CARBOXYLATION CATALYSTS

The use of a complex of the form Z—M—OR in the carboxylation of a substrate is described. The group Z is a two-electron donor ligand, M is a metal and OR is selected from the group consisting of OH, alkoxy and aryloxy. The substrate may be carboxylated at a C—H or N—H bond. The metal M may be copper, silver or gold. The two-electron donor ligand may be a phosphine, a carbene or a phosphite ligand. Also described are methods of manufacture of the complexes and methods for preparing isotopically labelled caboxylic acids and carboxylic acid derivatives. 134-. (canceled)25. A method of carboxylation of a substrate , the method comprising;{'sub': '2', 'contacting a complex of the form Z—M—OR ,wherein the group Z is a two-electron donor ligand, M is a metal, and OR is selected from the group consisting of OH, alkoxy and aryloxy; with a substrate and a source of CO.'}26. The method according to claim 25 , wherein the metal M is selected from the group consisting of copper claim 25 , silver and gold.27. The method according to claim 25 , wherein the carboxylation is carried out in the presence of a base.28. The method according to claim 27 , wherein the base is an alkali metal hydroxide or alkoxide.29. The method according to claim 25 , wherein the two-electron donor ligand Z is selected from the group consisting of phosphines claim 25 , carbenes claim 25 , or phosphites.30. The method according to claim 29 , wherein the two-electron donor ligand Z is a nitrogen containing heterocyclic carbene ligand.33. The method according to claim 26 , wherein the complex is selected from the group consisting of: [M(OH)(IMes)] claim 26 , [M(OH)(SIMes)] claim 26 , [M(OH)(IPr)] claim 26 , [M(OH)(ItBu)] claim 26 , and [M(OH)(SIPr)] claim 26 , where M is Au claim 26 , Ag or Cu.34. The method according to claim 25 , wherein the substrate is carboxylated at a C—H or N—H bond.35. The method according to claim 25 , wherein the substrate is a substituted or unsubstituted aromatic compound.36. The ...

Compounds Having Activating Effect on Subtypes of Peroxisome Proliferator-Activated Receptors and its Preparation Method and Uses

Phenyl propanoic acid compounds having activating effect on peroxisome proliferator-activated receptors (PPARα,δ,γ) and a preparation method and uses thereof are provided in the present invention. The compounds can be used for treating or preventing diseases associated with peroxisome proliferator-activated receptors (PPARα,δ,γ). 2. The compound according to claim 1 , wherein X is S claim 1 , O claim 1 , or NR claim 1 , Y is O.3. The compound according to claim 1 , wherein Ris independently H or C-Calkyl.4. The compound according to claim 3 , wherein Ris methyl or H.5. The compound according to claim 4 , wherein Gis selected from C-Calkyl.6. The compound according to claim 5 , wherein Gand Gare each independently selected from H claim 5 , C-Calkyl claim 5 , C-Calkoxy claim 5 , trifluoromethyl claim 5 , F claim 5 , Cl claim 5 , Br claim 5 , nitro claim 5 , NRR claim 5 , C-Calkylthio claim 5 , amido claim 5 , cyano claim 5 , carboxyl and tetrazolyl.7. The compound according to claim 6 , wherein Gis ethyl; G claim 6 , Gare F claim 6 , CFor methyl.9. A pharmaceutical composition claim 1 , comprising the compound according to or pharmaceutical acceptable salts thereof.10. The pharmaceutical composition according to claim 9 , with a dosage form selected from tablets claim 9 , film-coated tablets claim 9 , sugar coated tablets claim 9 , enteric coated tablets claim 9 , dispersible tablets claim 9 , capsules claim 9 , granules claim 9 , oral solutions and oral suspensions.11. Use of a compound according to in the manufacture of a medicament for treating or preventing diseases associated with α subtype claim 1 , δ subtype claim 1 , and γ subtype of peroxisome proliferator-activated receptors.12. The use according to claim 11 , wherein the diseases associated with α subtype claim 11 , δ subtype claim 11 , and γ subtype of peroxisome proliferator-activated receptors are selected from hyperglycaemia claim 11 , insulin resistance claim 11 , hyperlipidemia and obesity.13. Use of ...

SPIRO COMPOUNDS AND PHARMACEUTICAL USE THEREOF

The spiro compound represented by the following general formula [Ia], its pharmaceutically acceptable salt or a solvate thereof 3. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 , wherein the number of the double bond in ring A of the spiro-ring AB is 0 or 1.4. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 , wherein the number of the double bond in ring B of the spiro-ring AB is 0 or 1.5. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 , wherein n3 is 1 or 2.6. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed claim 1 , wherein the spiro-ring AB may be substituted by 1 to 3 same or different substituent(s).7. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 ,{'sup': '1', 'wherein Ris'}(1) a hydrogen atom,{'sub': 1', '6, '(2) a C-Calkyl group,'}{'sub': 2', '6, '(3) a C-Calkenyl group,'}{'sub': 2', '6, '(4) a C-Calkynyl group,'}{'sub': 1', '6, '(5) a C-Calkoxy group,'}{'sub': 1', '6', '1', '6, '(6) a C-Calkoxy(C-C)alkyl group,'}{'sup': 11', '12', '11', '12, 'sub': 1', '6, '(7) —CONRRin which Rand Rare the same or different and each represents a hydrogen atom or a C-Calkyl group, or'}{'sub': 1', '6, '(8) a five-membered heteroaryl group which has at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and which may be substituted by a C-Calkyl group.'}8. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 ,{'sup': '1', 'wherein Ris'}(1) a hydrogen atom,{'sub': 2', '6, '(2) a C-Calkenyl group,'}{'sub': 2', '6, '(3) a C-Calkynyl group,'}{'sub': 1', '6, '(4) a C-Calkoxy group or'}{'sub': 1', '6, '(5) a five- ...

Polymorphs of an Active Pharmaceutical Ingredient

The present invention relates to crystalline form I of Febuxostat as well as to pharmaceutical compositions camprising crystalline form I as an active pharmaceutical ingredient. Furthermore the present invention relates to a further polymorphic form of Febuxostat designated as form II and to a novel solvate of Febuxostat. The present invention also relates to methods of making crystalline form I, form II and the novel solvate of Febuxostat. 115-. (canceled)16. A crystalline form of Febuxostat having an X-ray powder diffraction pattern as measured using CuKα radiation comprising peaks at 2-theta angles of 6.6±0.2° , 12.8±0.2° , 24.5±0.2 , 25.8±0.2° , 26.6±0.2°.17. The crystalline form of Feboxostat according to characterized by an IR spectrum comprising absorption bands at wavenumbers of about 2960±2 cm claim 16 , 2874±2 cm claim 16 , 2535±2 cm claim 16 , 2229±2 cm claim 16 , 1673±2 cm claim 16 , 1605±2 cm claim 16 , 1509±2 cm claim 16 , 1422±2 cm claim 16 , 1368±2 cm claim 16 , 1323±2 cm claim 16 , 1274±2 cm claim 16 , 1166±2 cm claim 16 , 1116±2 cm claim 16 , 1045±2 cm claim 16 , 1013±2 cm claim 16 , 911±2 cm claim 16 , 820±2 cm claim 16 , 763±2 cmand 725±2 cm.18. The crystalline form of Febuxostat according to characterized by a moisture sorption/desorption curve as shown in .19. A pharmaceutical composition comprising a crystalline form of Febuxostat according to claim 16 , further comprising at least one pharmaceutically acceptable excipient.20. The pharmaceutical composition according to claim 19 , which is an oral dosage form preferably a capsule or a tablet.21. A process for the production of a pharmaceutical composition according to claim 19 , comprising the step of mixing a crystalline form of Febuxostat according to with a pharmaceutically acceptable excipient.22. A crystalline form of Febuxostat characterized by an X-ray powder diffraction pattern as measured using CuKα radiation comprising peaks at 2-theta angles of 2.9±0.2° claim 19 , 5.8±0.2° claim 19 ...

PREPARATION OF FEBUXOSTAT

Processes for preparing febuxostat. 2. The process of claim 1 , wherein a reaction medium comprises a Cto Clinear or branched chain alcohol.3. The process of claim 1 , wherein a reaction medium comprises isopropanol.4. The process of claim 1 , wherein a solid compound of Formula II is separated without cooling a reaction mass.5. The process of claim 1 , wherein a solid compound of Formula II is separated at about 30° C. to about 60° C.6. A process for purifying ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate by recrystallizing claim 1 , slurrying claim 1 , or both in a solvent comprising chloroacetyl chloride claim 1 , formic acid claim 1 , or ethyl 2-chloroacetoacetate.7. The process of claim 6 , wherein a solvent for purification comprises chloroacetyl chloride.8. Ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate having a purity at least 99 percent by weight.10. A process for preparing febuxostat claim 6 , comprising hydrolyzing ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate in the presence of a ketone solvent.11. The process of claim 10 , wherein a ketone solvent comprises acetone claim 10 , ethyl methyl ketone claim 10 , or methyl isobutyl ketone.12. The process of claim 10 , wherein a ketone solvent is acetone.13. The process of claim 10 , wherein hydrolyzing comprises reacting with lithium hydroxide.14. The process of claim 13 , wherein lithium hydroxide is used in the form of an aqueous solution.15. A process for the preparation of crystalline Form III of febuxostat claim 13 , comprising recrystallizing febuxostat from a solution in a combination of an ester solvent and a hydrocarbon solvent.16. The process of claim 15 , wherein an ester solvent comprises ethyl acetate claim 15 , n-propyl acetate claim 15 , isopropyl acetate claim 15 , n-butyl acetate claim 15 , or tertiary-butyl acetate.17. The process of claim 15 , wherein a hydrocarbon solvent comprises toluene claim 15 , xylene claim 15 , n-hexane ...

