Abstract: The present invention relates to the preparation of compounds of formula IV: wherein R is alkyl, aryl or benzyl.

Abstract: The present invention relates in a first aspect to a method of preparing a crystalline lanthanum-carboxylate coordination polymer and the crystalline lanthanum-carboxylate coordination polymer obtained or obtainable by the method. In another aspect of the present invention, also provides a method of detecting a target nucleic acid sequence in a sample.

Abstract: The present invention relates to the preparation of compounds of formula III: wherein R is alkyl, aryl or benzyl.

Abstract: The present invention relates to intermediates in the preparation of carbamoylpyridone derivatives, such as compounds of formula (III) and/or compounds of formula (IV): wherein R is alkyl, aryl or benzyl.

Abstract: The present invention relates to methods for lowering stroke damages and/or lowering blood pressure in a subject with a stroke in need thereof, comprising administering to the subject an effective amount of a pharmaceutical composition comprising a short acting dihydropyridine compound, preferably clevidipine or a pharmaceutically acceptable salt or ester thereof. Also provided are related medicaments, pharmaceutical compositions, and methods for preparing the medicaments.

Abstract: A negative electrode active material for a sodium-ion battery includes a compound including an aromatic ring structure and two or more COOX groups in which X is Li or Na, and which are bonded to ends of the aromatic ring structure, the aromatic ring structure including an aromatic heterocyclic ring that contains nitrogen in the ring.

Abstract: The invention provides small molecule drugs that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the small molecule drug not attached to the water soluble oligomer.

Abstract: The invention provides 1,4-dihydropyridine derivatives of formula (I) wherein R1 is optionally substituted C6-24aryl group or 5 to 6 membered heteroaryl group comprising 1 to 3 nitrogen atoms or other heteroatoms like oxygen and sulphur, and combinations thereof; R2 and R3 are independently hydrogen or C1-6alkyl group; R4 and R5 are independently hydrogen, C1-6alkyl group optionally substituted with amino, mono- or di(C1-6alkyl)amino, or with 5 to 24 membered optionally fused heterocyclic ring attached by nitrogen and optionally comprising additional 1 to 3 N, O, S heteroatoms and optionally substituted with C1-6alkyl group or C1-6 alkoxy group; R6 is C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-6alkyl or arylC1-6alkyl group; and stereoisomers including enantiomers, diastereomers, racemic mixtures, mixture of enantiomers and combination thereof, as well as polymorphs, pharmaceutically acceptable salts, solvates, esters and prodrugs thereof for use in the therapeutic or prophylactic treatment of a disorder medi

Abstract: The present invention relates to a probe for iFRET and use thereof. Specifically, the present invention relates to a novel probe for iFRET, a method for preparing the probe for iFRET, a method for searching a target protein-specific binding site or a molecule having the binding site using the probe for iFRET, and a method for imaging the target protein using the probe for iFRET. The probe for iFRET according to the present invention utilizes an amino acid in a protein as a fluorescent donor, unlike the conventional FRET method. Therefore, only one fluorescent material is used, and its emission wavelength is distinct from the intrinsic fluorescence of the protein. Thus, high specificity and sensitivity are ensured, and the quantity, activity and mechanism of various proteins can be analyzed in an easy and accurate manner.

Abstract: A process for manufacturing 5-chloromethyl-2,3-pyridine dicarboxylic acid anhydrides (I) wherein Z is hydrogen or halogen; Z1 is hydrogen, halogen, cyano or nitro; comprising the steps of (i) reacting a compound of formula (II), wherein the symbols have the meaning given in formula (I), with a chlorinating agent, optionally in the presence of a radical initiator in a solvent selected from halogenated hydrocarbons, and (ii) crystallizing the compound (I) formed in step (i) from a solvent selected from chlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene, dichloroethane, trichloromethane, dichloromethane, toluene, xylenes, ethyl acetate, methyl tert.-butyl ether, and mixtures thereof. Compounds (I) are useful intermediates in the synthesis of herbicidal imidazolinones.

Abstract: The present invention relates to novel heterocyclic compounds and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula (I): wherein Q1, Q2, R2, R3, R4, R5, and R6 are as described herein. The invention also relates to methods for the preparation of the compounds, and to pharmaceutical compositions containing such compounds.

