

The invention relates to 7- 5-hydroxy-2-(hydroxyhydrocarbyl or heteroatom-substituted hydroxy hydrocarbyl)-3-hydroxycyclopentyl(enyl)! heptanoic or heptenoic acids and derivatives of said acids, wherein one or more of said hydroxy groups are replaced by an ether group. The compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma.

Cyclopentane (ene) heptenoic or heptanoic acids and derivatives thereof useful as therapeutic agents

The invention relates to 7-[5-hydroxy-2-(hydroxyhydrocarbyl or heteroatom-substituted hydroxy hydrocarbyl)-3-hydroxycyclopentyl(enyl)] heptanoic or heptenoic acids and derivatives of said acids, wherein one or more of said hydroxy groups are replaced by an ether group. The compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma.

Cyclopentane(ENE)heptenoic or heptanoic acids and derivatives thereof useful as therapeutic agents

The invention relates to 7-[5-hydroxy-2-(hydroxyhydrocarbyl or heteroatom-substituted hydroxy hydrocarbyl)-3-hydroxy-cyclopentyl(enyl)] heptanoic or heptenoic acids and derivatives of said acids, wherein one or more of said hydroxy groups are replaced by an ether group. The compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma.

Cyclopentane(ENE) heptenoic or heptanoic acids and derivatives thereof useful as therapeutic agents

The invention relates to 7-[5-hydroxy-2-(hydroxyhydrocarbyl or heteroatom-substituted hydroxy hydrocarbyl)-3-hydroxy-cyclopentyl(enyl)] heptanoic or heptenoic acids and derivatives of said acids, wherein one or more of said hydroxy groups are replaced by an ether group. The compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma.

Cyclopentane(ene) heptenoic or heptanoic acids and derivatives thereof useful as therapeutic agents

The invention relates to 7-[5-hydroxy-2-(hydroxyhydrocarbyl or heteroatom-substituted hydroxy hydrocarbyl)-3-hydroxycyclopentyl(enyl)] heptanoic or heptenoic acids and derivatives of said acids, wherein one or more of said hydroxy groups are replaced by an ether group. The compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma.

Cyclopentane heptenoic or heptanoic acids and derivatives thereof useful as therapeutic agents

The invention relates to 7-[5-hydroxy-2-(hydroxyhydrocarbyl or heteroatom-substituted hydroxy hydrocarbyl)-3-hydroxy-cyclopentyl(enyl)] heptanoic or heptenoic acids and derivatives of said acids, wherein one or more of said hydroxy groups are replaced by an ether group. The compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma.

Fluorinated prostaglandin derivatives and medicines

Fluorinated prostaglandin derivatives represented by general formula (1) or salts thereof; and medicines containing the same as the active ingredient, particularly ones to be used for preventing or treating eye diseases. In said formula A represents vinylene, ethylene, ethynylene, etc.; R1 represents aryloxyalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, etc.; R?2 and R3¿ represent each hydrogen, acyl, etc.; Z represents -OR4, -NHCOR5, -NHSO¿2?R?6, -SR7¿ (wherein R?4, R5, R6 and R7¿ represent each hydrogen, alkyl, etc.); and the combination of the solid line with the broken line represents a single bond, a cis double bond or a trans double bond. The medicines are excellent as a medicine for eye diseases with high pharmacological effects and low side effects.

Prostaglandin derivatives

7-[3,5-dihydroxy-2-(3-hydroxy-5-phenyl-pent-1-enyl)-cyclopentyl]-n-ethyl-hept-5-enamide (bimatoprost) in crystalline form ii, methods for preparation, and methods for use thereof

本发明提供了一种比马前列素的新晶型，称为晶型II。该新晶型是迄今为止比马前列素的最稳定形式。而且，已经发现比马前列素的晶型II可以容易地由晶型I制备。

Method of producing 11-desoxy-16-aryloxy-w-tetranorprostaglandines or salts thereof

Prostaglandin analogs and their uses

本発明は、プロスタグランジンアナログまたはその薬学的に許容可能な塩を有効成分として含む、Ｎｕｒｒ１に関連する疾患、障害または状態の予防または治療用薬学的組成物であって、前記化合物はＮｕｒｒ１を誘導するにあたって卓越した効果を有し、したがって、Ｎｕｒｒ１に関連する疾患、障害または状態、特に癌、関節リウマチのような自己免疫疾患、統合失調症、うつ病および、例えばアルツハイマー病やパーキンソン病のような神経変性疾患に有用である。

7-[3,5-dihydroxy-2- (3-hydroxy-5-phenyl-pent-1-enyl)- cyclopentyl]-N-ethyl-hept-5-enamide (bimatoprost) in crystalline form II, methods for preparation, and methods for use thereof

The present invention provides a new crystalline form of bimatoprost, designated as crystalline form II. This new crystalline form is the most stable form known to date of bimatoprost. Moreover, it has been found that bimatoprost crystalline form II is readily prepared from crystalline form I.