PROCESS TO PREPARE ETHYL 4-METHYL-2-(4-(2-METHYLPROPYLOXY)-3-CYANOPHENYL)-5-THIAZOLECARBOXYLATE

Disclosed is a process for the preparation of Ethyl 4-methyl-2-(4-(2-methylpropyloxy)-3-cyanophenyl)-5-thiazolecarboxylate (I) the key intermediate for the preparation of [2-[3-cyano-4-(2-Methyl-propoxy)phenyl]-4-methyl-5-thiazole carboxylic acid (Febuxostat, I(A)) is approved under the trademark Uloric® by the US Food and Drug Administration for the treatment of hyperuricemia and gouty arthritis. 2. Process as claimed in wherein the step(a) comprises:i. Charging 98% formic acid and 3-bromo-4-hydroxy benzaldehyde and stirring for 15 minutesii. Charging hydroxylamine hydrochloride and sodium acetateiii. Heating reaction mass to 105° to 110° C. and maintaining for five hoursiv. Cooling reaction mass to room temperature and adding water and stirring for 2 hoursv. Filtering followed by drying and taking (XVII) to next stage3. Process as claimed in wherein the step(b) comprises:i. Charging Isopropyl alcoholic hydrogen chloride to the compound (XVII) and stirring for 15 minutesii. Charging thioacetamide and heating to 50-55° C.iii. Maintaining reaction mass at the same temperature for two hoursiv. Bringing reaction mass to room temperaturev. Charging water to the reaction mass and coolingvi. Filtering, washing with water and drying and taking compound (XVIII) to next stage4. Process as claimed in wherein the step(c) comprises:I. Charging Isopropyl alcohol to the compound of formula (XVIII) and stirring for 5 minutesII. Charging Ethyl-2-chloroacto acetate and heating to reflux temperatureIII. Maintaining five hours at reflux temperatureIV. Bringing reaction mass to room temperatureV. Filtering and drying to yield compound (XIX)5. Process as claimed in wherein the step(d) comprises:I. Charging compound (XIX) and DMFII. Charging potassium carbonate and Isobutyl bromideIII. Heating reaction mass to 80-85° C. and maintaining for six hoursIV. Bringing reaction mass to room temperature and quenching into waterV. Filtering and washing with waterVI. Suspending wet salt in a ...

COMPOUND HAVING DETRUSOR MUSCLE-CONTRACTING ACTIVITY AND URETHRAL SPHINCTER MUSCLE-RELAXING ACTIVITY

Since a compound represented by formula (I) wherein all of the symbols are the same as defined in the specification, a salt thereof, a solvate thereof, a prodrug thereof, a mixture with a diastereomer thereof in an arbitrary ratio, or a cyclodextrin clathrate thereof have a contracting activity of bladder detrusor and a relaxing activity of urethral sphincter, they can ameliorate bladder contraction dysfunction and/or urethral relaxation dysfunction, and for example, are effective for underactive bladder. Additionally, the compound of the present invention has little risk of side effects on the urinary system, the circulatory system and the digestive system, and exhibits excellent pharmacokinetics, such as oral absorbability etc. Therefore, the compound of the present invention is useful as a superior agent for preventing, treating and/or ameliorating underactive bladder. 2. The compound of claim 1 , wherein the compound is(1) 2-[(2-{(1R,5R)-2-oxo-5-[(1E)-7,8,8-trifluoro-4-hydroxy-4-methyl-1,7-octadien-1-yl]cyclopentyl}ethyl)thio]-1,3-thiazole-4-carboxylic acid,(2) 2-[(2-{(1R,5R)-2-oxo-5-[(1E,4S)-7,8,8-trifluoro-4-hydroxy-4-methyl-1,7-octadien-1-yl]cyclopentyl}ethyl)thio]-1,3-thiazole-4-carboxylic acid, or(3) 2-[(2-{(1R,5R)-2-oxo-5-[(1E,4R)-7,8,8-trifluoro-4-hydroxy-4-methyl-1,7-octadien-1-yl]cyclopentyl}ethyl)thio]-1,3-thiazole-4-carboxylic acid.3. The mixture in an arbitrary ratio of claim 1 , wherein the compound is 2-[(2-{(1R claim 1 ,5R)-2-oxo-5-[(1E claim 1 ,4S)-7 claim 1 ,8 claim 1 ,8-trifluoro-4-hydroxy-4-methyl-1 claim 1 ,7-octadien-1-yl]cyclopentyl}ethyl)thio]-1 claim 1 ,3-thiazole-4-carboxylic acid and the diastereomer is 2-[(2-{(1S claim 1 ,5R)-2-oxo-5-[(1E claim 1 ,4S)-7 claim 1 ,8 claim 1 ,8-trifluoro-4-hydroxy-4-methyl-1 claim 1 ,7-octadien-1-yl]cyclopentyl}ethyl)thio]-1 claim 1 ,3-thiazole-4-carboxylic acid.5. The pharmaceutical composition of claim 4 , wherein the pharmaceutical composition is an agent for contracting the bladder detrusor and ...

PROCESS FOR PREPARING THE CRYSTALLINE FORM II OF FEBUXOSTAT

The present invention relates to a novel process for preparing the crystalline form II of febuxostat by crystallization of a solvent selected from ethyl acetate, methyl acetate or ethyl formiate. 1. A process for preparing the crystalline form II of febuxostat , comprising the following steps:a) Dissolving febuxostat in a solvent selected from the group consisting of ethyl acetate, methyl acetate and ethyl formiate in a proportion from 10 to 60 ml of solvent per gram of solute, at a temperature between 50° C. and boiling temperature of the solution;b) Forming the crystals by cooling the solution from step a) at a temperature between 20° C. and 45° C., optionally over a period of 0.5-2 hours under stirring;c) Cooling the suspension from step b) at a temperature between 0° C. and 30° C. over a period of 0.5-3 hours; andd) Isolating the crystalline form II of febuxostat by filtration and drying.2. The process according to claim 1 , step a) claim 1 , wherein the proportion of solvent per gram of solute is from 15 to 50 ml.3. The process according to claim 1 , step b) claim 1 , wherein the temperature ranges from 33° C. to 37° C.4. The process according to claim 1 , step b) claim 1 , wherein the period is 1 hour.5. The process according to claim 1 , which comprises -between step b) and step c)-increasing yield of step b) by eliminating 40-80% of the solvent by distillation under reduced pressure at a temperature between 30° and 40° C.6. The process according to claim 5 , wherein the temperature ranges from 33° C. to 37° C. The present invention relates to a process for preparing the crystalline form II of febuxostat (2-[3-cyano-4-(2-i-butoxy)phenyl]-4-methyl-5-thiazole-carboxylic acid). Febuxostat is an inhibitor of xanthine oxidase that is indicated in the treatment of hyperuricemia. Its structural formula is as follows:CN101139325A relates to two crystalline forms of febuxostat by using ethanol, ethyl acetate or acetone. Among them form II is described, but operational ...

SUBSTANTIALLY PURE SALTS OF FEBUXOSTAT AND PROCESSES FOR PREPARATION THEREOF

Substantially pure salts of febuxostat of Formula (IA): wherein Y is Na, K, Li, Mg, Ca, Zn, Ba, Sr, choline, epolamine and N(R)and processes for preparation thereof are disclosed. 3. Febuxostat sodium having purity greater than 99.5% by area percentage of HPLC.5. Febuxostat potassium having purity greater than 99.5% by area percentage of HPLC.7. The process as claimed in claim 6 , wherein the base comprises one or more of sodium hydroxide claim 6 , potassium hydroxide claim 6 , lithium hydroxide claim 6 , calcium hydroxide claim 6 , barium hydroxide claim 6 , strontium hydroxide claim 6 , zinc hydroxide claim 6 , choline hydroxide claim 6 , epolamine hydroxide claim 6 , sodium carbonate claim 6 , potassium carbonate claim 6 , lithium carbonate claim 6 , magnesium carbonate claim 6 , calcium carbonate claim 6 , sodium bicarbonate claim 6 , potassium bicarbonate claim 6 , lithium bicarbonate claim 6 , sodium methoxide claim 6 , potassium t-butoxide claim 6 , magnesium methoxide claim 6 , and the like.8. The process as claimed in claim 6 , wherein the organic solvent comprises one or more of aliphatic alcohols claim 6 , aliphatic ketones claim 6 , polar aprotic solvents claim 6 , or mixtures thereof.9. The process as claimed in claim 8 , wherein the alcohol comprises one or more of methanol claim 8 , ethanol claim 8 , n-propanol claim 8 , isopropanol claim 8 , n-butanol claim 8 , and tert-amyl alcohol.10. The process as claimed in claim 8 , wherein the aliphatic ketones comprises one or more of acetone claim 8 , methylethylketone claim 8 , and methylisobutyl ketone.11. The process as claimed in claim 8 , wherein the polar aprotic solvent comprises one or more of dimethylformamide claim 8 , dimethylacetamide claim 8 , dimethylsulfoxide claim 8 , and N-methylpyrrolidone.12. The process as claimed in claim 6 , wherein the isolation comprises one or more of filtration claim 6 , filtration under vacuum claim 6 , evaporation claim 6 , decantation claim 6 , centrifugation ...

POLYMORPHS OF FEBUXOSTAT

The present invention provides new crystalline forms of febuxostat, pharmaceutical compositions comprising same, methods for their preparation and use thereof in treating hyperuricaemia. 153-. (canceled)54. A crystalline anhydrous febuxostat (Form IX) having an X-ray powder diffraction pattern with diffraction peaks at 2-theta values of about 4.6±0.1 , 6.1±0.1 , 7.3±0.1 , 9.2±0.1 , 11.6±0.1 , 13.3±0.1 , 16.3±0.1 , 17.3±0.1 , 18.5±0.1 , 23.0±0.1 , 25.7±0.1 , 26.5±0.1 and 28.3±0.1.5542. The crystalline anhydrous febuxostat (Form IX) according to having an X-ray powder diffraction pattern substantially as shown in any of or .56. The crystalline anhydrous febuxostat (Form IX) according to claim 54 , further characterized by:{'figref': {'@idref': 'DRAWINGS', 'FIG. 32'}, 'b': '43', '(a) a DSC profile substantially as shown in any of or ; or'}{'figref': {'@idref': 'DRAWINGS', 'FIG. 33'}, 'b': '44', '(b) TGA profile substantially as shown in any of or ; or'}{'figref': {'@idref': 'DRAWINGS', 'FIG. 34'}, '(c) an IR spectrum substantially as shown in ; or'}{'figref': {'@idref': 'DRAWINGS', 'FIG. 35'}, '(d) an FT-Raman spectrum substantially as shown in .'}57. The crystalline anhydrous febuxostat (Form IX) according to claim 56 ,{'sup': '−1', 'wherein the IR spectrum has characteristic peaks at about 657±4, 715±4, 764±4, 825±4, 874±4, 911±4, 952±4, 1010±4, 1037±4, 1114±4, 1168±4, 1281±4, 1328±4, 1370±4, 1389±4, 1427±4, 1450±4, 1511±4, 1606±4, 1687±4, 2235±4, 2868±4 and 2962±4 cm; or'}{'sup': '−1', 'wherein the FT-Raman spectrum has characteristic peaks at about 392±4, 467±4, 585±4, 748±4, 1047±4, 1175±4, 1332±4, 1374±4, 1431±4, 1512±4, 1609±4, 1842±4, 1892±4, 1973±4, 2081±4, and 2235±4 cm.'}59. A crystalline febuxostat NMP solvate (Form IV) having an X-ray powder diffraction pattern with diffraction peaks at 2-theta values of about 4.0±0.1 claim 56 , 4.9±0.1 claim 56 , 6.4±0.1 claim 56 , 6.9±0.1 claim 56 , 7.5±0.1 claim 56 , 8.0±0.1 claim 56 , 8.3±0.1 claim 56 , 10.1±0.1 claim ...