Abstract: A method for purification calcium ion channel blocker medicament of dihydropyridine type and pharmaceutically acceptable salts thereof through the ultrasonic crystallization technology and direct preparation of nanoparticles thereof.

Abstract: A process for manufacturing a 5-formyl-pyridine-2,3-dicarboxylic acid ester (I) wherein Z is hydrogen or halogen; Z1 is hydrogen, halogen, cyano or nitro and R1, R2 are independently C1-C10-alkyl, comprising the steps of (i) reacting a compound of formula (II), wherein the symbols are as in formula (I), with a nitrosation agent (III) R3—O—N?O (III) wherein R3 is C1-C8-alkyl, in the presence of an alkali metal or alkaline earth metal alcoholates or carbonates in a polar aprotic solvent at a temperature of from ?45 to 40° C., to obtain an oxime compound (IV) where Z, Z1, R1 and R2 are as in formula (I), and (ii) reacting oxime compound (IV) with an aliphatic C1-C10-aldehyde in the presence of a Lewis acid at a temperature in the range of from 0 to 100° C. The compounds of formula (I) are useful intermediates in the synthesis of herbicidal imidazolinones, like imazamox.

Abstract: A composition having clevidipine as an active ingredient is described. The composition includes clevidipine as an active ingredient and an amount of the impurity H168/79 that is no greater than about 1.5%, or where the ratio between clevidipine and H168/79 is equal or above 60 to 1.

Abstract: The present invention relates to novel heterocyclic compounds and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula (I): wherein Q1, Q2, R2, R3, R4, R5, and R6 are as described herein. The invention also relates to methods for the preparation of the compounds, and to pharmaceutical compositions containing such compounds.

Abstract: A resist composition including a base material component whose solubility in a developing solution changes by the action of an acid and an acid generator component which generates an acid upon exposure. The acid generator component includes an acid generator that includes a compound containing nitrogen atoms having proton acceptor properties and sites capable of generating an acid upon exposure in the same molecule, the number of the sites being larger than the number of the nitrogen atoms.

Abstract: New compounds of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid ester type having general formula I wherein R is a lower alkyl group, which is methyl or ethyl R1 and R2 is sodium carboxylate-methyl ester, having synergistic cytotoxic effect combined with 5-fluorouracil.

Abstract: The invention relates to a method and compounds for the preparation of clevidipine butyrate, a very short acting hypertensive calcium antagonist, as well as the synthesis of these compounds useful for the preparation of clevidipine (also known as clevidipine butyrate). Moreover the invention also discloses polymorphic forms of clevidipine butyrate, useful for the preparation of pharmaceutical compositions, and processes to prepare them.

Abstract: 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid ester type compounds having general formula I wherein R is hydrogen or carboxylate-methyl ester, R1 is sodium carboxylate-methyl ester R2 is methyl, ethyl or sodium carboxyate-methyl ester possessing antiviral efficacy.

Abstract: The present invention relates to a process for preparation of optically pure (S)-amlodipine-L-hemitartrate DMF solvate comprising the steps of treating (R,S) amlodipine base with L-tartaric acid in the presence of dimethyl formamide and a co-solvent. The invention also relates to a process for converting (R) or (S)-amlopidine-L-hemitartrate DMF solvate into their besylates without isolating free chiral amlopidine base after solution.

Abstract: Disclosed is a method for the separation of S-(?)-amlodipine from a racemic amlodipine. Featuring the use of inexpensive L-tartaric acid as an optical resolution agent and DMAC as a solvent, the separation method allows the resolution of S-(?)-amlodipine from racemic amlodipine at high yield and to a satisfactory enantiomeric excess and thus is economically favorable and applicable to the mass production of the optical isomer.

Abstract: New triaminophenol compositions and related compounds are disclosed, as are processes for their preparation and for the preparation of novel salts and diacid complexes from such compounds. Polymers prepared from these compositions can be made into high strength fiber, film, and tape and are useful in applications such as protective apparel, aircraft, automotive components, personal electronics, and sports equipment.

Abstract: Disclosed are crystalline S-(?)-amlodipine adipic acid salt anhydrous and a preparation method thereof. The crystalline S-(?)-amlodipine adipic acid salt anhydrous exhibits excellent physical and chemical properties including non-hygroscopicity, solubility, thermal stability, and photostability, and is superior in formulation processability and long-term storage safety.

