Compositions, Synthesis, and Methods of Using Cycloalkylmethylamine Derivatives

The present invention provides novel cycloalkylmethylamine derivatives, and methods of preparing cycloalkylmethylamine derivatives. The present invention also provides methods of using cycloalkylmethylamine derivatives and compositions of cycloalkylmethylamine derivatives. The pharmaceutical compositions of the compounds of the present invention can be advantageously used for treating and/or preventing obesity and obesity related co-morbid indications and depression and depression related co-morbid indications.

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. 2. The compound of wherein Ris selected from the group consisting of halo claim 1 , OR claim 1 , SR claim 1 , NO claim 1 , CN claim 1 , NC claim 1 , Calkyl claim 1 , haloCalkyl claim 1 , OCF claim 1 , Cheteroalkyl claim 1 , and hydroxyCalkyl claim 1 ,and n is 0, 1, or 2.3. The compound of wherein Ris selected from the group consisting of Calkyl claim 1 , halo claim 1 ,{'sup': 'a', 'and OR, and n is 0, 1, or 2.'}4. The compound of wherein Ris selected from the group consisting of F claim 1 , Br claim 1 , Cl claim 1 , OH claim 1 , NO claim 1 , OCH claim 1 , OCF claim 1 , CF claim 1 , CH claim 1 , and CH claim 1 , and n is 0 or 1.6. The compound of wherein Ris F claim 5 , Br claim 5 , Cl claim 5 , OH claim 5 , NO claim 5 , OCH claim 5 , OCF claim 5 , CF claim 5 , CH claim 5 , or CH claim 5 ,and n is 0 or 1.7. The racemic mixture of a compound of .8. (canceled)9. The (+) enantiomer of substantially free of the (−) enantiomer.10. (canceled)11. The (−) enantiomer of substantially free of the (+) enantiomer.12. (+)-trans(S claim 1 ,S)-[2-(2-Cyclopropylmethyloxy-5-fluorophenyl)cyclopropyl]methylamine Hydrochloride claim 1 ,(+)-trans(S,S)-[2-(2-Cyclopropylmethyloxy-5-hydroxyphenyl)cyclopropyl]methylamine Hydrochloride, or a pharmaceutically acceptable salt or hydrate thereof.13. A composition comprising (a) compound of claim 1 , (b) optionally a second therapeutic agent useful in the treatment of a disease or condition wherein modulation of 5-HT(2C) provides a benefit claim 1 , and (c) an excipient and/or pharmaceutically acceptable carrier.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 ...

AROMATIC BUTAN-2-OL COMPOUNDS AND PREPARATION AND USES THEREOF

Aromatic butan-2-ol compounds, preparation methods for making the compounds, and uses of the compounds are provided. Specifically, the compound of Formula I, or an optical isomer, racemate, diastereomer, pharmaceutically acceptable salt, or solvate thereof, is provided, where each of the substituents is defined. In addition, a pharmaceutical composition containing the compound, and the use of the compound in manufacture of a medicament for the treatment and/or prophylaxis of a disease or disorder caused by infection, is provided. 2. The compound of Formula I according to claim 1 , or an optical isomer claim 1 , racemate claim 1 , diastereomer claim 1 , pharmaceutically acceptable salt claim 1 , or solvate thereof claim 1 , wherein{'sub': '1', 'Rrepresents hydrogen, fluoro, chloro, bromo, iodo, or methoxy;'}{'sub': '2', 'Rrepresents hydrogen, fluoro, chloro, bromo, or iodo;'}{'sub': 3', '1-8, 'Rrepresents hydrogen, fluoro, chloro, bromo, iodo, or a Calkyl substituted at an o-, m-, or p-position of the phenyl ring;'}{'sub': '4', 'Rrepresents phenyl, substituted phenyl, or naphthyl; and'}{'sub': 5', '1-8, 'Rrepresents hydroxy, thiol, a Calkoxy, or methylthio.'}3. The compound of Formula I according to claim 2 , or an optical isomer claim 2 , racemate claim 2 , diastereomer claim 2 , pharmaceutically acceptable salt claim 2 , or solvate thereof claim 2 , wherein{'sub': '1', 'Rrepresents hydrogen, fluoro, chloro, bromo, or iodo;'}{'sub': 3', '1-6, 'Rrepresents hydrogen, fluoro, chloro, bromo, iodo, or a Calkyl substituted at an o-, m-, or p-position of the phenyl ring;'}{'sub': '4', 'Rrepresents phenyl, phenyl substituted with one or more halogens, or naphthyl; and'}{'sub': 5', '1-6, 'Rrepresents hydroxy or a Calkoxy.'}4. The compound of Formula I according to claim 3 , or an optical isomer claim 3 , racemate claim 3 , diastereomer claim 3 , pharmaceutically acceptable salt claim 3 , or solvate thereof claim 3 , wherein{'sub': '1', 'Rrepresents hydrogen, chloro, or bromo ...

POLYMORPHIC FORM OF A CALCIMIMETIC COMPOUND

The present invention relates to the crystalline, polymorphic Form X of the calcimimetic compound {4-[(1R,3S)-3-((R)-1-Naphthalen-1-yl-ethylamino)-cyclopentyl]-phenoxy}-acetic acid, to methods of preparation thereof, to methods of characterization thereof by single crystal X-Ray crystallography (XRC), X-Ray Powder diffractometry, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, Solid State NMR spectroscopy and Differential Scanning Calorimetry (DSC), and to its use. The invention also relates to the preparation of Form X by crystallization from a saturated solution of {4-[(1R,3S)-3-((R)-1-Naphthalen-1-yl-ethylamino)-cyclopentyl]-phenoxy}-acetic acid in a C-Calkyl alcohol, or alternatively by precipitation from a neutralized saponification reaction mixture following the alkaline hydrolysis of a C-Calkyl ester of {4-[(1R,3S)-3-((R)-1-Naphthalen-1-yl-ethylamino)-cyclopentyl]-phenoxy}-acetic acid. 1. A crystalline form of {4-[(1R ,3S)-3-((R)-1-Naphthalen-1-yl-ethylamino)-cyclopentyl]-phenoxy}-acetic acid.2. The crystalline form according to which belongs to the orthorhombic space group P222having unit-cell parameters a=8.7299(17) Å claim 1 , b=14.822(3) Å and c=16.353(3) Å.3. The crystalline form according to which has an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2θ at approximately 8.0 claim 1 , 11.3 claim 1 , 11.4 claim 1 , 15.0 claim 1 , 18.2 and/or 21.5 (±0.05 degrees) (underlined primary) claim 1 , respectively.4. The crystalline form according to which has an X-ray powder diffraction pattern substantially as appears from Graph 2b.5. The crystalline form according to which has a differential scanning calorimetry curve comprising an event with an onset at about 255° C. (±2° C.).6. The crystalline form according to which has a differential scanning calorimetry curve substantially as appears from Graph 4b.7. The crystalline form according to which has Solid State NMR spectrum substantially as ...

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 ...

METHODS OF TREATMENT USING ARYLCYCLOPROPYLAMINE COMPOUNDS

Described herein are methods of treating Parkinson's disease using arylcyclopropylamine compounds. 2. The method of claim 1 , wherein R claim 1 , R claim 1 , Rand Rare hydrogen.3. The method of claim 1 , wherein Ris selected from Chaloalkyl claim 1 , halo claim 1 , Calkoxy claim 1 , and Caryloxy.4. The method of claim 1 , wherein Rand Rare taken together with the carbon atoms to which they are attached to form a Cheterocyclyl ring.5. The method of claim 4 , wherein Rand Rare taken together to form a five-membered heterocyclyl ring.6. The method of claim 1 , wherein Ris hydrogen.818.-. (canceled)20. The method of claim 19 , wherein A is a heterocyclyl ring.21. The method of claim 19 , wherein A is a bicyclic heterocyclyl ring.27. The method of claim 26 , wherein Xand Xare O.28. The method of claim 26 , wherein n is 1.2939.-. (canceled) This application claims priority to U.S. Provisional Patent Application No. 61/579,872, filed on Dec. 23, 2011, the entire contents of which are hereby incorporated by reference.This invention was made with United States Government support awarded by National Institutes of Health, Grant No. GM65539. The U.S. Government has certain rights in this invention.Although there is no known cure for Parkinson's disease (PD), one of the two most common neurodegenerative diseases of aging, dopamine (DA) replacement therapy by administration of the DA biosynthetic precursor levodopa (L-DOPA or LD) has been employed for over 40 years as the gold standard for treatment of PD-associated symptoms. However, the efficacy of this treatment may wane with time, and the drug may have a number of long-term side-effects including L-DOPA-induced dyskinesias (LIDs), fluctuations in motor performance, and hallucinations. Often these effects can become dose limiting at a time when patients are in need of more medication and not less. DA agonists, as well as several other classes of drugs directly or indirectly affecting DA function (monoamine oxidase (MAO) ...

PROCESS FOR THE SYNTHESIS OF TAPENTADOL AND INTERMEDIATES THEREOF

The object of the present invention is a new process for the synthesis of tapentadol, both as free base and in hydrochloride form, which comprises the step of alkylation of the ketone (VII) to yield the compound (VIII), as reported in Diagram 1, with high stereoselectivity due to the presence of the benzyl group as substituent of the amino group. It was surprisingly found that this substitution shifts the keto-enol equilibrium towards the desired enantiomer and amplifies the capacity of the stereocenter present in the compound (VII) to orient the nucleophilic addition of the organometallic compound at the carbonyl towards the desired stereoisomer. This substitution thus allows obtaining a considerable increase of the yields in this step, and consequently allows significantly increasing the overall yield of the entire tapentadol synthesis process. 130-. (canceled)32. The process according to claim 31 , wherein the halide is bromide and the metal is zinc or magnesium.33. The process according to claim 31 , wherein the ethyl metal halide is ethylmagnesium bromide.34. The process according to claim 32 , wherein the ethyl metal halide is used in a quantity between 1 and 5 equivalents with respect to compound (VIII).35. The process according to claim 31 , wherein the alkylation is carried out at a temperature between 0° C. and the boiling temperature of the solvent.36. The process according to claim 35 , wherein the alkylation is carried out at a temperature between 10 and 30° C.38. The process according to claim 37 , wherein the chiral acid is selected from D(−) mandelic acid claim 37 , D(−) 2-chloromandelic acid claim 37 , D(−) tartaric acid claim 37 , and (2R claim 37 ,3R)-O claim 37 ,O′-dibenzoyl tartaric acid.39. The process according to claim 38 , wherein the chiral acid is D(−) mandelic acid.40. The process according to claim 37 , wherein the polar solvent of step a′) is selected from: water claim 37 , aliphatic ketones and/or aliphatic alcohols claim 37 , used ...

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 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. 76. (canceled)78. The compound of or a pharmaceutically acceptable salt thereof claim 77 , wherein Yand Yare each independently a phenyl claim 77 , or 1- or 2-napthyl.79. The compound of or a pharmaceutically acceptable salt thereof claim 78 , wherein Yis independently a phenyl or 2-napthyl; and Yis independently a phenyl or 1-naphthyl.80. The compound of or a pharmaceutically acceptable salt thereof claim 79 , wherein Ris a methyl; and Ris a hydrogen.82. The compound of or a pharmaceutically acceptable salt thereof wherein the cycloaliphatic ring is selected from the group consisting of: cyclopropyl claim 77 , cyclobutyl claim 77 , cyclopentyl claim 77 , cyclopropylmethyl claim 77 , and cyclohexyl.838284. A pharmaceutical composition comprising a pharmaceutically acceptable carrier claim 77 , and a compound of any one of - or or a pharmaceutically acceptable salt thereof.84. The compound of or a pharmaceutically acceptable salt thereof claim 77 , wherein Alkyl is a C-Chydrocarbon having spor sphybridization and further comprises linear or branched moieties claim 77 , or a combination ...