Bridged Spiro[2.4]heptane Ester Derivatives

The invention relates to a method for preparing linear polymers having an amide end or having a star architecture comprising an amide core, by means of a ring opening using lactide and glycolide monomers or a lactide monomer ring in the presence of a catalyst, wherein the method includes the steps of: (i) reacting the excess monomer(s) with an initiator in a solvent, said initiator being selected from among an amine and an amino alcohol, given that the initiator has at least one primary or secondary amine function; (ii) adding a catalyst, said catalyst being a non-nucleophilic base and including at least one neutral sp2 nitrogen atom; and (iii) neutralizing the reaction mixture. Said novel method is particularly advantageous in that it can be easily monitored and enables better modulation of the polymers, and thus of the properties thereof, than the methods of the prior art. The invention also relates to novel polymers that are obtainable by means of said method. 2. The compound according to claim 1 , whereinY represents a bond or a methandiyl group;{'sup': '1', 'sub': 1', '4', '1', '4', '1', '2, 'Rrepresents an aryl- or a heteroaryl-group, wherein the groups are independently unsubstituted, mono- or di-substituted, wherein the substituents are independently halogen, (C-C)alkyl, (C-C)alkoxy or (C-C)fluoroalkyl;'}{'sup': '2', 'claim-text': [{'sup': 3', '4, 'sub': '2', 'cyclopentyl or cyclohexyl, which are independently unsubstituted or mono-substituted with RRN—CH— or heterocyclyl-methyl;'}, {'sub': 2', '6', '1', '4, 'sup': 3', '4', '5', '6, '(C-C)alkyl, which is mono-substituted with —NRR, —C(O)NRR, or (C-C)alkoxy which is mono-substituted with heterocyclyl, wherein the heterocyclyl is unsubstituted or mono- or di-substituted at one of the carbon atoms with fluoro; or'}, {'sub': 1', '6, 'claim-text': [{'sub': 1', '4, 'with heterocyclyl, wherein the heterocyclyl is unsubstituted, or mono-substituted at a nitrogen atom with (C-C)alkyl and/or mono- or di-substituted at ...

CRYSTALLINE FORMS OF FEBUXOSTAT

New forms of Febuxostat have bean, prepared and characterized. These forms are useful for examples in the chronic management of hyperuricemia in patients with gout. 110. A crystalline form of Febuxostat , designated Form F10 , characterized by data selected from one or more of the following: an X-ray powder diffraction pattern having peaks at 6.7° , 7.7° , 12.8° , 13.3° and 20.0°±0.2° 2θ; an X-ray powder diffraction pattern substantially as depicted in ; a solid-state C NMR spectrum with signals at 112.7 , 125.7 , 132.4 and 168.3±0.2 ppm; a solid-state C NMR spectrum having chemical shifts differences between the signal exhibiting the lowest chemical shift and another in the chemical shift range of 100 to 180 ppm of 11.7 , 24.7 , 31.4 and 67.3±0.1 ppm; a solid-state C NMR spectrum substantially as depicted in or ; and combinations thereof.2. The crystalline form of Febuxostat claim 1 , designated Form F10 claim 1 , according to claim 1 , characterized by a solid-state C NMR spectrum with signals at 112.7 claim 1 , 125.7 claim 1 , 132.4 and 168.3±0.2 ppm.3. The crystalline form of Febuxostat according to claim 1 , further characterized by an X-ray powder diffraction pattern having peaks at 3.3° claim 1 , 16.3° claim 1 , 16 claim 1 ,9° claim 1 , 24.5° and 25.8°±0.2° 2θ.43. A crystalline form of Febuxostat claim 1 , designated Form F1 claim 1 , characterized by data selected from one or more of the following: a powder XRD pattern with peaks at 5.8° claim 1 , 6.8° claim 1 , 8.1° claim 1 , 11.8° and 17.4°±0.2° 2θ; an XRPD pattern substantially as depicted in ; a solid-state C NMR spectrum with signals at 123.8 claim 1 , 163.1 and 168.5±0.2 ppm; a solid-state C NMR spectrum having chemical shifts differences between the signal exhibiting the lowest chemical shift and another in the chemical shift range of 100 to 180 ppm of 23.4 claim 1 , 62.7 and 68.1±0.1 ppm; a solid-state C NMR spectrum substantially as depicted in or ; and combinations thereof.5. The crystalline form ...

PROCESS FOR THE PREPARATION OF FEBUXOSTAT

An improved and efficient process for the preparation of 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid (febuxostat) that is substantially free from amide by-product is provided. 2. The process according to claim 1 , wherein the hydrolysis is carried out in the presence of barium oxide.3. The process according to claim 1 , wherein the hydrolysis is carried out in the presence of barium hydroxide octahydrate.5. The process according to claim 4 , wherein febuxostat of Formula I is substantially free of amide by-product.6. The process according to claim 4 , wherein febuxostat of Formula I contains 0.07% amide by-product.7. The process according to claim 4 , wherein in febuxostat of Formula I contains less than 0.07% amide by-product. An improved and efficient process for the preparation of 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid (febuxostat) that is substantially free from amide by-product is provided.Febuxostat is a non-purine xanthine oxidase inhibitor known from U.S. Pat. No. 5,614,520. It is chemically designated as 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid having the structure as represented by Formula I.Febuxostat is marketed in the United States under the brand name Uloric® and in Europe under the brand name Adenuric® for the chronic management of hyperuricemia in patients with gout. It works by non-competitively blocking the channel leading to the active site on xanthine oxidase. Xanthine oxidase is needed to successively oxidate both hypoxanthine and xanthine to uric acid. Hence, febuxostat inhibits xanthine oxidase, therefore, reducing production of uric acid.Processes for the preparation of febuxostat and intermediates thereof are disclosed in U.S. Pat. No. 5,614,520; Japanese Patent Nos. JP 2834971; JP 3202607; JP 2706037, JP 10139770 and JP 3169735.U.S. Pat. No. 5,614,520 discloses preparation of febuxostat by hydrolysis of its corresponding ester using sodium ...

PROCESS FOR THE PREPARATION OF 2-ARYLTHIAZOLE DERIVATIVES

The present invention relates an improved process for the preparation of 2-arylthiazole derivatives which are intermediates of Febuxostat and further conversion to Febuxostat or pharmaceutically acceptable salts thereof. 2. The process according to claim 1 , wherein the organic solvent is selected from the group consisting of dimethyl sulfoxide claim 1 , dimethylacetamide claim 1 , dimethyl formamide and acetonitrile.3. The process according to claim 1 , wherein the acyl halide is selected from the group consisting of acetyl bromide and acetyl chloride.4. The process according to claim 1 , wherein the sulfonyl chloride is selected from the group consisting of methane sulfonyl chloride and para-toluene sulfonyl chloride.5. The process according to claim 1 , wherein the base is an alkali metal carbonate.6. The process according to claim 1 , wherein the compound of formula-II is further hydrolyzed to Febuxostat or a pharmaceutically acceptable salts thereof.7. The process according to claim 6 , wherein the compound of formula-II is hydrolyzed by using aqueous ethanol claim 6 , aqueous methanol claim 6 , aqueous acetone claim 6 , aqueous acetonitrile or aqueous isopropyl alcohol.10. (canceled)12. The process according to claim 5 , wherein the alkali metal carbonate is potassium carbonate or sodium carbonate. This application claims priority to Indian patent application No. 3312/CHE/2010 filed on Nov. 4, 2010.The present invention relates an improved process for the preparation of 2-Arylthiazole derivatives which are intermediates of Febuxostat and further conversion to Febuxostat or pharmaceutically acceptable salts thereof.2-Arylthiazole derivatives are used as xanthine oxidase inhibitors for use in the treatment of hyperuricemia and gout.Febuxostat, 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid of Formula-I is an example of 2-arylthiazole derivatives used as xanthine oxidase inhibitors for use in the treatment of hyperuricemia and gout.Febuxostat ...

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: 1. (canceled)2. The process of claim 18 , where X is selected from pyrazole claim 18 , imidazole claim 18 , triazole claim 18 , benzotriazole claim 18 , furan claim 18 , pyrrole claim 18 , tetrazole claim 18 , pyrazine claim 18 , thiophene claim 18 , oxazole claim 18 , isoxazole claim 18 , thiazole claim 18 , isothiazole claim 18 , oxadiazole claim 18 , thiadiazole claim 18 , pyridazine claim 18 , pyridine claim 18 , pyrimidine claim 18 , pyran claim 18 , benzimidazole claim 18 , benzoxazole claim 18 , benzothiazole claim 18 , pyridylimidazole claim 18 , and pyridyltriazole.3. The process of claim 2 , where X is selected from pyrazole claim 2 , triazole claim 2 , benzotriazole claim 2 , tetrazole claim 2 , oxazole claim 2 , isoxazole claim 2 , thiazole claim 2 , pyridazine claim 2 , pyrimidine claim 2 , and pyridyltriazole.4. The process of claim 18 , where Ris selected from —ORand —NRR claim 18 , where Ris H claim 18 , Ris H or —OH claim 18 , and Ris H.7. The process of claim 18 , where Ris H.8. The process of claim 18 , where Ris absent or is selected from H; halo; —Calkylene-OH; —NH; —Calkyl; —CF; —Ccycloalkyl; —Calkylene-O—Calkyl; —C(O)R; —Calkylene-COOR; —C(O)NRR; —NHC(O)R; ═O; —NO; —C(CH)═N(OH); phenyl optionally substituted with one or two groups independently selected from halo claim 18 , —OH claim 18 , —CF claim 18 , —OCH claim 18 , —NHC(O)CH claim 18 , and phenyl; naphthalenyl; pyridinyl; pyrazinyl; pyrazolyl optionally substituted with methyl; thiophenyl optionally substituted with methyl or halo; furanyl; and —CH-morpholinyl; and Ris H.10. The process of claim 18 , where Ris absent or is selected from H; halo; —Calkylene-OH; —Calkyl; —Ccycloalkyl; —Calkylene-O—Calkyl; —C(O)R; —Calkylene-COOR; —C(O)NRR; —NHC(O)R; —NHC(O)R; ═O; phenyl optionally substituted with one or two groups independently selected from halo claim 18 , —OH claim 18 , and —OCH; pyridinyl; and pyrazinyl; Ris —Calkyl; ...