Abstract: Pharmaceutical compositions, and a method of stabilizing pharmaceutical compositions having clevidipine, or any pharmaceutically acceptable salt thereof, as the active ingredient is described. The method includes the slowing down or inhibiting of the oxidation pathway of clevidipine. This can be accomplished by reducing the amount the pharmaceutical composition is exposed to oxygen and/or light during the manufacturing and storing processes. According to this method, oxygen must be removed or replaced, or light must be sufficiently blocked such that light energy cannot reach the active ingredient of the composition, or is reduced to a level that the light-induced oxidation reaction converting clevidipine to H324/78 is minimized, such that the total detectable level of H324/78 in a given composition sample does not exceed about 0.2% on a weight-by-weight basis, or the ratio of clevidipine to H324/78 is equal to or greater than about 450 to 1 on a weight-to-weight basis.

Abstract: A composition having clevidipine as an active ingredient is described. The composition includes clevidipine as an active ingredient and an amount of the impurity H168/79 that is no greater than about 1.5%, or where the ratio between clevidipine and H168/79 is equal or above 60 to 1.

Abstract: The present invention relates to a microwave apparatus, a method or use of the apparatus and a method of carrying out chemical reactions on a continuous basis with the apparatus, wherein the apparatus is particularly suitable for microwave-assisted organic synthesis.

Abstract: A dihydropyridine (DHP) calcium antagonist compound and its preparation method and medical use are related to preparation methods of compounds of general formulas (I) and (II) as shown below and their pharmaceutical salts and applications for treating cardiovascular diseases, and R1 represents a substituted or unsubstituted heterocyclic, aromatic ring or aralkyl group, and the substituent may be C1-C4 alkyl, C1-C4 alkoxyl, halogen, cyano, trifluoromethyl, trifluoromethoxyl, methylthio, nitro, amino or hydroxyl group; R2 represents a C1-C8 alkyl group; R3 and R4 are the same or different, and each represents a hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxyl, methylthio, nitro or amino group or a C1-C4 alkyl, C1-C4 alkoxyl, C1-C4 alkenyl, or C1-C4 alkinyl group; R5 and R6 are the same or different, and each represents a C1-C4 alkyl group; X represents O, S or a single bond; m=0-6, n=1-6, and m and n are the same or different.

Abstract: The invention includes benzisoxazole piperidine compositions and methods of using them for modulating sleep.

Abstract: New compounds of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid ester type having general formula I wherein R is a lower alkyl group, which is methyl or ethyl R1 and R2 is sodium carboxylate-methyl ester, having synergistic cytotoxic effect combined with 5-fluorouracil.

Abstract: Processes for the purification of lercanidipine hydrochloride are provided which uses a binary system of an alcohol-containing solvent such as methanol and an aliphatic ester-containing solvent such as isopropyl acetate. Processes for the preparation of substantially amorphous lercanidipine hydrochloride are also provided. Also provided is lercanidipine hydrochloride substantially in polymorph form V.

Abstract: The present invention provides a liquid curable epoxy resin composition that has excellent storage stability and curing properties and provides a cured product having excellent properties, particularly, excellent organic solvent resistance. For that purpose, a clathrate containing a carboxylic acid compound and at least one selected from the group consisting of an imidazole compound represented by formula (I), wherein R1 to R4 each represent a hydrogen atom or the like, and 1,8-diazabicyclo[5.4.0]undecene-7 (DBU) is mixed in an epoxy resin. The liquid curable epoxy resin composition uses a liquid epoxy resin or an organic solvent.

Abstract: The invention relates to a method and compounds for the preparation of clevidipine butyrate, a very short acting hypertensive calcium antagonist, as well as the synthesis of these compounds useful for the preparation of clevidipine (also known as clevidipine butyrate). Moreover the invention also discloses polymorphic forms of clevidipine butyrate, useful for the preparation of pharmaceutical compositions, and processes to prepare them.

