PROCESS FOR THE PREPARATION OF 2-HYDROXY-4-PHENYL-3,4-DIHYDRO-2H-CHROMEN-6-YL-METHANOL AND (R)-FESO-DEACYL

The present invention regards an improved and industrially advantageous process for the preparation of the 2-hydroxy-4-phenyl-3,4-dihydro-2H-chromen-6-yl-methanol intermediates, also called “feso chromenyl” and (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenol, also called “(R)-feso deacyl”, which are in turn used in the synthesis of fesoterodine and in particular of fesoterodine fumarate. This process utilises reagents which are non-toxic and manageable at industrial level and enables obtaining a new stable and non-hygroscopic crystalline form of the key intermediate “(R)-feso deacyl”, called form B. 2. Process according to claim 1 , wherein said silylating agent is selected from among RRRSiX where R claim 1 , R claim 1 , Rare C-Clinear or branched alkyl or aryl residues possibly substituted claim 1 , X is a halogen or a sulfonate group; CYCO(MeSi)═NH(MeSi) claim 1 , where Y is hydrogen or halogen; or (MeSiNH)C═O.3. Process according to claim 1 , wherein said silylating agent is used in presence of a base.4. Process according to claim 1 , wherein said selective deprotection of the phenolic hydroxyl of the compound of formula (B) is conducted in presence of a salt of alkaline metals.5. Process according to claim 1 , wherein said cyclic secondary amine is selected from among morpholine claim 1 , N-methyl-piperazine claim 1 , N-benzyl-piperazine claim 1 , pyrrolidine and piperazine.6. Process according to claim 1 , wherein said deprotection of the compound of formula (D) is conducted in presence of fluoride ion.7. Process according to claim 1 , wherein said hydrolysis occurs by mixing the reaction mixture with an aqueous solution having a pH below 1.8. Process according to claim 7 , wherein 5 to 100 volumes of aqueous solution per volume of reaction mixture are used.9. Process according to claim 1 , wherein the compounds of formula (B) claim 1 , (D) and/or (E) are not isolated.11. Process according to claim 10 , wherein said metal hydride is sodium ...

SOLID STATE FORMS OF TAPENTADOL SALTS

Provided herein are novel solid state forms of tapentadol salts, process for their preparation, pharmaceutical compositions, and method of treating thereof. The tapentadol salts include an L-(−)-camphorsulfonate salt, a dibenzoyl-(L)-tartrate salt, a dibenzoyl-(D)-tartrate salt, a malate salt, a maleate salt, or a salicylate salt. 1. Solid state form of a salt of 3-[(1R ,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol (tapentadol salt) , wherein the salt of tapentadol is an L-(−)-camphorsulfonate salt , a dibenzoyl-(D)-tartrate salt , a malate salt , a maleate salt , or a salicylate salt.2. The solid state form of tapentadol salt of claim 1 , which is in a crystalline form or in an amorphous form claim 1 , and wherein the solid state form is anhydrous and/or solvent-free form claim 1 , or a hydrate and/or a solvate form.3. The solid state form of tapentadol salt of claim 1 , having the following characteristics claim 1 , wherein: [{'figref': {'@idref': 'DRAWINGS', 'FIG. 1'}, 'i) a powder X-ray diffraction pattern substantially in accordance with ;'}, 'ii) a powder X-ray diffraction pattern having peaks at about 3.93, 5.66, 14.94, 16.16 and 21.52±0.2 degrees 2-theta;', 'iii) a powder X-ray diffraction pattern having additional peaks at about 8.01, 11.36, 14.10, 15.27, 15.91, 16.72, 19.06, 19.88, 21.85, 22.56, 23.92 and 27.12±0.2 degrees 2-theta; and', {'figref': {'@idref': 'DRAWINGS', 'FIG. 2'}, 'iv) a differential scanning calorimetric (DSC) thermogram substantially in accordance with ;'}], 'a) the solid state form of tapentadol L-(−)-camphorsulfonate salt is characterized by one or more of the following properties [{'figref': {'@idref': 'DRAWINGS', 'FIG. 5'}, 'i) a powder X-ray diffraction pattern substantially in accordance with ;'}, 'ii) a powder X-ray diffraction pattern having peaks at about 8.52, 9.39, 11.81, 12.28, 13.46, 14.06, 17.77, 17.97, 18.33, 18.79, 19.58 and 20.05±0.2 degrees 2-theta;', 'iii) a powder X-ray diffraction pattern having additional ...

STEREOSELECTIVE SYNTHESIS OF TAPENTADOL AND ITS SALTS

A process for the synthesis of a salt of tapentadol. 2. The process according to claim 1 , wherein the suitable solvent of steps (a) to (g) are each organic solvents claim 1 , preferably anhydrous organic solvents.3. The process according to claim 1 , wherein the suitable solvent of step (a) is anhydrous dimethylformamide (DMF) claim 1 , anhydrous dimethylsulfoxide (DMSO) claim 1 , anhydrous dimethyl acetamide (DMAc) claim 1 , anhydrous ethanol claim 1 , anhydrous methanol claim 1 , anhydrous n-propanol claim 1 , anhydrous 2-butanol claim 1 , anhydrous 1-butanol claim 1 , anhydrous tetrahydrofuran (THF) claim 1 , anhydrous 2-methyltetrahydrofuran (2-MeTHF) claim 1 , anhydrous dioxane claim 1 , anhydrous toluene claim 1 , anhydrous ethyl acetate claim 1 , anhydrous isopropyl acetate claim 1 , or a mixture thereof.4. The process according to claim 1 , wherein the suitable solvent of step (b) is anhydrous 2-MeTHF claim 1 , anhydrous THF claim 1 , anhydrous toluene claim 1 , anhydrous dioxane claim 1 , anhydrous methyl tert-buyl ether (MTBE) claim 1 , anhydrous cyclopentyl methyl ether claim 1 , or anhydrous diethyl ether.5. The process according to claim 1 , wherein step (b) is accomplished using a suitable reducing agent claim 1 , the reducing agent preferably selected from lithium borohydride claim 1 , sodium borohydride claim 1 , lithium aluminum hydride claim 1 , disobutyl aluminum hydride claim 1 , or RedAl.6. The process according to claim 1 , wherein the suitable solvent of step (c) is THF claim 1 , 2-MeTHF claim 1 , toluene claim 1 , dioxane claim 1 , MTBE claim 1 , cyclopentyl methyl ether claim 1 , diethyl ether claim 1 , or a mixture thereof.7. The process according to claim 1 , wherein claim 1 , the organometallic catalyst of step (d) is [Ir(COD)Cl]or [Ir(COE)Cl].8. The process according to claim 1 , wherein the suitable solvent of step (d) is dichloromethane claim 1 , THF claim 1 , toluene claim 1 , dioxane claim 1 , MTBE claim 1 , cyclopentyl methyl ether ...

Highly Selective 5-HT(2C) Receptor Agonists That Show Anti-Psychotic Effects with Antagonist Activity at the 5-HT(2B) Receptor

Highly selective 5-HT(2C) receptor agonists receptors are disclosed. The 5-HT(2C) receptor agonists are used in the treatments of disease and conditions wherein modulation of 5-HT(2C) receptors provides a benefit, such as obesity and psychiatric disorders. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)14. The composition of wherein the second therapeutic agent comprises a therapeutic agent useful in a treatment of a psychiatric disorder claim 13 , a metabolic disorder claim 13 , or an eating disorder.15. (canceled)17. The method of wherein the 5-HT(2C) receptors are activated.18. (canceled)19. (canceled)20. (canceled)21. The method of wherein the disease or condition is selected from the diseases and conditions disclosed in paragraphs [0100] through [0102].22. The method of wherein the disease or condition is a central nervous system disorder or a damage to the central nervous system.23. The method of wherein the central nervous system disorder is anxiety claim 22 , a panic disorder claim 22 , a schizoaffective disorder claim 22 , schizophrenia claim 22 , psychosis claim 22 , an adjustment disorder claim 22 , dystonia claim 22 , clinical depression claim 22 , bipolar disorder claim 22 , an addictive behavior claim 22 , a compound addiction claim 22 , obsessive compulsive disorder claim 22 , a movement disorder claim 22 , or a cognition disorder.24. The method of wherein the disease or condition is a metabolic or eating disorder selected from the group consisting of dyslipidemia claim 16 , Type 2 diabetes claim 16 , diabetes insipidus claim 16 , metabolic syndrome claim 16 , and obesity.25. (canceled)26. The method of wherein the disease or condition is a gastrointestinal disorder claim 16 , sleep apnea claim 16 , hypertension claim 16 , hyperlipidemia claim 16 , a cardiovascular disease claim 16 , dementia claim 16 , memory deficit claim 16 , mild ...

Crystalline Forms of (-)-(1R, 2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride

A hitherto unknown crystalline form of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence. 1. A process for producing a (−)-(1R ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A , said process comprising:dissolving a (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B in acetone, acetonitrile or isopropanol to form a solution;leaving the solution to crystallize andisolating crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A.2. The process of claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B is dissolved in acetonitrile claim 1 , and further comprising the steps of:stirring the solution;removing insoluble residue by filtering andevaporating the acetonitrile leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize.3. The process according to claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at temperatures above room temperature claim 1 , and after complete dissolution no further heat is provided and further comprising:adding seed crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A and then cooling the mixture down to ≦15° C.4. The process of claim 3 , wherein said (−)-(1R claim 3 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at a temperature above 65° C. but not exceeding 80° C.5. The process of claim 3 , wherein said mixture is cooled down to ≦10 ...

Substituted n-pentanamide compounds, preparation method and the use thereof

The present invention relates to a (2R, 3R)-3-(3-substituted phenyl)-2-methyl n-pentanamide compounds as shown in the formula I and the preparation method thereof, wherein, the substituents are as defined in the specification, the present invention further relates to a use of the above compounds for the preparation of tapentadol II or its pharmaceutically acceptable salt, and the intermediates involved in the preparation process. 2. The (2R claim 1 ,3R)-3-(3-substituted phenyl)-2-methyl n-pentanamide compound according to claim 1 , wherein R and the phenolic hydroxyl group form an ether group or an ester group; wherein R is selected from C1-C6 linear or branched alkyl claim 1 , substituted or unsubstituted aryl claim 1 , substituted or unsubstituted arylalkyl claim 1 , alkylsilyl claim 1 , C1-C6 alkoxymethyl claim 1 , C1-C6 alkyloyl claim 1 , substituted or unsubstituted aryloyl; wherein the substituent is hydroxy claim 1 , halogen claim 1 , C1-C6 alkyl or C1-C6 alkoxy; said aryl is phenyl or naphthyl;wherein X is O; and Y is O;{'sub': '1', 'wherein Ris C1-C6 alkyl group, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, wherein the substituent on phenyl or benzyl is 1 to 3 substituent(s) selected from hydroxy, halogen, C1-C6 alkyl and C1-C6 alkoxy;'}{'sub': 2', '3, 'wherein Rand Rare each independently selected from H, C1-C6 alkyl and phenyl.'}3. The (2R claim 2 ,3R)-3-(3-substituted phenyl)-2-methyl n-pentanamide compound according to claim 2 ,wherein R is benzyl, methyl, t-butyl, triphenylmethyl, methoxymethyl, trimethylsilyl, t-butyldimethylsilyl, acetyl or benzoyl;wherein X is O; and Y is O;{'sub': '1', 'wherein Ris phenyl; phenyl substituted with 1 to 3 substituent(s) selected from hydroxy, halogen, C1-C6 alkyl and C1-C6 alkoxy; benzyl;'}{'sub': 2', '3, 'wherein Rand Rare each independently selected from H, C1-C6 alkyl and phenyl.'}6. The method according to claim 5 , wherein claim 5 ,said hydrocarbylation agent is any one of methyl ...

ONO PINCER LIGANDS AND ONO PINCER LIGAND COMPRISING METAL COMPLEXES

Embodiments of the invention are directed to ONO pincer ligands that can be in a trianionic, protonated or protonated equivalent form. The ONO pincer ligand can be combined with a transition metal comprising compound to form an ONO pincer ligand comprising transition metal complex. By choice of the ONO pincer ligand structure, the steric and electronic properties of the transition metal complexes therefrom can be controlled. The ONO pincer ligands comprise a central nitrogen atom that is disubstituted with a pair of three atom comprising bridges where the three atoms are three sphybridized carbons or the three atoms are a pair of sphybridized carbons and an sphybridized carbon or silicon. 5. A method of preparing an ONO pincer ligand precursor according to claim 1 , comprising condensing a nucleophilic oxygen or nucleophilic nitrogen comprising compound with an electrophilic carbon comprising compound further comprising the bridge structure of the resulting ONO pincer ligand.6. A trianionic ONO pincer ligand comprising transition metal complex comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'at least one ONO trianionic pincer ligand derived from the ONO trianionic pincer ligand precursor of ; and'}a transition metal from group III through group X of the periodic table.7. The trianionic ONO pincer ligand comprising transition metal complex of claim 6 , wherein the transition metal is an early transition metal complex from group III through group VI.18. The method of preparing an ONO pincer ligand comprising transition metal complex of claim 17 , wherein the precursor metal compound further comprises a metal alkylidyne claim 17 , further comprising adding the OH or NH of the ONO pincer ligand precursor across the metal alkylidyne to form the anionic ONO pincer ligand comprising metal complex. This application is a continuation-in-part of International Patent Application No. PCT/US2012/037302, filed May 10, 2012, which claims the benefit of U.S. ...