METHODS OF TREATING OR PREVENTING ALZHEIMER'S DISEASE USING INDANE ACETIC ACID DERIVATIVES

The present invention provides indane acetic acid and their derivatives and methods for the treating and/or preventing of Alzheimer's diseases. 3. The method according to wherein:R is H,{'sup': '1', 'Ris H,'}{'sup': '2', 'Ris H,'}{'sup': '3', 'sub': 1', '6, 'Ris C-Calkyl,'}X is O, and{'sup': 4', '6', '6, 'sub': 1', '6', '1', '6, 'Ris a phenyl substituted with R, wherein Ris C-Calkoxyl or C-Calkyl.'}5. The method according to wherein the compound is a pharmaceutically acceptable salt thereof claim 1 , wherein the pharmaceutically acceptable salt is selected from the group consisting of alkali metal salts claim 1 , alkaline earth metal salts claim 1 , ammonium salts with organic bases claim 1 , and basic nitrogen containing groups in the conjugate base that is quaternized with agents selected from the group consisting of alkyl halides and aralkyl.6. The method according to wherein the compound is a meglumine claim 5 , potassium or sodium salt thereof.7. The method according to wherein said compound is administered intravenously claim 1 , orally claim 1 , buccally claim 1 , transdermally claim 1 , rectally claim 1 , nasally claim 1 , optically claim 1 , intrathecally or intra-cranially8. The method according to further comprising administration of one or more additional therapeutic agent.9. The method according to wherein said one or more additional therapeutic agent is used to treat or prevent Alzheimer's disease.10. The method according to wherein said one or more additional therapeutic agents is at least one of acetylcholinesterase inhibitor claim 9 , and a NMDA receptor antagonist.11. The method according to wherein said additional therapeutic agent is selected from the group consisting of tacrine claim 10 , galantamine claim 10 , rivastigamine claim 10 , donepezil and memantine.12. The method according to wherein said one or more additional therapeutic agents regulates beta amyloid plaque disease is selected from the group consisting of an antioxidant claim 9 , an ...

OXAZOLE COMPOUND AND PHARMACEUTICAL COMPOSITION

The present invention provides a oxazole compound represented by Formula (1), or a salt thereof: 2. The compound according to claim 1 ,{'sup': '1', 'wherein Ris a phenyl group which has 1 to 3 substituents selected from the following (1-2), (1-3), (1-4) and (1-5)(1-2) unsubstituted or halogen-substituted lower alkoxy groups,(1-3) lower alkenyloxy groups,(1-4) lower alkynyloxy groups, and{'sub': '3-8', '(1-5) cyclo Calkyl lower alkoxy groups;'}{'sup': '2', 'Ris a phenyl group or a pyridyl group each of which may have 1 to 3 substituents selected from the group consisting of the following (2-2), (2-3), (2-4) and (2-5)(2-2) unsubstituted or halogen-substituted lower alkoxy groups,(2-3) unsubstituted or halogen-substituted lower alkyl groups,(2-4) lower alkenyloxy groups, and(2-5) halogen atoms; {'br': None, 'sup': 1', '1, '—Y-A-\u2003\u2003Formula (i)'}, 'W is a divalent group represented by Formula (i)'}{'sup': '1', 'wherein Ais a lower alkylene group, and'}{'sup': 1', '3, 'Yis —C(═O)— or —C(═O)—N(R)—'}{'sup': '3', 'wherein Ris a hydrogen atom.'}3. The compound according to claim 2 ,{'sup': '1', 'wherein Ris a phenyl group having two substituents selected from the following'}(1-2), (1-3), (1-4) and (1-5):(1-2) unsubstituted or halogen-substituted lower alkoxy groups,(1-3) lower alkenyloxy groups,(1-4) lower alkynyloxy groups, and{'sub': '3-8', '(1-5) cyclo Calkyl lower alkoxy groups;'}{'sup': '2', 'Ris a phenyl group or a pyridyl group each of which may have 1 to 2 substituents selected from the following (2-2), (2-3), (2-4) and (2-5)(2-2) unsubstituted or halogen-substituted lower alkoxy groups,(2-3) unsubstituted or halogen-substituted lower alkyl groups,(2-4) lower alkenyloxy groups, and(2-5) halogen atoms; and {'br': None, 'sup': 1', '1, '—Y-A-\u2003\u2003Formula (i)'}, 'W is a divalent group represented by Formula (i);'}{'sup': '1', 'wherein Ais a lower alkylene group, and'}{'sup': 1', '3, 'Yis —C(═O)— or —C(═O)—N(R)—'}{'sup': '3', 'wherein Ris a hydrogen atom.'} ...

Ribosome-mediated incorporation of peptides and peptidomimetics

Modified ribosomes that were selected using a dipeptidyl-puromycin aminonucleoside are used to mediate site-specific incorporation of one or more peptides and peptidomimetics into protein in a cell free translation system. In addition, new fluorescent dipeptidomimetics have been synthesized and incorporated into proteins, as well as modified proteins containing one or more non-naturally occurring dipeptides.

COMPOUNDS FOR INFLAMMATION AND IMMUNE-RELATED USES

The invention relates to compounds of formula (I): 187-. (canceled)89. The compound of claim 88 , wherein Ais CH.90. (canceled)91. The compound of claim 88 , wherein Yis a substituted phenyl claim 88 , an optionally substituted pyridyl claim 88 , or an optionally substituted [1 claim 88 ,2 claim 88 ,3]-thiadiazolyl.92. The compound of claim 88 , wherein Yis a substituted phenyl.94. (canceled)95. A compound selected from the group consisting of:3-Fluoro-N-(2′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(2′-methyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(3′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-nicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-isonicotinamide;4-Trifluoromethyl-N-(2′-trifluoromethyl-biphenyl-4-yl)-nicotinamide;Pyridine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;Pyrazine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;2-methyl-pyridine-3-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;1-methyl-1H-imidazole-5-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethoxy-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-dimethoxybiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-methylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethylbiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid (2′-methoxy-5′-acetylbiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-difluoromethoxy-5′-chlorobiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid {2′-(N,N-dimethylamino)-5′-trifluoromethoxybiphenyl-4- ...

ORGANIC LIGHT EMITTING ELEMENT, DISPLAY DEVICE, IMAGE INFORMATION PROCESSING DEVICE, LIGHTING DEVICE, IMAGE FORMING DEVICE, EXPOSURE DEVICE, AND ORGANIC PHOTOELECTRIC CONVERSION ELEMENT

The present disclosure provides an organic light emitting element which has a pair of electrodes and an organic compound layer disposed therebetween and in which the organic compound layer contains an organic compound represented by the following general formula [1], 2. The composition according to claim 1 , wherein the Arand Arare each substituted by a substituent selected from the group consisting of a tert-butyl group claim 1 , a halogen atom claim 1 , a cyano group claim 1 , and a heterocyclic group having a nitrogen atom.3. The composition according to claim 1 , wherein the Arand Arare each substituted by a substituent selected from the group consisting of a tert-buthyl group and a halogen atom.4. The composition according to claim 1 , wherein Rand R claim 1 , Rand Reach may form the ring claim 1 , the ring is a benzene ring.5. An organic light-emitting element comprising:a first electrode;a second electrode; andan organic compound layer disposed between the first electrode and the second electrode,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein the organic compound layer contains the composition according to .'}6. An organic light-emitting element comprising:a first electrode;a second electrode;a light emitting layer disposed between the first electrode and the second electrode; andan organic compound layer disposed between the first electrode and the light emitting layer,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein the organic compound layer contains the composition according to .'}7. The organic light-emitting element according to claim 6 , wherein the first electrode is a cathode claim 6 , and the second electrode is an anode.8. The organic light-emitting element according to claim 7 , wherein the first electrode is in contact with the organic compound layer.9. A display device comprising:{'claim-ref': {'@idref': 'CLM-00006', 'claim 6'}, 'a plurality of pixels, at least one of the pixels comprising the organic light-emitting element ...

ORGANIC LIGHT EMITTING ELEMENT, DISPLAY DEVICE, IMAGE INFORMATION PROCESSING DEVICE, LIGHTING DEVICE, IMAGE FORMING DEVICE, EXPOSURE DEVICE, AND ORGANIC PHOTOELECTRIC CONVERSION ELEMENT

The present disclosure provides an organic light emitting element which has a pair of electrodes and an organic compound layer disposed therebetween and in which the organic compound layer contains an organic compound represented by the following general formula [1], 3. The organic light emitting element according to claim 2 , wherein the Arand Areach have at least one fluorine atom as a substituent.4. The organic light emitting element according to claim 2 , wherein the Arand Areach have at least one tert-butyl group as a substituent.5. The organic light emitting element according to claim 2 , wherein the organic compound layer further contains a compound different from the organic compound represented by the general formula [1].6. The organic light emitting element according to claim 5 , wherein the weight rate of the compound different from the organic compound represented by the general formula [1] is more than 0 to 80 percent by weight when the total of the organic compound represented by the general formula [1] and the compound different therefrom is assumed to be 100 percent by weight.7. The organic light emitting element according to claim 2 , wherein the organic compound layer is in contact with the cathode.8. The organic light emitting element according to claim 2 , wherein the organic light emitting element has a plurality of light emitting layers including the above light emitting layer claim 2 ,at least one of the plurality of light emitting layers is a light emitting layer emitting color light different from that of the rest of the plurality of light emitting layers, andthe organic light emitting element emits white light.9. A display device comprising: a plurality of pixels claim 2 , wherein the pixels each have the organic light emitting element according to and an active element connected thereto.10. The display device according to claim 9 , wherein the active element is a transistor claim 9 , and the transistor has an oxide semiconductor in an ...

COMPOUNDS FOR INFLAMMATION AND IMMUNE-RELATED USES

The invention relates to compounds of formula (I): 187-. (canceled)89. The compound of claim 88 , wherein Ais CH.90. (canceled)91. The compound of claim 88 , wherein Yis a substituted phenyl claim 88 , an optionally substituted pyridyl claim 88 , or an optionally substituted [1 claim 88 ,2 claim 88 ,3]-thiadiazolyl.92. The compound of claim 88 , wherein Yis a substituted phenyl.94. (canceled)95. A compound selected from the group consisting of:3-Fluoro-N-(2′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(2′-methyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(3′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-nicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-isonicotinamide;4-Trifluoromethyl-N-(2′-trifluoromethyl-biphenyl-4-yl)-nicotinamide;Pyridine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;Pyrazine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;2-methyl-pyridine-3-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;1-methyl-1H-imidazole-5-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethoxy-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-dimethoxybiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-methylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethylbiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid (2′-methoxy-5′-acetylbiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-difluoromethoxy-5′-chlorobiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid {2′-(N,N-dimethylamino)-5′-trifluoromethoxybiphenyl-4- ...