ANALGESIC COMPOUNDS, METHODS, AND FORMULATIONS

Provided are analgesic compounds, and salts thereof, of formula: (I) wherein A is: (A) Additionally, pharmaceutical formulations and methods of use employing the above compounds are provided. 128-. (canceled)32. The compound of wherein it is 2-dimethylaminomethyl-3-(3-methoxy-phenyl)-bicyclo[3.2.1]octan-3-ol; 2-dimethylaminomethyl-3-(3-fluoro-5-methoxy-phenyl)-bicyclo[3.2.1]octan-3-ol; 2-dimethylaminomethyl-3-(5-methoxy-2-trifluoromethoxy-phenyl)-bicyclo[3.2.1]octan-3-ol; 2-dimethylaminomethyl-3-(2-fluoro-5-methoxy-phenyl)-bicyclo[3.2.1]octan-3-ol; 2-dimethylaminomethyl-3-(4-fluoro-3-methoxy-phenyl)-bicyclo[3.2.1]octan-3-ol; 2-dimethylaminomethyl-3-(2-fluoro-3-methoxy-phenyl)-bicyclo[3.2.1]octan-3-ol; 2-dimethylaminomethyl-3-(3-methoxy-5-methyl-phenyl)-bicyclo[3.2.1]octan-3-ol; 3-(2-chloro-5-methoxy-phenyl)-2-dimethylaminomethyl-bicyclo[3.2.1]octan-3-ol; 3-(3-chloro-5-methoxy-phenyl)-2-dimethylaminomethyl-bicyclo[3.2.1]octan-3-ol; 2-dimethylaminomethyl-3-(5-methoxy-2-methyl-phenyl)-bicyclo[3.2.1]octan-3-ol; 2-dimethylaminomethyl-3-(3-methoxy-4-methyl-phenyl)-bicyclo[3.2.1]octan-3-ol; 2-dimethylaminomethyl-3-(3-hydroxy-phenyl)-bicyclo[3.2.1]octan-3-ol;2-dimethylaminomethyl-3-(2-fluoro-5-hydroxy-phenyl)-bicyclo[3.2.1]octan-3-ol;2-dimethylaminomethyl-3-(3-fluoro-5-hydroxy-phenyl)-bicyclo[3.2.1]octan-3-ol;2-dimethylaminomethyl-3-(3-hydroxy-5-trifluoromethyl-phenyl)-bicyclo[3.2.1]octan-3-ol;2-dimethylaminomethyl-3-(5-hydroxy-2-trifluoromethoxy-phenyl)-bicyclo[3.2.1]octan-3-ol;2-dimethylaminomethyl-3-(3-hydroxy-4-trifluoromethyl-phenyl)-bicyclo[3.2.1]octan-3-ol;2-dimethylaminomethyl-3-(4-fluoro-3-hydroxy-phenyl)-bicyclo[3.2.1]octan-3-ol;2-dimethylaminomethyl-3-(2-fluoro-3-hydroxy-phenyl)-bicyclo[3.2.1]octan-3-ol;2-dimethylaminomethyl-3-(3-hydroxy-5-methyl-phenyl)-bicyclo[3.2.1]octan-3-ol;3-(2-chloro-5-hydroxy-phenyl)-2-dimethylaminomethyl-bicyclo[3.2.1]octan-3-ol;3-(3-chloro-5-hydroxy-phenyl)-2-dimethylaminomethyl-bicyclo[3.2.1]octan-3-ol;2-dimethylaminomethyl-3-(5- ...

AMINOTETRALINE DERIVATIVES

The present application relates generally to amino tetraline derivative compounds and methods of use, specifically, embodiments including compounds of formula (I) described herein, pharmaceutically acceptable salts and solvates. More specifically, this application relates to amino tetraline derivative compounds and uses of such compounds producing medicaments for the treatment of various disease and conditions including movement disorders and disorders of the central nervous system. 2. The method of claim 1 , wherein the movement disorder is an L-DOPA associated dyskinesia.3. The method of wherein R of the compound of formula I is OR1 claim 1 , wherein R1 is methyl claim 1 , hydrogen or a group —C(═O)R2 claim 1 , wherein R2 is (C1-C6)alkyl or (C1-C6)alkyloxy.4. The method of wherein Cy of the compound of formula I is a 5 or 6 membered aromatic or heteroaromatic ring which is selected from the group of phenyl claim 1 , thienyl claim 1 , furanyl claim 1 , imidazolyl claim 1 , 1 claim 1 ,2 claim 1 ,3-triazolyl claim 1 , 1 claim 1 ,2 claim 1 ,4-triazolyl claim 1 , pyrazolyl claim 1 , pyridyl claim 1 , pyrimidyl claim 1 , and unsubstituted or substituted with one or two groups R4.5. The method according to wherein the compound of formula I administered to a recipient is selected fromN-(8-Hydroxytetralin-2-yl)-N-propyl-N-[2-(2-thienyl)ethyl]amine,(R)—N-(8-Hydroxytetralin-2-yl)-N-propyl-N-[2-(2-thienyl)ethyl]amine,(S)—N-(8-Hydroxytetralin-2-yl)-N-propyl-N-[2-(2-thienyl)ethyl]amine,N-(8-Methoxytetralin-2-yl)-N-propyl-N-[2-(2-thienyl)ethyl]amine,(R)—N-(8-Methoxytetralin-2-yl)-N-propyl-N-[2-(2-thienyl)ethyl]amine,(S)—N-(8-Methoxytetralin-2-yl)-N-propyl-N-[2-(2-thienyl)ethyl]amine,N-[2-(4-Hydroxyphenyl)ethyl]-N-(8-hydroxytetralin-2-yl)-N-propylamine,N-[2-(4-Methoxyphenyl)ethyl]-N-(8-methoxytetralin-2-yl)-N-propylamine,N-[2-(2,5-Dimethylphenyl)ethyl]-N-(8-hydroxytetralin-2-yl)-N-propylamine,N-[2-(2,5-Dimethylphenyl)ethyl]-N-(8-methoxytetralin-2-yl)-N-propylamine,N-[2-(1- ...

HIF-2-ALPHA INHIBITOR POLYMORPHS

Chemical compounds that modulate HIF-2α activity, their polymorphs, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with HIF-2α, are described herein. 2. The composition of claim 1 , wherein greater than about 90% of the compound of Formula I is polymorph Form A.3. The composition of claim 1 , wherein greater than about 95% of the compound of Formula I is polymorph Form A.4. The composition of claim 1 , wherein greater than about 99% of the compound of Formula I is polymorph Form A.5. The composition of any one of the preceding claims claim 1 , wherein said polymorph Form A is characterized by having X-ray powder diffraction (XRPD) peaks at about 17.8 claim 1 , about 18.5 claim 1 , about 20.3 and about 21.2 degrees 2θ.6. The composition of any one of the preceding claims claim 1 , wherein said polymorph Form A is characterized by having X-ray powder diffraction (XRPD) peaks at about 6.8 claim 1 , about 15.9 claim 1 , about 17.8 claim 1 , about 18.5 claim 1 , about 20.3 claim 1 , about 20.5 claim 1 , about 21.2 claim 1 , about 22.1 claim 1 , about 22.7 and about 24.7 degrees 2θ.7. The composition of any one of the preceding claims claim 1 , wherein the polymorph Form A comprises cubic crystals.8. The composition of any one of the preceding claims claim 1 , wherein the polymorph Form A has a chemical purity of greater than about 90%.9. The composition of any one of the preceding claims claim 1 , wherein the polymorph Form A has a chemical purity of greater than about 95%.10. The composition of any one of the preceding claims claim 1 , wherein the polymorph Form A has a chemical purity of greater than about 99%.11. The composition of any one of the preceding claims claim 1 , wherein the chemical purity of the polymorph Form A is measured by HPLC analysis.12. The composition of any one of the preceding claims claim 1 , wherein the polymorph Form A has an enantiomeric purity of greater than about 90%.13. The composition of any ...

NOVEL ALKOXYMETHYL-SUBSTITUTED BISPHENOL COMPOUND

The present invention addresses the problem of providing a novel alkoxymethyl-substituted bisphenol compound having exceptional storage stability and exceptional solvent solubility, heat resistance, and optical properties when used as a resin raw material. This problem can be solved by using an alkoxymethyl-substituted bisphenol compound represented by General Formula (1): 1. An alkoxymethyl-substituted bisphenol compound represented by General Formula (1):wherein each R independently represents an alkyl group having 1 to 4 carbon atoms. The present invention relates to a novel alkoxymethyl-substituted bisphenol compound. Specifically, the present invention relates to an alkoxymethyl-substituted bis(4-hydroxyphenyl)sulfone compound.Conventionally, bisphenol compounds are widely used as raw materials for thermoplastic engineering resins such as polycarbonate and polyacrylate, thermosetting resins such as epoxy resin and polyimide resin, and further photosensitive resists, epoxy resin, curing agents for these, color developers for thermal recording, anti-fading agents, storage stabilizers, anti-oxidants, bactericides, fungicides, and so forth.In recent years, particularly in the field of electric and electronic devices, accompanied by miniaturization of and improvement in the performance of devices and electronic elements, improvement in heat resistance, solvent resistance, optical characteristics, and so forth has been increasingly demanded, and in particular, in a manufacturing process of semiconductor devices, microfabrication by lithography using a photoresist composition is performed, and development of resins and additives compatible with various lithography techniques is made.With the progress of processing technology, problems such as resist pattern collapse due to increase in aspect ratio, and notching caused by reflection of exposure light from a substrate has become non-negligible. As a method to solve these problems, antireflective films and processes ...

Process of preparing grignard reagent

A novel process of preparing a Grignard reagent is disclosed. The process is effected by electrochemically reacting a Grignard precursor with an electrode which comprises a metal for forming the Grignard reagent, in the presence an electrolyte solution that comprises a room temperature ionic liquid (RTIL). Electrochemical cells and systems for performing the process, and uses thereof in various applications are also disclosed.

Serotonin Receptor-Targeting Compounds and Methods

This invention relates to, in part, compositions and methods that are useful for, inter alia, the treatment of various diseases, including those linked to binding at a serotonin receptor. The compositions include chiral tetrahydronaphthalen-2-amine derivatives. Accordingly, the present invention provides for compositions and methods that agonize or antagonize one or more serotonin receptors and which find Use in the treatment of various neuropsychiatric diseases or disorders including, without limitation, autism spectrum disorder (ASD) or associated symptoms. 2. The pharmaceutical composition of claim 1 , wherein:{'sup': 1', '2', '1', '2, 'each of Rand Ris independently hydrogen or alkyl, or Rand Rcome together to form an optionally substituted heterocyclic ring;'}{'sup': 3', '4', '5', '6', '7', '8', '9', '10, 'each of R, R, R, R, R, R, R, and Ris independently hydrogen, hydroxy, acyl, acyloxy, alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, alkoxycarbonyl, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, and amido, and wherein any two adjacent R groups may optionally come together to form a carbocyclic or heterocyclic ring system;'}and a pharmaceutically acceptable excipient or carrier.3. The pharmaceutical composition of claim 1 , wherein the composition comprises at least about 70% claim 1 , or at least about 80% claim 1 , or at least about 85% claim 1 , or at least about 90% claim 1 , or at least about 95% claim 1 , or at least about 97% claim 1 , or at least about 99% of a single enantiomer.4. The pharmaceutical composition of any of the above claims claim 1 , wherein the dual partial agonist binds to serotonin 5-HTreceptor and/or the 5-HTreceptor with a binding affinity (K) of less than about 100 nM claim 1 , or less than about 50 nM claim 1 , or less than about 25 nM claim 1 , or less than about 20 nM claim 1 , or less than about 10 nM claim 1 , or less than about 5 nM claim 1 , or less than about 2 nM claim 1 , or less than about 1 ...

Substituted Phenethylamines with Serotoninergic and/or Norepinephrinergic Activity

Chemical syntheses and medical uses of novel inhibitors of the uptake of monoamine neurotransmitters and pharmaceutically acceptable salts and prodrugs thereof, for the treatment and/or management of psychotropic disorders, anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, attention deficit hyperactivity disorder, fibromyalgia, irritable bowel syndrome, and/or premature ejaculation are described.