Crystalline Forms of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride

A hitherto unknown crystalline form of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence. 1. A process for producing a (-)-(1R ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A , said process comprising:dissolving a (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B in acetone, acetonitrile or isopropanol to form a solution;leaving the solution to crystallize andisolating crystals of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A.2. The process of claim 1 , wherein said (-)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B is dissolved in acetonitrile claim 1 , and further comprising the steps of:stirring the solution;removing insoluble residue by filtering andevaporating the acetonitrile leaving (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize.3. The process according to claim 1 , wherein said (-)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at temperatures above room temperature claim 1 , and after complete dissolution no further heat is provided and further comprising:adding seed crystals of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A and then cooling the mixture down to ≦15° C.4. The process of claim 3 , wherein said (-)-(1R claim 3 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at a temperature above 65° C. but not exceeding 80° C.5. The process of claim 3 , wherein said mixture is cooled down to ≦10 ...

PHENALKAMINE EPOXY CURING AGENTS AND EPOXY RESIN COMPOSITIONS CONTAINING THE SAME

The present invention relates to a new structural class of phenalkamines, curing agent compositions comprising the phenalkamines, their use, as well as and methods of producing such phenalkamines and compositions. The phenalkamines of the present invention can be prepared by reacting cardanol with an aldehyde compound and triaminononane. These curing-agent compositions may be used to cure, harden, and/or crosslink an epoxy resin. The curing-agent compositions of this invention are of low viscosity and can be used neat or dissolved in a minimum amount of an organic solvent or diluent to effect cure of epoxy resins. 2. A curing agent composition comprising the phenalkamine according to .3. The curing agent composition of further comprising an additional amine having at least two amine functionalities.4. An amine-epoxy composition comprising the reaction product of the curing agent composition according to and an epoxy component.5. The amine-epoxy composition of claim 4 , wherein the epoxy component comprises at least one multifunctional epoxy resin.6. The amine-epoxy composition of claim 5 , wherein the at least one multifunctional epoxy resin is selected from the group consisting of aromatic epoxy resins claim 5 , alicyclic epoxy resins claim 5 , aliphatic epoxy resins claim 5 , glycidyl ester resins claim 5 , thioglycidyl ether resins claim 5 , N-glycidyl ether resins claim 5 , and combinations thereof.7. The amine-epoxy composition of claim 6 , wherein the at least one multifunctional epoxy resin comprises a glycidyl ether of polyhydric phenol.8. The amine-epoxy composition of claim 6 , wherein the at least one multifunctional epoxy resin comprises at least one glycidyl ether selected from the group of glycidyl ethers of: resorcinol claim 6 , hydroquinone claim 6 , bis-(4-hydroxy-3 claim 6 ,5-difluorophenyl)-methane claim 6 , 1 claim 6 ,1-bis-(4-hydroxyphenyl)-ethane claim 6 , 2 claim 6 ,2-bis-(4-hydroxy-3-methylphenyl)-propane claim 6 , 2 claim 6 ,2-bis-(4-hydroxy ...

Crystalline Forms of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride

A hitherto unknown crystalline form of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence. 1. A process for producing a (-)-(1R ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A , said process comprising:dissolving a (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B in acetone, acetonitrile or isopropanol to form a solution;leaving the solution to crystallize andisolating crystals of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A.2. The process of claim 1 , wherein said (-)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B is dissolved in acetonitrile claim 1 , and further comprising the steps of:stirring the solution;removing insoluble residue by filtering andevaporating the acetonitrile leaving (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize.3. The process according to claim 1 , wherein said (-)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at temperatures above room temperature claim 1 , and after complete dissolution no further heat is provided and further comprising:adding seed crystals of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A and then cooling the mixture down to ≤15° C.4. The process of claim 3 , wherein said (-)-(1R claim 3 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at a temperature above 65° C. but not exceeding 80° C.5. The process of claim 3 , wherein said mixture is cooled down to ≤10 ...

Diphenethylamine Derivatives Which Are Inter Alia Useful As Analgesics And Method For Their Production

Diphenethylamine derivatives for use as highly active analgesics, diuretics, anxiolytics, for the treatment of neurode-generative, psychiatric and neuropsychiatric disorders, and also as anti-itch, anti-addiction, anti-inflammatory, anti-obesity, anti-epileptic, anti-convulsant, anti-seizure, anti-stress, anti-psychotic and anti-depressant medications and their pharmaceutically acceptable salts and easily accessible derivatives thereof (e.g. esters, ethers, amides), processes for their preparation and their application in the manufacture of pharmaceutical products. 2. A compound according to claim 1 , wherein{'sub': 1', '7', '12', '3', '12', '2', '12', '2', '12', '1', '12', '2', '12', '3', '12', '3', '6', '4', '16', '5', '16', '5', '16', '7', '16', '8', '16', '8', '16, 'Ris selected from C-C-unbranched alkyl; C-C-branched alkyl; C-C-alkenyl; C-C-alkynyl; C-C-monohydroxyalkyl; C-C-dihydroxyalkyl; C-C-trihydroxyalkyl; C-C-cycloalkyl; C-C-cycloalkylalkyl; C-C-cycloalkylalkenyl; C-C-cycloalkylalkynyl; C-C-arylalkyl; C-C-arylalkenyl; C-C-arylalkynyl;'}{'sub': 2', '3', '4', '5', '6, 'R, R, R, R, and Rare as defined above.'}3. A compound of claim 1 , wherein{'sub': 1', '3', '5', '2', '6', '2', '6', '1', '6', '2', '6', '3', '6', '3', '6', '4', '12', '3', '6', '1', '6', '5', '12', '3', '6', '2', '6', '5', '12', '3', '6', '2', '6', '7', '12', '6', '1', '6', '8', '12', '6', '2', '6', '8', '12', '6', '2', '6, 'Ris selected from C-C-branched alkyl; C-C-alkenyl; C-C-alkynyl; C-C-monohydroxyalkyl; C-C-dihydroxyalkyl; C-C-trihydroxyalkyl; C-C-cycloalkyl; C-C-cycloalkylalkyl, where cycloalkyl is C-C-cycloalkyl and alkyl is C-C-alkyl; C-C-cycloalkylalkenyl, where cycloalkyl is C-C-cycloalkyl and alkenyl is C-C-alkenyl; C-C-cycloalkylalkynyl, where cycloalkyl is C-C-cycloalkyl and alkynyl is C-C-alkynyl; C-C-arylalkyl where aryl is C-aryl and alkyl is C-C-alkyl; C-C-arylalkenyl where aryl is C-aryl and alkenyl is C-C-alkyl; C-C-arylalkynyl where aryl is C-aryl and alkynyl is C-C-alkyl ...

COMPOSITIONS FOR THE TREATMENT OF FIBROSIS AND FIBROSIS-RELATED CONDITIONS

The present invention relates to novel compounds and their use in the prophylactic and/or therapeutic treatment of fibrosis and fibrosis-related conditions. 2. The compound according to claim 1 , wherein the saturated claim 1 , partly saturated or unsaturated 5- or 6-membered heterocyclyl contains one or more of N claim 1 , S or O claim 1 , optionally substituted with one or more oxo claim 1 , Calkyl claim 1 , amino claim 1 , hydroxyl or halo substituents.3. The compound according to claim 1 , wherein the saturated claim 1 , partly saturated or unsaturated 5- or 6-membered heterocyclyl is selected from pyrrolyl claim 1 , pyrazolyl claim 1 , imidazolyl claim 1 , triazolyl claim 1 , imidazolidinyl claim 1 , pyrrolidinyl claim 1 , pyrrolidinylidene claim 1 , dihydropyrrolyl claim 1 , isoxazolyl dihydrooxazolyl claim 1 , isoxazolidinyl claim 1 , oxazolidinyl and oxazolyl claim 1 , optionally substituted with one or more oxo claim 1 , Calkyl claim 1 , amino claim 1 , hydroxyl or halo substituents.4. The compound according to claim 1 , wherein the Calkoxyl amine is aminooxymethyl.5. The compound according to claim 1 , wherein the Calkyl amine is optionally substituted with one or more of Calkyl claim 1 , Chalo alkyl claim 1 , hydroxyl or halo claim 1 , preferably mono- claim 1 , di- or tri-substituted halo alkyl claim 1 , most preferably tri-fluoro methane.6. The compound according to claim 1 , wherein the Calkyl carboxylic acid is carboxylic acid.7. The compound according to claim 1 , wherein the Calkyl hydroxyl is methyl hydroxyl.8. The compound according to claim 1 , wherein the Calkyl bicyclic heterocyclyl is selected from indolyl claim 1 , isoindolyl claim 1 , insolinyl and isoindolinyl claim 1 , optionally substituted with one or more oxo claim 1 , preferably dioxo.9. The compound according to claim 1 , wherein the Calkoxyl bicyclic heterocyclyl is selected indolyl claim 1 , isoindolyl claim 1 , insolinyl and isoindolinyl claim 1 , optionally substituted with one or ...

AMINE FOR RAPID-CURING EPOXY RESIN COMPOSITIONS

An amine of formula (I) which is particularly suitable for use as a curing agent for epoxy resins. The amine of formula (I) is devoid of non-incorporable toxic phenols, and is low-viscosity and pale in colour. It allows the production of easily-workable, low-emission or emission-free epoxy resin products which cure rapidly even at relatively low ambient temperatures thus obtaining a high degree of hardness and a nice surface with hardly any yellowing. This is particularly suited to use in floor or top coatings. 2. The amine as claimed in claim 1 , wherein m is 0 or 1 claim 1 , n is 1 claim 1 , and R is a hydrogen radical or methyl radical.3. The amine as claimed in claim 1 , wherein (m+n) is 3 claim 1 , R is a hydrogen radical claim 1 , and X is an N claim 1 ,N-dialkyl radical which optionally contains one or two hydroxyl groups claim 1 , or is an N-alkyl radical which optionally contains a hydroxyl group or one or two amine nitrogens claim 1 , or is an N-pyrrolidinylmethyl or N-piperidinylmethyl or N-morpholinylmethyl radical.5. The process as claimed in claim 4 , wherein it is carried out with a ratio between the number of 1 claim 4 ,2-propylenediamine molecules and the number of aldehyde or keto groups in the aldehyde or ketone of the formula (II) of at least 1.5/1.6. The process as claimed in claim 4 , wherein it is carried out with salicylaldehyde or 2′-hydroxyacetophenone as aldehyde or ketone of the formula (II).7. The process as claimed in claim 4 , wherein it is carried out with a ratio between the number of 1 claim 4 ,2-propylenediamine molecules and the number of aminoalkyl substituents in the Mannich base of the formula (III) of at least 1/1.8. The process as claimed in claim 4 , wherein it is carried out with 2 claim 4 ,4 claim 4 ,6-tris(N claim 4 ,N-dimethylaminomethyl)phenol as Mannich base of the formula (III).9. A hardener for epoxy resins comprising at least one amine as claimed in .10. A hardener for epoxy resins claim 1 , comprising at least one ...

CRYSTALLINE FORMS OF (-)-(1R,2R)-3-(3-DIMETHYLAMINO-1-ETHYL-2-METHYLPROPYL)-PHENOL HYDROCHLORIDE

A hitherto unknown crystalline form of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence. 1. A process for producing a (−)-(1R ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A , said process comprising:dissolving a (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B in acetone, acetonitrile or isopropanol to form a solution;leaving the solution to crystallize andisolating crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A.2. The process of claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B is dissolved in acetonitrile claim 1 , and further comprising the steps of:stirring the solution;removing insoluble residue by filtering andevaporating the acetonitrile leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize.3. The process according to claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at temperatures above room temperature claim 1 , and after complete dissolution no further heat is provided and further comprising:adding seed crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A and then cooling the mixture down to ≤15° C.4. The process of claim 3 , wherein said (−)-(1R claim 3 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at a temperature above 65° C. but not exceeding 80° C.5. The process of claim 3 , wherein said mixture is cooled down to ≤10 ...

KINASE INHIBITOR COMPOUNDS

The invention relates to kinase inhibitor compounds and methods of identifying and using them. The invention further relates to pharmaceutical compositions and methods for treating disorders, especially cancer. 118-. (canceled)19. A method of treating cancer in a subject comprising administering to the subject identified as in need thereof a compound of Table 1 or Table 2 , or a salt , hydrate or solvate thereof.20. The method of claim 19 , wherein the cancer is selected from the group consisting of: leukemias claim 19 , lymphomas claim 19 , myelomas claim 19 , and solid tumors.21. The method of claim 20 , wherein the leukemia is selected from the group consisting of: chronic myelogenous leukemia (CML) claim 20 , acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL).2224-. (canceled)25. A method of inhibiting JAK2 in a subject identified as in need of such treatment claim 20 , comprising: administering a compound of Table 1 or Table 2 claim 20 , or a salt claim 20 , hydrate or solvate thereof.26. The method of claim 19 , wherein the compound is 2-(diethylaminomethyl)-4-[4-[3-(diethylaminomethyl)-4-hydroxy-phenyl]hex-3-en-3-yl]phenol (G6) claim 19 , or a derivative thereof.27. The method of claim 26 , wherein the G6 derivative is a compound selected from Table 2 claim 26 , or a salt claim 26 , hydrate or solvate thereof.28. The method of claim 27 , wherein the G6 derivative compound is selected from the group consisting of: D4 claim 27 , D5 claim 27 , D28 and D30.29. The method of claim 19 , wherein the compound or a salt claim 19 , hydrate or solvate thereof claim 19 , is an inhibitor of the Jak2-V617F mutant.30. The method of claim 19 , wherein the compound or a salt claim 19 , hydrate or solvate thereof claim 19 , inhibits Jak2 autophosphorylation.31. The method of claim 30 , wherein the compound or a salt claim 30 , hydrate or solvate thereof does not inhibit c-Src or Tyk2 autophosphorylation as effectively as Jak2 autophosphorylation.3239-. ( ...