AGONISTS OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA AND METHODS OF USE

Benzyl derivative compounds having peroxisome proliferator-activated receptor α (PPARα) agonistic activity, compositions containing such compounds, and methods of their use in enhancing PPARα activity for treating diseases and/or conditions involving inflammation and/or angiogenesis, particularly ocular diseases and/or conditions such as but not limited to retinal inflammation, retinal neovascularization, retinal vascular leakage, retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and diabetic macular edema are disclosed. 2. A composition claim 1 , comprising one or more compounds of disposed in a pharmaceutically-acceptable carrier claim 1 , vehicle claim 1 , or diluent.3. The composition of claim 2 , formulated to provide a delayed release claim 2 , controlled release claim 2 , extended release claim 2 , and/or sustained release of the one or more compounds.4. A kit claim 2 , comprising the composition of claim 2 , and instructions for use thereof in a treatment of a disorder or condition in a subject.5. The kit of claim 4 , wherein the disorder or condition is an ocular disorder or condition selected from the group consisting of retinal inflammation claim 4 , retinal neovascularization claim 4 , retinal vascular leakage claim 4 , retinopathy of prematurity (ROP) claim 4 , diabetic retinopathy (DR) claim 4 , an age-related macular degeneration (AMD) claim 4 , macular edema claim 4 , diabetic macular edema (DME) claim 4 , keratitis claim 4 , endophthalmitis claim 4 , blepharitis claim 4 , conjunctivitis claim 4 , scleritis claim 4 , herpetic inflammation claim 4 , uveitis claim 4 , vasculitis claim 4 , arteritis claim 4 , orbital inflammations claim 4 , optic neuritis claim 4 , sympathetic ophthalmia claim 4 , retinitis claim 4 , glaucoma claim 4 , proliferative vitreoretinopathy claim 4 , corneal edema claim 4 , uveal edema claim 4 , and retinal edema.8. The method of claim 7 , wherein the disorder or condition is selected from the ...

PROCESS FOR FEBUXOSTAT

The present invention provides a process for the preparation of 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester. The present invention also provides a process for the preparation of 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester. The present invention further provides novel crystalline Forms of febuxostat, processes for their preparation and pharmaceutical compositions comprising them. The present invention further provides febuxostat crystalline particles having a mean particle size of less than about 25 μm, the methods for the manufacture of said crystalline particles, and pharmaceutical compositions comprising said crystalline particles. 1. A process for the preparation of 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester , which comprises reacting the 4-hydroxythiobenzamide with 2-chloroacetoacetic acid ethyl ester in the presence of an alcoholic solvent.2. The process according to claim 1 , wherein the alcoholic solvent is a solvent or mixture of solvents selected from methanol claim 1 , ethanol claim 1 , isopropanol and n-butanol.3. The process according to claim 2 , wherein the alcoholic solvent is isopropanol.4. A process for the preparation of 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester claim 2 , which comprise:a. reacting the 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester with trifluoroacetic acid in the presence of hexamethyl tetramine;b. heating the reaction mixture obtained in step (a) at above 60° C.;c. cooling the reaction mass obtained in step (b) at below 35° C.;d. extracting the reaction mass into toluene;e. removing the solvent from the reaction mass obtained in step (d) to obtain a residual solid;f. slurring the residual solid obtained in step (e) with cyclohexane; andg. isolating the 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester.5. The process according to claim 4 , wherein the reaction in step (b) is ...

AMINE SALT OF (1R, 3S)-3-(5-CYANO-4-PHENYL-1,3-THIAZOL-2-YLCARBAMOYL)CYCLOPENTANE CARBOXYLIC ACID

The present invention relates to the tromethamine salt of (1R,3S)-3-(5-cyano-4-phenyl-1,3-thiazol-2-ylcarbamoyl)cyclopentane carboxylic acid, a process for obtaining said salt, combination products and pharmaceutical compositions comprising said salts and their medical uses, in particular for the treatment or prevention of diseases known to ameliorate by Aadenosine receptor antagonism. 1. A tromethamine salt of (1R ,3S)-3-(5-cyano-4-phenyl-1 ,3-thiazol-2-ylcarbamoyl)cyclopentane carboxylic acid.2. The salt according to claim 1 , wherein tromethamine and (1R claim 1 ,3S)-3-(5-cyano-4-phenyl-1 claim 1 ,3-thiazol-2-ylcarbamoyl)cyclopentane carboxylic acid are in a 1:1 molar ratio.3. The salt according to claim 1 , characterized by being in a crystalline form having an X-ray powder diffraction pattern comprising 2θ° peaks at 8.7 claim 1 , 18.0 claim 1 , 18.4 claim 1 , 21.7 and 26.1±0.20 2θ°.4. The salt according to claim 3 , further comprising 2θ° peaks in the X-ray powder diffraction pattern at 12.3 claim 3 , 13.0 claim 3 , 13.4 claim 3 , 16.3 claim 3 , 16.8 claim 3 , 17.3 claim 3 , 19.5 claim 3 , 20.9 claim 3 , 23.8 and 24.6±0.20 2θ°.5. A process for the preparation of the tromethamine salt of claim 1 , comprising:a) mixing (1R,3S)-3-(5-cyano-4-phenyl-1,3-thiazol-2-ylcarbamoyl)cyclopentane carboxylic acid and tromethamine in presence of a solvent, andb) isolating the (1R,3S)-3-(5-cyano-4-phenyl-1,3-thiazol-2-ylcarbamoyl) cyclopentane carboxylic acid tromethamine salt obtained in step a).6. The process according to claim 5 , wherein the mixture of step a) is heated at the reflux temperature of the solvent.7. The process according to claim 5 , wherein the solvent is selected from the group consisting of alkanols claim 5 , aliphatic hydrocarbons claim 5 , aromatic hydrocarbons claim 5 , ethers claim 5 , ketones claim 5 , esters claim 5 , dichloromethane claim 5 , chloroform claim 5 , dimethylsulfoxide claim 5 , acetonitrile claim 5 , water claim 5 , and mixtures thereof. ...

Bi-Aromatic And Tri-Aromatic Compounds As NADPH Oxidase 2 (Nox2) Inhibitors

Bi- and tri-aromatic compounds of the formula (I) wherein R1 to RIO and X are as defined, are Nox2 inhibitors that are useful as medicaments for the treatment of a disease or condition selected from: cardiovascular diseases, respiratory diseases, inflammatory diseases, cancers, ageing and age related disorders, kidney diseases, neurodegenerative diseases, diabetes and conditions associated with diabetes. The compounds, their preparation and pharmaceutical compositions comprising them are disclosed. 6. A compound according to any one of the preceding to , wherein{'sup': 1', '2', '3', '4', '5, 'Rand Rare OH and R, Rand Rare H; or'}{'sup': 4', '5', '1', '2', '3, 'Rand Rare OH and R, Rand Rare H.'}7. A compound according to any one of the preceding to , wherein Ris methyl , hydroxymethyl or OH; Ris methyl , hydroxymethyl or OH; and Rand Rare H.8. A compound which is selected from:2,3-dihydroxyphenyl)methyl 4-hydroxy-3-(hydroxymethyl)benzoate;3-(2,3-dihydroxyphenyl)-1-(4-hydroxy-3-(hydroxymethyl)phenyl)propan-1-one;3-(2,3-dihydroxyphenyl)-1-(3,4-dihydroxyphenyl)propan-1-one;N-(2,3-dihydroxybenzyl)-4-hydroxy-3-(dihydroxymethyl)benzamide;N-(2,3-dihydroxybenzyl)-3,4-dihydroxybenzamide;N-(2,3-dihydroxybenzyl)-3-hydroxy-4-(hydroxmethyl)benzamine;2,3-dihydroxybenzyl 4-hydroxy-3-(hydroxymethyl)benzimine;2,3-dihydroxybenzyl 4-hydroxy-3-(3-hydroxybenzyl)benzoate;2,3-dihydroxybenzyl 3-benzyl-4-hydroxybenzoate;2,3-dihydroxybenzyl 3-(hydroxymethyl)-4-(hydroxymethyl)benzoate;2,3-dihydroxybenzyl 3,4-dihydroxybenzoate;2,3-dihydroxybenzyl 3-hydroxy-4-methylbenzoate;2,4-dihydroxybenzyl 3-hydroxy-4-(hydroxymethyl)benzoate;2,3-dihydroxybenzyl 2-napthoate;2,3-dihydroxybenzyl 6-hydroxy-7-(4-hydroxyphenyl)-2-napthoate;2,3-dihydroxybenzyl 6-hydroxy-7-phenyl-2-napthoate;2,3-dihydroxybenzyl 6-hydroxy-7-methyl-2-napthoate;2,3-dihydroxybenzyl 6-hydroxy-7-(hydroxymethyl)-2-napthoate;2,3-dihydroxybenzyl 6,7-dihydroxy-2-napthoate;2,3-dihydroxybenzyl 7-hydroxy-2-napthoate;2,3-dihydroxybenzyl 6,8- ...

SEMICARBAZIDE-SENSITIVE AMINE OXIDASE INHIBITORS FOR USE AS ANALGESICS IN TRAUMATIC NEUROPATHY AND NEUROGENIC INFLAMMATION

The invention relates to a compound having SSAO/VAP-1 inhibitor activity for use in the treatment of hyperalgesia and allodynia implicated in traumatic neuropathy or neurogenic inflammation. Accordingly, the invention relates to a compound having SSAO/VAP-1 inhibitor activity for use in the inhibition of pathological activation and dysfunctions of peptidergic sensory nerves caused by mechanical damage or chemical activation of peptidergic sensory nerves in neurogenic inflammation. 1. A compound having SSAO/VAP-1 inhibitor activity for use in the treatment of hyperalgesia and allodynia implicated in traumatic neuropathy or neurogenic inflammation.3. A compound according to which is selected from the following group:3-methoxy-2-methylbenzaldehyde oxime;8-Pyrrolidino-1-naphthaldehyde oxime;5-Hydroxy-1,3-benzodioxole-4-carbaldehyde oxime;5-Ethoxy-1,3-benzodioxole-4-carbaldehyde oxime;5-(Allyloxy)-1,3-benzodioxole-4-carbaldehyde oxime;5-Bromo-1,3-benzodioxole-4-carbaldehyde oxime;5-{2-[(Hydroxyimino)methyl]phenyl}-1,3-benzodioxole-4-carbaldehyde oxime;6-Ethoxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde oxime;6-Methoxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde oxime;1,3-Dimethyl-2,4-dioxo-6-propoxy-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde oxime;6-Ethoxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde-O-methyloxime;1,3-Dimethyl-2,4-dioxo-6-(propylthio)-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde oxime;1,3-Dimethyl-6-(methylthio)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde oxime;6-(Ethylthio)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde oxime;1,3-Dimethyl-2,4-dioxo-6-(phenylthio)-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde oxime;6-(Ethylthio)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde-O-methyloxime;6-[Allyl(methyl)amino]-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde oxime;3-(4,5-Diphenyl-1,3-oxazol-2-yl)propanal oxime and1-(4- ...