Method of preparing prostaglandin or their c15 or c9 andt c15 epimers

1456513 Cyclopenta[b]furan derivatives PFIZER Inc 7 Nov 1973 [8 Nov 1972] 23950/76 Divided out of 1456512 Heading C2C The invention comprises cyclopenta[b]furan derivatives of the Formulµ III, IV and V wherein Ar is 3,4-dimethoxyphenyl, 3,4-methylenedioxyphenyl, 3,4,5 - trimethoxyphenyl, 1- or 2-naphthyl or phenyl optionally monosubstituted by halogen, trifluoromethyl, phenyl C 1-6 alkyl or C 1-6 alkoxy; m and n each are 0 to 3 with the proviso that the sum of n and m does not exceed 3; Q is p-biphenylylcarbonyl; Z is a single or trans-double bond; R is H or C 1-6 alkyl; Q<SP>1</SP> is H or p-phenylylcarbonyl; and Y is oxo, with the proviso in compounds of Formula IV that when R and Q<SP>1</SP> are both H, Z is a trans double bond, n and m are 0, Ar is 3,4-methylenedioxyphenyl, 3,4,5 - trimethoxyphenyl, 1- or 2-naphthyl or biphenylyl; and with the proviso in compound of Formula V that when R is H Z is a trans double bond, m and n are 0, Ar is as defined immediately above; and their preparation. The compounds are obtained by known methods used to obtain analogous compounds.

Derivatives of 2,3,4-trinor-1,5-inter-m-phenylenprostacycline having cytoprotective properties

New 2,3,4-trinor-1,5-inter-m-phenylene-PGI2 derivatives (wherein A stands for carboxy, cyano, tetrazolyl or -COOR<3> or -CONR<1>R<2>; R<3> is C1-4 alkyl or an equivalent of a pharmacologically acceptable cation: R<1> and R<2> each stands for hydrogen, phenyl; C1-5 alkyl, optionally substituted by carboxy, hydroxy, phenyl or C2-5 alkoxycarbonyl; or C1-4 alkyl-sulfonyl; or R<1> and R<2> together form an alpha , omega -alkylene chain containing 3-6 carbon atoms; B stands for oxygen or methylene; Y is optionally bromo-substituted vinylene or a -C=C- group: R<4> stands for hydrogen or tetrahydro-pyran-2-yl; R<5> represents an alkyl group containing 5-9 carbon atoms, which can be optionally interrupted by one or more oxygen atom(s) or -CH=CH- or -C=C- group(s) and/or optionally substituted by halogen; or a phenoxymethyl group optionally substituted by halogen or trifluoromethyl; or an alkenyloxymethyl group containing 3-5 carbon atoms; R<6> is hydrogen or C1-4 alkyl; R<7> stands for hydrogen, halogen, cyano, C1-4 alkyl or C1-4 alkoxy; R<8> is hydrogen, halogen, cyano, nitro, hydroxy or C2-5 alkanoylamido; with the proviso that if R<5> stands for an alkyl group containing 5-9 carbon atoms which is unsubstituted or not interrupted by an oxygen atom or a -CH=CH- or -C=C- group; or a phenoxymethyl group optionally substituted by halogen or trifluoromethyl, then either R<7> or R<8> is other than hydrogen, or A is other than carboxy or -COOR<3>) and a process for the preparation thereof. The new compounds of the general Formula I exhibit prolonged cytoprotecting and aggregation inhibiting and a low hypotensive effect and are superior to prostacycline in the prolonged duration of their activity.