Crystalline Forms of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride

A hitherto unknown crystalline form of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence. 1. A process for producing a (−)-(1R ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A , said process comprising:dissolving a (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B in acetone, acetonitrile or isopropanol to form a solution;leaving the solution to crystallize andisolating crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A.2. The process of claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B is dissolved in acetonitrile claim 1 , and further comprising the steps of:stirring the solution;removing insoluble residue by filtering andevaporating the acetonitrile leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize.3. The process according to claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at temperatures above room temperature claim 1 , and after complete dissolution no further heat is provided and further comprising:adding seed crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A and then cooling the mixture down to ≦15° C.4. The process of claim 3 , wherein said (−)-(1R claim 3 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at a temperature above 65° C. but not exceeding 80° C.5. The process of claim 3 , wherein said mixture is cooled down to ≦10 ...

MESCALINE DERIVATIVES WITH MODIFIED ACTION

A composition for use in substance-assisted therapy, wherein: R is hydrogen, methyl, or ethyl, and R′ is C-Cbranched or unbranched alkyl with the alkyl optionally substituted with F-Ffluorine substituents up to a fully fluorinated alkyl, C-Ccycloalkyl optionally and independently substituted with one or more substituents such as F-Ffluorine and/or C-Calkyl, (C-Ccycloalkyl)-C-Cbranched or unbranched alkyl optionally substituted with one or more substituents such as F-Ffluorine and/or C-Calkyl, or C-Cbranched or unbranched alkenyl with E or Z vinylic, cis or trans allylic, E or Z allylic or other double bond position in relation to the attached ether function, where any of the carbons of the branched or unbranched alkenyl substituent is optionally substituted independently with one or more C-Calkyl, with F-Ffluorine or with D-Ddeuteron substituents. 1. A composition comprising a compound represented by , which ischaracterized in that R is one of the following substituents: hydrogen, methyl, or ethyl, and further characterized in that R′ is one of the following substituents{'sub': 1', '5', '1', '5, 'C-Cbranched or unbranched alkyl with the alkyl optionally substituted with F-Ffluorine substituents up to a fully fluorinated alkyl, or'}{'sub': 3', '6', '1', '5', '1', '2, 'C-Ccycloalkyl optionally and independently substituted with one or more substituents such as F-Ffluorine and/or C-Calkyl, or'}{'sub': 3', '6', '1', '2', '1', '5', '1', '2, '(C-Ccycloalkyl)-C-Cbranched or unbranched alkyl optionally substituted with one or more substituents such as F-Ffluorine and/or C-Calkyl, or'}{'sub': 2', '5', '1', '2', '1', '5', '1', '5, 'C-Cbranched or unbranched alkenyl with E or Z vinylic, cis or trans allylic, E or Z allylic or other double bond position in relation to the attached ether function, where any of the carbons of the branched or unbranched alkenyl substituent is optionally substituted independently with one or more C-Calkyl, with F-Ffluorine or with D-Ddeuteron ...

PHARMACEUTICAL SALTS

The invention relates to pharmaceutical salts comprised of a pharmaceutical active substance and of at least one sugar substitute, to medicaments containing these salts, and to the use of these salts for producing medicaments. 1. A pharmaceutical salt of a salt-forming pharmaceutical active compound and at least one salt-forming sugar substitute , wherein the salt-forming pharmaceutical active compound is a salt-forming 1-phenyl-3-dimethylaminopropane compound selected from the group consisting of: (a) (−)-(1R ,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol; (b) (1RS ,3RS ,6RS)-6-Dimethylaminomethyl-1-(3-methoxy-phenyl)-cyclohexane-1 ,3-diol; and (c) (−)-(1R ,2R)-3-(2-Dimethylaminomethyl-cyclohexyl)-phenol.2. The pharmaceutical salt according to claim 1 , wherein the salt-forming pharmaceutical active compound is (−)-(1R claim 1 ,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol.3. The pharmaceutical salt according to claim 1 , wherein the salt-forming pharmaceutical active compound is (1RS claim 1 ,3RS claim 1 ,6RS)-6-Dimethylaminomethyl-1-(3-methoxy-phenyl)-cyclohexane-1 claim 1 ,3-diol.4. The pharmaceutical salt according to claim 1 , wherein the salt-forming pharmaceutical active compound is (−)-(1R claim 1 ,2R)-3-(2-Dimethylaminomethyl-cyclohexyl)-phenol.5. A pharmaceutical composition comprising a therapeutically effective amount of the pharmaceutical salt according to and optionally one or more physiologically tolerable excipients.6. A method of controlling pain comprising administering to a patient in need thereof a pain-controlling effective amount of the pharmaceutical salt of .7. A method of controlling urinary incontinence comprising administering to a patient in need thereof an urinary incontinence-controlling effective amount of the pharmaceutical salt of . This application is a continuation of U.S. application Ser. No. 13/295,242 filed Nov. 14, 2011, now allowed; which is a continuation of U.S. application Ser. No. 12/487,760 filed Jun. ...

DESFESOTERODINE SALTS

The invention relates to substantially pure Desfesoterodine salts, Desfesoterodine salts, solid state forms thereof and pharmaceutical compositions comprising one or more of the Desfesoterodine salts and/or solid state forms thereof. 1. A succinate salt of Desfesoterodine.2. The succinate salt of Desfesoterodine of claim 1 , wherein the succinate salt of Desfesoterodine is isolated.3. The succinate salt of Desfesoterodine of claim 1 , wherein the succinate salt is in an anhydrous form.4. The succinate salt of claim 1 , wherein the succinate salt of Desfesoterodine is in solid form.5. The succinate salt of Desfesoterodine of claim 1 , wherein the molar ratio between Desfesoterodine and succinic acid is 1:1 to 1:1.5 claim 1 , respectively.6. The succinate salt of Desfesoterodine of claim 1 , having a chemical purity of at least 95% claim 1 , >98% claim 1 , or >99% by HPLC/UV (area %).7. The succinate salt of Desfesoterodine of claim 1 , wherein the salt is in a crystalline form.8. The succinate salt of Desfesoterodine of claim 7 , wherein the crystalline form of Desfesoterodine succinate is designated as Form S1 and is characterized by data selected from the group consisting of:an X-ray powder diffraction pattern having peaks at 7.4, 16.8, 18.0, 21.7 and 27.4 degrees two theta±0.2 degrees two theta;{'figref': {'@idref': 'DRAWINGS', 'FIG. 5'}, 'an X-ray powder diffraction pattern substantially as depicted in ;'}and combinations thereof.9. The succinate salt of Desfesoterodine of claim 8 , wherein the crystalline form of Desfesoterodine succinate is further characterized by data selected from the group consisting of:an X-ray powder diffraction pattern having any one, two, three, four or five additional peaks selected from peaks at 9.3, 12.2, 14.6, 19.6 and 24.5 degrees two theta±0.2 degrees two theta;a DSC curve having an endothermic peak at about 169° C.±2,{'figref': {'@idref': 'DRAWINGS', 'FIG. 3'}, 'a DSC curve substantially as depicted in ;'}and combinations thereof ...

Novel D3 Dopamine Receptor Agonists to Treat Dyskinesia in Parkinson's Disease

The present invention provides a method of inhibiting, suppressing or preventing levodopa-induced dyskinesia in a patient suffering from Parkinson's Disease, comprising the step of administering to the patient a pharmaceutical composition comprising at least one compound of the invention. The present invention further provides a method of inhibiting, suppressing or preventing Parkinson's Disease in a patient, comprising the step of administering to the patient a pharmaceutical composition comprising at least one compound of the invention. 16-. (canceled)8. The method of claim 7 , wherein in formula (I) R claim 7 , Rand Rare independently selected from the group consisting of H claim 7 , cyano claim 7 , halo claim 7 , alkoxy claim 7 , nitro claim 7 , Calkyl claim 7 , and carboxy.9. The method of claim 7 , wherein in formula (I) Rand Rare independently selected from the group consisting of H claim 7 , Calkyl claim 7 , and substituted Calkyl.10. The method of claim 7 , wherein in formula (I) n is 2.11. (canceled)12. The method of claim 7 , wherein said at least one compound is selected from the group consisting of:2-amino-4-(2-chlorophenyl)butan-1-ol;2-(3-aminohexyl)phenol;4-(2-chlorophenyl)-2-methylamino-butane;4-(2-fluorophenyl)butan-2-amine;4-(2-bromophenyl)butan-2-amine;4-(2-iodophenyl)butan-2-amine;4-(2-methoxyphenyl)butan-2-amine;2-(3-aminobutyl)phenol;3-(3,4-diethoxyphenyl)propan-1-amine;4-(4-chlorophenyl)butan-2-amine;4-(4-methoxyphenyl)butan-2-amine;mixtures thereof, or a pharmaceutically acceptable salt thereof.13. The method of claim 7 , wherein said composition further comprises a drug selected from the group consisting of levodopa claim 7 , clozapine claim 7 , bromocriptine claim 7 , pergolide claim 7 , pramipexole claim 7 , ropinirole claim 7 , piribedil claim 7 , cabergoline claim 7 , apomorphine claim 7 , and lisuride claim 7 , a salt thereof and mixtures thereof.14. The method of claim 7 , wherein said pharmaceutical composition is co-administered to ...

Novel D3 Dopamine Receptor Agonists to Treat Dyskinesia in Parkinson's Disease

The present invention provides a method of inhibiting, suppressing or preventing levodopa-induced dyskinesia in a patient suffering from Parkinson's Disease, comprising the step of administering to the patient a pharmaceutical composition comprising at least one compound of the invention. The present invention further provides a method of inhibiting, suppressing or preventing Parkinson's Disease in a patient, comprising the step of administering to the patient a pharmaceutical composition comprising at least one compound of the invention. 2. The pharmaceutical composition of claim 1 , wherein in formula (I) R claim 1 , Rand Rare independently selected from the group consisting of H claim 1 , cyano claim 1 , halo claim 1 , alkoxy claim 1 , nitro claim 1 , Calkyl claim 1 , and carboxy.3. The pharmaceutical composition of claim 1 , wherein in formula (I) Rand Rare independently selected from the group consisting of H claim 1 , Calkyl claim 1 , and substituted Calkyl.4. The pharmaceutical composition of claim 1 , wherein in formula (I) n is 2.5. (canceled)721-. (canceled)23. The compound of claim 22 , wherein in formula (I) R claim 22 , Rand Rare independently selected from the group consisting of H claim 22 , cyano claim 22 , halo claim 22 , alkoxy claim 22 , nitro claim 22 , Calkyl claim 22 , and carboxy.24. The compound of claim 22 , wherein in formula (I) Rand Rare independently selected from the group consisting of H claim 22 , Calkyl claim 22 , and substituted Calkyl.25. The compound of claim 22 , wherein in formula (I) n is 2.26. (canceled)28. A pharmaceutical composition comprising 4-(2-chlorophenyl)-butan-2-amine. The present application is a 35 U.S.C. §371 national phase application of, and claiming priority to, International Application No. PCT/US2011/047263, filed Aug. 10, 2011, and published under PCT Article 21(2) in English, which claims priority to U.S. Provisional Application No. 61/372,733, filed Aug. 11, 2010, all of which applications are hereby ...

Method For Synthesizing Catecholamines By Using Plasma Polymerization

A method is provided for preparing a catecholamine-based compound by using plasma polymerization, and more specifically, to a method for artificially synthesizing various catecholamines, that is, monomolecular compounds capable of having a hydroxyl group (—OH) as an ortho group of a benzene ring and various alkylamines as a para group thereof from a catecholamine precursor material such as phenol or aniline by using dry plasma polymerization. 1. A method for synthesizing a catecholamine using a plasma polymerization method , wherein the plasma polymerization method is conducted using at least one compound selected from the group consisting of benzene , aniline , phenol , benzylamine , phenethylamine , pyrocatechol , 2-hydroxypyridine , 3-hydroxypyridine , 4-hydroxypyridine , anthracene , naphthalene , 2-naphthol , 9-anthracenol , 2-anthracenol , and 1-anthracenol as a starting material.2. The method for synthesizing a catecholamine of claim 1 , wherein the starting material is the benzene claim 1 , the aniline or the phenol.3. The method for synthesizing a catecholamine of claim 2 , wherein the starting material is the aniline.4. The method for synthesizing a catecholamine of claim 1 , wherein the plasma polymerization method is a dry plasma polymerization method.5. The method for synthesizing a catecholamine of claim 1 , wherein the catecholamine thus synthesized is formed as a thin film shape.6. The method for synthesizing a catecholamine of claim 1 , wherein the catecholamine is selected from the group consisting of dopamine claim 1 , dopamine-quinone claim 1 , alpha-methyldopamine claim 1 , norepinephrine claim 1 , epinephrine claim 1 , alphamethyldopa claim 1 , droxidopa claim 1 , and 5-hydroxydopamine.7. The method for synthesizing a catecholamine of claim 6 , wherein the catecholamine is dopamine.8. The method for synthesizing a catecholamine of claim 4 , wherein the dry plasma polymerization method uses:an argon or nitrogen gas as a carrier gas; andat least ...