HETEROCYCLIC INHIBITORS OF NECROPTOSIS

The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I) and (Ia)-(Ie) and are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring the compounds of the invention. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role. 2. The compound of claim 1 , wherein{'sup': '1', 'Ris selected from methyl, ethyl, propyl, and butyl;'}{'sup': '2', 'Ris selected from hydrogen, halogen and cyano; and'}{'sup': '3', 'Ris selected from hydrogen, (S)-methyl, (S)-ethyl, (S)-propyl, and (S)-butyl;'}or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.3. The compound of claim 2 , wherein{'sup': '1', 'Ris selected from methyl and isopropyl;'}{'sup': '2', 'Ris selected from hydrogen, chlorine, bromine and cyano;'}{'sup': '3', 'Ris selected from hydrogen and (S)-methyl; and'}{'sup': 1', '2, 'each Xand Xis independently chlorine or fluorine;'}or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.4. The compound of claim 3 , wherein Ris methyl claim 3 , Ris cyano claim 3 , Ris (S)-methyl claim 3 , Xis chlorine claim 3 , and Xis fluorine;or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.8. The compound of claim 7 , wherein Ris F claim 7 , Ris H claim 7 , and Ris Cl claim 7 ,or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.9. The compound of claim 7 , wherein Ris F claim 7 , Ris a halogen claim 7 , and Ris Cl claim 7 ,or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.10. The compound of claim 7 , wherein Ris F claim 7 , Ris H claim 7 , and Ris F claim 7 ,or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.11. The compound of claim 7 ...

COMPOSITIONS AND METHODS FOR THE MODULATION OF SPECIFIC AMIDASES FOR N-ACYLETHANOLAMINES FOR USE IN THE THERAPY OF INFLAMMATORY DISEASES

The present invention regards compositions and methods for the modulation of amidases capable of hydrolysing N-acylethanolamines useable in the therapy of inflammatory diseases. In particular, the present invention regards a compound of general formula (I): enantiomers, diastereoisomers, racemes and mixtures, polymorphs, salts, solvates thereof, wherein: (a) R is a linear alkyl radical having 13 to 19 carbon atoms or alkenyl radical having 13 to 19 carbon atoms carrying a double bond; (b) X is 0 or S; (c) Y is a 2 or 3 carbon atom alkylene residue, optionally substituted with one or two groups equal or different from each other and selected from among the group consisting of: —CH, —CHOH, —COOCH, —COOH. Y may preferably be: —CH—CH—, —CH—CH—CH—, CH(CH)—CH—, —CH—CH(CH)—, —CH—C(CH)—, —CH—CH(CHOH)—, —CH—C((CHOH))—, —CH═CH—, —CH—CH(COOCH)—, —CH—CH(COOH)—, for use as a medicine. 2. A compound according to claim 1 , for use as an inhibitory modulator of the activity of the FAAH and NAAA enzymes.3. A compound according to claim 1 , for use as an anti-inflammatory.4. A compound according to claim 1 , for use in the treatment of neuro-immunogenic inflammatory processes at the level of peripheral organs and systems of the organism which support diseases such as a) the irritable bowel syndrome claim 1 , Crohn's disease claim 1 , coeliac disease; b) interstitial cystitis claim 1 , recurrent cystitis claim 1 , inflammations associated to chemotherapy treatments used in the treatment of bowel carcinoma; c) vulvodynia claim 1 , vestibulodynia claim 1 , vulvar vestibulitis; d) vaginitis of different aetiology; e) endometriosis lesions; f) chronic nonbacterial prostatitis claim 1 , benign prostatic hypertrophy; g) myasthenia gravis; h) arthropathies of traumatic or degenerative or immunological origin affecting the mobile and/or semimobile joints; i) the painful diseases of the intervertebral discs due to neo-innervation and neo-vascularisation of the cartilaginous tissue and of the ...

Method of producing n-phenyl-n'-phenylsulfonyl piperazine derivative and intermediate thereof

Disclosed is a salt and crystal of a 2-(oxazole-2-yl)phenol derivative which are the intermediate in the process of producing a N-phenyl-N′-phenylsulfonyl piperazine derivative. Further disclosed is a method of producing the salt and the crystal of the compound represented by Formula(I): wherein X is halogen; as well as a process of producing N-phenyl-N′-phenylsulfonyl piperazine derivative through the salt.

Heterocyclic compounds as immunomodulators

Disclosed are compounds of Formula (I), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.

THE NEW DERIVATIVES OF (Z)-1,2-DIPHENYLETHENE

The present invention relates to the new chemical compounds containing (Z)-1,2-diphenylethene moiety in the structures, particularly the new derivatives of cis-stilbene, the new derivatives of 4,5-diphenyl-1,3-oxazole, the new derivatives of 1-methyl-4,5-diphenyl-1H-imidazole and pharmaceutically acceptable salts thereof. The invention relates also to the application of aforementioned compounds as a microtubule-interfering agents (MIAs). The new derivatives, because of their potential antimitotic and antiangio-genic activity, can be used as ingredients in the preparations used in the treatment of cancer. 2. The application of a compounds of general formula 1 , wherein R , R , R , R , R , R , R , R , Rhave the above-mentioned meaning , as a microtubule-interfering agents in the preparations used in the treatment of cancer.4. The new compounds of the general formula 2 , wherein R , R , R , R , R , Rhave the above-mentioned meaning , being pharmaceutically acceptable salts.5. The application of a compounds of general formula 2 , wherein R , R , R , R , R , Rhave the above-mentioned meaning , as a microtubule-interfering agents in the preparations used in the treatment of cancer.7. The new compounds of the general formula 3 , wherein R , R , R , R , R , Rhave the above-mentioned meaning , being pharmaceutically acceptable salts.8. The application of a compounds of general formula 3 , wherein R , R , R , R , R , Rhave the above-mentioned meaning , as a microtubule-interfering agents in the preparations used in the treatment of cancer.9. The new compounds according to claim 4 , wherein pharmaceutically acceptable salts mean chlorides claim 4 , bromides claim 4 , phosphates claim 4 , hydrogen sulfates (VI) claim 4 , sulfates (VI) claim 4 , acetates claim 4 , citrates claim 4 , tartrates or lactates.10. The new compounds according to claim 7 , wherein pharmaceutically acceptable salts mean chlorides claim 7 , bromides claim 7 , phosphates claim 7 , hydrogen sulfates (VI) ...

HETEROCYCLIC COMPOUNDS AS IMMUNOMODULATORS

Disclosed are compounds of Formula (I), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections. 239-. (canceled)40. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Cy is phenyl claim 1 , 2 claim 1 ,3-dihydro-1 claim 1 ,4-benzodioxin-6-yl claim 1 , 2-fluorophenyl claim 1 , 2-fluoro-3-methoxyphenyl claim 1 , or 1-methyl-1H-indazol-4-yl.41. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R claim 1 , Rand Rare each independently selected from H claim 1 , Calkyl claim 1 , Ccycloalkyl claim 1 , Ccycloalkyl-Calkyl- claim 1 , Caryl claim 1 , Caryl-Calkyl claim 1 , 5-10 membered heteroaryl claim 1 , 4-10 membered heterocycloalkyl claim 1 , (5-10 membered heteroaryl)-Calkyl- claim 1 , (4-10 membered heterocycloalkyl)-Calkyl- claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , halo claim 1 , CN claim 1 , OH claim 1 , Calkoxy claim 1 , Chaloalkyl claim 1 , Chaloalkoxy claim 1 , NH claim 1 , —NH—Calkyl claim 1 , —N(Calkyl) claim 1 , NHOR claim 1 , C(O)R claim 1 , C(O)NRR claim 1 , C(O)OR claim 1 , OC(O)R claim 1 , OC(O)NRR claim 1 , NRC(O)R claim 1 , NRC(O)OR claim 1 , NRC(O)NRR claim 1 , C(═NR) R claim 1 , C(═NR) NRR claim 1 , NRC(═NR) NRR claim 1 , NRS(O)R claim 1 , NRS(O)R claim 1 , NRS(O)NRR claim 1 , S(O)R claim 1 , S(O)NRR claim 1 , S(O)R claim 1 , and S(O)NRR claim 1 , wherein each Ris independently selected from H claim 1 , Calkyl claim 1 , Calkoxy claim 1 , Ccycloalkyl claim 1 , Ccycloalkyl-Calkyl- claim 1 , Caryl claim 1 , Caryl-Calkyl claim 1 , 5-10 membered heteroaryl claim 1 , 4-10 membered heterocycloalkyl claim 1 , (5-10 membered heteroaryl)-Calkyl- claim 1 , and (4-10 membered heterocycloalkyl)-Calkyl- claim 1 , wherein the Calkyl claim 1 , Calkoxy claim 1 , Ccycloalkyl claim 1 , Ccycloalkyl-Calkyl- claim 1 , Caryl ...

PHOTOSENSITIVE COMPOUND, PHOTOSENSITIVE RESIN, AND PHOTOSENSITIVE COMPOSITION

A photosensitive compound represented by formula (1) or formula (2). (Chemical formula 1) (In formula (1) and formula (2), n is an integer of 1-3; Ris a linear or branched alkyl group having 1-6 carbon atoms or an alkylene group having 2-6 carbon atoms formed from two Rtogether; Ris —NRR; Rand Rare each independently a linear or branched alkyl group or alkenyl group having 1-6 carbon atoms, a linear or branched alkylene group having 2-6 carbon atoms formed by Rand Rtogether, or a linear or branched alkylene group or alkenylene group having 3-8 carbon atoms optionally containing an oxygen atom or nitrogen atom.) 19-. (canceled)12. A photosensitive resin formed by attaching the photosensitive compound according to to a polymer having a structure in which at least two repeating units derived from vinyl alcohol are linked together claim 10 , via an acetal bond in a pendant manner.14. The photosensitive resin according to claim 12 , wherein the polymer is a copolymer of vinyl alcohol and at least one species selected from the group consisting of vinyl acetate claim 12 , diacetoneacrylamide claim 12 , acrylamide claim 12 , acrylic acid claim 12 , and polyethylene glycol.15. The photosensitive resin according to claim 13 , wherein the polymer is a copolymer of vinyl alcohol and at least one species selected from the group consisting of vinyl acetate claim 13 , diacetoneacrylamide claim 13 , acrylamide claim 13 , acrylic acid claim 13 , and polyethylene glycol.16. A photosensitive composition comprising:{'claim-ref': {'@idref': 'CLM-00012', 'claim 12'}, 'the photosensitive resin according to ; and'}water.17. A photosensitive composition comprising:{'claim-ref': {'@idref': 'CLM-00013', 'claim 13'}, 'the photosensitive resin according to ; and'}water.18. A photosensitive composition comprising:{'claim-ref': {'@idref': 'CLM-00014', 'claim 14'}, 'the photosensitive resin according to .'} An aspect of the present invention relates to a novel photosensitive compound, to a novel ...