Process for producing phenoxyprostatrienoic acid derivative

Prostaglandin f2alpha derivatives for reducing intraocular pressure

Изобретение относится к медицинской химии, конкретно к соединению указанной ниже общей формулы или его фармацевтически приемлемым солям, которые обладают способностью снижать внутриглазное давление, при этом имеют низкую цитотоксичность и способны стимулировать образование эндогенного оксида азота в клетках. В указанной общей формуле R 1 =Н, , где n=1-4, или R 1 =Н, , где R 3 =СНМе 2 , HNCH 2 CH 2 ONO 2 , OCH 2 CH 2 ONO 2 , OCH(CH 2 ONO 2 ) 2 , или R 1 =H, , где R 4 =Н, СНМе 2 ; R 5 =Н, ОН; R 6 =Н, ОН, ONO 2 , СН 2 ОН, CH 2 ONO 2 , или R 1 =Н, R 2 =CH 2 CH 2 OC(O)NHCH 2 CH 2 ONO 2 , или R 1 =Н, R 2 =CH 2 CH 2 OC(O)OCH(CH 2 ONO 2 ) 2 , или , где n=1, 2. 2 з.п. ф-лы, 3 табл., 1 ил., 7 пр. РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 718 744 C2 (51) МПК C07C 405/00 (2006.01) C07D 207/08 (2006.01) A61K 31/5575 (2006.01) A61P 27/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07C 405/00 (2019.02); C07D 207/08 (2019.02); A61K 31/5575 (2019.02); A61P 27/00 (2019.02) (21)(22) Заявка: 2018118157, 17.05.2018 (24) Дата начала отсчета срока действия патента: Дата регистрации: 14.04.2020 (43) Дата публикации заявки: 18.11.2019 Бюл. № 32 (45) Опубликовано: 14.04.2020 Бюл. № 11 (56) Список документов, цитированных в отчете о поиске: WO 01/58866 A2, 16.08.2001. JP 4969636, 05.07.1974. US 2011/0092590 A1, 21.04.2011. RU 2474426 C1, 10.02.2013. C 2 C 2 Адрес для переписки: 121205, Москва, территория инновационного центра "Сколково", ул. Нобеля, 5, оф. 125, ООО "ЦИС "Сколково", Котлову Дмитрию Владимировичу 2 7 1 8 7 4 4 (73) Патентообладатель(и): Общество с ограниченной ответственностью "Гурус БиоФарм" (RU) Приоритет(ы): (22) Дата подачи заявки: 17.05.2018 2 7 1 8 7 4 4 R U 17.05.2018 (72) Автор(ы): Безуглов Владимир Виленович (RU), Серков Игорь Викторович (RU), Любимов Игорь Иванович (RU), Грецкая Наталья Михайловна (RU) (54) Производные простагландина F 2 альфа для снижения внутриглазного давления (57) Реферат: Изобретение ...

Method of producing dimethyl-2-oxo-3-phenoxypropyl phosphate

FLUORED PROSTAGLAND DERIVATIVES AND MEDICINES

OXIMES PREPARATION PROCESS

AMINOCYCLOPENTANE-ALKENOIC ACIDS AND THEIR ESTERS, THEIR PREPARATION AND THEIR USE IN PHARMACEUTICAL COMPOSITIONS

Positively charged water-soluble prodrugs of prostaglandins and related compounds with very high skin penetration rates

The novel positively charged pro-drugs of prostaglandins, prostacyclins and related compounds in the general formula (2) 'Structure 2' were designed and synthesized. The compounds of the general formula (2) 'Structure 2' indicated above can be prepared from protected prostaglandins, prostacyclins, and related compounds, by reaction with suitable alcohols, thiols, or amines and coupling reagents, such as N, N'-Dicyclohexylcarbodiimide, N, N'-Diisopropylcarbodiimide, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, Benzotriazol-1-yl-oxy-tris (dimethylamino)phosphonium hexafluorophosphate, et al. The positively charged amino groups of these pro-drugs not only largely increases the solubility of the drugs in water, but also bonds to the negative charge on the phosphate head group of membranes and pushes the pro-drug into the cytosol. The results suggest that the pro-drugs diffuse through human skin ~1000 times faster than do prostaglandins, prostacyclins, and related compounds. In plasma, more than 90% of these pro-drugs can change back to the parent drugs in a few minutes. The prodrugs can be used medicinally in treating any prostaglandins, prostacyclins, and related compounds-treatable conditions in humans or animals. The prodrugs can be administered transdermally for any kind of medical treatments and avoid most of the side effects of prostaglandins, prostacyclins, and related compounds. Controlled transdermal administration systems of the prodrug enable prostaglandins, prostacyclins, and related compounds to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of prostaglandins, prostacyclins, and related compounds. Another great benefit of transdermal administration of these pro-drugs is that administering medication, especially to children, will be much easier.