PROCESS FOR PRODUCING PHENALKAMINES

The present invention relates to a new method of making phenalkamines, products produced by such method, and use of such products. The method provides for phenalkamines obtained by an amine exchange reaction of a cardanol derived Mannich base with a compound with at least one alkylene or aralkylene group and at least two amino groups. These products may be used to cure, harden, and/or crosslink an epoxy resin. The curing agent compositions of this invention are of low viscosity and can be used neat or dissolved in a minimum amount of an organic solvent or diluent to effect cure of epoxy resins. 2. A method according to claim 1 ,wherein the secondary amine is dimethylamine.3. A method according to claim 1 , {'br': None, 'sub': 2', '2', 'x', 'm, 'NH[(CH)NH]—Z \u2003\u2003(VIII)'}, 'wherein the compound with at least one alkylene or aralkylene group is represented by the following formula (VIII)'}{'sub': 2', 'p, 'wherein x=2-10, m=1-10, Z is H or (CH)(OH) and p is 2 or 3.'}6. A method according to claim 3 ,wherein the compound of formula (VIII) is a mixture of triethylenetetramine, tetraethylenepentamine, hydroxyethyl diethylenetriamine and hydroxyethyl triethylenetetramine.7. A method according to claim 3 ,wherein in formula (VIII) Z═H, m=5-10 and x=2.8. A method according to claim 3 ,wherein the compound of formula (VIII) is N,N′-1,2-ethanediyl-bis-1,3-propanediamine.9. A phenalkamine produced by a process according to .10. (canceled)11. (canceled)14. An amine-epoxy composition comprising the reaction product of a phenalkamine according to and an epoxy component.15. An article of manufacture comprising the amine-epoxy composition according to .16. The article of manufacture of claim 15 , wherein the article is an adhesive claim 15 , a coating claim 15 , a primer claim 15 , a sealant claim 15 , a curing compound claim 15 , a construction product claim 15 , a flooring product claim 15 , a composite product claim 15 , a laminate claim 15 , a potting compound claim 15 , ...

Crystalline Forms of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride

A hitherto unknown crystalline form of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence. 1. A process for producing a (−)-(1R ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A , said process comprising:dissolving a (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B in acetone, acetonitrile or isopropanol to form a solution;leaving the solution to crystallize andisolating crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A.2. The process of claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B is dissolved in acetonitrile claim 1 , and further comprising the steps of:stirring the solution;removing insoluble residue by filtering andevaporating the acetonitrile leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize.3. The process according to claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at temperatures above room temperature claim 1 , and after complete dissolution no further heat is provided and further comprising:adding seed crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A and then cooling the mixture down to ≦15° C.4. The process of claim 3 , wherein said (−)-(1R claim 3 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at a temperature above 65° C. but not exceeding 80° C.5. The process of claim 3 , wherein said mixture is cooled down to ≦10 ...

STABLE POLYMORPH FORM B OF TAPENTADOL HYDROCHLORIDE

The present disclosure relates to Tapentadol Hydrochloride in the polymorphic crystalline Form B, which is substantially free of polymorphic Form A as well as essentially free of low alkyl carboxylic acids or esters of such acids. Furthermore, the present disclosure provides a process to produce this polymorphic Form B substantially free of Form A and its preparation and use for pharmaceutical compositions. This process as well as the specific crystalline form is uncommon, improved and industrially advantageous. Furthermore, the disclosure relates to pharmaceutical compositions and uses thereof. 1. A Tapentadol Hydrochloride in stable polymorphic crystal Form B which is substantially free of polymorphic crystal Form A , wherein the composition exhibits a PXRD pattern in which the intensity of peaks at 2Theta 18.89° , 22.58° and 24.28° (+−0.3°) are each ≦1.5% , preferably ≦1% relative to the peak at 2Theta 14.55° (+−0.3°) , more specifically at 2Theta 18.25° , 18.89° , 22.58° and 24.28° (+−0.3°) are each ≦1.5% , preferably ≦1% relative to the peak at 2Theta 14.55° (+−0.3°).2. The Tapentadol Hydrochloride according to claim 1 , wherein the composition exhibits a PXRD pattern having peaks at 2Theta 17.99° claim 1 , 19.58° and 21.99° (+−0.3°) claim 1 , wherein the Full-Width-at-Half-Maximum (FWHM) of each of these peaks is ≦0.2 claim 1 , preferably ≦0.16.3. The Tapentadol Hydrochloride according to claim 2 , wherein the composition exhibits a PXRD pattern furthermore has a peak at 2Theta 28.17° (+−0.3°) claim 2 , wherein the Full-Width-at-Half-Maximum (FWHM) of the peak is ≦0.2 claim 2 , preferably ≦0.16.4. A process of preparing Tapentadol Hydrochloride substantially in a stable polymorphic pure Form B claim 2 , wherein the process comprises the removal of nucleation centers and subsequent crystallization.5. A process of preparing Tapentadol Hydrochloride substantially in a stable polymorphic pure Form B claim 2 , wherein the process comprises the step of filtering a ...

METHODS FOR TREATING INFLAMMATION AND HYPERTENSION WITH GAMMA-KETOALDEHYDE SKAVENGERS

A method of treating at least one of inflammation, psoriasis, and/or hypertension comprising administering to a patient in need there of an effective gamma-ketoaldehyde scavenging amount of a gamma-ketoaldehyde scavenging compound.

Curing Agent for Low Temperature Cure Applications

The present invention provides Mannich base derivatives of N,N′-dimethyl secondary diamine polymers including Mannich base derivatives of methylamine-terminated poly-(N-methylazetidine) and Mannich base derivatives of methylamine-terminated poly-(N-methylazacycloheptane). Amine curing agent compositions and amine-epoxy compositions containing Mannich base derivatives of N,N′-dimethyl secondary diamine polymers are also disclosed.

METHODS FOR PREVENTING AND TREATING URINARY INCONTINENCE

The disclosure relates to novel uses and methods for preventing and/or treating urinary incontinence, which employ a therapeutically effective amount of an ActRII receptor antagonist, e.g., an ActRII receptor binding molecule, e.g., an ActRII receptor antibody, such as the bimagrumab antibody. 1. A method for treating urinary incontinence , comprising administering an effective amount of an ActRII receptor antagonist to a subject having symptoms of urinary incontinence or at risk for developing urinary incontinence.2. The method according to claim 1 , wherein said urinary incontinence is selected from the group consisting of stress urinary incontinence claim 1 , urge urinary incontinence and reflex urinary incontinence.3. The method according to claim 1 , wherein the ActRII receptor antagonist is an ActRII receptor binding molecule.4. The method according to claim 1 , wherein the ActRII receptor antagonist is an anti-ActRII receptor antibody or an antigen-binding portion thereof.5. The method according to claim 1 , wherein the ActRII receptor antagonist is an anti-ActRII antibody or an antigen-binding portion thereof that binds to an epitope of ActRIIB consisting of amino acids 19-134 of SEQ ID NO: 181 (SEQ ID NO: 182).6. The method according to claim 1 , wherein the ActRII receptor antagonist is an anti-ActRII receptor antibody or an antigen-binding portion thereof claim 1 , and wherein the antibody or an antigen-binding portion thereof comprises a heavy chain variable region CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-14; a heavy chain variable region CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 15-28; a heavy chain variable region CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 29-42; a light chain variable region CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 43-56; a light chain variable ...

A NOVEL PROCESS FOR THE PREPARATION OF TAPENTADOL

The present invention relates to a novel process for the preparation of Tapentadol and intermediate compound 2R,3R)-3-(-methoxyphenyl)-N,N,2-trimethylpentanamine (compound of formula IIa). 2. The process according to claim 1 , wherein the at least one hydrosilane reagent is selected from the group consisting of triethylsilane claim 1 , trimethylsilane claim 1 , dimethylphenylsilane claim 1 , phenyl silane claim 1 , triphenylsilane claim 1 , trichlorosilane claim 1 , tris(trimethylsilyl)silane claim 1 , polymethylhydrosiloxane claim 1 , and mixtures thereof.3. The process according to claim 1 , wherein the at least one first acid is selected from the group consisting of titanium tetrachloride claim 1 , aluminium chloride claim 1 , aluminium bromide claim 1 , boron trifluoride claim 1 , boron tribromide claim 1 , tin tetrachloride claim 1 , tin tetrabromide claim 1 , stannous chloride claim 1 , ferric chloride claim 1 , zinc chloride claim 1 , trifluoroacetic acid claim 1 , p-toluolosulfonic acid claim 1 , methanesulfonic acid claim 1 , and mixtures thereof.4. (canceled)5. The process according to claim 1 , wherein the compound of formula IIIa is in the form of an acid addition salt.6. The process according to claim 5 , wherein the acid addition salt is a hydrochloride salt or a hydrobromide salt.7. (canceled)8. The process according to claim 2 , wherein the at least one first acid is selected from the group consisting of titanium tetrachloride claim 2 , aluminium chloride claim 2 , aluminium bromide claim 2 , boron trifluoride claim 2 , boron tribromide claim 2 , tin tetrachloride claim 2 , tin tetrabromide claim 2 , stannous chloride claim 2 , ferric chloride claim 2 , zinc chloride claim 2 , trifluoroacetic acid claim 2 , p-toluolosulfonic acid claim 2 , methanesulfonic acid claim 2 , and mixtures thereof.9. The process according to claim 1 , further comprising:treating the compound of formula IIa with at least one second acid to form an acid addition salt via the ...

Macrocyclic Ghrelin Receptor Modulators and Methods of Using the Same

The present invention provides novel conformationally-defined macrocyclic compounds that can function as selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, bone disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders. 2. The method of claim 1 , wherein the gastroparesis is diabetic gastroparesis or postsurgical gastroparesis syndrome.3. The method of claim 1 , wherein the compound is administered orally.4. The method of claim 1 , wherein the compound is administered parenterally.5. The method of claim 1 , wherein the subject is a mammal.6. The method of claim 1 , wherein the subject is a human.7. The method of claim 1 , wherein the subject is a horse.8. The method of claim 1 , wherein the compound is co-administered with an additional agent useful for stimulating gastrointestinal motility.10. The method of claim 9 , wherein the gastroparesis is diabetic gastroparesis or postsurgical gastroparesis syndrome.11. The method of claim 9 , wherein the compound is administered orally.12. The method of claim 9 , wherein the compound is administered parenterally.13. The method of claim 9 , wherein the subject is a mammal.14. The method of claim 9 , wherein the subject is a human.15. The method of claim 9 , wherein the subject is a horse.16. The method of claim 9 , wherein the compound is co-administered with an additional agent useful for stimulating gastrointestinal motility. This application is a continuation of U.S. patent application Ser. No. 15/178, ...

Crystalline Forms of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride

A hitherto unknown crystalline form of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence. 1. A process for producing a (−)-(1R ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A , said process comprising:dissolving a (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B in acetone, acetonitrile or isopropanol to form a solution;leaving the solution to crystallize andisolating crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A.2. The process of claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B is dissolved in acetonitrile claim 1 , and further comprising the steps of:stirring the solution;removing insoluble residue by filtering andevaporating the acetonitrile leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize.3. The process according to claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at temperatures above room temperature claim 1 , and after complete dissolution no further heat is provided and further comprising:adding seed crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A and then cooling the mixture down to ≤15° C.4. The process of claim 3 , wherein said (−)-(1R claim 3 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at a temperature above 65° C. but not exceeding 80° C.5. The process of claim 3 , wherein said mixture is cooled down to ≤10 ...

PHENOLIC EPOXY COMPOUNDS

Disclosed herein are compositions and methods of making phenolic compounds, and resins comprising these phenolic compounds. The compounds include multifunctional epoxies, amino glycidyl derivatives, and multi-functional amines prepared from hydroxymethyl derivatives of phenols and bisphenols 2. The method of claim 1 , wherein the phenolic compound is phenol claim 1 , bisphenol A claim 1 , bisphenol F claim 1 , bisphenol S claim 1 , bisphenol sulphone claim 1 , bisphenol sulfoxide claim 1 , bisphenol chloral claim 1 , bisphenolvinylidene dichloride claim 1 , or bisphenol methylenedifluoride.3. The method of claim 1 , wherein the hydroxymethyl compound is trihydroxymethyl phenol claim 1 , tetrahydroxymethyl bisphenol A claim 1 , tetrahydroxymethyl bisphenol F claim 1 , tetrahydroxymethyl bisphenol S claim 1 , tetrahydroxymethyl bisphenol sulphone claim 1 , tetrahydroxymethyl bisphenol sulfoxide claim 1 , tetrahydroxymethyl bisphenol chloral claim 1 , tetrahydroxymethyl bisphenolvinylidene dichloride claim 1 , or tetrahydroxymethyl bisphenol methylenedifluoride.4. The method of claim 1 , wherein contacting the phenolic compound with the formaldehyde or the paraformaldehyde comprises contacting about 1 mole of the phenolic compound with about 3 moles to about 5 moles of the formaldehyde or the paraformaldehyde in presence of a basic catalyst.5. The method of claim 4 , wherein contacting the phenolic compound with the formaldehyde or the paraformaldehyde in the presence of the basic catalyst comprises mixing the phenolic compound claim 4 , the formaldehyde or the paraformaldehyde claim 4 , and the basic catalyst in a solution having a pH of about 8 to about 10.6. The method of claim 4 , wherein contacting the phenolic compound with the formaldehyde or the paraformaldehyde in the presence of the basic catalyst comprises heating the phenolic compound claim 4 , the formaldehyde or the paraformaldehyde claim 4 , and the basic catalyst to a temperature of about 50° C. to ...