COMPOSITIONS, SYNTHESIS, AND METHODS OF USING PHENYLCYCLOALKYLMETHYLAMINE DERIVATIVES

The present invention provides novel phenylcycloalkylmethylamine derivatives, and methods of preparing phenylcycloalkylmethylamine derivatives. The present invention also provides methods of using phenylcycloalkylmethylamine derivatives and compositions of phenylcycloalkylmethylamine derivatives. The pharmaceutical compositions of the compounds of the present invention can be used for treating and/or preventing obesity and obesity related co-morbid indications and depression and depression related co-morbid indications. 2. The compound according to claim 1 , wherein Rand Rare independently Calkoxy or halogen.3. The compound according to claim 1 , wherein Ris isobutyl.4. The compound according to claim 1 , wherein Ris H and Ris halogen or alkoxy.5. The compound according to claim 1 , wherein Ris ethyl.6. The compound according to claim 1 , wherein X is S(O)(O).7. The compound according to claim 1 , wherein X is NR.8. The compound according to claim 1 , which is at least about in 95% enantiomeric excess in R-form over S-form.9. The compound according to claim 8 , which is an optical pure R-form.10. The compound according to claim 1 , which is at least about in 95% enantiomeric excess in S-form over R-form.11. The compound according to claim 10 , which is an optical pure S-form.12. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable vehicle. This application is a Continuation of U.S. patent application Ser. No. 13/731,670, filed Dec. 31, 2012, now U.S. Pat. No. 9,238,625; which claims priority to U.S. Provisional Application No. 61/582,201, filed Dec. 30, 2011; the contents of the above identified applications are incorporated herein by reference in their entirety.The present invention relates to phenylcycloalkylmethylamine derivatives, synthesis of phenylcycloalkylmethylamine derivatives and methods of using phenylcycloalkylmethylamine derivatives for the pharmacological treatment of obesity, depression and obesity related co- ...

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. ...

NOVEL MODULATORS OF CORTICAL DOPAMINERGIC- AND NMDA-RECEPTOR-MEDIATED GLUTAMATERGIC NEUROTRANSMISSION

The present invention relates to novel substituted phenoxyethylamine derivatives, useful as modulators of cortical and basal ganglia dopaminergic and N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention. 1. A phenoxy-ethyl-amine derivative , wherein the phenoxy-ethyl-amine derivative is N-[2-(3-fluoro-5-methylsulfonyl-phenoxy)ethyl]propan-1-amine , or a pharmaceutically acceptable salt thereof.2. The phenoxy-ethyl-amine derivative of claim 1 , wherein the phenoxy-ethyl-amine derivative is a hydrochloric acid salt of N-[2-(3-fluoro-5-methylsulfonyl-phenoxy)ethyl]propan-1-amine.3. A pharmaceutical composition comprising a therapeutically effective amount of the phenoxy-ethyl-amine derivative of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , together with at least one pharmaceutically acceptable carrier claim 1 , excipient claim 1 , or diluent.4. A method of treatment of a disease or a disorder or a condition of a patient claim 1 , which disorder claim 1 , disease or condition is selected from the group consisting of psychosis claim 1 , schizophrenia claim 1 , schizophreniform disorder claim 1 , bipolar disorder claim 1 , anxiety disorder claim 1 , depression claim 1 , obsessive-compulsive disease claim 1 , dementia claim 1 , age-related cognitive impairment claim 1 , Autism spectrum disorders claim 1 , attention deficit hyperactivity disorder (ADHD) claim 1 , Gilles de la Tourette's syndrome claim 1 , eating disorder claim 1 , Parkinson's disease claim 1 , parkinsonian syndrome claim 1 , L-3 claim 1 ,4-dihydroxyphenylalanine (L-DOPA) induced dyskinesia claim 1 , Tardive dyskinesia claim 1 , dystonia claim 1 , Huntington's disease claim 1 , and Alzheimer's disease claim 1 , which method comprises the step of administering to such as patient in need thereof a ...

NEW METHOD FOR THE PREPARATION OF HIGHLY PURE IVABRADINE BASE AND SALTS THEREOF

A method for the preparation of purified ivabradine and salts thereof, a method for the purification of ivabradine and salts thereof, a new reactant used in said methods and the use of said reactant for the preparation of ivabradine. 2. A method according to wherein after step a) and before step b) the amount of (S)—N-[4 claim 1 ,5-dimethoxybenzocyclobut-1-yl)-methyl] N-methylamine of formula (II) in the mixture of step a) is determined and wherein the amount of (1S)-(+)-10 camphorsulfonic acid used in step b) is selected so that the molar ratio of (1 S)-(+)-10 cam phorsulfonic acid to (S)—N-[4 claim 1 ,5-dimethoxybenzocyclobut-1-yl)-methyl] N-methylamine of formula (II) is comprised between 0.5 and 1.5.3. A method according to claim 1 , wherein the mixture of step a) is dissolved or suspended in a solvent (S2) selected from the group consisting of acetone claim 1 , methyl ethyl ketone claim 1 , methanol claim 1 , ethanol claim 1 , isopropanol claim 1 , acetonitrile claim 1 , tetrahydrofuran claim 1 , ethyl acetate claim 1 , toluene and mixtures thereof.4. A method according to wherein the solvent (S2) is selected from toluene claim 3 , acetonitrile and mixtures thereof.5. A method according to wherein (1S)-(+)-10 camphorsulfonic acid is dissolved claim 1 , prior to its addition to the mixture of ivabradine and compound of formula (II) claim 1 , in a solvent (S3) selected from the group consisting of acetone claim 1 , methyl ethyl ketone claim 1 , methanol claim 1 , ethanol claim 1 , isopropanol claim 1 , acetonitrile claim 1 , tetrahydrofuran claim 1 , ethyl acetate claim 1 , and mixtures thereof claim 1 , or mixtures of the above-mentioned solvents with toluene.6. A method according to wherein the solvent (S3) is selected from acetonitrile and mixtures of acetonitrile with toluene.7. A method according to wherein step b) is carried out at a temperature comprised between 0° C. and 30° C.8. A method according to wherein step b) is carried out at a temperature ...

Substituted Phenethylamines with Serotoninergic and/or Norepinephrinergic Activity

Chemical syntheses and medical uses of novel inhibitors of the uptake of monoamine neurotransmitters and pharmaceutically acceptable salts and prodrugs thereof, for the treatment and/or management of psychotropic disorders, anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, attention deficit hyperactivity disorder, fibromyalgia, irritable bowel syndrome, and/or premature ejaculation are described.

PHENYL SUBSTITUTED CYCLOALKYLAMINES AS MONOAMINE REPUTAKE INHIBITORS

Phenyl-substituted cyclohexylamine derivatives and methods for their synthesis and characterization are disclosed. Use of these compounds to treat/prevent neurological disorders as well as methods for their synthesis are set forth herein. Exemplary compounds of the invention inhibit reuptake of endogenous monoamines, such as dopamine, serotonin and norepinephrine (e.g., from the synaptic cleft) and modulate one or more monoamine transporter. Pharmaceutical formulations incorporating compounds of the invention are also provided. 2. The compound of claim 1 , wherein Rand Rare members independently selected front the group consisting of substituted or unsubstituted C-Calkyl and substituted or unsubstituted C-Cheteroalkyl.3. The compound of claim 1 , wherein Rand Rare members independently selected from the group consisting of substituted or unsubstituted alkenyl claim 1 , substituted or unsubstituted alkynyl and substituted or unsubstituted cycloalkyl.6. The compound of claim 4 , wherein Y and X are members independently selected from the group consisting of H claim 4 , halogen claim 4 , CN and CF.7. The compound of claim 6 , wherein Y and X are chloro.8. The compound of claim 7 , wherein s is 1.9. The compound of claim 8 , wherein n is 1.12. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , vehicle or diluent.13. A method for treating or preventing a neurological disorder claim 1 , said method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof.14. The method of claim 13 , wherein said neurological disorder is a member selected from the group consisting of substance abuse claim 13 , fibromyalgia claim 13 , pain claim 13 , sleep disorder claim 13 , attention deficit disorder (ADD) claim 13 , attention deficit ...

NANOSTRUCTURED FORMULATIONS FOR THE DELIVERY OF SILIBININ AND OTHER ACTIVE INGREDIENTS FOR TREATING OCULAR DISEASES

Formulations are described, containing silibinin or other active ingredients incorporated in lipid nanoparticle systems of the SLN and NLC type, and based on calixarenes, possibly mucoadhesive, or in micellar and nanoparticle systems based on amphiphilic inulin copolymers for use in the treatment of neurodegenerative ocular diseases. The versatility of the calixarene compound is also described, capable of charging and releasing active ingredients characterized by low water solubility, easy chemical and enzymatic degradation, low bioavailability, either of natural origin or not, to be used in the treatment of ocular diseases. 18-. (canceled)10. Formulations according to claim 9 , wherein said ocular diseases are neurodegenerative ocular diseases.11. Formulations according to claim 9 , wherein said lipid nanoparticle systems consist of lipids selected from: triglycerides claim 9 , diglycerides claim 9 , monoglycerides claim 9 , aliphatic alcohols claim 9 , fatty acids (C10-C22); fatty acid esters with fatty alcohols claim 9 , mixtures of mono- claim 9 , di- and triglycerides of pegylated behenic acid claim 9 , mono- claim 9 , di- and triglycerides of pegylated captylic and caproic acids.12. Formulations according to claim 9 , wherein said mucoadhesives are selected from:inulin polymers bearing amino groups, low molecular weight polymers and cationic surfactants.13. Formulations according to claim 9 , wherein said nanoparticle systems have an average diameter in the range between 50 and 200 nm with a polydispersity index below 0.5.14. Formulations according to claim 11 , wherein said systems incorporate an amount of active ingredient selected from: silibinin claim 11 , sorafenib claim 11 , curcumin claim 11 , latanoprost in the range between 1 and 15% w/w.15. Formulations according to claim 9 , wherein said neurodegenerative ocular diseases are selected from: choroidal neovascularization (CNV) claim 9 , age-related macular degeneration (AMD) claim 9 , macular edema ...

Polyethylene Glycol Derivative And Preparation Method Thereof

The present invention relates to a polyethylene glycol derivative and a preparation method thereof. A preparation process of a polyethylene glycol derivative, according to the present invention, may provide a novel polyethylene glycol derivative which can be utilized in various ways as a drug linker, and is appropriate and effective for mass production and is advantageous in reproducible mass production of high-quality products. 2. The method according to claim 1 , wherein the step (5) of producing the compound of Formula 7 is carried out in the presence of a metal catalyst.3. The method according to claim 1 , wherein step (5) is carried out in the presence of a compound represented by Formula A:{'br': None, 'sub': a', 'b', 'c, 'N—RRR\u2003\u2003[Formula A]'}{'sub': a', 'b', 'c', '1', '5', 'a', 'b', 'c, 'wherein R, R, and Rare each independently H or a linear or branched Cto Calkyl group, and at least one of R, R, and Ris H, and n is an integer from 3 to 2000.'}4. The method according to claim 2 , wherein step (5) is carried out in the presence of hydrogen (H).5. The method according to claim 1 , wherein Rand Rare each independently selected from the group consisting of methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , and butyl.6. The method according to claim 1 , wherein n is an integer from 50 to 500.7. The method according to claim 6 , wherein n is an integer from 100 to 500.8. The method according to claim 7 , wherein n is an integer from 150 to 250.9. The method according to claim 1 , wherein the base is selected from the group consisting of sodium methoxide claim 1 , sodium ethoxide claim 1 , sodium t-butoxide claim 1 , sodium t-pentoxide claim 1 , potassium t-butoxide claim 1 , potassium t-pentoxide claim 1 , trimethylamine claim 1 , triethylamine claim 1 , tributylamine claim 1 , and mixtures thereof.10. The method according to claim 1 , wherein the compound of Formula 2-1 in step (2) is selected from the group consisting of dimethoxy-1- ...

Fluorine-based Compound, Organic Light-emitting Device Using Same and Method for Preparing Same

The present specification relates to a fluorene-based compound of Formula 1, a coating composition comprising the fluorene-based compound of Formula 1, an organic light emitting device using the same, and a manufacturing method thereof. 3. The fluorene-based compound of claim 1 , wherein L is a substituted or unsubstituted arylene group having 6 to 30 carbon atoms; or a substituted or unsubstituted heteroarylene group having 2 to 30 carbon atoms.4. The fluorene-based compound of claim 1 , wherein Ar1 and Ar2 are the same as or different from each other claim 1 , and are each independently a substituted or unsubstituted aryl group having 6 to 30 carbon atoms; or a substituted or unsubstituted heteroarylene group having 2 to 30 carbon atoms.6. A coating composition comprising the fluorene-based compound of .7. The coating composition of claim 6 , further comprising:a p-doping material.8. The coating composition of claim 7 , wherein the p-doping material is F4TCNQ; or a compound comprising a boron anion.9. The coating composition of claim 6 , further comprising:a single molecule comprising a thermosetting group or a photocurable group; ora single molecule comprising an end group capable of forming a polymer by heat.10. The coating composition of claim 6 , wherein the coating composition has a thin film retention rate of 95% or more in a thin film retention test claim 6 , after a heat treatment at 250° C. or less.11. An organic light emitting device comprising:a first electrode;a second electrode; andan organic material layer having one or more layers provided between the first electrode and the second electrode,{'claim-ref': {'@idref': 'CLM-00006', 'claim 6'}, 'wherein one or more layers of the organic material layer comprise the coating composition of or a cured product thereof, and'}the cured product of the coating composition is in a state where the coating composition is cured by a heat treatment or a light treatment.12. The organic light emitting device of claim ...