N-CYCLOBUTYL-THIAZOL-5-CARBOXAMIDES WITH NEMATICIDAL ACTIVITY

The present invention relates to compounds of the formula (I), in which the substituents are as defined in claim , which are suitable for use as nematicides. 3. The compound according to whereinB is phenyl which is unsubstituted or substituted by one or more R5;{'sub': 3', '2, 'R1 is selected from CFand CHF;'}R5 is independently selected from halogen, cyano, C1-C4-haloalkyl, C1-C4-haloalkoxy, C2-C6-haloalkenyl, 5- or 6-membered heterocycle or C3-C6-cycloalkyl wherein the heterocycle and the cycloalkyl are each optionally substituted by one or more substituents R6;R6 is independently selected from halogen, C1-C4-alkyl or C1-C4-haloalkyl.4. The compound according to whereinB is phenyl which is unsubstituted or substituted by one or more R5;R5 is independently selected from halogen, cyano, C1-C4-haloalkyl, C1-C4-haloalkoxy or C3-C6-cycloalkyl optionally substituted by one or more substituents R6;R6 is independently selected from halogen, C1-C4-alkyl or C1-C4-haloalkyl.5. The compound according to whereinB is phenyl which is unsubstituted or substituted by one or more R5;{'sub': 3', '2, 'R1 is selected from CFand CHF;'}R5 is independently selected from halogen or trifluoromethyl.8. The compound according to wherein the compound is selected fromrac-4-(trifluoromethyl)-N-[(1,2 cis)-2-[2-(trifluoromethyl)phenyl]cyclobutyl]thiazole-5-carboxamide;rac-(4-(trifluoromethyl)-N-[(1,2 cis)-2-[4-(trifluoromethyl)phenyl]cyclobutyl]thiazole-5-carboxamide;rac-N-[(1,2 cis)-2-[4-(trifluoromethoxy)phenyl]cyclobutyl]-4-(trifluoromethyl)thiazole-5-carboxamide;N-[(1 S,2S)-2-(4-chlorophenyl)cyclobutyl]-4-(trifluoromethyl)thiazole-5-carboxamide;N-[(1 S,2S)-2-(2-chloro-4-fluoro-phenyl)cyclobutyl]-4-(trifluoromethyl)thiazole-5-carboxamide;N-[(1 S,2S)-2-(2,4-difluorophenyl)cyclobutyl]-4-(trifluoromethyl)thiazole-5-carboxamide;N-[(1 S,2S)-2-(2,4-dichlorophenyl)cyclobutyl]-4-(trifluoromethyl)thiazole-5-carboxamide;4-(difluoromethyl)-N-[(1S,2S)-2-(2,4-difluorophenyl)cyclobutyl]thiazole-5- ...

DUAL-ACTING OXAZOLE ANTIHYPERTENSIVE AGENTS

In one aspect, the invention relates to compounds having the formula: 2. (canceled)5. The compound of claim 1 , where Ris propyl claim 1 , ethyl claim 1 , butyl claim 1 , or ethoxy.6. The compound of claim 1 , where Ris —CHSH claim 1 , —CHN(OH)C(O)H claim 1 , —CHC(O)NH(OH) claim 1 , —CH(OH)C(O)NH(OH) claim 1 , —CH(OH)COOH claim 1 , or —CHCOOH.7. The compound of claim 1 , where Ris —CH—S—C(O)CH claim 1 , —CH(OH)COOCH claim 1 , or —CHCOOCH.8. The compound of claim 1 , where Ris i-butyl claim 1 , —CH-furan-2-yl claim 1 , —CH-thiophen-3-yl claim 1 , benzyl claim 1 , 2-bromobenzyl claim 1 , 2-chlorobenzyl claim 1 , 2-fluorobenzyl claim 1 , 3-fluorobenzyl claim 1 , 4-fluorobenzyl claim 1 , 2-methylbenzyl claim 1 , or 2-trifluoromethylbenzyl.12. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.13. The pharmaceutical composition of further comprising a second therapeutic agent selected from the group consisting of diuretics claim 12 , βadrenergic receptor blockers claim 12 , calcium channel blockers claim 12 , angiotensin-converting enzyme inhibitors claim 12 , ATreceptor antagonists claim 12 , neprilysin inhibitors claim 12 , non-steroidal anti-inflammatory agents claim 12 , prostaglandins claim 12 , anti-lipid agents claim 12 , anti-diabetic agents claim 12 , anti-thrombotic agents claim 12 , renin inhibitors claim 12 , endothelin receptor antagonists claim 12 , endothelin converting enzyme inhibitors claim 12 , aldosterone antagonists claim 12 , angiotensin-converting enzyme/neprilysin inhibitors claim 12 , vasopressin receptor antagonists claim 12 , and combinations thereof.16. A method for treating hypertension or heart failure claim 1 , comprising administering to a patient a therapeutically effective amount of a compound of . This application claims the benefit of U.S. Provisional Application No. 61/227,473, filed on Jul. 22, 2009; the entire disclosure of which is incorporated herein by reference.1. Field of the ...

OXAZOLE COMPOUND AND PHARMACEUTICAL COMPOSITION

The present invention provides an oxazole compound represented by Formula (1), or a salt thereof: 1. A method for obtaining cells expressing phosphodiesterase (PDE) 4 , comprising:preparing a vector containing cDNA encoding human PDE4,introducing the vector into mammalian cells,cultivating the cells in a medium, andcollecting the cells.2. The method of claim 1 , wherein the cells are COS-7 cells.3. The method of claim 1 , wherein the vector is a plasmid vector.5. The method of claim 4 , wherein the disease is at least one selected from the group consisting of bronchial asthma claim 4 , chronic obstructive pulmonary disease claim 4 , dermatoses claim 4 , psoriasis claim 4 , toxic and allergic contact eczema claim 4 , atopic dermatitis claim 4 , alopecia areata claim 4 , learning claim 4 , memory claim 4 , and/or cognition disorders associated with Alzheimer's or Parkinson's diseases claim 4 , manic-depressive psychosis claim 4 , schizophrenia claim 4 , anxiety disorder claim 4 , systemic and local arthritic disorders claim 4 , knee osteoarthritis claim 4 , articular rheumatism claim 4 , gastrointestinal diffuse inflammation claim 4 , Crohn's disease and ulcerative colitis claim 4 , allergic and/or chronic immune-mediated inflammatory diseases in the upper respiratory tract claim 4 , allergic rhinitis/sinusitis claim 4 , chronic rhinitis/sinusitis claim 4 , and allergic conjunctivitis.6. The method of claim 4 , wherein Ris a phenyl group which has 1 to 3 substituents selected from the following (1-2) claim 4 , (1-3) claim 4 , (1-4) and (1-5):(1-2) unsubstituted or halogen-substituted lower alkoxy groups,(1-3) lower alkenyloxy groups,(1-4) lower alkynyloxy groups, and{'sub': '3-8', '(1-5) cyclo Calkyl lower alkoxy groups;'}{'sup': '2', 'Ris a phenyl group or a pyridyl group each of which may have 1 to 3 substituents selected from the group consisting of the following (2-2), (2-3), (2-4) and (2-5)(2-2) unsubstituted or halogen-substituted lower alkoxy groups,(2-3) ...

PROCESS FOR 4-METHYLOXAZOLE-5-CARBOXAMIDE

A process for the preparation of 4-methyl-oxazole-5-carboxamide, an intermediate in the synthesis of pyridoxine, by reacting lower alkyl 4-methyl-oxazole-5-carboxy-late with a molar excess of anhydrous, liquid ammonia. 1. A process for the preparation of 4-methyl-oxazole-5-carboxamide characterized by reacting lower alkyl 4-methyl-oxazole-5-carboxylate with a molar excess of anhydrous , liquid ammonia.2. The process of wherein the reaction is carried out in the presence of a catalyst selected from the group consisting of ammonium salts claim 1 , quaternary ammonium salts and alkali metal phosphates.3. The process of wherein the temperature is in the range of 10 to 50° C.4. The process of wherein the reaction is carried out under a pressure of 5 to 20 bara.5. The process of wherein the lower alkyl 4-methyl-oxazole-5-carboxylate is ethyl 4-methyl-oxazole-5-carboxylate.6. The process of wherein the catalyst is an ammonium halogenide salt claim 2 , preferably ammonium chloride.7. A process for the preparation of vitamin B(pyridoxine) and acid addition salts thereof claim 1 , characterized in that 4-methyl-oxazole-5-carboxamide obtained according to a process as claimed in is converted into pyridoxine or an acid addition salt thereof. The present invention is concerned with a novel process for the preparation of 4-methyloxazole-5-carboxamide (MOXA). This compound is a valuable intermediate in the synthesis of pyridoxine (vitamin B).Several processes for the manufacture of pyridoxine have already been described. A summary of the most important ones is to be found, e.g., in Ullmann's Encyclopedia of Industrial Chemistry, fifth edition, 1996, vol. A 27, p. 533ff. For the industrial synthesis of pyridoxine there is now used nearly exclusively the approach described by Kondratyeva, G. Y., Khim. Nauka Promst. 2, 666 (1957), in which approach the pyridine ring is obtained by a Diels-Alder reaction of oxazoles with maleic acid or its derivatives. A particularly preferred oxazole ...