CRYSTALLINE FORMS OF (-)-(1R,2R)-3-(3-DIMETHYLAMINO-1-ETHYL-2-METHYLPROPYL)-PHENOL HYDROCHLORIDE

A hitherto unknown crystalline form of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence. 1. A process for producing a (−)-(1R ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A , said process comprising:dissolving a (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B in acetone, acetonitrile or isopropanol to form a solution;leaving the solution to crystallize andisolating crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A.2. The process of claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B is dissolved in acetonitrile claim 1 , and further comprising the steps of:stirring the solution;removing insoluble residue by filtering andevaporating the acetonitrile leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize.3. The process according to claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at temperatures above room temperature claim 1 , and after complete dissolution no further heat is provided and further comprising:adding seed crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A and then cooling the mixture down to ≤15° C.4. The process of claim 3 , wherein said (−)-(1R claim 3 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at a temperature above 65° C. but not exceeding 80° C.5. The process of claim 3 , wherein said mixture is cooled down to ≤10 ...

HOLE TRANSPORTING ORGANIC MOLECULES CONTAINING ENAMINE GROUPS FOR OPTOELECTRONIC AND PHOTOELECTROCHEMICAL DEVICES

The present invention relates to a compound of formula (I) based on enamine derivatives and used as organic hole conductors or hole transporting material in an optoelectronic or photoelectrochemical device. The present invention relates to the hole transporting compounds based on enamine derivatives for efficiency perovskite or dye sensitized solar cells and optoelectronic devices, organic light-emitting diode (OLED), field-effect transistors (FET). 2. The compound of the general formula (I) according to being selected from any one of compounds:9-ethyl-3-{N,N-bis[2,2-bis(4-methoxyphenyl)vinyl]amino}-9H-carbazole (1);9-butyl-3-{N,N-bis[2,2-bis(4-methoxyphenyl)vinyl]amino}-9H-carbazole (2);9-hexyl-3-{N,N-bis[2,2-bis(4-methoxyphenyl)vinyl]amino}-9H-carbazole (3);9-(2-ethylhexyl)-3-{N,N-bis[2,2-bis(4-methoxyphenyl)vinyl]amino}-9H-carbazole (4);9-butyl-6-(-butyl)-3-{N,N-[2,2-bis(4-methoxyphenyl)vinyl]amino}-9H-carbazole (5);4-{N,N-bis[2,2-bis(4-methoxyphenyl)vinyl]amino}triphenylamine (6);9-butyl-3,6-bis {N3,N3,N6,N6-tetrakis(2,2-bis[4-methoxyphenyl)vinyl]amino}-9H-carbazole (7);9-(2-ethylhexyl)-3,6-bis {N3,N3,N6,N6-tetrakis(2,2-bis[4-methoxyphenyl)vinyl]-amino}-9H-carbazole (8).3. The compound of the general formula (I) according to for use in photovoltaic device as nonpolymeric hole transporting materials.4. A hole transporting material comprising at least one small molecule hole transporting material being selected from one of compounds of general formula (I) according to .5. A photovoltaic device comprising a compound of formula (I) according to .6. The photovoltaic device according to comprising a hole transporting material claim 5 , wherein said hole transporting material comprises the compound of formula (I).7. The photovoltaic device according to which is selected from an organic photovoltaic device claim 5 , a photovoltaic solid state device claim 5 , an p-n heterojunction claim 5 , an organic solar cell claim 5 , a dye sensitized solar cell claim 5 , and solid ...

Process for preparing tetracyclic heterocycle compounds

The present invention is directed to a process for preparing Tetracyclic Heterocycle Compounds of formula (I): which are useful as HCV NS5A inhibitors. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

Compounds and Methods for Preparing Substituted 3-(1-amino-2-methylpentane-3-yl)phenyl Compounds

Compounds and methods for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds from an isomerically pure starting material are described. In particular, methods of preparing a 3-(1-(dimethylamino)-2-methylpentane-3-yl)phenol as a substantially optically pure (R,R) stereoisomer are described. Using a method of the present invention, only the (R,R) and (S,S) stereoisomers of the target compound are produced, increasing the yield and stereoselectivity of the desired (R,R) stereoisomer. 17-. (canceled)9. (canceled)10. The method according to claim 8 , wherein the (R claim 8 ,R) stereoisomer is separated from the (S claim 8 ,S) stereoisomer by chromatography.11. The method of claim 10 , wherein the chromatography comprises one or more selected from the group consisting of batch chromatography claim 10 , supercritical fluid chromatography claim 10 , and continuous chromatography.12. The method of claim 10 , wherein the chromatography comprises a simulated moving bed chromatography.16. (canceled)18. The method according to claim 17 , wherein Rrepresents a hydrogen claim 17 , and Rrepresents a methyl.20. The method according to claim 19 , wherein Rrepresents a hydrogen claim 19 , and Rrepresents a methyl.22. The method according to claim 21 , wherein Rrepresents a hydrogen claim 21 , and Rrepresents a methyl.2324-. (canceled) Embodiments of the present invention relate to compounds and methods for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds with improved stereoselectivity and increased yield of the desired stereoisomers and method for preparing the compounds. In particular, the present invention relates compounds and methods for preparing a substantially optically pure (R,R) stereoisomer of 3-(1-(dimethylamino)-2-methylpentane-3-yl)phenol (tapentadol) from a substantially isomerically pure starting material.Substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds have potent analgesic effects. One 3-(1-amino-2-methylpentane-3 ...

PHENALKAMINE EPOXY CURING AGENTS AND EPOXY RESIN COMPOSITIONS CONTAINING THE SAME

The present invention relates to a new structural class of phenalkamines, curing agent compositions comprising the phenalkamines, their use, as well as and methods of producing such phenalkamines and compositions. The phenalkamines of the present invention can be prepared by reacting cardanol with an aldehyde compound and triaminononane. These curing-agent compositions may be used to cure, harden, and/or crosslink an epoxy resin. The curing-agent compositions of this invention are of low viscosity and can be used neat or dissolved in a minimum amount of an organic solvent or diluent to effect cure of epoxy resins.

SOLID STATE FORMS OF TAPENTADOL SALTS

Provided herein are novel solid state forms of tapentadol salts, process for their preparation, pharmaceutical compositions, and method of treating thereof. The tapentadol salts include an L-(−)-camphorsulfonate salt, a dibenzoyl-(L)-tartrate salt, a dibenzoyl-(D)-tartrate salt, a malate salt, a maleate salt, or a salicylate salt. 1. A solid state form of a salt of 3-[(1R ,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol (tapentadol salt) , wherein the salt of tapentadol is a maleate salt.2. The solid state form of tapentadol salt of claim 1 , which is in a crystalline form or in an amorphous form claim 1 , and wherein the solid state form is anhydrous and/or solvent-free form claim 1 , or a hydrate and/or a solvate form.3. The solid state form of tapentadol salt of claim 1 , wherein the solid state form of tapentadol maleate salt is characterized by one or more of the following properties:{'figref': {'@idref': 'DRAWINGS', 'FIG. 9'}, 'i) a powder X-ray diffraction pattern substantially in accordance with ;'}ii) a powder X-ray diffraction pattern having peaks at about 15.31, 16.08, 21.08, 27.95, 28.53 and 29.51±0.2 degrees 2-theta;iii) a powder X-ray diffraction pattern having peaks at about 19.13, 20.44, 22.90, 24.76, 30.66, 31.06, 31.81, 33.80, 34.84, 35.29, 38.31, 40.26, 40.68 and 43.16±0.2 degrees 2-theta; and{'figref': {'@idref': 'DRAWINGS', 'FIG. 10'}, 'iv) a differential scanning calorimetric (DSC) thermogram substantially in accordance with ;'}4. A process for the preparation of solid state form of tapentadol salt of claim 1 , comprising:a) providing a first solution or a suspension of tapentadol free base in a solvent, wherein the solvent is water, an alcohol, a ketone, a nitrile, a polar aprotic solvent, or a mixture thereof;b) combining the first solution or suspension with an acid to produce a second solution or suspension containing a tapentadol acid addition salt, wherein the acid is maleic acid; andc) isolating and/or recovering the solid state form ...

COMPOSITIONS AND METHODS OF REGULATING CANCER RELATED DISORDERS AND DISEASES

Provided herein are naphthylic derivative compounds, or pharmaceutically acceptable salts thereof, that are useful for inhibiting cancers. Also provided herein are methods of using effective amounts of said compounds, optionally with pharmaceutical carriers, for the treatment of cancers within human subjects. 2. The compound of claim 1 , wherein{'sub': 1', '3, 'Rand Rare either hydrogen or alkyl groups;'}{'sub': '4', 'Ris hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted alkyl chains terminating in a substituted or unsubstituted aryls;'}{'sub': '2', 'Ris a substituted or unsubstituted naphthyl group optionally linked by a substituted or unsubstituted alkyl chain; and'}{'sub': 1', '8, 'each Y-Yare independently selected from hydrogen, deuterium, halogen (F, Cl, Br, I), hydroxyl, alkoxy, primary amines, substituted secondary and tertiary amines, thiols, sulfoxides, sulfones, sulfanamides, substituted or unsubstituted alkyl and substituted or unsubstituted aryls.'}3. The compound of claim 1 , wherein{'sub': 1', '3, 'Rand Rare either hydrogen or alkyl groups;'}{'sub': '4', 'Ris hydrogen, substituted or unsubstituted aryl or substituted or unsubstituted alkyl chains terminating in a substituted or unsubstituted aryls;'}{'sub': '2', 'Ris a substituted or unsubstituted naphthyl group optionally linked by a substituted or unsubstituted alkyl chain; and'}{'sub': 1', '8, 'each Y-Yare independently selected from hydrogen, deuterium, halogen (F, Cl, Br, I), hydroxyl, alkoxy, primary amines, substituted secondary and tertiary amines, thiols, sulfoxides, sulfones, sulfanamides, substituted or unsubstituted alkyl and substituted or unsubstituted aryls.'}4. The compound of claim 1 , wherein{'sub': 1', '3, 'Rand Rare either hydrogen or alkyl groups;'}{'sub': '4', 'Ris hydrogen or a substituted or unsubstituted alkyl chains terminating in a substituted or unsubstituted aryls;'}{'sub': '2', 'Ris a substituted or ...

CRYSTALLINE FORMS OF (-)-(1R,2R)-3-(3-DIMETHYLAMINO-1-ETHYL-2-METHYLPROPYL)-PHENOL HYDROCHLORIDE

A hitherto unknown crystalline form of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence. 1. A process for producing a (−)-(1R ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A , said process comprising:dissolving a (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B in acetone, acetonitrile or isopropanol to form a solution;leaving the solution to crystallize andisolating crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A.2. The process of claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B is dissolved in acetonitrile claim 1 , and further comprising the steps of:stirring the solution;removing insoluble residue by filtering andevaporating the acetonitrile leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize.3. The process according to claim 1 , wherein said (−)-(1R claim 1 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at temperatures above room temperature claim 1 , and after complete dissolution no further heat is provided and further comprising:adding seed crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A and then cooling the mixture down to ≤15° C.4. The process of claim 3 , wherein said (−)-(1R claim 3 ,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B is dissolved in isopropanol at a temperature above 65° C. but not exceeding 80° C.5. The process of claim 3 , wherein said mixture is cooled down to ≤10 ...

Synthesis of benzylanilinyl phenyl phenol ligands

Synthetic methods for the preparation of ligands and metal-ligand complexes are disclosed.

苄基苯胺基苯基苯酚配体的合成

公开用于制备配体和金属‑配体络合物的合成方法。

Stable polymorph form b of tapentadol hydrochloride

The present invention relates to Tapentadol Hydrochloride in the polymorphic crystalline Form B, which is substantially free of polymorphic Form A as well as essentially free of low alkyl carboxylic acids or esters of such acids. Furthermore, the present invention provides a process to produce this polymorphic Form B substantially free of Form A and its preparation and use for pharmaceutical compositions. This process as well as the specific crystalline form is uncommon, improved and industrially advantageous. Furthermore, the invention relates to pharmaceutical compositions and uses thereof.

Process for the preparation of (1r,2r)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol

The present invention relates to a process for the preparation of (1 R,2R)-3- dimethylamino-1-ethyl-2-methyl-propyl)-phenol.

Preparation of 3-[(1r,2r)-3-(dimethylamino)-1ethyl-2-methylpropyl]phenol

The present invention relates to an improved process for the preparation of 3- [(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol monohydrochloride.

Preparation of 3-[(1R,2R)-3-(Dimethylamino)-1Ethyl-2-Methylpropyl]phenol

The present invention relates to an improved process for the preparation of 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol monohydrochloride.

Process for the Preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol

The present invention relates to a process for the preparation of (1R,2R)- 3 -dimethylamino- 1 -ethyl- 2 -methyl-propyl)-phenol.

NOVEL HYDROXYPHENETHYLAMINE DERIVATIVE AND ITS SALTS, METHOD OF PREPARATION, APPLICATION AS MEDICAMENTS AND USE AS A SPECIFIC PHARMACOLOGICAL TOOL

Improvements in or relating to propylamine derivatives

Calcium receptor-active molecules

The present invention features molecules which can modulate one or activities of an inorganic ion receptor. Preferably, the molecule can mimic or block the effect of extracellular Ca 2+ on a calcium receptor. The preferred use of such molecules is to treat diseases or disorders by altering inorganic ion receptor activity, preferably calcium receptor activity.