CYCLOPROPYLMETHANAMINES AS SELECTIVE 5-HT(2C) RECEPTOR AGONISTS

Disclosed are 2-phenyl-cyclopropylmethanamines which are selective 5-HT(2C) receptor agonists and are used in the treatments of diseases and conditions wherein modulation of 5-HT(2C) receptors provides a benefit, such as obesity and psychiatric disorders. 2. The compound of wherein Ris fluoro or chloro.3. The compound of wherein when n is 1 claim 1 , Ris fluoro or chloro claim 1 , and when n is 2 claim 1 , Ris fluoro and fluoro claim 1 , chloro and chloro claim 1 , or fluoro and chloro.4. (canceled)68.-. (canceled)9. The compound of wherein Ris —CHCH—O—CHor —CHCH—S—CH.1115.-. (canceled)16. A compound selected from the group of compounds disclosed in paragraph [0396] herein.17. A compound selected from the group consisting of(+) (2-(2-(allyloxy)-5-fluorophenyl)cyclopropyl)methanamine;(+) (2-(5-fluoro-2-(2-fluoroethoxy)phenyl)cyclopropyl)methanamine;(+) (2-(5-chloro-2-(3-fluoropropoxy)phenyl)cyclopropyl)methanamine; and(+) (2-(5-chloro-2-((2-fluoroallyl)oxy)phenyl)cyclopropyl)methanamine;or a salt thereof.18. A composition comprising (a) compound of claim 1 , (b) a second therapeutic agent useful in the treatment of a disease or condition wherein modulation of 5-HT(2C) provides a benefit claim 1 , and (c) an optional excipient and/or pharmaceutically acceptable carrier.19. The composition of wherein the second therapeutic agent comprises a therapeutic agent useful in a treatment of a psychiatric disorder claim 18 , a metabolic disorder claim 18 , a neurological disorder claim 18 , or an eating disorder.20. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier or vehicle.21. A method of treating a disease or condition wherein modulation of 5-HT(2C) receptors provides a benefit comprising administering a therapeutically effective amount of a compound of to an individual in need thereof.2224.-. (canceled)25. The method of wherein the disease or condition is a central nervous system disorder claim 21 , damage to the central ...

DERIVATIVES OF (-)-VENLAFAXINE AND METHODS OF PREPARING AND USING THE SAME

Methods of preparing, and compositions comprising, derivatives of (−)-venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders. 1. A pharmaceutical composition which comprises (−)-venlafaxine derivative , or a pharmaceutically acceptable salt thereof , substantially free of its (+) stereoisomer and a pharmaceutically acceptable carrier or excipient.2. The pharmaceutical composition of wherein the (−)-venlafaxine derivative is selected from the group consisting of (−)-O-desmethylvenlafaxine claim 1 , (−)-N-desmethylvenlafaxine claim 1 , (−)-N claim 1 ,O-didesmethylvenlafaxine claim 1 , and (−)-N claim 1 ,N-didesmethylvenlafaxine.3. The pharmaceutical composition of wherein the (−)-venlafaxine derivative is (−)-O-desmethylvenlafaxine or (−)-N claim 2 ,O-didesmethylvenlafaxine.4. The pharmaceutical composition of adapted for intravenous infusion claim 1 , transdermal delivery claim 1 , or oral delivery.5. The pharmaceutical composition of wherein the amount of (−)-venlafaxine derivative claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , comprises greater than about 90% by weight of the total amount of racemic venlafaxine derivative.6. The pharmaceutical composition of wherein the (−)-venlafaxine derivative comprises a hydrochloride salt thereof.7. The pharmaceutical composition of wherein said pharmaceutically acceptable excipient comprises lactose claim 1 , croscarmellose sodium claim 1 , microcrystalline cellulose claim 1 , pre-gelatinized starch claim 1 , and magnesium stearate.8. The pharmaceutical composition of wherein said pharmaceutical composition is substantially free of all mono- or di-saccharides. ...

NOVEL PROCESS FOR THE MANUFACTURE OF 4-AMINOBENZOAMIDINE DIHYDROCHLORIDE

The present invention relates to a process for the preparation of 4-aminobenzoamidine (4-AMBA) salts of general formula (I) 13-. (canceled)5. The process for the preparation of a compound of formula according to claim 4 , wherein the alcoholic solvent or alcoholic solution is ethanolic or methanolic.6. The process for the preparation of a compound of formula (I) or (II) according to claim 4 , wherein the alcoholic solvent or alcoholic solution is methanolic.7. (canceled)8. The process according to claim 4 , wherein the HCl or HBr in step (A) or step (B) is in a concentration from 5% to 30% (weight %) in alcohol.9. The process according to claim 4 , wherein a molar ratio of HCl or HBr to compound (III) is from 2:1 to 20:1.10. The process according to wherein the reaction according to step (A) is conducted at a temperature from −10° C. to 80° C.1113-. (canceled) The present invention relates to a process for the preparation of 4-aminobenzoamidine (4-AMBA) salts of general formula (I)preferably the salts thereof with hydrochloric or hydrobromic acid, particularly preferred the dichloride salt.A compound of formula (I) is a key intermediate for Dabigatran etexilate, which is known as an orally active prodrug for the reduction of stroke and systemic embolism. It was first disclosed in WO 98/37075. Processes for the manufacture of dabigatran etexilate are also known from WO 2006/000353 or described by Hauel et al. (J. Med. Chem, 2002, 45. 1757 ff).Another process for the manufacture of Dabigatran is described by Zerban et al. (WO2006000353), However this process requires the use of an ecologically unfavorable dehydration agent.Therefore a new process was developed by Gnad et al., as described in WO 2011/061080, circumventing the use of this dehydration agent. This process requires the use of the herein described intermediate 4-AMBA.One of the current manufacturing routes of 4-aminobenzoamidine starts from 4-aminobenzonitrile via the 4-amino-N-hydroxybenzamidine ...

ENDODONTIC POST SYSTEM

The present invention provides processes for the preparation of a compound of Formula 2 or a salt thereof, wherein Ris selected from the group consisting of H, C-Calkyl, and C(0)R; Ris selected from the group consisting of C-Calkyl, C-Caryl and C-Carylalkyl; the carbon atom marked with “*” is racemic, enantiomerically enriched in the (R)-configuration, or enantiomerically enriched in the (S)-configuration. Also provided are intermediate compounds of the processes. 2. The process of wherein the catalyst is selected from the group consisting of: palladium claim 1 , platinum and Raney™ Nickel.3. The process of wherein the catalyst is selected from the group consisting of: palladium hydroxide on carbon and palladium on carbon.6. The process of wherein the leaving group is selected from the group consisting of: bromide claim 5 , iodide claim 5 , sulfonyloxy groups and carbonates.9. The process of or wherein the reductive amination is conducted with a hydride reducing agent selected from the group consisting of: sodium borohydride claim 5 , potassium borohydride claim 5 , lithium borohydride claim 5 , sodium cyanoborohydride and sodium triacetoxyborohydride.10. The process of any one of to wherein{'sup': '1', 'sub': 1', '3, 'Ris C-Calkyl;'}{'sup': '2', 'Ris methyl;'}Ar is selected from the group consisting of: naphthyl, phenyl, and substituted phenyl;the carbon atom marked with “*” is enriched in the (S)-configuration; andthe carbon atom marked with “**” is enriched in the (R)-configuration.14. The process of or wherein the reductive amination is conducted with a hydride reducing agent selected from the group consisting of:sodium borohydride, potassium borohydride, lithium borohydride, sodium cyanoborohydride and sodium triacetoxyborohydride.21. The process of any one of to further comprising converting the compound of Formula 2 or a salt thereof to Rotigotine or a pharmaceutically acceptable salt thereof. The present invention relates to the field of synthesis of organic ...

Processes for the Preparation of Rotigotine and Intermediates Thereof

The present invention provides processes for the preparation of a compound of Formula 2 or a salt thereof, wherein Ris selected from the group consisting of H, C-Calkyl, and C(0)R; Ris selected from the group consisting of C-Calkyl, C-Caryl and C-Carylalkyl; the carbon atom marked with “*” is racemic, enantiomerically enriched in the (R)-configuration, or enantiomerically enriched in the (S)-configuration. Also provided are intermediate compounds of the processes. 2. The process of claim 1 , wherein the catalyst is selected from the group consisting of: palladium claim 1 , platinum and Raney™ Nickel.3. The process of claim 1 , wherein the catalyst is selected from the group consisting of: palladium hydroxide on carbon and palladium on carbon.6. The process of claim 5 , wherein the leaving group is selected from the group consisting of: bromide claim 5 , iodide claim 5 , sulfonyloxy groups and carbonates.9. The process of claim 7 , wherein the reductive amination is conducted with a hydride reducing agent selected from the group consisting of: sodium borohydride claim 7 , potassium borohydride claim 7 , lithium borohydride claim 7 , sodium cyanoborohydride and sodium triacetoxyborohydride.10. The process of claim 1 , wherein{'sup': '1', 'sub': 1', '3, 'Ris C-Calkyl;'}{'sup': '2', 'Ris methyl;'}Ar is selected from the group consisting of: naphthyl, phenyl, and substituted phenyl;the carbon atom marked with “*” is enriched in the (S)-configuration; andthe carbon atom marked with “**” is enriched in the (R)-configuration.14. The process of claim 12 , wherein the reductive amination is conducted with a hydride reducing agent selected from the group consisting of: sodium borohydride claim 12 , potassium borohydride claim 12 , lithium borohydride claim 12 , sodium cyanoborohydride and sodium triacetoxyborohydride.18. (canceled)20. (canceled)21. The process of claim 1 , further comprising converting the compound of Formula (2) or a salt thereof to Rotigotine or a ...

SUBSTITUTED PHENETHYLAMINES WITH SEROTONINERGIC AND/OR NOREPINEPHRINERGIC ACTIVITY

Chemical syntheses and medical uses of novel inhibitors of the uptake of monoamine neurotransmitters and pharmaceutically acceptable salts and prodrugs thereof, for the treatment and/or management of psychotropic disorders, anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, and/or premature ejaculation are described. 3. The compound of claim 1 , wherein said compound is a mixture of enantiomers.4. The compound of claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 10%.5. The compound of claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 20%.6. The compound of claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 50%.7. The compound of claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 70%.8. The compound of claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 90%.9. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to and a pharmaceutically acceptable carrier.10. The pharmaceutical composition of claim 9 , formulated for oral claim 9 , parenteral claim 9 , or intravenous infusion administration.11. The pharmaceutical composition of claim 9 , formulated as a tablet or a capsule.12. The pharmaceutical composition of claim 9 , wherein said therapeutically effective amount is about 0.5 milligram to about 400 milligram total daily.13. A method of treating a mammal ...

Heat-Sensitive Recording Material And Diphenylsulfone

The content of compound(s) having a molecular weight of 650-670, typically a molecular weight of 660, as measured by mass spectrometry, is reduced to 0.5 mass % or less in a heat-sensitive recording material comprising 3,3′-diallyl-4,4′-dihydroxy diphenylsulfone, or in a diphenylsulfone or a color-developing agent. Provided is, thereby, a heat-sensitive recording material, a color-developing agent, or a diphenylsulfone which cause less background fogging under moisture and heat conditions and which has excellent preservation stability of a colored image. 1. A heat-sensitive recording material comprising 3 ,3′-diallyl-4 ,4′-dihydroxydiphenylsulfone , wherein the content of a compound generated as a by-product during synthesis of the 3 ,3′-diallyl-4 ,4′-dihydroxydiphenylsulfone and having a molecular weight of 650 to 670 , typically having a molecular weight of 660 , is less than 0.8% by mass in mass spectrometry.2. The heat-sensitive recording material according to claim 1 , wherein the content of the compound having a molecular weight of 650 to 670 claim 1 , typically having a molecular weight of 660 claim 1 , is 0.5% by mass or less.3. The heat-sensitive recording material according to claim 1 , wherein the 3 claim 1 ,3′-diallyl-4 claim 1 ,4′-dihydroxydiphenylsulfone has a crystal form characterized by an X-ray diffraction diagram having peaks at least at diffraction angles (2θ) [°] of 7.2 and 22.0 in a powder X-ray diffraction method with a Cu-Kα ray.4. The heat-sensitive recording material according to claim 3 , wherein the 3 claim 3 ,3′-diallyl-4 claim 3 ,4′-dihydroxydiphenylsulfone has a crystal form characterized by an X-ray diffraction diagram having peaks at least at diffraction angles (2θ) [°] of 7.2 claim 3 , 16.3 claim 3 , 20.0 claim 3 , 22.0 claim 3 , 24.7 and 29.0 in a powder X-ray diffraction method with a Cu-Kα ray.5. The heat-sensitive recording material according to claim 3 , wherein the 3 claim 3 ,3′-diallyl-4 claim 3 ,4′-dihydroxydiphenylsulfone ...