Cyclopentane heptan (ene) acyl sulfonamide, 2-alkyl or 2-arylalkyl, or 2-heteroarylalkenyl derivatives as therapeutic agents for the treatment of ocular hypertension

The present invention provides a method treating ocular hypertension glaucoma which comprises administering to an animal having ocular hypertension or glaucoma therapeutically effeceive amount of a compound represented by general formula 1; wherein a hatched line represents the .alpha. configuration, a triangle represents the .beta. configuration, a straight line, e.g. at the 9, 11 or 15 position represents either the .alpha. or .beta. configuration, a dotted line represents the presence or absence of a double bond; a wavy line represents a cis or trans bond; X is O, S, NH or (CH2)n ; n is 0 or an integer of from 1 to 4; Y is C1 C5 n-alkyl, C3 C7 cycloalky, phenyl, furanyl, thienyl, pyridinyl, thiazolyl, benzothieny, benzofurany, napthyl, or substituted derivaties thereof, wherein the substituents maybe selected from the group consisting of C1-C5 alkyl, halogen, CF3, CN, NO2, N(R2)2, CO2R2 and OR2, z is (CH2)n or a covalent bond; R is c1-C6 lower alkyl or Z-CF3 or mesylate or triflate; R1 is H, R2 or COR2R2; and R2 is H or C1-C5 lower alkyl or 9, 11 or 15 esters thereof.

Method of preparing w-tetranoprostaglandins or their c15 epimers or their salts

Patent FR2449680B1

PROSTACYCLINE ANALOGUES AND THEIR PREPARATION

L'invention est relative à de nouveaux analogues de prostacycline et à leur préparation. Les nouveaux analogues suivant l'invention sont des dérivés 9-désoxy-6,9-époxyméthano de prostaglandines du type F1 alpha . Ces nouveaux analogues s'utilisent aux mêmes fins pharmaceutiques que la prostacycline mais avec des résultats supérieurs. The invention relates to novel prostacyclin analogs and their preparation. The new analogs according to the invention are 9-deoxy-6,9-epoxymethano derivatives of prostaglandins of the F1 alpha type. These new analogues are used for the same pharmaceutical purposes as prostacyclin but with superior results.

OBTAINING LATANOPROSTIN BUNODA OF NECESSARY PRELIMINARY QUALITY BY CHROMATOGRAPHY WITH GRAVITATIONAL ELUTION

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2018 124 293 A (51) МПК C07C 405/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2018124293, 11.11.2016 (71) Заявитель(и): ХИНОИН ДЬЕДЬСЕР ЕШ ВЕДЬЕСЕТИ ТЕРМЕКЕК ДЬЯРА ЗРТ. (HU) Приоритет(ы): (30) Конвенционный приоритет: 04.12.2015 HU P15 00594 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 04.07.2018 (86) Заявка PCT: (87) Публикация заявки PCT: WO 2017/093771 (08.06.2017) R U (54) ПОЛУЧЕНИЕ ЛАТАНОПРОСТИНА БУНОДА НЕОБХОДИМОГО ПРЕДВАРИТЕЛЬНО ЗАДАННОГО КАЧЕСТВА ПОСРЕДСТВОМ ХРОМАТОГРАФИИ С ГРАВИТАЦИОННЫМ ЭЛЮИРОВАНИЕМ (57) Формула изобретения 1. Способ получения латанопростина бунода формулы (I) со степенью чистоты более 95%, отличающийся тем, что неочищенный латанопростина бунод формулы (I) очищают посредством хроматографии путем применения колоночной хроматографии на силикагеле с нормальной фазой с гравитационным элюированием с применением в качестве силикагеля a.) силикагеля для нормальной фазы с частицами неправильной формы с размером частиц 63-200 микрон или Стр.: 1 A 2 0 1 8 1 2 4 2 9 3 A Адрес для переписки: 129090, Москва, ул. Б. Спасская, 25, стр. 3, ООО "Юридическая фирма Городисский и Партнеры" 2 0 1 8 1 2 4 2 9 3 HU 2016/000071 (11.11.2016) R U (43) Дата публикации заявки: 14.01.2020 Бюл. № 2 (72) Автор(ы): ТАКАЧ Ласло (HU), ФЕКЕТЕ Ибойя (HU), БУЗДЕР-ЛАНТОШ Петер (HU), ЛАСЛОФИ Иштван (HU), ХОРТОБАДЬИ Ирен (HU), ХАВАШИ Габор (HU), КАРДОШ Жужанна (HU) A 2 0 1 8 1 2 4 2 9 3 R U ≤ 0,15% ≤ 0,50% Латанопрост ≤ 0,10% Кислота латанопроста ≤ 0,10% Неидентифицированные примеси по отдельности ≤ 0,10% Неидентифицированные примеси, всего ≤ 0,30% Сумма примесей ≤ 0,80% 14. Чистый латанопростина бунод формулы (I), соответствующий следующим техническим требованиям по качеству: Стр.: 2 A 15S-Латанопростина бунод 5,6-транс-Латанопростина бунод 2 0 1 8 1 2 4 2 9 3 Латанопростина бунод Родственные примеси (HPLC) R U b.) силикагеля для нормальной фазы с частицами ...