Calcium receptor-active molecules

The present invention relates to the different roles inorganic ion receptors have in cellular and body processes. The present invention features: (1) molecules which can modulate one or more inorganic ion receptor activities, preferably the molecule can mimic or block an effect of an extracellular ion on a cell having an inorganic ion receptor, more preferably the extracellular ion is Ca 2+ and the effect is on a cell having a calcium receptor; (2) inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (3) nucleic acids encoding inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (4) antibodies and fragments thereof, targeted to inorganic ion receptor proteins, preferably calcium receptor protein; and (5) uses of such molecules, proteins, nucleic acids and antibodies.

Patent FR2356417B1

Processo para preparacao de tolterodina

Synthesis of benzylanilinyl phenyl phenol ligands

Synthetic methods for the preparation of ligands and metal-ligand complexes are disclosed.

Method of producing (1r,2r)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol

FIELD: chemistry. SUBSTANCE: invention relates to an improved method of producing (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol or acid addition salt thereof. The method involves reaction of a compound of formula (V): , where R is -C 1-6 -alkyl, -C 3-8 -cycloalkyl, -C 1-3 -alkylene-phenyl, -C 1-3 -alkylene-naphthyl, tetrahydropyranyl or -C(=O)-C 1-6 -alkyl, with dimethylamine hydrochloride and paraformaldehyde in an inert reaction medium in Mannich conditions to obtain a compound of formula (VI): , separating the compound of formula (VI) by reaction with a chiral acid, and subsequent reaction with ethylmagnesium halide in an inert reaction medium in Grignard conditions to obtain a compound of formula (II): . Further, the compound of formula (II) undergoes dehydration and hydrogenation in the presence of a catalyst and hydrogen to obtain a compound of formula (III): , and protection is removed from the compound of formula (III) to obtain (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol. EFFECT: method enables to obtain a product with high output and high purity. 8 cl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 466 124 (13) C2 (51) МПК C07C 213/00 C07C 215/54 (2006.01) (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2009105817/04, 23.07.2007 (24) Дата начала отсчета срока действия патента: 23.07.2007 R U Приоритет(ы): (30) Конвенционный приоритет: 24.07.2006 EP 06015338.4 (72) Автор(ы): ХЕЛЛЬ Вольфганг (DE), ЦИММЕР Освальд (DE), БУШМАНН Хельмут Генрих (ES), ХОЛЕНЦ Йёрг (SE), ГЛАДОВ Штефан (CH) (73) Патентообладатель(и): ГРЮНЕНТАЛЬ ГМБХ (DE) (43) Дата публикации заявки: 27.08.2010 Бюл. № 24 (56) Список документов, цитированных в отчете о поиске: RU 2150465 С1, 10.06.2000. DD 124521 A1, 02.03.1977. WO 2004108658 A1, 16.12.2004. ЕР 0799819 А1, 08.10.1997. SU 446963 A3, 15.10.1974. KAMETANI T. et al. Synthesis of analgesics. XXVIII. Synthesis of 4-amino-3methyl-1, 2-diphenyl-2- ...

PROCESS FOR THE PREPARATION OF N, N-DIISOPROPYL-3-2-HYDROXY-5-METHYLPHENYL-3-PHENYL-PROPABAMMINE

Production method of optically active epoxy compound, complex used for the method and production method of the complex

[Problem] To provide a production method of optically active epoxy compound, and a complex used for the production method and a production method of the complex. [Means for solving the problem] The skeleton that is necessary for expressing a high catalyst activity of optically active titanium salan complex of formulae (1) and (1′) and the substituent that is useful therefor and the position of the substituent are identified, and it is found that optically active epoxy compounds can be produced with a high enantioselectivity and a high chemical yield compared with a case where the prior optically active titanium salan complex is used. The production method comprises subjecting a prochiral compound (formula (4), (5) or (6)) having carbon-carbon double bond in the molecule to asymmetric epoxidation to produce an optically active epoxy compound (formula (7), (8) or (9)). The present invention relates also to a complex used for the production method and a production method of the complex.

苯烷基胺衍生物、其作为环氧树脂组合固化剂的用途及含有这类化合物的可固化环氧树脂组合物

本发明涉及式(1)的化合物，式中：n是0、2、4或6；a、b和c彼此独立，是1或0；R 1-1a 、R 1-1b 和R 1-1c 彼此独立，是氢、含1～10个碳原子的烃基，该烃基是烷基、芳基、亚烷基、芳烷基或烷芳基，或含1～10个碳原子和至少1个杂原子的烃基，该杂原子可以是氧、硫或氮；R 2-1a 、R 3-1a 、R 4-1a 、R 5-1a 、R 2-1b 、R 3-1b 、R 4-1b 、R 5-1b 、R 2-1c 、R 3-1c 、R 4-1c 和R 5-1c ，是氢或C 1 -C 4 烷基；R 6-1a 、R 7-1a 、R 6-1b 、R 7-1b 、R 6-1c 和R 7-1c ，是C 1 -C 4 烷基；以及A是含5～7个碳原子的芳族或脂环族的环。本发明进一步涉及由槚如坚果壳液提取物与至少一种芳族或脂环族多胺和至少一种醛化合物相化合而制得的一种曼尼期碱反应产物、含有该产物的环氧树脂组合物和可固化配方以及使用这种组合物的方法。

Tertiary amine-containing polyols prepared in a mannich condensation reaction using a mixture of alkanolamines

Mannich polyols of low viscosity and reduced reactivity are prepared by condensing a phenolic compound with formaldehyde and a mixture of diethanolamine and at least one other alkanol amine. The condensation product is the alkoxylated to form a polyol which is particularly useful in preparing rigid polyurethane foam. The Mannich polyols of this invention are characterized by having surprisingly lower viscosities and reactivities as compared to Mannich polyols which are prepared using either diethanolamine or the other alkanolamine alone in the condensation reaction.

Process for preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol

本发明涉及(1R，2R)-3-(3-二甲胺基-1-乙基-2-甲基丙基)苯酚的制备方法。

Method of preparing racemic tolterodine

본 발명은 하기 화학식 (I)로 표시되는 N,N-디이소프로필-3-(2-하이드록시-5-메틸페닐)-3-페닐프로판아민('톨테로딘 라세미체'라고도 함)을 제조하는 방법에 관한 것으로, 6-메틸-4-페닐-3,4-디히드로쿠마린을 환원시켜 개환하고, 얻어진 알코올을 알킬술포닐 또는 아릴술포닐화하여 얻어진 화합물을 N,N-디이소프로필아민과 반응시키고, 이로부터 얻어진 화합물을 가수분해하여 톨테로딘 라세미체를 고순도로 용이하게 제조하기 위한 방법이다. 톨테로딘, 톨테로딘 라세미체, N,N-디이소프로필-3-(2-하이드록시-5-메틸페닐)-3-페닐프로판아민, (R)-N,N-디이소프로필-3-(2-하이드록시-5-메틸페닐)-3-페닐프로판아민, 6-메틸-4-페닐-3,4-디히드로쿠마린

Producing 3-[(1r,2r)-3-(dimethylamino)-1-ethyl-2-methylpropyl]-phenol

FIELD: chemistry. SUBSTANCE: present invention relates to an improved method of producing 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]-phenol of formula VIII or acid addition salt thereof, preferably hydrochloric acid. The method is characterised by the following steps: a) acylation of a compound of formula (VI), where R denotes a C 1-3 alkyl substituted with phenol (VI) (VII) with an acylating agent; b) hydrogenolysis of the obtained compound of formula (VII), where the acyl is selected from CH 3 -CO-, CF 3 -CO-, CH 2 Cl-CO-, CHCl 2 -CO and CCl 3 -CO-, using a palladium catalyst in an inert solvent in reaction conditions in the presence of hydrogen to form a product VIII with R 1 =H: (VIII) and d) optional conversion of the obtained unprotected product into an acid addition salt. EFFECT: novel intermediate compounds of formula (VII) are obtained, which are the subject of the present invention, wherein formation of undesirable isomers is reduced and aggressive highly flammable substances are not used. 13 cl, 4 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 463 290 (13) C2 (51) МПК C07C C07C C07C C07D 213/08 (2006.01) 215/54 (2006.01) 219/22 (2006.01) 309/12 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2009106169/04, 23.07.2007 (24) Дата начала отсчета срока действия патента: 23.07.2007 (73) Патентообладатель(и): ГРЮНЕНТАЛЬ ГМБХ (DE) (43) Дата публикации заявки: 27.08.2010 Бюл. № 24 (56) Список документов, цитированных в отчете о поиске: ЕР 693475 В1, 24.01.1996. WO 2005/000788 А1, 06.01.2005. Т HIYAMA «А Facile route to (±)-2-arylpropanoic acids», Synthesis, 1986, p.645-647. RU 2197474 C2, 27.01.2003. 2 4 6 3 2 9 0 R U (86) Заявка PCT: EP 2007/006514 (23.07.2007) C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 24.02.2009 (87) Публикация заявки РСТ: WO 2008/012046 (31.01.2008) Адрес для переписки: 105082, Москва, Спартаковский пер., 2, стр. 1, секция 1, этаж 3, "ЕВРОМАРКПАТ ...

Biocatalysts and methods for the synthesis of (S)-3-(1-aminoethyl)-phenol

The present disclosure provides engineered transaminase polypeptides having improved properties as compared to naturally occurring transaminases including the ability of converting the substrate, 3′-hydroxyacetophenone to (S)-3-(1-aminoethyl)-phenol in enantiomeric excess and high percentage conversion. Also provided are polynucleotides encoding the engineered transaminases, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases to synthesize (S)-3-(1-aminoethyl)-phenol and related compounds useful in the production of active pharmaceutical ingredients.

Method for prevention and treatment of urethra strictures and urethrostoma occlusion in cats

FIELD: veterinary science.SUBSTANCE: invention relates to methods for prevention and treatment of urethra strictures and urethrostoma occlusion in cats. That is ensured by administering bovhyaluronidaze azoximer into rectum in 750 ME 10 times every 2 days, and then 10 times, once every 3 days.EFFECT: invention provides prevention of urethra strictures and urethrostoma occlusion, as well as treatment of fibrous changes of urethral walls and scar changes of postoperative sutures after surgical intervention on bladder and urethra in animals.1 cl, 1 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 723 994 C1 (51) МПК A61K 38/16 (2006.01) A61P 19/04 (2006.01) A61P 13/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК A61K 38/16 (2020.02); A61P 19/04 (2020.02); A61P 13/00 (2020.02) (21)(22) Заявка: 2019132457, 14.10.2019 (24) Дата начала отсчета срока действия патента: 18.06.2020 Приоритет(ы): (22) Дата подачи заявки: 14.10.2019 (45) Опубликовано: 18.06.2020 Бюл. № 17 (54) Способ профилактики и лечения стриктур уретры и зарастания урестостомы у кошек (57) Реферат: Изобретение относится к способам профилактику структур уретры и зарастания профилактики и лечения стриктур уретры и уретростом, а также в лечение фиброзных зарастания уретростомы у кошек. Для этого изменений стенок уретры и рубцовых изменений бовгиалуронидазу азоксимер вводят ректально послеоперационных швов после хирургического по 750 ME 10 раз 1 раз в 2 дня, а затем еще 10 раз вмешательства на мочевом пузыре и уретре у 1 раз в 3 дня. Изобретение обеспечивает животных. 1 табл. R U 2 7 2 3 9 9 4 (56) Список документов, цитированных в отчете о поиске: RU 2217066 C2, 27.11.2003. CN 105998706 A, 12.10.2016. WO 2009053842 A3, 30.04.2009. СЕМЕНОВ Б.С. и др. Перинеальная уретростомия у котов: "за" и "против" // Международный вестник ветеринарии. - 2018, N2, с.130-135. TOBIAS, KAREN М. Perineal Urethrostomy in the Cat / Karen M. Tobias // NAVC clinician`s brief. - ...

Process for preparing tetracyclic heterocycle compounds

The present invention is directed to a process for preparing Tetracyclic Heterocycle Compounds of formula (I): which are useful as HCV NS5A inhibitors. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

Process for making group II metal carbonated, overbased Mannich condensation products of alkylphenols

This invention is directed to a novel process for making Group II metal carbonated, overbased Mannich condensation products of alkylphenols, which process uses ethylene carbonate as both a source of carbon dioxide and ethylene glycol. In particular, under the reaction conditions using ethylene carbonate in the present invention, carbonation and overbasing Mannich condensation products of alkylphenols is possible while at the same time the viscosity of the carbonated, overbased Mannich condensation products of alkylphenols remains within acceptable levels, typically under 1000 cSt at 100° C. The present invention is also directed to carbonation of Mannich condensation products of alkylphenols using a C 2 -C 6 alkaline glycol and carbon dioxide. The present invention is also directed to a detergent-dispersant antioxidant additive composition comprising Group II metal carbonated, overbased Mannich condensation products of alkylphenols, wherein the Group II metal carbonated, overbased Mannich condensation products of alkylphenols have a CO 2 to Ca ratio of at least 0.01.

Phellodendrine analogs and allergy type iv suppressor containing the same as active ingredient

Phellodendrine analogs represented by general formula (I), wherein A represents the group (a); B represents hydrogen, lower alkyl or lower acyl, or alternatively A and B together with the adjacent nitrogen atom form a substituted 1,2,3,4-tetrahydroisoquinoline ring represented by general formula (II), R₁₁, R₁₂, R₂₁, R₂₂, R₃₁ and R₃₂ represent each hydrogen, hydroxyl or lower alkoxy; n₁ represents a number of 0 to 2; n₂ represents a number of 1 and 2; and m₁ represents a number of 0 to 1, provided tsat when A represents the group (b), and n₂ is 2, B is lower acyl, and that when A and B together form a substituted 1,2,3,4-tetrahydroisoquinoline ring, n₁ is 1 and m₁ is not 0. These analogs (I) and related compounds have an excellent activity of suppressing allergy type IV and hence are utilizable as a medicine efficacious against diseases wherein allergy type IV participates, such as chronic hepatitis, intractable asthma, nephrotic syndrome or rheumatism.