NOVEL PROCESS FOR THE MANUFACTURE OF 4-AMINOBENZOAMIDINE DIHYDROCHLORIDE

The present invention relates to a process for the preparation of 4-aminobenzoamidine (4-AMBA) salts of general formula (I) 1. A compound of formula (II), The present invention relates to a process for the preparation of 4-aminobenzoamidine (4-AMBA) salts of general formula (I)preferably the salts thereof with hydrochloric or hydrobromic acid, particularly preferred the dichloride salt.A compound of formula (I) is a key intermediate for Dabigatran etexilate, which is known as an orally active prodrug for the reduction of stroke and systemic embolism. It was first disclosed in WO 98/37075. Processes for the manufacture of dabigatran etexilate are also known from WO 2006/000353 or described by Hauel et al. (J. Med. Chem, 2002, 45. 1757 ff).Another process for the manufacture of Dabigatran is described by Zerban et al. (WO2006000353), However this process requires the use of an ecologically unfavorable dehydration agent.Therefore a new process was developed by Gnad et al., as described in WO 2011/061080, circumventing the use of this dehydration agent. This process requires the use of the herein described intermediate 4-AMBA.One of the current manufacturing routes of 4-aminobenzoamidine starts from 4-aminobenzonitrile via the 4-amino-N-hydroxybenzamidine intermediate (IV) (see Scheme 2).This process requires usage of the expensive catalyst Pd/C and the hazardous reagent NHOH, which is explosive and potentially mutagenic (Zerban Georg et al WO 2007/071743). It is well known that imidates can be prepared through the so called Pinner reaction by condensing a nitrile and an alcohol in the presence of anhydrous hydrogen chloride, hydrogen bromide or a base (Journal of Polymer Science, Part B: Polymer Physics (2011), 49, 649).The prior art already describes a process for preparing Intermediate (II) (R=ethyl) Ethyl 4-aminobenzimidine and subsequent transformation to 4-AMBA (I) through Pinner reaction. However this process suffers from serious drawbacks for application on ...

OXYGENATED AROMATIC AMINES AND USE AS ANTIOXIDANTS

Described are compounds, compositions, and methods that include oxygenated aromatic amines, such as an aminophenol-, phenyl-p-phenylenediamine-, and diaminobenzene-based compound useful as antioxidants. The oxygenated aromatic amine includes a secondary and/or tertiary amine group having a nitrogen that is attached to one or two carbon-containing group(s), the carbon-containing group(s) having a hydroxyl and/or ether group separated from the nitrogen by one or more carbon atoms. 2. The method of wherein the organic compound comprises an ethylenically unsaturated group claim 1 , the organic compound optionally being an olefin or alkene.3. The method of wherein the organic compound is present in a fuel composition or a lubricant composition claim 1 , the fuel composition optionally comprising a gasoline or gasoline blend.4. The method of wherein the gasoline or gasoline blend comprises pyrolysis gasoline claim 3 , a refined product of pyrolysis gasoline claim 3 , an alcohol such as ethanol claim 3 , or a combination thereof.5. The method of wherein the compound of Formula I is present in the composition in an amount in the range of 1 ppm to 5000 ppm claim 1 , in the range of 10 ppm to 2500 ppm claim 1 , or in the range of 50 ppm to 1500 ppm.6. The method of wherein the organic compound is present in (a) a rubber composition claim 1 , a plastic composition claim 1 , or an adhesive composition claim 1 , or (b) a food or beverage composition.7. The method of claim 1 , wherein at least one of —R claim 1 , —R claim 1 , —R claim 1 , —R claim 1 , and —Ris —OH claim 1 , and preferably —Ris —OH.8. The method of claim 1 , wherein the one or more hydroxyl group(s) are separated from the N atom by two or more carbon atoms claim 1 , and preferably by two carbon atoms.9. The method of wherein one or both of Rand Rare of the formula: —(CR)(CHOH)(CH)R claim 1 , Ris independently selected from —H and alkyl claim 1 , wherein q and z are independently (—) (a covalent bond) claim 1 , or ...

PHARMACEUTICALLY ACTIVE DIMERS LINKED THROUGH PHENOLIC HYDROXYL GROUPS

Pharmaceutically active homo-dimers of opioid and other pharmaceutically active agents characterized by a single phenolic hydroxyl group wherein the respective monomers are ether-linked through such groups by an ethylene residue. The dimers share the receptor pharmacology of the corresponding monomer, in particular cases are non-absorbed, and the ether link of the dimers is particularly resistant to metabolism when administered to a subject, all conferring divers advantages relative to the corresponding monomers. Exemplary of the dimers are those of buprenorphine, naloxone, naltrexone, des-venlafaxine, albuterol and acetaminophen. 1. A homo-dimer compound of a pharmaceutically active agent selected from the group consisting of buprenorphine , naloxone , naltrexone , desvenlafaxine , and albuterol wherein two such agents are covalently ether-linked through phenolic hydroxyl groups of the agents by an ethylene residue , or a pharmaceutically acceptable salt or solvate thereof.2. A homo-dimer compound according to claim 1 , wherein the compound is in the form of a pharmaceutically acceptable salt.3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a dimer compound according to .4. The pharmaceutical composition of claim 3 , wherein said composition is formulated as an oral tablet or extended release oral tablet.10. (canceled) This application is a continuation of U.S. application Ser. No. 14/697,155, filed Apr. 27, 2015, which application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 61/985,207, filed Apr. 28, 2014; U.S. Provisional Application Ser. No. 62/101,768, filed Jan. 9, 2015; and U.S. Provisional Application +Ser. No. 62/176,883, filed Jan. 9, 2015, the disclosures of each being incorporated herein by reference.Not ApplicableNot ApplicableBuprenorphine (Formula 1) is a semisynthetic opioid derivative of thebaine. It is a mixed agonist—antagonist opioid receptor ...

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.

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.

Compositions, synthesis, and methods of using cycloalkylmethylamine derivatives

The present invention provides novel cycloalkylmethylamine derivatives, and methods of preparing cycloalkylmethylamine derivatives. The present invention also provides methods of using cycloalkylmethylamine derivatives and compositions of cycloalkylmethylamine derivatives. The pharmaceutical compositions of the compounds of the present invention can be advantageously used for treating and/or preventing obesity and obesity related co-morbid indications and depression and depression related co-morbid indications.

Amino substituted benzenepropanols

Hypotensive activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein R 1 is hydrogen or alkyl; R 2 and R 3 are each independently phenyl, substituted phenyl, cycloalkyl, or R 2 is hydrogen and R 3 is heteroaryl; R 4 and R 5 are the same or different and each is hydrogen, hydroxy, alkoxy, alkanoyl or alkyl; R 6 is hydrogen or alkyl; and n is 1, 2, 3 or 4; with the proviso that if R 2 and R 3 are each phenyl, at least one of R 1 , R 4 , R 5 and R 6 is other than hydrogen.

Processes for the Preparation of Arylamine Compounds

A process for the preparation of N-arylamine compounds, the process including: reacting a compound having an amino group with an acylating compound in the presence of a base and a transition metal catalyst under reaction conditions effective to form an N-arylamine compound; wherein the transition metal catalyst comprises a complex of a Group 8-10 metal and at least one chelating ligand comprising (R)-(−)-1-[(S)-2-dicyclohexylphosphino]-ferrocenyl]ethyldi-t-butylphosphine.

Processes for the preparation of arylamine compounds

A process for the preparation of N-arylamine compounds, the process including: reacting a compound having an amino group with an acylating compound in the presence of a base and a transition metal catalyst under reaction conditions effective to form an N-arylamine compound; wherein the transition metal catalyst comprises a complex of a Group 8-10 metal and at least one chelating ligand comprising (R)-(−)-1-[(S)-2-dicyclohexylphosphino]-ferrocenyl]ethyldi-t-butylphosphine.

아릴아민 화합물의 제조 방법

본 발명은 N-아릴아민 화합물을 형성하기에 효과적인 반응 조건하에서 염기 및 전이 금속 촉매의 존재하에 아미노기를 갖는 화합물을 아릴화 화합물과 반응시키는 단계를 포함하며, 여기서 전이 금속 촉매는 8 내지 10족 금속과 (R)-(-)-1-[(S)-2-디시클로헥실포스피노]-페로세닐]에틸디-t-부틸포스핀을 포함하는 1종 이상의 킬레이트 리간드의 착물을 포함하는 것인, N-아릴아민 화합물의 제조 방법에 관한 것이다.

Processes for the preparation of arylamine compounds

A process for the preparation of N-arylamine compounds, the process including: reacting a compound having an amino group with an arylating compound in the presence of a base and a transition metal catalyst under reaction conditions effective to form an N-arylamine compound; wherein the transition metal catalyst comprises a complex of a Group 8-10 metal and at least one chelating ligand comprising (R)-(-)-l-[(S)-2-dicyclohexylphosphino]- ferrocenyl]ethyldi-t-butylphosphine.

Processes for the preparation of arylamine compounds

A process for the preparation of N-arylamine compounds, the process including: reacting a compound having an amino group with an arylating compound in the presence of a base and a transition metal catalyst under reaction conditions effective to form an N-arylamine compound; wherein the transition metal catalyst comprises a complex of a Group 8-10 metal and at least one chelating ligand comprising (R)-(-)-l-[(S)-2-dicyclohexylphosphino]- ferrocenyl]ethyldi-t-butylphosphine.

芳基胺化合物制备方法

一种制备N-芳基胺化合物的方法，该方法包括：使具有氨基的化合物与芳基化化合物在碱和过渡金属催化剂的存在下，在有效形成N-芳基化合物的反应条件下进行反应；其中该过渡金属催化剂包括第8-10族金属和至少一种包括(R)-(-)-1-[(S)-2-二环己基膦基]-二茂铁基]乙基二叔丁基膦的螯合配体的络合物。

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 venlafaxin

A process for the preparation of venlafaxin and/or the physiologically acceptable addition salts thereof that consists of reacting a compound of general formula (II) where R is a C1-C10 alkyl, aryl, aralkyl or cycloalkyl group of 3 to 6 atoms of carbon, with a organomagnesium compound of general formula (III) where X is an atom of halogen and, if desired, a salt of the thus obtained venlafaxin is formed by reaction thereof with a physiologically acceptable acid. <CHEM>

Processes for the preparation of arylamine compounds

A process for the preparation of N-arylamine compounds, the process including: reacting a compound having an amino group with an arylating compound in the presence of a base and a transition metal catalyst under reaction conditions effective to form an N-arylamine compound; wherein the transition metal catalyst comprises a complex of a Group 8-10 metal and at least one chelating ligand comprising (R)-(-)-l-[(S)-2-dicyclohexylphosphino]- ferrocenyl]ethyldi-t-butylphosphine.