16-FLUORO-16,17-DIDESHYDRO-PROSTANOIDS, PROCESS FOR THEIR PREPARATION, INTERMEDIATE PRODUCTS OF THEIR PREPARATION AND THEIR THERAPEUTIC USES, IN PARTICULAR IN THE INDICATIONS OF NATURAL PROSTAGLANDINS

16-FLUORO-16,17-DIDESHYDRO-PROSTANOIDES, LEUR PREPARATION, PRODUITS INTERMEDIAIRES DE LEUR PREPARATION ET LEURS UTILISATIONS THERAPEUTIQUES. CES COMPOSES REPONDENT A LA FORMULE: (CF DESSIN DANS BOPI) DANS LAQUELLE R REPRESENTE -OH OU -OR, 16-FLUORO-16,17-DIDESHYDRO-PROSTANOIDES, THEIR PREPARATION, INTERMEDIARIES OF THEIR PREPARATION AND THEIR THERAPEUTIC USES. THESE COMPOUNDS MEET THE FORMULA: (CF DRAWING IN BOPI) IN WHICH R REPRESENTS -OH OR -OR,

Esterification of prostaglandins - using acetals of dimethyl formamide as esterifying agent

Esterification of prostanoic acids to give cpds. of formula (I): prim, or sec. 12 C alkanol, alkenol, cycloalkanol, or arylalkanol (excepting neopentyl), also beta-dialkylaminoethyl, gamma-dialkylaminopropyl, beta-pyrrolidinoethyl, beta-piperidinoethyl, beta-morpholinoethyl, gamma-pyrrolidinopropyl, gamma-piperidinopropyl, gamma-morpholinopropyl; CH2XCH2XCO-; Z is -CH2XCH2- or -CH:CH-(cis or trans); is and alpha or beta-linkage) consists of reacting corresp. prostanoic acid with an acetal of dimethylformamide of formula: The process is simpler than those using silver prostanoates or diazo cpds.

9-halogen prostaglandins

ABSTRACT OF THE DISCLOSURE 9-Halogen prostane derivatives of formula I (I), wherein Hal is a chlorine or fluorine atom in the .alpha. or .beta. -position, R1 is the radical CH20H or -C-OR2 with R2 is a hydrogen atom, an alkyl, cycloalkyl, aryl or heterocyclic radical or R1 is the radical , with R3 is an acid radical or the radical R2 A is a -CH2-CH2-, a trans-CH=CH- or a -C?C- group, W is a free functionally modified hydroxymethylene group or a free or func-tionally modified group, whereln the OH group may be in the .alpha. or .beta. -position, D and E together form a direct bond or D is a straight-chain, branched-chain or cyclic alkylene group wtth 1 to 10 C-atoms, which may be substituted by fluorine atoms, E represents an oxy-gen or sulfur atom, a direct bond, a -C?C- bond or a -CR6=CR7-group, where R6 and R7 are different and are a hydrogen atom, a chlorine atom or a C1-C4-alkyl group, R4 a free or functionally modified hydroxy group, and R5 is a hydrogen atom, an alkyl, an alkenyl, a halogen-substituted alkyl, a cycloalkyl, an aryl or a heterocyclic group or when D and E forms a direct bond an alkenyl group and, where R2 is a hydrogen atom, its salts with physiolog-ically tolerable bases useful as pharmaceuticals having compound effects over material prostaglandins.