Abstract: A process for manufacturing a 5-formyl-pyridine-2,3-dicarboxylic acid ester (I) wherein Z is hydrogen or halogen; Z1 is hydrogen, halogen, cyano or nitro and R1, R2 are independently C1-C10-alkyl, comprising the steps of (i) reacting a compound of formula (II), wherein the symbols are as in formula (I), with a nitrosation agent (III) R3—O—N?O (III) wherein R3 is C1-C8-alkyl, in the presence of an alkali metal or alkaline earth metal alcoholates or carbonates in a polar aprotic solvent at a temperature of from ?45 to 40° C., to obtain an oxime compound (IV) where Z, Z1, R1 and R2 are as in formula (I), and (ii) reacting oxime compound (IV) with an aliphatic C1-C10-aldehyde in the presence of a Lewis acid at a temperature in the range of from 0 to 100° C. The compounds of formula (I) are useful intermediates in the synthesis of herbicidal imidazolinones, like imazamox.

Abstract: A process for manufacturing 5,6-disubstituted-3-pyridylmethyl ammonium bromides (I), wherein Q is a tertiary aliphatic or cyclic, saturated, partially unsaturated or aromatic amine; Z is hydrogen or halogen; Z1 is hydrogen, halogen, cyano or nitro; Y and Y1 are each independently OR1, NR1R2, or when taken together YY1 is —O—, —S— or NR3—; R1 and R2 are each independently hydrogen, C1-C4 alkyl optionally substituted with C1-C4 alkoxy or phenyl optionally substituted with one to three C1-C4 alkyl groups, C1-C4 alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C1-C4 alkyl groups, C1-C4 alkoxy groups or halogen atoms; R3 is hydrogen or C1-C4 alkyl; comprises the steps of (i) reacting a compound of formula (II), wherein the symbols have the meaning given in formula (I), with bromine in the presence of a radical initiator in a solvent mixture comprising an aqueous phase and an organic phase, where the organic phase comprises a solvent selected from 1,2-dichloroethane,

Abstract: A process for manufacturing 5-chloromethyl-2,3-pyridine dicarboxylic acid anhydrides (I) wherein Z is hydrogen or halogen; Z1 is hydrogen, halogen, cyano or nitro; comprising the steps of (i) reacting a compound of formula (II), wherein the symbols have the meaning given in formula (I), with a chlorinating agent, optionally in the presence of a radical initiator in a solvent selected from halogenated hydrocarbons, and (ii) crystallizing the compound (I) formed in step (i) from a solvent selected from chlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene, dichloroethane, trichloromethane, dichloromethane, toluene, xylenes, ethyl acetate, methyl tert.-butyl ether, and mixtures thereof. Compounds (I) are useful intermediates in the synthesis of herbicidal imidazolinones.

Abstract: A dihydropyridine (DHP) calcium antagonist compound and its preparation method and medical use are related to preparation methods of compounds of general formulas (I) and (II) as shown below and their pharmaceutical salts and applications for treating cardiovascular diseases, and R1 represents a substituted or unsubstituted heterocyclic, aromatic ring or aralkyl group, and the substituent may be C1-C4 alkyl, C1-C4 alkoxyl, halogen, cyano, trifluoromethyl, trifluoromethoxyl, methylthio, nitro, amino or hydroxyl group; R2 represents a C1-C8 alkyl group; R3 and R4 are the same or different, and each represents a hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxyl, methylthio, nitro or amino group or a C1-C4 alkyl, C1-C4 alkoxyl, C1-C4 alkenyl, or C1-C4 alkinyl group; R5 and R6 are the same or different, and each represents a C1-C4 alkyl group; X represents O, S or a single bond; m=0-6, n=1-6, and m and n are the same or different.

Abstract: The present invention relates to the treatment of protozoal diseases by administering cytotoxic and/or cytostatic compounds, in particular those used in anticancer therapy, to patients. In particular, the invention relates to the use of anticancer agents that can penetrate into the CNS for treatment of late stage African sleeping sickness or cerebral malaria.

Abstract: The invention provides small molecule drugs that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the small molecule drug not attached to the water soluble oligomer.

Abstract: The present invention describes a method for the synthesis of enantiomerically pure 3-amidinophenylalanine derivatives, which are used as pharmaceutically effective urokinase inhibitors, by starting from 3-cyanophenylalanine derivatives. The methods of manufacture comprising only one synthesis step lead to new intermediates, namely 3-hydroxyamidino- and 3-amidrazonophenylalanine derivatives. These intermediates or their acetyl derivatives can be reduced into the desired 3-amidino-phenylalanine derivatives under gentle conditions (H2 or ammonium formiate, Pd/C (approx. 10%), ethanol/water, room temperature, normal pressure or also H2, Pd/C, AcOH or HCl/ethanol, 1-3 bar) in excellent yields and in an enantiomeric excess of up to 99.9%.