Venlafaxine production process

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。

A photo-alignment compound, a photo-alignment composition, a display substrate having an alignment layer, and a method of manufacturing the display substrate

광배향 화합물, 광배향 조성물, 배향막을 포함하는 표시 기판 및 이의 제조 방법에서, 광배향 화합물은 화학식 1로 나타낸다. In a display substrate comprising a photo-alignment compound, a photo-alignment composition, and an alignment film, and a process for producing the same, the photo-alignment compound is represented by the general formula (1). <화학식 1> &Lt; Formula 1 > 화학식 1에서, x는 1 내지 4의 정수를 나타내고 R 1 및 R 2 는 각각 독립적으로 -(CH 2 ) n -를 나타내고(n=1 내지 6의 정수), R 1 의 하나 이상의 -CH 2 -는 각각 독립적으로 , , , 또는 로 치환될 수 있고, R 3 은 -(CH 2 ) m CH 3 를 나타내고(m=1 내지 12의 정수), R 3 의 수소 원자들은 각각 F 또는 Cl로 치환될 수 있고, R 4 는 아미노기, 아닐린기, 카르복시기, 히드록실기, 시안기, 알킬렌기(x가 1인 경우, 알킬기) 또는 열반응기를 나타내고, 상기 화학식 1의 수소 원자들은 각각 독립적으로 -O(CH 2 ) k CH 3 , -(CH 2 ) k CH 3 , F 또는 Cl로 치환될 수 있고, 상기 k는 각각 독립적으로 0 또는 1 내지 3의 정수를 나타낸다. 이에 따라, 배향막 제조의 신뢰성, 배향막의 배향 신뢰성 및 배향 안정성을 향상시킬 수 있다. In formula 1, x are each from 1 to an integer of 4 R 1 and R 2 independently - (CH 2) n - represents an (integer of n = 1 to 6), one or more of R 1 -CH 2 - Are each independently , , , or And R 3 represents - (CH 2 ) m CH 3 (m = an integer of 1 to 12), the hydrogen atoms of R 3 may each be substituted with F or Cl, and R 4 represents an amino group, A hydrogen atom, an aniline group, a carboxy group, a hydroxyl group, a cyano group, an alkylene group (alkyl group when x is 1), or a thermal reactor, and the hydrogen atoms of Formula 1 are each independently -O (CH 2 ) k CH 3 , (CH 2 ) k CH 3 , F or Cl, and each k is independently 0 or an integer of 1 to 3. This makes it possible to improve the reliability of the alignment film production, the alignment reliability of the alignment film and the alignment stability. 광배향, 광반응, 시나메이트, 에테르, 에스테르, 이성질, 중합 Photo-alignment, photoreaction, cinnamate, ether, ester, isomer, polymerization

New Alkoxy Methyl Substituted Bisphenol Compound

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

Process for the Resolution of Tramadol

본 발명은 분별제로서 O,O-디-p-톨루일타르타르산의 실질적으로 단일한 거울상 이성질체를 사용하여 전형적인 염 분별법에 의하여 진행되는 트라마돌의 실질적으로 단일한 거울상 이성질체 또는 약제학적으로 수용가능한 이들의 염을 제조하기 위한 방법에 관한 것이다.

Triphenylamine derivatives, and charge transport material and electrophotographic photoreceptor prepared therefrom

Triphenylamine derivatives represented by general formula (1), wherein R?1, R2, R3, R4, R5 and R6¿ represent each hydrogen, lower alkyl, alkoxy, halogeno or optionally substituted aryl; and m and n represent each 0 or 1.

Crystalline venlafaxine base and novel polymorphs of venlafaxine hydrochloride, processes for preparing thereof

Crystalline form of venlafaxine hydrochloride

Bis phenols polymer for dentistry

본 발명은 치과용 재료로서 사용되는 하기 일반식(I)의 화합물을 제공한다. The present invention provides a compound of formula (I) below for use as a dental material. 식 중, R 1 , R 2 , R 3 및 R 4 는 각각 독립적으로 -OH, -OCOCH=CH 2 , 또는 -OCOCCH 3 =CH 2 이다. 다만, R 1 및 R 2 중 적어도 하나는 -OH가 아니고, 동시에 R 3 및 R 4 중 적어도 하나는 -OH가 아니다. Wherein, R 1, R 2, R 3 and R 4 are each independently -OH, -OCOCH = CH 2, or -OCOCCH 3 = CH 2. Provided that at least one of R 1 and R 2 is not -OH, and at least one of R 3 and R 4 is not -OH.

METHOD FOR PRODUCING (S) - (-) - 2- (N-PROPYLAMINO) -5-METHOKETRALIN AND (S) - (-) - 2- (N-PROPYlamino) -5-HYDROXYTETRALIN, THEIR SALTS WITH N-3,5 -DINITROBENZOYL) -α-Phenylglycine, METHOD FOR PRODUCING (6S) - (-) - 5,6,7,8-TETRAHYDRO-6- [PROPYL (2-THIENYL) Ethyl] AMINO-1-NAPHTOL (ROTHOTINE) (OPTIONS)

1. Способ получения оптически активных (S)-(-)-2-(N-пропиламино)-5-метокситетралина и (S)-(-)-2-(N-пропиламино)-5-гидрокситетралина формул S-(II) и S-(III) соответственно: ! ! включающий оптическое разделение соответствующих соединений формул (II) и (III): ! ! в присутствии оптически активной формы N-(3,5-динитробензоил)-α-фенилглицина. ! 2. Способ по п.1, в котором получение оптически активного соединения S-(II) включает оптическое разделение соответствующего соединения (II) в присутствии (+)-N-(3,5-динитробензоил)-α-фенилглицина. ! 3. Способ по п.1, в котором получение оптически активного соединения S-(III) включает оптическое разделение соответствующего соединения (III) в присутствии (-)-N-(3,5-динитробензоил)-α-фенилглицина. ! 4. Соль (S)-(-)-2-(N-пропиламино)-5-метокситетралина, S-(II) и (+)-N-(3,5-динитробензоил)-α-фенилглицина формулы (V): ! ! 5. Соль (S)-(-)-2-(N-пропиламино)-5-гидрокситетралина, S-(III) и (-)-N-(3,5-динитробензоил)-α-фенилглицина формулы (VI): ! ! 6. Применение оптически активного соединения S-(II), полученного способом по п.2, в качестве промежуточного соединения при получении (6S)-(-)-5,6,7,8-тетрагидро-6-[пропил(2-тиенил)этил]амино-1-нафтола (ротиготина). ! 7. Применение оптически активного соединения S-(III), полученного способом по п.3, в качестве промежуточного соединения при получении (6S)-(-)-5,6,7,8-тетрагидро-6-[пропил(2-тиенил)этил]амино-1-нафтола (ротиготина). ! 8. Применение соли формулы (V) по п.4, в качестве промежуточного соединения при получении (6S)-(-)-5,6,7,8-тетрагидро-6-[пропил(2-тиенил)этил]амино-1-нафтола (ротиготина). ! 9. Применение соли формулы (VI) по п.5, в качестве промежуточного соединения при получении (6S)-(-)-5,6,7,8-тетрагидро-6-[пропил(2-тиенил)этил]амино-1-нафтола (ротиготина). РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2011 119 224 (13) A (51) МПК C07C 213/10 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (71) Заявитель(и): Интерким, С.А. (ES) (21)(22) Заявка: ...

Diamine compound, polyamic acid, polyimide and liquid crystal aligning agent

액정 배향 처리제의 원료로 한 경우, 액정의 프레틸트각을 크게 하는 효과를 갖고, 적은 사용 비율로도 액정을 수직으로 배향시킬 수 있으며, 또한 액정 배향 처리제의 용액에 도포성을 높이는 빈용매를 혼합했을 때에도 석출되기 어려운 신규 디아민을 제공한다. 하기 식 (1) 로 나타내는 디아민. When the liquid crystal alignment treatment agent is used as a raw material, it has an effect of increasing the pretilt angle of the liquid crystal, and can orient the liquid crystal vertically even with a small use ratio. Further, a poor solvent The present invention provides a novel diamine which is hardly precipitated. A diamine represented by the following formula (1). (식 (1) 중, R 1 은 페닐렌이고, R 2 는 시클로헥실렌 또는 페닐렌이며, R 3 은 시클로헥실렌이다. R 4 는 탄소수 3 ∼ 12 의 알킬기, 탄소수 3 ∼ 12 의 플루오로알킬기, 탄소수 3 ∼ 12 의 알콕시기, 또는 탄소수 3 ∼ 12 의 플루오로알콕시기의 어느 것이다) (Wherein R 1 is phenylene, R 2 is cyclohexylene or phenylene, and R 3 is cyclohexylene, R 4 is an alkyl group having 3 to 12 carbon atoms, a fluoro group having 3 to 12 carbon atoms An alkyl group, an alkoxy group having 3 to 12 carbon atoms, or a fluoroalkoxy group having 3 to 12 carbon atoms)

Method for preparing tapentadolhydrochloride and intermediate thereof

本发明涉及他喷他多的制备方法及其中间体。更具体而言，涉及结构如式II所示的化合物及其对映异构体、非对映异构体、外消旋体、对映异构体或非对映异构体的混合物以及它们的盐；式II化合物的制备方法；式II化合物用于制备他喷他多的用途；用于制备式II化合物的中间体。本发明提供的他喷他多的制备方法条件温和、操作简便、立体选择性高、安全环保、适合大规模商业化生产，并且原料和催化剂市场供应充足，价格便宜。

METHOD FOR PRODUCING ARYLAMINE COMPOUNDS

1. Способ получения N-ариламиновых соединений, включающий следующие стадии:осуществление реакции между соединением, имеющим амино-группу, и арилирующим соединением в присутствии основания и катализатора на основе переходного металла при условиях реакции, эффективных для образования N-ариламинового соединения, в течение промежутка времени менее чем или равного 180 мин;причем катализатор на основе переходного металла присутствует в ходе реакции в концентрации, составляющей от примерно 0,03 до примерно 1,0 мол.%, в расчете на общее количество соединения, имеющего амино-группу, арилирующего соединения и катализатора на основе переходного металла;причем катализатор на основе переходного металла включает комплексное соединение палладия и, по меньшей мере, один хелатирующий лиганд, включающий (R)-(-)-1-[(S)-2-дициклогексилфосфино]-ферроценил]этилди-трет-бутилфосфин; ипричем арилирующее соединение включает, по меньшей мере, одно соединение, имеющее формулу:в которой Х представляет собой атом галогена или серосодержащую замещаемую группу, a R, R, R, R, Rнезависимо выбирают из группы, включающей Н, CN, алкил, алкокси, винил, алкенил, формил, СF, ССl, галогенид, CH, амид, ацил, сложную эфирную группу, алкокси-группу, аминогруппу, тиоалкокси-группу, фосфино-группу и комбинации перечисленного.2. Способ по п.1, дополнительно включающий получение катализатора на основе переходного металла по реакции предшественника палладиевого катализатора и хелатирующего лиганда.3. Способ по п.2, в котором предшественником палладиевого катализатора является ацетат палладия (II) (Pd(OAc)).4. Способ по любому из предшествующих пунктов, в котором соединение, имеюще� РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2011 123 090 (13) A (51) МПК C07C 209/10 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (71) Заявитель(и): ЮНИВЕЙШН ТЕКНОЛОДЖИЗ, ЛЛК (US) (21)(22) Заявка: 2011123090/04, 21.10.2009 Приоритет(ы): (30) Конвенционный приоритет: 10.11.2008 US 61/198,852 (72) Автор( ...

Cationic lipids and method for preparing the same

본 발명은 하기 화학식 1로 표시되는 양이온성 지질, 이의 제조방법과 상기 양이온성 지질을 사용하여 세포내로 음이온성 분자물질을 효과적으로 전달하는 방법에 관한 것이다. 상기 지질은 안정성 및 전달효율이 높아 유전자치료에 적합하다. The present invention relates to a cationic lipid represented by Chemical Formula 1, a method for preparing the same, and a method for effectively delivering an anionic molecular material into a cell using the cationic lipid. The lipids are suitable for gene therapy because of their high stability and delivery efficiency. 화학식 1 Formula 1 상기 식에서 y 및 z는 서로 같거나 다른 1 내지 20 사이의 자연수이고; R 1 ∼R 5 는 서로 같거나 다른 수소, 탄소수 1∼10 사이의 알킬 또는 하이드록시 알킬기, 또는 탄소수 7∼11 사이의 아릴 또는 알알킬기이며; R 6 은 콜레스테롤 라디칼이고; X는 약학적으로 허용 가능한 할로겐 음이온이다. Wherein y and z are natural numbers between 1 and 20, the same as or different from each other; R 1 to R 5 are the same or different hydrogen, an alkyl or hydroxy alkyl group having 1 to 10 carbon atoms, or an aryl or alalkyl group having 7 to 11 carbon atoms; R 6 is a cholesterol radical; X is a pharmaceutically acceptable halogen anion.