NOVEL PROSTAGLANDIN DERIVATIVES, PROCESS FOR THEIR PREPARATION AND MEDICAMENTS CONTAINING THEM

Patent FR2402644B1

ANALOGUES OF 5,6-DIHYDRO-PROSTACYCLINE AND THEIR PREPARATION

ANALOGUES OF PROSTAGLANDIN E AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

L'INVENTION CONCERNE DES ANALOGUES DE LA PROSTAGLANDINE E. CES COMPOSES ONT LA FORMULE CI-DESSOUS DANS LAQUELLE RALCOYLE DE 1 A 4 C, RLIAISON SIMPLE OU ALCOYLENE DE 1 A 5 C, RH, ALCOYLE OU ALCOXY DE 1 A 8 C, CYCLOALCOYLE OU CYCLOACOYLOXY DE 4 A 7 C, SUBSTITUES OU NON, OU PHENYLE OU PHENOXY SUBSTITUES OU NON, RH OU GROUPE PROTECTEUR D'HYDROXY, ELIMINABLE EN MILIEU ACIDE, XETHYLENE OU VINYLENE CIS. APPLICATIONS PHARMACOLOGIQUES, EN PARTICULIER POUR L'INTERRUPTION DE GROSSESSE, LE DECLENCHEMENT DU TRAVAIL EN OBSTRETRIQUE, LA CONTRACEPTION ET LA REGULATION MENSTRUELLE. (CF DESSIN DANS BOPI)

Preparation of prostamides

The present invention provides a process for the preparation of a prostamide which comprises the steps of (d) reacting first intermediate having the general formula (I) with DIBAL wherein Z is a protecting group and the dotted line represents the presence or absence of a double bond to yield a second intermediate having the general Formula (II) (b) reacting said second intermediate with Na(TMS)2N and (C6H5)3P+(CH2)6CONR2X wherein R is a C1-5 alkyl or hydrogen and X is an anion to yield a third intermediate having the general formula (III) (c) reacting said third intermediate with a protecting agent to yield a fourth intermediate having the general formula IV (e) reacting said fourth intermediate to remove said protecting groups and yield a prostamide having the general formula V

Patent FR2415629B1

Patent FR2182928A1

DERIVATIVES OF COMPOUNDS OF THE INTER-PHENYLENE-PROSTAGLANDIN TYPE AND PHARMACEUTICAL COMPOSITIONS IN CONTAINING

L'invention est relative à des dérivés de composés du type inter-phénylène-prostaglandine. Il s'agit de dérivés amido, cycloamido, carbonylamido, sulfonylamido et hydrazino de composés du type inter-phénylène-PG. Ces dérivés ont une activité thérapeutique prolongée par voie orale, notamment à titre d'agents antithrombotiques. The invention relates to derivatives of compounds of the inter-phenylene-prostaglandin type. These are amido, cycloamido, carbonylamido, sulfonylamido and hydrazino derivatives of compounds of the inter-phenylene-PG type. These derivatives have a prolonged therapeutic activity by the oral route, in particular as antithrombotic agents.

5,6-DIHYDRO-PROSTACYCLINE ANALOGS AND THEIR PREPARATION

ESTERS AND AMIDES OF 13 14-BISDEHYDROPROSTAGLANDINS

LES MEDICAMENTS SELON L'INVENTION CONTIENNENT COMME PRODUITS ACTIFS DES COMPOSES DE FORMULE GENERALE (I): (CF DESSIN DANS BOPI) THE MEDICINAL PRODUCTS ACCORDING TO THE INVENTION CONTAIN AS ACTIVE PRODUCTS COMPOUNDS OF GENERAL FORMULA (I): (CF DRAWING IN BOPI)

Antihypertensive prostaglandin phthalazinyl-hydrazides - prepd. by reaction of a prostanoic acid deriv and phthalazinyl hydrazine

Prostaglandin phthalazinyl hydrazides of formula (I): (where A=-(CH2)3, -CO-CH=CH-, -CO-CH2-CH- or -CH-CH2-CH R and R'=H, ethyl or methyl; Y=-(CH2)3-, -CH2CH2CH(OH), (cis or trans); and the symbol indicates the alpha- or beta-configuration) are useful as antihypertensives. Cpds. (I) are prepd. by reaction of 1-hydrazino phthalazine with a prostanoic deriv.