Abstract: Disclosed herein is a novel method for preparing lercanidipine hydrochloride which is highly effective for treating hypertension. The method comprises the steps of reacting 2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid with a substituted chlorophosphate derivative to obtain a substituted phosphonoester derivative, and reacting the substituted phosphonoester derivative with 2, N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol. According to the preparation method, since little by-products are formed, the yield is improved, as compared to cases of conventional methods. In addition, the method involves simple isolation and purification processes of lercanidipine, thus realizing a high-quality product. Furthermore, the method has advantages of low preparation costs, substantial waste-free environmental-friendly process and applicability to industrial mass-production.

Abstract: The present invention relates to a process for preparation of optically pure (S)-amlodipine-L-hemitartrate DMF solvate comprising the steps of treating (R,S) amlodipine base with L-tartaric acid in the presence of dimethyl formamide and a co-solvent. The invention also relates to a process for converting (R) or (S)-amlopidine-L-hemitartrate DMF solvate into their besylates without isolating free chiral amlopidine base after solution.

Abstract: The present invention relates to a process for preparation of optically pure (S)-amlodipine-L-hemitartrate DMF solvate comprising the steps of treating (R,S) amlodipine base with L-tartaric acid in the presence of dimethyl formamide and a co-solvent. The invention also relates to a process for converting (R) or (S)-amlopidine-L-hemitartrate DMF solvate into their besylates without isolating free chiral amlopidine base after solution.

Abstract: A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity.

Abstract: This invention pertains to a class of autophagy inducing compounds that treat diseases caused by misfolded protein aggregates and a screening method for identifying these compounds.

Abstract: The present invention relates to dihydropyridine mineralocorticoid receptor modulating compounds having the structure: and their use in treating cardiovascular events.

Abstract: A method for the in-situ treatment of a pyridine-2,3-dicarboxylic acid ester with an oxidizing agent, such as hydrogen peroxide, to improve product quality is provided. The method for the in-situ removal of impurities from a saponified solution of pyridine-2,3-dicarboxylic acid ester comprises the steps of providing a solution of pyridine-2,3-dicarboxylic acid ester, saponifying the solution with a base to form the corresponding pyridine-2,3-dicarboxylic acid salt, reacting the solution with an oxidizing agent in an amount effective to remove impurities, acidifying the solution with an acid to convert the pyridine-2,3-dicarboxylic acid into the corresponding pyridine-2,3-dicarboxylic acid, and collecting a purified solution comprising pyridine-2,3-dicarboxylic acid. Further provided is a method for the preparation of herbicidal 2-(2-imidazolin-2-yl)nicotinic acids, esters, and salts by using a pyridine-2,3-dicarboxylic acid salt prepared by the above method as an intermediate.

Abstract: Methods of forming soft connective tissue compositions such as skin equivalents, compositions made by the methods and their uses.

Abstract: The present invention relates to a method for optical resolution of amlodipines by using isopropanol solvent and optically active O,O?-dibenzoyl tartaric acid as chiral reagent. More particularly, the present invention relates to a method comprising (a) obtaining (R)- or (S)-amlodipine dibenzoyl tartrate salt or solvate thereof by reacting (R,S)-amlodipines with optically active O,O?-dibenzoyl tartaric acid in isopropanol solvent, and (b) treating the (R)- or (S)-amlodipine salt with a base, thus obtaining optically active amlodipine.

Abstract: The invention provides a novel process for the preparation of lercanidipine or a pharmaceutical acceptable salt using novel intermediates. Thus, 2,N-dimethyl-N-(3,3-diphenylpropy1)-1-amino-2-propanol is reacted with trimethylsilyl chloride in presence of triethyl amine in methylene chloride to give 2,N-dimethyl-2-(trimethylsilyloxy)-N-(3,3-diphenylpropy1)-1-propanamine, which is then reacted with 2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl chloride for 2 hours and crystallized to obtain lercanidipine hydrochloride.

Abstract: The present invention relates to novel heterocyclic compounds and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula (I): wherein Q1, Q2, R2, R3, R4, R5, and R6 are as described herein. The invention also relates to methods for the preparation of the compounds, and to pharmaceutical compositions containing such compounds.