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-

NEW CRYSTALLINE POLYMORPH VENLAXAXIN HYDROCHLORIDE AND WAYS OF ITS PRODUCTION

ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (51) ÌÏÊ 7 (11) 2004 120 285 (13) A C 07 C 217/74 ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÇÀßÂÊÀ ÍÀ ÈÇÎÁÐÅÒÅÍÈÅ (21), (22) Çà âêà: 2004120285/04, 03.12.2002 (71) Çà âèòåëü(è): ÓÀÉÒ (US) (30) Ïðèîðèòåò: 05.12.2001 US 60/335,822 (43) Äàòà ïóáëèêàöèè çà âêè: 10.04.2005 Áþë. ¹ 10 (74) Ïàòåíòíûé ïîâåðåííûé: Åãîðîâà Ãàëèíà Áîðèñîâíà (86) Çà âêà PCT: US 02/38401 (03.12.2002) Àäðåñ äë ïåðåïèñêè: 129010, Ìîñêâà, óë. Á.Ñïàññêà , 25, ñòð.3, ÎÎÎ "Þðèäè÷åñêà ôèðìà Ãîðîäèññêèé è Ïàðòíåðû", ïàò.ïîâ. Ã.Á. Åãîðîâîé (54) ÍÎÂÛÉ ÊÐÈÑÒÀËËÈ×ÅÑÊÈÉ ÏÎËÈÌÎÐÔ ÃÈÄÐÎÕËÎÐÈÄÀ ÂÅÍËÀÔÀÊÑÈÍÀ È ÑÏÎÑÎÁÛ R U Ôîðìóëà èçîáðåòåíè 1. Ãèäðîõëîðèä âåíëàôàêñèíà, èìåþùèé ðåíòãåíîãðàììó ðåíòãåíîñòðóêòóðíîãî àíàëèçà ïîðîøêà, ïî ñóùåñòâó òàêóþ æå, êàê ïîêàçàííà íà ôèã.1. 2. Ãèäðîõëîðèä âåíëàôàêñèíà ïî ï.1, îòëè÷àþùèéñ òåì, ÷òî ãèäðîõëîðèä âåíëàôàêñèíà âë åòñ áåçâîäíûì. 3. Ãèäðîõëîðèä âåíëàôàêñèíà ïî ï.1, îòëè÷àþùèéñ òåì, ÷òî òåìïåðàòóðà ïëàâëåíè ãèäðîõëîðèäà âåíëàôàêñèíà ñîñòàâë åò ïðèìåðíî 219°Ñ. 4. Ïî ñóùåñòâó ÷èñòûé ãèäðîõëîðèä âåíëàôàêñèíà, èìåþùèé ðåíòãåíîãðàììó ðåíòãåíîñòðóêòóðíîãî àíàëèçà ïîðîøêà, ïî ñóùåñòâó òàêóþ æå, êàê êàðòèíà, ïîêàçàííà íà ôèã.1. 5. Êðèñòàëëè÷åñêèé ïîëèìîðô ãèäðîõëîðèäà âåíëàôàêñèíà, èìåþùèé ðåíòãåíîãðàììó ðåíòãåíîñòðóêòóðíîãî àíàëèçà ïîðîøêà, èìåþùóþ õàðàêòåðèñòè÷åñêèå ïèêè, âûðàæåííûå â ãðàäóñàõ 2θ, ïðèìåðíî ïðè 5,67, 7,28, 9,14, 9,67, 10,77, 11,31, 14,01, 14,54, 14,85, 15,48, 15,81, 16,17, 16,94, 17,68, 18,02, 18,48, 19,29, 19,69, 20,46, 20,74, 21,86, 22,33, 22,67, 22,95, 23,17, 24,06, 24,61, 25,13, 26,62, 26,97, 27,64, 28,25, 29,01, 29,96, 31,01, 31,61, 32,75, 34,54, 35,50, 35,95 è 36,91 ãðàäóñîâ. 6. Êðèñòàëëè÷åñêèé ïîëèìîðô ãèäðîõëîðèäà âåíëàôàêñèíà, èìåþùèé ðåíòãåíîãðàììó ðåíòãåíîñòðóêòóðíîãî àíàëèçà ïîðîøêà, èìåþùóþ õàðàêòåðèñòè÷åñêèå ïèêè, âûðàæåííûå â ãðàäóñàõ 2θ, ïðèìåðíî ïðè 5,67, 7,28, 9,14, 9,67, 10,77, 14,01, 14,54, 16,17, 19,69 è 20,74 ãðàäóñîâ. 7. Ôàðìàöåâòè÷åñêà êîìïîçèöè , ñîäåðæàùà ...

2-Phenyl-2-(1-hydroxycycloalkyl or 1-hydroxycycloalk-2-enyl)ethylamine derivatives

This invention provides a group of hydroxycycloalkanephenethyl amine antidepressant derivatives of the following structural formula: ##STR1## in which A is a moiety of the formula ##STR2## where the dotted line represents optional unsaturation; R 1 is hydrogen or alkyl; R 2 is alkyl; R 4 is hydrogen, alkyl, formyl or alkanoyl; R 5 and R 6 are, independently, hydrogen, hydroxyl, alkyl, alkoxy, alkanoyloxy, cyano, nitro, alkylmercapto, amino, alkylamino, dialkylamino, alkanamido, halo, trifluoromethyl or, taken together, methylenedioxy; R 7 is hydrogen or alkyl; and n is 0, 1, 2, 3 or 4; or a pharmaceutically acceptable salt thereof.

Diamine compound, polyamic acid, polyimide and liquid crystal aligning agent

本发明提供新的二胺，该二胺作为液晶定向处理剂的原料使用时，具有加大液晶的预倾角的效果，以较少的使用比例就能够使液晶垂直定向，且即使液晶定向处理剂的溶液中混合了用于提高涂布性的弱溶剂时聚合物也不易析出。下式(1)表示的二胺， 式(1)中，R 1 为亚苯基，R 2 为亚环己基或亚苯基，R 3 为亚环己基，R 4 为碳数3～12的烷基、碳数3～12的氟代烷基、碳数3～12的烷氧基或碳数3～12的氟代烷氧基中的任一种。

D9-Deuterated Venlafaxine

Polimorfo de la sal de clorhidrato del clorhidrato de d9-1-[2-dimetilamino-1-(4-metoxifenil)-etil]-ciclohexanol que tiene la fórmula estructural:**Fórmula** en el que dicho polimorfo presenta picos de difracción de alta intensidad a ángulos de difracción (2q) de 6,683, 10,201, 13,441, 15,517, 18,198, 19,719, 20,258, 21,68, 22,658, 25,543, 28,022 y 35,02 en análisis de difracción de rayos X de polvo. Polymorph of the hydrochloride salt of d9-1- [2-dimethylamino-1- (4-methoxyphenyl) -ethyl] -cyclohexanol hydrochloride having the structural formula: ** Formula ** in which said polymorph has diffraction peaks High intensity at diffraction angles (2q) of 6,683, 10,201, 13,441, 15,517, 18,198, 19,719, 20,258, 21.68, 22,658, 25,543, 28,022 and 35.02 in powder X-ray diffraction analysis.

Tetrahydroethanonaphthaleneamine derivatives

Tetrahydronaphthaleneamine derivatives having the formula ##STR1## wherein R, R', R 1 and R 2 are as defined herein, are novel calcium channel blockers.

METHOD OF PRODUCING (S)-(-)-2-(N-PROPYLAMINO)-5-METHOXYTETRALINE AND (S)-(-)-2-(N-PROPYLAMINO)-5-HYDROXYTETRALINE, SALTS THEREOF WITH N-3,5-(DINITROBENZOYL)-α-PHENYLGLYCINE, METHOD OF PRODUCING (6S)-(-)-5,6,7,8-TETRAHYDRO-6-[PROPYL(2-THIENYL)ETHYL]AMINO-1-NAPHTHOL(ROTIGOTINE) (VERSIONS)

FIELD: chemistry. SUBSTANCE: invention relates to a method of producing optically active compounds: (S)-(-)-2-(N-propylamino)-5-methoxytetraline and (S)-(-)-2-(N-propylamino)-5-hydroxytetraline. Said method involves optical separation of a mixture of enantimers of 2-(N-propylamino)-5-methoxytetraline and 2-(N-propylamino)-5-hydroxytetraline in the presence of an optically active form of N-(3,5-dinitrobenzoyl)-α-phenylglycine. The method enables to obtain a product with high optical purity. EFFECT: invention also relates to use of salts of (S)-(-)-2-(N-propylamino)-5-methoxytetraline and (S)-(-)-2-(N-propylamino)-5-hydroxytetraline as intermediate compounds when producing rotigotine. 7 cl, 6 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 473 538 (13) C2 (51) МПК C07C C07C C07C C07B 213/10 (2006.01) 215/44 (2006.01) 217/52 (2006.01) 57/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2011119224/04, 09.10.2009 (24) Дата начала отсчета срока действия патента: 09.10.2009 (73) Патентообладатель(и): Интерким, С.А. (ES) (45) Опубликовано: 27.01.2013 Бюл. № 3 2 4 7 3 5 3 8 (56) Список документов, цитированных в отчете о поиске: CUSACK N.J. ЕТ AL, "N-0923. Dopamine D2 agonist". Drugs of the future, vol.18(11), p.10051008. WO 9013294 A, 15.11.1990. WO 1981003491 A, 10.12.1981. RU 2086535 C1, 10.08.1997. 2 4 7 3 5 3 8 R U (86) Заявка PCT: EP 2009/063207 (09.10.2009) C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 13.05.2011 (87) Публикация заявки РСТ: WO 2010/043571 (22.04.2010) Адрес для переписки: 127055, Москва, а/я 11, Н.К. Попеленскому (54) СПОСОБ ПОЛУЧЕНИЯ (S)-(-)-2-(N-ПРОПИЛАМИНО)-5-МЕТОКСИТЕТРАЛИНА И (S)-(-)2-(N-ПРОПИЛАМИНО)-5-ГИДРОКСИТЕТРАЛИНА, ИХ СОЛИ С N-(3,5-ДИНИТРОБЕНЗОИЛ)α-ФЕНИЛГЛИЦИНОМ, СПОСОБ ПОЛУЧЕНИЯ (6S)-(-)-5,6,7,8-ТЕТРАГИДРО-6-[ПРОПИЛ(2ТИЕНИЛ)ЭТИЛ]АМИНО-1-НАФТОЛА (РОТИГОТИНА) (ВАРИАНТЫ) (57) Реферат: Изобретение относится к новому способу получения оптически активных ...

Crystal forms of o-desmethylvenlafaxine

Methods for preparing crystalline forms of O-desmethylvenlafaxine are described.

A 4,4'-dihydroxydiphenylsulfone monomer composition and a process for production thereof

A 4,4'-dihydroxydiphenylsulfone monomer composition comprises a salt of an organic acid in the amount corresponding to an amount of the metal component of 10 to 10,000 ppm by weight of the composition. A process for production of a 4,4'-dihydroxydiphenylsulfone monomer composition comprises adding a salt of an organic acid to a solution of 4,4'-dihydroxydiphenylsulfone and drying the mixture to form a composition comprising the salt of an organic acid in the amount corresponding to an amount of the metal component of 10 to 10,000 ppm by weight. Another process for production of a 4,4'-dihydroxydiphenylsulfone monomer composition comprises providing a salt of an organic acid, in the amount corresponding to an amount of the metal component of 10 to 10,000 ppm by weight, to 4,4'-dihydroxydiphenylsulfone in the process of synthesizing a crude 4,4'-dihydroxydiphenylsulfone or in the process of purifying a crude 4,4'-dihydroxydiphenylsulfone. The 4,4'-dihydroxydiphenylsulfone monomer composition is useful as a material in the field of the polymer industry, such as plastics having excellent resistance to yellowing.

CRYSTALLINE VENLAFAXIN BASE AND NEW VENLAFAXIN HYDROCHLORIDE MODIFICATIONS AND METHOD FOR THE PRODUCTION THEREOF

Kristalline Venlafaxin-Base, wobei die Venlafaxin-Base in der Form von weißen Kristallen vorliegt. Crystalline venlafaxine base, the venlafaxine base being in the form of white crystals.

Process for the preparation of highly pure 1-[2-dimethylamino-(4-methoxyphenyl) ethyl]cyclohexanol hydrochloride

The invention encompasses processes for the preparation of highly pure venlafaxine hydrochloride, l-[2-dimethylamino-(4-methoxyphenyl)ethyl]cyclohexanol hydrochloride as well as intermediates thereof.