AMINOCYCLOPENTANE-ALKENOIC ACIDS AND THEIR ESTERS, THEIR PREPARATION AND USE IN PHARMACEUTICAL COMPOSITIONS

L'INVENTION CONCERNE DES ESTERS ET ACIDES AMINOCYCLOPENTANE ALCENOIQUES. LES COMPOSES REPONDENT A LA FORMULE GENERALE: (CF DESSIN DANS BOPI) OU X REPRESENTE UN GROUPE CIS OU TRANS -CHCH-; R EST UN GROUPE ALKYLE EN C-C A TERMINAISON -COOR OU R EST H, ALKYLE EN C-C OU ARALKYLE EN C-C; Y REPRESENTE UN GROUPE AMINO HETEROCYCLIQUE SATURE A 5, 8CHAINONS CYCLIQUES; ET R REPRESENTE UN GROUPE ALCANOYLE EN C-C, ALCENYLE EN C-C, ALKYLE EN C-C, PHENYLALKYLE, THIENYLALKYLE, FURANNYLALKYLE, BIPHENYLALKYLE OU NAPHTYLALKYLE. CES COMPOSES INHIBENT LA THROMBO-AGGLUTINATION ET LA BRONCHOCONSTRICTION. THE INVENTION CONCERNS ESTERS AND AMINOCYCLOPENTANE ALCENOIC ACIDS. THE COMPOUNDS MEET THE GENERAL FORMULA: (CF DRAWING IN BOPI) OR X REPRESENTS A CIS OR TRANS -CHCH- GROUP; R IS A C-C ALKYL GROUP WITH -COOR TERMINATION OR R IS H, C-C ALKYL OR C-C ARALKYL; REPRESENTS A SATURATED HETEROCYCLIC AMINO GROUP WITH 5, 8 CYCLIC CHAINS; AND R REPRESENTS A GROUP C-C ALKANOYL, C-C ALKENYL, C-C ALKYL, PHENYLALKYL, THIENYLALKYL, FURANNYLALKYL, BIPHENYLALKYL OR NAPHTYLALKYL. THESE COMPOUNDS INHIBIT THROMBO-AGGLUTINATION AND BRONCHOCONSTRICTION.

Novel prostaglandin derivative

The present invention relates to: a novel prostaglandin derivative having an alkynyl group in a ?-chain, particularly a novel prostaglandin derivative having a double bond at position-2 and also having an alkynyl group in a ?-chain; and a medicine containing the compound as an active ingredient. According to the present invention, it becomes possible to provide: a compound represented by formula (1) [wherein each symbol is as defined in the description], a pharmaceutically acceptable salt of the compound, or a cyclodextrin inclusion complex of the compound or the pharmaceutically acceptable salt; and a medicine which contains the compound as an active ingredient, particularly which can be used for the prevention or treatment of a blood flow disturbance associated with spinal canal stenosis or chronic arterial occlusive disease.

Patent FR2205335B1

Patent FR2193613A1

Patent FR2193613B1

DIALKYL PHOSPHONATES

NEW 6-HEMICETAL OR 6-CETO DERIVATIVES OF PROSTAGLANDIN, THEIR PREPARATION PROCESS AND THE MEDICINAL PRODUCT CONTAINING THEM

L'invention concerne de nouveaux dérivés de prostaglandine (PG1 ) à fonction 9-déoxy-6,9-époxy ainsi que 6-hémicétal ou 6-céto. Elle concerne également la préparation de ces dérivés. Les nouveaux dérivés de l'invention sont doués d'activité pharmacologique. The invention relates to novel 9-deoxy-6,9-epoxy-functional prostaglandin (PG1) derivatives as well as 6-hemiketal or 6-keto. It also relates to the preparation of these derivatives. The new derivatives of the invention are endowed with pharmacological activity.

AMINOCYCLOPENTANONE AMIDES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

L'INVENTION CONCERNE DES AMIDES. LES COMPOSES CONFORMES A L'INVENTION REPONDENT A LA FORMULE(1), DANS LAQUELLE R REPRESENTE UN GROUPE CINNAMYLE, NAPHTYL-, THIENYL- OU PHENYL-ALKYLE SUBSTITUE OU NON, R REPRESENTE H, UN GROUPE METHYLE OU ALKYLE SUBSTITUE PAR UN GROUPE ALCOXY OU -COOH, W REPRESENTE UN GROUPE ALKYLENE, X REPRESENTE UN GROUPE CIS OU TRANS -CHCH- OU -CHCH- ET Y REPRESENTE UN GROUPE AMINO HETEROCYCLIQUE SATURE A 5-8CHAINONS, AINSI QUE LES SELS ET SOLVATES DE CES COMPOSES. CES COMPOSES INHIBENT LA THROMBO-AGGLUTINATION ET LA BRONCHOCONSTRICTION ET SERVENT D'AGENTS ANTI-THROMBOTIQUES ET ANTI-ASTHMATIQUES. (CF DESSIN DANS BOPI) THE INVENTION RELATES TO AMIDS. THE COMPOUNDS CONFORMING TO THE INVENTION RESPOND TO FORMULA (1), IN WHICH R REPRESENTS A CINNAMYL, NAPHTYL-, THIENYL- OR PHENYL-ALKYL GROUP SUBSTITUTES OR NOT, R REPRESENTS H, A METHYL OR ALKYL GROUP SUBSTITUTED BY A METHYL OR ALKYL GROUP SUBSTITUTED BY AN ALCOYL GROUP OR -COOH, W REPRESENTS AN ALKYLENE GROUP, X REPRESENTS A CIS OR TRANS -CHCH- OR -CHCH- GROUP AND REPRESENTS A 5-8 CHAIN SATURATED HETEROCYCLIC AMINO GROUP, AS WELL AS THE SALTS AND SOLVATES OF THESE COMPOUNDS. THESE COMPOUNDS INHIBIT THROMBO-AGGLUTINATION AND BRONCHOCONSTRICTION AND SERVE AS ANTI-THROMBOTIC AND ANTI-ASTHMATIC AGENTS. (CF DRAWING IN BOPI)