Process for preparation of a substance having a diuretic activity

FIELD: pharmaceuticals. SUBSTANCE: invention relates to chemical-pharmaceutical industry, namely to method for producing an agent having a diuretic activity. Method consists in that the leaves of barren myrtle are extracted with 70 % ethyl alcohol, first performing two extractions at room temperature for 24 hours, and then when heated in a boiling water bath for 30 minutes; the combined recovery is evaporated in vacuo, mixed with silica gel in a ratio of the initial mass of the raw material and the sorbent 3:1, and dried in air; the dried powder is applied to a silica gel layer formed as a slurry in chloroform and subjected to chromatographic separation using chloroform mixtures and ethyl alcohol in a gradient mode, followed by separation from the fractions obtained by elution with a mixture of ethyl chloroform-ethyl alcohol -75:25 and 70:30, 1,3,6-trigalloylglucose – substances with diuretic activity. EFFECT: above-described method allows to obtain a compound with a high diuretic activity. 1 cl, 1 dwg, 1 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 671 408 C1 (51) МПК A61K 36/45 (2006.01) B01D 11/02 (2006.01) A61P 13/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК A61K 36/45 (2006.01); B01D 11/02 (2006.01); A61P 13/00 (2006.01); A61K 2121/00 (2006.01) (21)(22) Заявка: 2017136358, 13.10.2017 (24) Дата начала отсчета срока действия патента: Дата регистрации: 31.10.2018 (45) Опубликовано: 31.10.2018 Бюл. № 31 2 6 7 1 4 0 8 R U (56) Список документов, цитированных в отчете о поиске: КАЧАЛИНА Т.В. Разработка технологии получения твердых лекарственных форм, содержащих растительные экстракты //Автореф.дис. канд. фарм. наук. научно-исслед. институт фармации, Москва, 1994. RU 2064301 C1, 27.07.1996. RU 2174004 C1, 27.09.2001. RU 2205655 C1, 10.06.2003. (54) Способ получения вещества, обладающего диуретической активностью (57) Реферат: Изобретение относится к химиковысушенный порошок наносят на слой ...

Novel arylaminopropane analogues and their use for the treatment of glaucoma

Arylaminopropane analogues are disclosed. Also disclosed are methods for the lowering and controlling of normal or elevated intraocular pressure as well as a method for the treatment of glaucoma using compositions containing one or more of the compounds of the present invention.

Process for the preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol

본 발명은 (1R,2R)-3-(3-디메틸아미노-1-에틸-2-메틸-프로필)-페놀의 제조방법에 관한 것이다. The present invention relates to a process for the preparation of (1R, 2R) -3- (3-dimethylamino-1-ethyl-2-methyl-propyl) -phenol. (1R,2R)-3-(3-디메틸아미노-1-에틸-2-메틸-프로필)-페놀 (1R, 2R) -3- (3-dimethylamino-1-ethyl-2-methyl-

Method of synthesis of tolterodine and intermediate compound

FIELD: organic chemistry, chemical technology. SUBSTANCE: invention relates to method of synthesis of tolterodine of the formula (I) and 3,4-dihydro-6-methyl-4-phenyl-2H-benzo-pyrane-2-ol of the formula (IV) as a novel intermediate compound. Method involves reduction reaction of lactone of the formula (III) Этс9Ьс ПЧ с» РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) (13) (11) КО 2176 246 С2 57 МК С 070 311/20, С 07С 215/54 (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 99116356/04, 18.12.1997 (24) Дата начала действия патента: 18.12.1997 (30) Приоритет: 31.12.1996 Ц$ 60/033,961 (43) Дата публикации заявки: 20.05.2001 (46) Дата публикации: 27.11.2001 (71) Заявитель: ФАРМАЦИЯ ЭНД АПДЖОН КОМПАНИ (15$) (72) Изобретатель: ГЕЙДЖ Джеймс Р. (4$), КАБАДЖ Джон Е. (15) (73) Патентообладатель: ФАРМАЦИЯ ЭНД АПДЖОН КОМПАНИ (15$) (74) Патентный поверенный: (56) Ссылки: ЕР 0325511 А, 26.07.1989. Ц$ 5382600 Лебедева Наталья Георгиевна А, 17.01.1996. Ч$ 3446901 А, 27.05.1969. КУ 94035964 АЛ, 21.05.1997. КУ 2089539 СЛ, 10.09.1997. (85) Дата перевода заявки РСТ на национальную фазу: 30.07.1999 (86) Заявка РСТ: 0$ 97/22521 (18.12.1997) (87) Публикация РСТ: М/О 98/29402 (09.07.1998) (98) Адрес для переписки: 129010, Москва, ул. Большая Спасская 25, стр.3, ООО "Юридическая фирма Городисский и Партнеры", Лебедевой Н.Г. (54) СПОСОБ ПОЛУЧЕНИЯ ТОЛТЕРОДИНА И ПРОМЕЖУТОЧНОЕ СОЕДИНЕНИЕ (57) Предметом изобретения является усовершенствованный способ получения толтеродина формулы \ и новое промежуточное соединение - 3,4-дигидро-6-метил-4-фенил-2Н-бензопиран-2 -ол формулы 1\. Способ заключается в восстановлении лактона формулы | с образованием гидроксисоединения формулы \/ с последующим — восстановительным аминированием его — диизопропиламином. --тартрат (К)-толтеродина полезен при лечении недержания мочи. Технический результат - получение полезного соединения упрощенным способом. 2 с. и 4 з.п.ф-лы. 2176246 С2:? Ко Этс9Ьс ПЧ с» д» «ТТТ» о о ОН о ъ ТУ» РЬ но До у ...

Arylalkyl-amines and -amides having anticonvulsant and neuroprotective properties

There is provided a method of treatment of neurological disorders, such as epilepsy, stroke and cerebral ischaemia, which comprises the administration of a compound of Formula I: ##STR1## wherein, Ar 1 and Ar 2 , which may be the same or different, independently represent phenyl or phenyl substituted by one or more of amino, nitro, halogen, hydroxy, C1 to 6 alkoxy, C1 to 6 alkyl or cyano; R 1 represents hydrogen, C1 to 6 alkyl, C1 to 6 alkoxycarbonyl; R 2 represents hydrogen or COCH 2 NH 2 ; R 3 represents hydrogen or C1 to 6 alkyl; in addition, when R 2 represents hydrogen either one or both of Ar 1 and Ar 2 may also represent 2-, 3- or 4-pyridinyl and R 1 may also represent trihalomethyl; or a pharmaceutically acceptable salt thereof. Some of the compounds of formula I are novel, and these are also provided, together with pharmaceutical compositions containing the novel compounds.

Method for preparing vanillyl hydrochloride

Method for obtaining n-hydroxymethylamines

Изобретение относится к способу получения новых N-оксиметиламинов, содержащих гем-дихлорциклопропанметиловый или циклоацетальметиловый фрагмент. Полученные соединения могут найти применение в качестве промежуточных соединений в синтезе ингибиторов коррозии металлов. Способ заключается в том, что проводят конденсацию соответствующего вторичного амина, содержащего гем-дихлорциклопропанметиловый или циклоацетальметиловый фрагмент, с формальдегидом в среде растворителя в присутствии гексагидрата хлорида железа (III) FeCl 3 ⋅6H 2 O. Преимущественно процесс проводят при температуре 50°С в течение 5 часов. Реакцию формальдегида с N-бензил-1-(2,2-дихлорциклопропил)метанамином проводят обычно в смеси этанола и хлороформа в качестве растворителя при следующем соотношении компонентов, мас.%: N-бензил-1-(2,2-дихлорциклопропил)метанамин 16,5; хлороформ 52,6; этанол 28; формальдегид 2; гексагидрат хлорида железа 0,9. Реакцию формальдегида с N-бензил-1-(1,3-диоксолан-4-ил)метанамином и N-бензил-1-(1,3-диоксолан-2-ил)метанамином проводят обычно в смеси этанола и хлороформа в качестве растворителя при следующем соотношении компонентов, мас.%: N-бензил-1-(1,3-диоксолан)метанамин 14; хлороформ 54,1; этанол 28,8; формальдегид 2,2; гексагидрат хлорида железа 0,9.Способ позволяет получить продукты высокого качества с высоким выходом (65-75%). 3 з.п. ф-лы, 1 табл., 3 пр. РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 654 065 C1 (51) МПК C07C 213/00 (2006.01) C07C 215/50 (2006.01) C07D 317/28 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07C 213/00 (2006.01); C07C 215/50 (2006.01); C07D 317/28 (2006.01) (21)(22) Заявка: 2017108863, 16.03.2017 (24) Дата начала отсчета срока действия патента: Дата регистрации: 16.05.2018 (45) Опубликовано: 16.05.2018 Бюл. № 14 2 6 5 4 0 6 5 R U (54) Способ получения N-оксиметиламинов (57) Реферат: Изобретение относится к способу получения новых N-оксиметиламинов, содержащих ...

Humanized anti-complement factor Bb antibodies

Provided herein are humanized anti-factor Bb antibodies, methods of producing the antibodies and methods of using the antibodies.

Flame retardant polyol

반응 시스템, 예를 들어, 경질 폴리우레탄 포옴을 형성시키기 위한 반응 시스템은 카르다놀 성분, 브롬 성분, 및 첨가제 성분의 브롬화된 반응 생성물인 난연성 폴리올을 포함한다. 카르다놀 성분은 카르다놀 성분의 총 중량을 기준으로 하여 적어도 80 중량%의 카르다놀을 포함하며, 그리고 브롬 성분은 브롬 성분의 총 중량을 기준으로 하여 적어도 80 중량%의 브롬을 포함한다. A reaction system, for example, a reaction system for forming a rigid polyurethane foam, includes a flame retardant polyol that is a brominated reaction product of a cardanol component, a bromine component, and an additive component. The cardanol component comprises at least 80 weight percent cardanol, based on the total weight of the cardanol component, and the bromine component comprises at least 80 weight percent bromine, based on the total weight of the bromine component.

Humanized anti-complement factor bb antibodies and uses thereof

Provided herein are humanized anti-factor Bb antibodies, methods of producing the antibodies and methods of using the antibodies.

Absorbent solution, useful for absorbing acidic compounds contained in a gaseous effluent, comprises water and at least one amino compound

Absorbent solution, comprises: water; and at least one amino compound (I). Absorbent solution, comprises: water; and at least one amino compound of formula (I). R1-R5 : groups A (comprising H), groups B1 (comprising 1-20C alkyl and/or -NH 2or NY1 2) or groups C1 (comprising amine group of formula ([-CR11R12-] m-NR13R14)); Y1 : 1-20C alkyl and/or OH, or -O-X-H; X : -[CR7R8-CR9R10-O-] n; R7-R10 : H or 1-20C alkyl; n : 1-20; R11, R12 : H or 1-20C alkyl; m : 1 or 2; R13, R14 : H or 1-20C alkyl; R6 : group A, group B1, group C, or phenyl group of formula (d); and Z : covalent bond or 1-20C alkylene unit (-R15-). Provided that when 2 or 3 groups of R1-R6 responds to the definition of group C, then at least one of R1-R6 responds to the definition of group A. An independent claim is included for process for removing acid compounds contained in a gaseous effluent comprising: absorption of acid compounds by contacting the effluent with an absorbent solution to obtain a gaseous effluent depleted in acid compounds and an absorbent solution laden with acid compounds; and at least one step of regeneration of the absorbent solution laden with acid compounds. [Image] [Image].

Alphaahalomethylamines

4,6-Disubstd-2-aminomethyl phenols - as antiinflammatory, diuretic and salidiuretic agents

Title cpds. of formula (I) (where X1 is 1-7C alkyl or 5-6C cycloalkyl and X2 is Hal3C) are prepd. either by hydrolysis of the N-acyl deriv. or redn. of the hydroxy benzaldehyde oxime. Pref. (I; X' = t-Bu X2 = CF3) is prepd. by hydrolysis of the N-chloroacetyl deriv.

Compositions and methods to treat urinary incontinence

A method is disclosed for treatment of urinary incontinence. The method includes the steps of providing to a person or animal, in the vicinity of a pubo-urethral ligament of the person or animal, a composition including collagen macromolecules that have hydroxyphenyl side groups substituted thereon, which are reacted to form dihydroxyphenyl linkages. In an embodiment, the collagen macromolecules are gelatin macromolecules. In another embodiment, the hydroxyphenyl side groups are tyramine side groups and the dihydroxyphenyl linkages are dityramine linkages. The composition can be injected into a space between a urethra and a pubis of the person or animal wherein the pubo-urethral ligament is disposed in the space. The method is advantageous, for example, based on being minimally invasive.