SECONDARY PARA-PHENYLENEDIAMINES CARRYING AN ALCOXY GROUP, TINCTORIAL COMPOSITION COMPRISING SAME, METHODS AND USES

Aromatic rings allylamine compound, its pharmaceutically acceptable salt, Its Preparation Method And Use

本发明涉及一种结构如通式(I)所示的芳香环丙基胺类化合物及其药学上可接受的盐，及其该类化合物的制备方法和该类化合物在制备预防或治疗耳聋的药物中的用途。其中，本发明所涉及的通式(I)中的R 1 、R 2 、R 3 、R 4 和R 5 如说明书和权利要求中所定义。

Substituted phenethylamines with serotoninergic and/or norepinephrinergic activity

Chemical syntheses and medical uses of novel inhibitors of the uptake of monoamine neurotransmitters and pharmaceutically acceptable salts and prodrugs thereof, for the treatment and/or management of psychotropic disorders, anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, attention deficit hyperactivity disorder, fibromyalgia, irritable bowel syndrome, and/or premature ejaculation are described.

2-SUBSTITUTED PARA-AMINOPHENOLS AND THEIR USE FOR DYEING KERATINIC FIBERS

Neutral aromatic bis-sulphates prepn. - from metal phenoxides and chlorosulphates

Neutral opt. symmetrical aromatic bis-sulphates or formula (I):-Z-O-SO2-OAr1-X-Ar2-O-SO2-O-Z (I) (where Ar1 and Ar2, the same or different, are opt. substd. aromatic radicals; X is a chemical bond or a gp. linking radicals Ar1 and Ar2; Z is an opt. substd. phenyl radical of type Ar'-X-Ar" in which Ar' and Ar" are defined as Ar1 and Ar2) are prepd. by reacting a metal deriv. of an aromatic cpd. contg. 1 or 2 phenol gps. with an aromatic chlorosulphate contg. 2 or 1 terminal chlorosulphate gps. in equimolar proportions w. r. t. reactive gps. in an anhydrous solvent. Reaction is pref. under an atmos. of dry inertgas, in, as solvent, o-dimethoxybenzene or veratrole, nitrobenzene, benzonitrile, alkylsulhpones, aliphatic nitriles or tert-aromatic amines. (I) are used as plasticiser in thermoplastic resins and as flame-retardants and antioxidants in plastics.

2-amino-1,2,3,4-tetrahydronaphthalene derivatives with cardiovascular activity, process for their preparation and pharmaceutical compositions containing them

ABSTRACT 5,6-Dimethoxy-2[[2-(4-hydroxyphenyl)-2-hydroxy-1-methylethyl]amino]-1,2,3,4-tetrahydronaphthalene has i-notropic and vasodilating activities and therefore can be used in the treatment of cardiocirculatory failure. The compound can be in form of a single stereoiso-mer or of mixtures of two or more stereoisomers.

PROCESS FOR THE PREPARATION OF AMINOBUTANOL DERIVATIVES, NOVEL PRODUCTS THUS OBTAINED AND THEIR USE AS PHARMACEUTICAL AGENTS FOR DISORDERS OF THE CIRCULATION

DES DERIVES D'AMINOBUTANOL UTILES COMME AGENTS PHARMACEUTIQUES POUR LES TROUBLES DE LA CIRCULATION TELS QUE L'ARYTHMIE SONT REPRESENTES PAR LA FORMULE SUIVANTE: (CF DESSIN DANS BOPI) OU R ET R SONT IDENTIQUES OU DIFFERENTS ET SONT CHOISIS DANS LE GROUPE SE COMPOSANT D'HYDROGENE, D'HALOGENE, DE GROUPE HYDROXY, DE GROUPE ALKYLE AYANT UN A QUATRE ATOMES DE CARBONE ET DE GROUPE ALCOXY AYANT UN A QUATRE ATOMES DE CARBONE ET R EST L'HYDROGENE OU LE GROUPE ISOBUTYLE. AMINOBUTANOL DERIVATIVES USEFUL AS PHARMACEUTICAL AGENTS FOR CIRCULATION DISORDERS SUCH AS ARRHYTHMIA ARE REPRESENTED BY THE FOLLOWING FORMULA: (CF DRAWING IN BOPI) OR R AND R ARE THE SAME OR DIFFERENT AND ARE CHOSEN FROM THE GROUP 'HYDROGEN, HALOGEN, HYDROXY GROUP, ALKYL GROUP HAVING ONE TO FOUR ATOMS OF CARBON AND ALCOXY GROUP HAVING ONE TO FOUR ATOMS OF CARBON AND R IS HYDROGEN OR THE ISOBUTYL GROUP.

Selective d1 dopamine receptor agonists and partial agonists/antagonists

Disclosed are compounds (1) and (2), and derivatives and analogs thereof, which are agonists for the D1 dopamine receptor. These compounds can be used to treat an individual with Parkinson's disease. Also disclosed are monohydroxy analogs of compounds (1) and (2), and derivatives and analogs thereof, which are partial D1 agonists or antagonists. These compounds can be used to treat an individual who abuses cocaine.

Process for the preparation of optically active (S)-(-)-2- (N-propylamino)-5-methoxytetraline and (S)-(-)-2- (N-propylamino)-5-hydroxytetraline compounds

The present invention describes a novel process for the preparation of optically active (S)-(-)-2-(N-propylamino)-5-methoxytetraline and (S)-(-)-2-(N-propylamino)-5- hydroxytetraline compounds based on the optical resolution of mixtures of the enantiomers of 2-(N-propylamino)-5-methoxytetraline and 2-(N-propylamino)-5- hydroxytetraline respectively. This process comprises (a) reacting a mixture of the enantiomers of said compounds with an optically active organic acid to form diastereoisomeric salts and separating the salts by crystallization. Said compounds are useful in the preparation of (6S)-(-)-5,6,7,8-tetrahydro-6-[propyl-(2- thienyl)ethyl]amino-1 -naphthol (Rotigotine). Rotigotine is a dopamine agonist and is indicated for the treatment of Parkinson's disease.

Process for the preparation of highly pure 1-[2-dimethylamino-(4-methoxyphenyl) ethyl]cyclohexanol hydrochloride

The invention encompasses processes for the preparation of highly pure venlafaxine hydrochloride, l-[2-dimethylamino-(4-methoxyphenyl)ethyl]cyclohexanol hydrochloride as well as intermediates thereof.

Active ingredient based on polyimide liquid crystals

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

Process for the preparation 3-methoxy-6-anilino toluene

A method for preparing 3-methoxy-6-anilinotoluene of formula (I) comprises reacting a cpd. of formula (II) with a cpd. of formula (III) in toluene or xylene in the presence of a catalyst at 110-140 deg.C for 5-6 hrs. Pref. the catalyst is selected from zinc chloride, sulfuric acid or p-sulfonic toluene. 3- Methoxy-6-anilinotoluene (I) is useful as an intermediate in the mfr. of a coloring dyestuff for heat sensitive papers.

2-substituted para-aminophenols and their use for dyeing keratinous fibres

2-Substituted para-aminophenols of general formula: ##STR1## where Y denotes oxygen or sulphur and R denotes a C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl or C 1 -C 6 haloalkyl or a C 2 -C 6 polyhydroxyalkyl, provided that when Y=O, R is not methyl or ethyl and when Y=S, R is not ethyl; and dye composition containing one or more compounds of formula (I) where Y denotes an oxygen or sulphur atom and R is C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 haloalkyl or C 2 -C 6 polyhydroxyalkyl.

Analgesic compounds, methods, and formulations

Provided are analgesic compounds, and salts thereof, of formula: ( I ) wherein A is: ( A ) Additionally, pharmaceutical formulations and methods of use employing the above compounds are provided.

Phosphate salts of 6-dimethylaminomethyl-1-(3-methoxyphenyl)-1,3-dihydroxy-cyclohexane compounds

Novel 6-dimethylaminomethyl-1-(3-methoxyphenyl)-1,3-dihydroxy-cyclohexane compounds in the form of phosphate salts, related polymorphs of these compounds, processes for their preparation, pharmaceutical formulations including these compounds and polymorphs and related methods of treating or inhibiting certain diseases or conditions.

Crystal forms of o-desmethylvenlafaxine fumarate

Provided are crystalline forms of O-desmethylvenlafaxine fumarate, methods for their preparation, and pharmaceutical composition thereof.

2-substituted para-aminophenols and their use for dyeing keratinic fibers

ABREGE DESCRIPTIF L'invention concerne de nouveaux para-aminophénols 2-substitués répondant à la formule générale: (I) dans laquelle Y désigne un atome d'oxygène ou de soufre et R désigne un radical alkyle en C1-C6, hydroxyalkyle en C1-C6, halogénoalkyle en C1-C6 ou polyhydroxyalkyle en C2-C6, sous réserve que lorsque Y désigne un atome d'oxygène, R n'est pas méthyle ou éthyle et lorsque Y désigne un atome de soufre, R n'est pas éthyle. L'inven-tion vise également les compositions tinctoriales renfermant un ou plusieurs composés de formule (I) dans laquelle Y désigne un atome d'oxygène ou de soufre et R désigne un radical alkyle en C1-C6, hydroxyalkyle en C1-C6, halogénoalkyle en C1-C6 ou polyhydroxyalkyle en C2-C6, lesquelles compositions sont utiles pour la coloration dite coloration d'oxydation ou teinture permanente.

Crystalline forms of venlafaxine hydrochloride

本发明发现了在说明书中被称为多晶型物A、B和D的盐酸文拉法辛晶形。此外，本发明涉及这些晶形的制备方法以及包含该晶形的药物组合物。

Heat-sensitive recording material and novel crystal of bisphenol s derivative

A heat-sensitive recording material in which a heat-sensitive color-developing layer comprising, as the main components, a usually colorless or light-colored color former and a developer capable of developing the color former upon heating on a support, characterized by comprising, as the developer, crystals of 3,3'-diallyl--4,4'-dihydroxy-diphenyl sulfone which have DSC (Te) of at least 149.degree.C and which are of a crystal form characterized by an X-ray diffraction pattern having peaks at least at diffraction angles (2.theta.) [.degree.] of 7.2 and 22.0, obtained by an X-ray powder diffractometry using Cu-K.alpha. rays. This heat--sensitive recording material is high in sensitivity, little in Discoloration of the ground in heat and moisture and excellent in image durability.

Preparation of (2r,3r)-3-(3-methoxyphenyl)-n,n,2-trimethylpentanamine

The present invention relates to an improved process for the preparation of (2R,3R)-3- (3-methoxyphenyl)-N,N,2-trimethylpentanamine which is an intermediate for the preparation of the analgesic tapentadol.

Process for preparing phenethylamine derivatives

本发明提供了制备式I化合物的方法，其中R 1 和R 2 为邻位或对位取代基，其独立地选自氢、羟基、C 1 -C 6 烷基、C 1 -C 6 烷氧基、C 7 -C 9 芳烷氧基、C 2 -C 7 烷酰氧基、C 1 -C 6 烷硫基、卤素和三氟甲基；R 3 为氢或C 1 -C 6 烷基；R 4 为氢、C 1 -C 6 烷基、甲酰基或C 2 -C 7 烷酰基；n为整数0、1、2、3或4之一；虚线表示任选的烯不饱和度；该方法包括在5℃到25℃的温度下在镍或钴催化剂的存在下氢化式(III)的化合物。

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

A process for the preparation of venlafaxin

Process for producing venlafaxine and/or physiologically acceptable addition salts thereof, consisting in reacting a compound having the general formula (II) wherein R is a C1-C10 alkyl group, aryl group, aralkyl group or cycloalkyl group having from 3 to 6 carbon atoms, with an organomagnesian compound having the general formula (III) wherein X is a halogen atom and, if desired, a salt of venlafaxine can be obtained by reaction with a physiologically acceptable acid.

Phenoxy diphenyl sulfones and their preparation

DEUTERATED d9-VENLAFAXINE

Process for preparation of phenethylamine derivatives

A process for the preparation of a compound of formula (I), wherein R1, and R2 are ortho or para substituents, independently selected from the group consisting of hydrogen, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C7-C9 aralkoxy, C2-C7 alkanoyloxy, C1-C6 alkylmercapto, halo and trifluoromethyl; R3 is hydrogen or C1-C6 alkyl; R4 is hydrogen, C1-C6 alkyl, formyl or C2-C7 alkanoyl; n is one of the integers 0, 1, 2, 3 or 4; and the dotted line represents optional olefinic unsaturation; comprising hydrogenating a compound of formula (III), in the presence of a nickel or cobalt catalyst at a temperature of about 5~C to 25~C.