Patent FR2362833B1

Process for preparing aminocyclopentane alkenoic acids and esters thereof

Aminocyclopentane alkenoic acid of formula (1) and their salts and solvates are new. X is cis or trans -CH=CH-; R1 is (CH2)nCOOR3; n is 2-4; R3 is H or C1-3 alkyl; Y is piperidino, morpholino, thiaamorpholino, dioxomorpholino, or homomorpholino; R2 is ph-substd. C3-6 alkenyl or C3-6 alkenyl; R'a is (CH2)nCOOR3, -(CH2)nCH2OH or - (CH2)nCHO; n is 2-4 ; R3 is H or C1-3 alkyl. (I) were prepd. by the oxidation of (II) for use as blood platelet aggregation inhibitors and bronchodilators.

PROSTAGLANDIN SYNTHESIS INTERMEDIATE

OUTSTANDING MATERIALS USED FOR THE PREPARATION OF SUBSTITUTED OMEGA-PENTANORPROSTAGLANDINES

19,20 -didehydro-19-hydroxy and 19-oxo-prostaglandin derivatives

AMINOCYCLOPENTANES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Prostaglandin F2 alpha derivatives for decreasing intraocular pressure

The invention relates to medical chemistry, specifically to new biologically active compounds - amide derivatives of prostaglandin F2 alpha. Said compounds have low cytotoxicity and are able to stimulate the formation of endogenous nitric oxide in mammalian cells. The synthesis of said compounds helps expand the range of biologically active prostaglandin F2 alpha derivatives that are able to decrease intraocular pressure.

Method of preparing prostaglandin derivatives or their c9 and c15 epimers

1456513 Cyclopenta[b]furan derivatives PFIZER Inc 7 Nov 1973 [8 Nov 1972] 23950/76 Divided out of 1456512 Heading C2C The invention comprises cyclopenta[b]furan derivatives of the Formulµ III, IV and V wherein Ar is 3,4-dimethoxyphenyl, 3,4-methylenedioxyphenyl, 3,4,5 - trimethoxyphenyl, 1- or 2-naphthyl or phenyl optionally monosubstituted by halogen, trifluoromethyl, phenyl C 1-6 alkyl or C 1-6 alkoxy; m and n each are 0 to 3 with the proviso that the sum of n and m does not exceed 3; Q is p-biphenylylcarbonyl; Z is a single or trans-double bond; R is H or C 1-6 alkyl; Q<SP>1</SP> is H or p-phenylylcarbonyl; and Y is oxo, with the proviso in compounds of Formula IV that when R and Q<SP>1</SP> are both H, Z is a trans double bond, n and m are 0, Ar is 3,4-methylenedioxyphenyl, 3,4,5 - trimethoxyphenyl, 1- or 2-naphthyl or biphenylyl; and with the proviso in compound of Formula V that when R is H Z is a trans double bond, m and n are 0, Ar is as defined immediately above; and their preparation. The compounds are obtained by known methods used to obtain analogous compounds.

Prostanoic acid hydrazides - with antilipolytic, luteolytic, hypotensive, bronchoconstrictor, vasodilator and other activities

Prostanoic acid hydrazides of formula (I): Z is -CH2XCH2-, -CH:CH-(cis or trans); is an alpha- or beta-linkage), are antilipolytic, luteolytic, hypotensive, broncho-constrictor and vasodilator activity, inducers of uterine contractions, adrenal activators.