NOVEL A-HALOGENOMETHYLPHENETHYLAMINES USEFUL IN PARTICULAR AS INHIBITORS OF DECARBOXYLASE OF AROMATIC AMINOACIDS AND THEIR PREPARATION METHOD

LES MEDICAMENTS SELON L'INVENTION SONT DES A-HALOGENOMETHYLPHENETHYLAMINES DE FORMULE GENERALE: (CF DESSIN DANS BOPI) DANS LAQUELLE Y ET R SONT TELS QUE DEFINIS DANS LA REVENDICATION ET CHACUN DES RESTES R, R, R, R ET R EST TEL QUE DEFINI DANS LE TABLEAU CI-DESSOUS: (CF DESSIN DANS BOPI) (CF DESSIN DANS BOPI) ET LEURS SELS ET LEURS ISOMERES OPTIQUES INDIVIDUELS. THE MEDICINAL PRODUCTS ACCORDING TO THE INVENTION ARE A-HALOGENOMETHYLPHENETHYLAMINES OF THE GENERAL FORMULA: (CF DRAWING IN BOPI) IN WHICH Y AND R ARE AS DEFINED IN THE CLAIM AND EACH OF THE REMAINERS R, R, R, R AND R IS AS DEFINED IN THE TABLE BELOW: (CF DRAWING IN BOPI) (CF DRAWING IN BOPI) AND THEIR SALTS AND THEIR INDIVIDUAL OPTICAL ISOMERS.

NOVEL N-ALKYL-HYDROXYBENZYLAMINES, PROCESS FOR THEIR PREPARATION, THEIR APPLICATIONS AND COMPOSITIONS CONTAINING SAME

The invention concerns novel N-alkyl-hydroxybenzylamines of formula (I) in which: R1 and R2, which are identical or different, represent a hydrogen atom or a monohydroxylated or polyhydroxylated C1-C8 alkyl radical, provided that R1 and R2 do not simultaneously represent each a hydrogen atom; Q represent a -OH or -NH2 radical; Z represents a hydrogen atom or the group (a) in which R1 and R2 have the same definitions as above and Y1 and Y2 represent a hydrogen atom or the radical -OH, provided that Y1 and Y2 do not simultaneously represent each a hydrogen atom. The invention is useful for treating metal surfaces both against corrosion and for improving subsequent paint adherence.

Patent FR2119066A1

Amine derivatives and method for producing the same

Novel amine derivatives represented by general formula (1) which are excellent in antifungal effect and salts thereof, wherein R1 represents optionally halogenated C1-5 alkyl; R2 represents 4-(1,1-dimethylalkyl)benzyl, 4-(1-methyl-1-phenylethyl)benzyl or 1- or 2-naphthylmethyl or a hydrocarbon carrying 3,3-dimethyl-1-butynyl or phenyl at the end and having 1 to 3 double bonds; R3 represents oxygen or methylene optionally substituted by C1-4 alkyl; and R4 represents 1- or 2-naphthyl or optionally substituted phenyl.

Hydroxy aromatic mannich base condensation products and the use thereof as soot dispersants in lubricating oil compositions

Low molecular weight Mannich base condensates of hydroxy aromatic compounds, an aldehyde; and an amine, wherein the combined number of substituent carbon atoms does not exceed 80. Such compounds are useful as soot dispersants in lubricating oils when used alone, or in combination with high molecular weight dispersants.

DERIVATIVES OF AMINOETHYLPHENOXYACETIC ACID AND AGENTS TO REDUCE PAIN AND PROMOTE THE ELIMINATION OF CALCULATIONS IN UROLITIASIS

Un derivado del ácido aminoetilfenoxiacético representadopor la fórmula general:(donde R1 representa un átomo de hidrógeno, un grupo alquilo inferior o un grupo aralquilo; R2 representa un átomo de halógeno;el átomo de carbono marcado con (R) representa un átomo de carbono en configuración (R), y el átomo de carbono marcado con (S) representa un átomo de carbono en configuración (S)) y una salfarmacéuticamente aceptable del mismo. A derivative of aminoethylphenoxyacetic acid represented by the general formula: (where R1 represents a hydrogen atom, a lower alkyl group or an aralkyl group; R2 represents a halogen atom; the carbon atom marked with (R) represents a carbon atom in (R) configuration, and the (S) -labeled carbon atom represents a carbon atom in (S) configuration) and a pharmaceutically acceptable salt thereof.

Coated formulations

A pharmaceutical composition of tolterodin, wherein sustained release is provided by use of a single coating layer.

2- (3-4-DIHYDROXYPHENYL) -ETHYLAMINE, THEIR PRODUCTION AND USE AS A MEDICINAL PRODUCT.

Method for preventing renal ischemia reperfusion injury by carbamylated darbepoetin in experiment

FIELD: medicine.SUBSTANCE: invention relates to medicine and is intended for the prevention of renal ischemia reperfusion injury in the experiment. When simulating renal ischemia reperfusion injury, male Wistar rats by imposing atraumatic clamps on the renal pedicle are injected with carbamylated darbepoetin at a dose of 50 mcg/kg subcutaneously in the top of shoulder 24 hours before ischemia induction for 40 minutes. Evaluation of nephroprotective properties carried out after 24 and 72 hours.EFFECT: method provides an increase in the effectiveness of the prevention of ischemia reperfusion disorders of the kidneys.1 cl, 1 ex, 2 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 678 768 C1 (51) МПК A61K 38/16 (2006.01) A61K 38/18 (2006.01) C07K 14/505 (2006.01) A61P 13/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК A61K 38/16 (2018.08); A61K 38/18 (2018.08); C07K 14/505 (2018.08); A61P 13/00 (2018.08) (21)(22) Заявка: 2018133675, 25.09.2018 (24) Дата начала отсчета срока действия патента: Дата регистрации: 01.02.2019 (45) Опубликовано: 01.02.2019 Бюл. № 4 Адрес для переписки: 308015, Белгородская обл., г. Белгород, ул. Победа, 85, НИУ "БелГУ", Цуриковой Н.Д (73) Патентообладатель(и): федеральное государственное автономное образовательное учреждение высшего образования "Белгородский государственный национальный исследовательский университет" (НИУ "БелГУ") (RU) (56) Список документов, цитированных в отчете о поиске: RU 2433181 C2, 10.11.2011. C 1 2 6 7 8 7 6 8 R U (54) Способ профилактики ишемически-реперфузионных повреждений почек карбамилированным дарбэпоэтином в эксперименте (57) Реферат: Изобретение относится к медицине и ножки на 40 минут вводят карбамилированный предназначено для профилактики ишемическидарбэпоэтин в дозе 50 мкг/кг подкожно в область реперфузионных повреждений почек в холки за 24 часа до индукции ишемии. Оценку эксперименте. Лабораторным крысам-самцам нефропротективных свойств проводят ...

Propylaminederivate.

Tolterodine, compositions and uses thereof, and preparation of the same

Racemic tolterodine free base in crystalline form, tolterodine with improved purity, compositions and uses thereof, and processes of preparing the same.

Humanized anti-complement factor bb antibodies and uses thereof

Provided herein are humanized anti-factor Bb antibodies, methods of producing the antibodies and methods of using the antibodies.

Derivatives of aminoethylphenoxyacetic acid and medicinal agents for pain relief and stone moving away relieve in cholelithiasis

FIELD: organic chemistry, medicine, gastroenterology. SUBSTANCE: invention relates to group of derivatives of aminoethylphenoxyacetic acid of the following formula: where R 1 means hydrogen atom, lower alkyl group or aralkyl group; R 2 means hydrogen atom or halogen atom being carbon atom with label (R) means carbon atom in (R)-configuration; carbon atom with label (S) means carbon atom in (S)- configuration, or their pharmaceutically acceptable salts and pharmaceutical compositions stimulating effect of β 2 - and β 3 -adrenoceptors and containing derivatives of aminoethylphenoxyacetic acid as active component, agents used for pain relief and method of pain relief. EFFECT: valuable medicinal properties of compounds. 9 cl, 1 tbl осгэбгс пы сэ (19) РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ ВИ "” 2 196 130 ' (51) МПК? 13) С2 С 07С 217/60, А 61 К 31/015, А 61 Р 13/04 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 2000101840/04, 15.07.1998 (24) Дата начала действия патента: 15.07.1998 (30) Приоритет: 25.07.1997 УР 9/233239 (43) Дата публикации заявки: 27.09.2001 (46) Дата публикации: 10.01.2003 (56) Ссылки: КУ 9400302 А, 10.08.1996. КЦ 94046148 А, 20.12.1995. МО 9813333 АЛ, 02.04.1998. ЕР 023385 АЛ, 04.02.1981. ОЕ 4424114 А, 18.01.1996. (85) Дата перевода заявки РСТ на национальную фазу: 24.01.2000 (86) Заявка РСТ: УР 9803163 (15.07.1998) (87) Публикация РСТ: М/О 99/05090 (04.02.1999) (98) Адрес для переписки: 129010, Москва, ул. Б.Спасская, 25, стр.3, ООО "Юридическая фирма Городисский и Партнеры", пат.пов. Н.Г.Лебедевой, рег. № 0112 (71) Заявитель: КИССЕИ ФАРМАСЬЮТИКАЛ КО., ЛТД. (4Р) (72) Изобретатель: ТАМАИ Тецуро (+Р), ТАНАКА Нобуюки (.Р), МУРАНАКА Хидеюки (УР), МУКАЙЯМА Харунобу (.Р), ХИРАБАЯСИ Акихито (/Р), САТО Масааки (Р), АКАХАНЕ Масуо (Р) (73) Патентообладатель: КИССЕИ ФАРМАСЬЮТИКАЛ КО., ЛТД. (Р) (74) Патентный поверенный: Лебедева Наталья Георгиевна (54) ПРОИЗВОДНЫЕ АМИНОЭТИЛФЕНОКСИУКСУСНОЙ КИСЛОТЫ И ЛЕКАРСТВЕННЫЕ СРЕДСТВА ...

Novel phenethylamines

Novel phenethylamines of the formula < IMAGE > I wherein X is selected from the group consisting of hydrogen, acyl of an aliphatic carboxylic acid of 2 to 6 carbon atoms and benzoyl and Y is selected from the group consisting of hydrogen and -OX and their non-toxic, pharmaceutically acceptable acid addition salts having dopaminergic stimulating activity and their preparation and novel intermediates.

Compound, salt of compound, neuromodulation agent, method for evaluating neuromodulation agent, method for producing compound, and method for producing salt of compound

Provided is a compound represented by general formula (I), or a salt thereof. (In the formula, X 1 , X 2 , X 3 and X 4 are a hydrogen atom, a C1-9 alkyl group, or a C3-9 unsaturated hydrocarbon group which has 1-4 triple bonds between carbon atoms and which may have a substituent (when the unsaturated hydrocarbon group has a methylene group at the end of the bond, the methylene group may be substituted with a carbonyl group); X 5 is a C2-8 unsaturated hydrocarbon group which has 1-4 triple bonds between carbon atoms and which may have a substituent; X 6 is a hydrogen atom, or a C3-9 unsaturated hydrocarbon group which has 1-4 triple bonds between carbon atoms and which may have a substituent; n 1 and n 3 are 0 or 1; and n 2 is an integer of 1-5.)

Derivatives of aminoethylphenoxyacetic acid as well as drugs capable to relieve pain and to assist in removing urinary calculus in urolithiasis cases

Novel aminoethylphenoxyacetic acid derivatives represented by the general formula: <CHEM> (wherein R<1> represents a hydrogen atom, a lower alkyl group or an aralkyl group; R<2> represents a hydrogen atom or a halogen atom; the carbon atom marked with (R) represents a carbon atom in (R) configuration; and the carbon atom marked with (S) represents a carbon atom in (S) configuration) and pharmaceutically acceptable salts thereof, which have stimulating effects on both beta 2- and beta 3-adrenoceptors and are useful as agents for relieving pain and promoting the removal of calculi in urolithiasis.

Aminoethylphenoxyacetic acid derivatives and drugs for pain remission and calculi removal promotion in urinary lithiasis

Novel aminoethylphenoxyacetic acid derivatives represented by the general formula: (wherein R 1 represents a hydrogen atom, a lower alkyl group or an aralkyl group; R 2 represents a hydrogen atom or a halogen atom; the carbon atom marked with (R) represents a carbon atom in ( R ) configuration; and the carbon atom marked with (S) represents a carbon atom in ( S ) configuration) and pharmaceutically acceptable salts thereof, which have stimulating effects on both β 2 - and β 3 -adrenoceptors and are useful as agents for relieving pain and promoting the removal of calculi in urolithiasis.

Preparation of 3-[(1r,2r)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol

The present invention relates to an improved process for the preparation of 3- [(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol monohydrochloride.

DERIVATIVES OF AMINO ETHYLENE PENOXYACETIC ACID AND MEDICINES THAT REDUCE PAIN AND FAVOR THE ELIMINATION OF CALCULATIONS IN URINARY LITHIASIS.

Nuevos derivados de ácido aminoetilfenoxiacetico representados por la **fórmula** en la que R1 representa un átomo de hidrógeno, un grupo alquilo inferior o un grupo aralquilo; R2 representa un átomo de hidrógeno o un átomo de halógeno; el átomo de carbono marcado con (R) representa un átomo de carbono en configuración (R) y el átomo de carbono marcado con (S) representa un átomo de carbono en configuración (S) y sus sales farmacéuticamente aceptables, que tienen efectos estimulantes sobre ambos beta-2 y beta-3-adrenoceptores y se utilizan como agentes para aliviar el dolor y promover la eliminación de los cálculos en urolitiasis. New aminoethylphenoxyacetic acid derivatives represented by the ** formula ** in which R 1 represents a hydrogen atom, a lower alkyl group or an aralkyl group; R2 represents a hydrogen atom or a halogen atom; the carbon atom marked with (R) represents a carbon atom in configuration (R) and the carbon atom marked with (S) represents a carbon atom in configuration (S) and its pharmaceutically acceptable salts, which have stimulating effects on both beta-2 and beta-3-adrenoceptors and are used as agents to relieve pain and promote the elimination of stones in urolithiasis.