PREPARATION OF FEBUXOSTAT

Processes for preparing febuxostat. 114.-. (canceled)15. A process for the preparation of crystalline Form III of febuxostat , comprising recrystallizing febuxostat from a solution in a combination of an ester solvent and a hydrocarbon solvent.16. The process of claim 15 , wherein an ester solvent comprises ethyl acetate claim 15 , n-propyl acetate claim 15 , isopropyl acetate claim 15 , n-butyl acetate claim 15 , or tertiary-butyl acetate.17. The process of claim 15 , wherein a hydrocarbon solvent comprises toluene claim 15 , xylene claim 15 , n-hexane claim 15 , n-heptane claim 15 , or cyclohexane.18. The process of claim 15 , wherein an ester solvent is ethyl acetate and a hydrocarbon solvent is n-hexane.1920.-. (canceled) Aspects of the present application relate to processes for the preparation of febuxostat. Further aspects relate to an intermediate in the processes. Aspects also relate to processes for the purification of an intermediate in the preparation of febuxostat, and processes for preparing a febuxostat crystalline polymorphic form.The drug compound having the adopted name “febuxostat” has a chemical name 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid, and has the structural formula shown as Formula I.Febuxostat is a xanthine oxidase inhibitor and is used for chronic management of hyperuricemia, in patients with gout. Febuxostat is the active ingredient in products sold under the trademark ULORIC®, as 40 and 80 mg tablets.U.S. Pat. No. 5,614,520 discloses febuxostat and its related compounds. The patent also discloses a process for its preparation, involving hydrolysis of ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate of Formula II. The intermediate of Formula II is prepared by reacting 3-cyano-4-isobutoxy benzothiamide with ethyl 2-chloroacetoacetate.Subsequent patents and articles disclose processes for the preparation of febuxostat. The disclosed processes also involve reaction of 3-cyano-4- ...

USP30 INHIBITORS

The application relates to phenyl- or naphthylsulfonamide derivatives of the structural formula (I). The compounds are described as inhibitors of USP30 (ubiquitin specific peptidase 30) useful for the treatment of conditions involving mitochondrial defects including neurodegenerative diseases such as Alzheimer's and Parkinson's or a neoplastic disease such as leukemia. 5. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris 3-7 membered cycloalkyl optionally substituted with one or more substituents selected from the group consisting of (C-C)alkyl claim 2 , (C-C)alkoxy claim 2 , (C-C)alkylthio claim 2 , hydroxyl claim 2 , halogen claim 2 , and halo(C-C)alkyl; phenyl optionally substituted with one or more substituents selected from the group consisting of halogen claim 2 , CN claim 2 , —COH claim 2 , —COMe claim 2 , (C-C)alkyl claim 2 , halo(C-C)alkyl claim 2 , (C-C)alkoxy claim 2 , and hydroxyl; 5-6 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of (C-C)alkyl claim 2 , halo(C-C)alkyl claim 2 , and (C-C)alkoxy;{'sub': 1', '4', '1', '4', '1', '4, '5-6 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of halogen, (C-C)alkyl, halo(C-C)alkyl, and (C-C)alkoxy; or adamantyl.'}6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris (C-C)alkyl optionally substituted with one or more substituents selected from the group consisting of halogen claim 5 , —CN claim 5 , hydroxyl claim 5 , (C-C)alkyl claim 5 , halo(C-C)alkyl claim 5 , (C-C)alkoxy claim 5 , halo(C-C)alkoxy claim 5 , and (C-C)alkylthio; 3-7 membered cycloalkyl optionally substituted with one or more substituents selected from the group consisting of halogen claim 5 , CN claim 5 , hydroxyl claim 5 , (C-C)alkyl claim 5 , halo(C-C)alkyl claim 5 , (C-C)alkoxy claim 5 , halo(C-C)alkoxy claim 5 , and (C-C)alkylthio; 5-6 ...

THERAPEUTIC SUBSTITUTED CYCLOPENTANES

Disclosed herein are compounds having formula (I) wherein a dashed line represents the presence or absence of a bond; Y is an organic acid functional group, or an amide or ester thereof; or Y is hydroxymethyl or an ester thereof; or Y is a tetrazolyl functional group; A is —(CH)—, cis-CHCH═CH—(CH)—, or —CHC═C—(CH)—, wherein 1 or 2 carbon atoms may be replaced by S or O; or A is —(CH)—Ar—(CH)—, wherein Ar is interarylene or heterointerarylene, the sum of m and o is 1, 2, 3, or 4, and wherein 1 —CH— may be replaced by S or O, and 1 —CH—CH— may be replaced by —CH═CH— or —C≡C—; Uand Uare independently selected from —H, ═O, —OH, —F, —Cl, and —CN; and B is aryl or heteroaryl, for use as acular hypotensive agent. 123.-. (canceled)26. The compound according to claim 24 , wherein B is substituted phenyl or pyridinyl.27. The compound according to claim 24 , wherein Uis —F.28. The compound according to claim 24 , wherein Uis —Cl.29. The compound according to claim 24 , wherein Uis —CN.32. The compound according to selected from the group consisting of:5-(3-(1R,2S,3R,5R)-5-fluoro-3-hydroxy-2-(phenylethynyl)cyclopentyl)propyl)thiophene-2-carboxylic acid;5-(3-(1R,2S,3R,5R)-5-chloro-3-hydroxy-2-(phenylethynyl)cyclopentyl)propyl)thiophene-2-carboxylic acid;Isopropyl 5-(3-(1R,2S,3R,5R)-5-chloro-3-hydroxy-2-(phenylethynyl)cyclopentyl)propyl)thiophene-2-carboxylate;5-(3-((1S,2S,3R,5R)-5-cyano-3-hydroxy-2-(phenylethynyl)cyclopentyl)propyl)thiophene-2-carboxylic acid;5-(3-((1R,2S,3R,5R)-5-chloro-2-((3,5-dichlorophenyl)ethynyl)-3-hydroxycyclopentyl)propyl)thiophene-2-carboxylic acid;5-(3-(1R,2S,3R,5R)-5-chloro-2-((3-ethylphenyl)ethynyl)-3-hydroxycyclopentyl)propyl)thiophene-2-carboxylic acid;5-(3-(1R,2S,3R,5R)-2-((3-(but-3-enyl)phenyl)ethynyl)-5-chloro-3-hydroxycyclopentyl)propyl)thiophene-2-carboxylic acid;5-(3-(1R,2S,3R,5R)-5-chloro-3-hydroxy-2-(thiophen-2-ylethynyl)cyclopentyl)propyl)thiophene-2-carboxylic acid;5-(3-(1R,2S,3R,5R)-5-chloro-3-hydroxy-2-(thiophen-3-ylethynyl)cyclopentyl) ...

NOVEL PROCESSES

The present invention provides novel processes for preparing compounds of formula (IV) and salts thereof 7. A process according to wherein X and Xare each independently chlorine.15. 6-(1H-Indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1 claim 1 ,3-oxazol-2-yl)-1H-indazole benzoate.16. A polymorph of 6-(1H-indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1 claim 1 ,3-oxazol-2-yl)-1H-indazole benzoate characterised in that it provides an XRPD pattern comprising peaks (° 2θ) at about 6.7 and/or about 8.7 and/or about 11.6 and/or about 12.9 and/or about 13.3 and/or about 16.2. The present invention is directed to novel processes for preparing compounds and salts thereof, which compounds are inhibitors of the activity or function of phosphoinositide 3′OH kinase isoform delta (PI3Kδ); novel intermediates; and a novel salt and polymorph thereof.International patent application PCT/EP2010/055666 (publication number WO2010/125082) describes compounds having the general formula (I):whereinR is 9- or 10-membered bicyclic heteroaryl wherein the 9- or 10-membered bicyclic heteroaryl contains from one to three heteroatoms independently selected from oxygen and nitrogen and is optionally substituted by Calkyl, Ccycloalkyl, halo, —CN or —NHSOR, or pyridinyl optionally substituted by one or two substituents independently selected from Calkyl, —OR, halo and —NHSOR;R and R, together with the nitrogen atom to which they are attached, are linked to form a 6- or 7-membered heterocyclyl wherein the 6- or 7-membered heterocyclyl optionally contains an oxygen atom or a further nitrogen atom and is optionally substituted by one or two substituents independently selected from Calkyl;R is hydrogen or methyl;R is hydrogen or Calkyl; andR and R are each independently Calkyl, or phenyl optionally substituted by one or two substituents independently selected from halo;and salts thereof.The examples of WO2010/125082 describe the preparation of 6-(1H-indol-4-yl)-4-(5-{[4-(1- ...

THERAPEUTIC AGENT AND PREVENTIVE AGENT FOR DEMYELINATING DISEASE

The object of the present invention is to provide a novel therapeutic or preventive agent for demyelinating disease. The present invention is a therapeutic or preventive agent for demyelinating disease, containing as an active ingredient a 2-phenylthiazole compound represented by Formula (I) 2. The therapeutic or preventive agent according to claim 1 , wherein the demyelinating disease is associated with hyperuricemia or gout;3. The therapeutic or preventive agent according to claim 1 , wherein the demyelinating disease is associated with impaired renal function;4. The therapeutic or preventive agent according to claim 1 , wherein the demyelinating disease is multiple sclerosis;5. The therapeutic or preventive agent according to claim 1 , wherein the 2-phenylthiazole compound represented by the above-mentioned Formula (I) is 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid or a pharmaceutically acceptable salt thereof. The present invention relates to a therapeutic agent and a preventive agent for demyelinating disease and to a therapeutic method and a preventive method using the same.Furthermore, the present invention relates to a therapeutic agent and a preventive agent for multiple sclerosis and to a therapeutic method and a preventive method using the same.Demyelinating disease is a kind of neurological disorders that is caused by damage to myelin sheath of myelinated axon; the damage to myelin sheath reduces nerve conduction velocity, which causes various neurological symptoms. Multiple sclerosis (MS), which is a representative disease of demyelinating disease, is a kind of autoimmune disease and has multifocal demyelinating lesions generated mainly in white matter such as the optic nerve, cerebrum, cerebellum and brainstem. Visual impairment, weakness, numbness, dizziness, fatigue, shivering and dysuria are the common symptoms. Usually the disease exhibits relapse and remitting phase and gradually progresses leading to the severe disability ...

OINTMENT CONTAINING AN OXAZOLE COMPOUND

An ointment is provided. The ointment stably comprises an oxazole compound that has specific inhibitory activity against PDE4 and that is represented by the following formula (11). The ointment can be efficiently absorbed into the skin. 2. The ointment according to claim 1 , comprising the oxazole compound dissolved in a base component.3. The ointment according to claim 2 , wherein the base component comprises a solvent for dissolving the oxazole compound in the solvent claim 2 , and an ointment base for dispersing or dissolving the solvent in the ointment base.4. The ointment according to claim 3 , wherein the ointment base comprises a hydrocarbon.5. The ointment according to claim 3 , wherein the solvent comprises a polar compound that is a liquid at room temperature.6. The ointment according to claim 3 , wherein the ointment base is an ointment base for dispersing the solvent in the ointment base claim 3 , and the solvent in the form of droplets claim 3 , in which the oxazole compound is dissolved claim 3 , is dispersed in the ointment base.7. The ointment according to claim 3 , wherein the ointment base comprises at least beeswax.8. The ointment according to claim 7 , wherein the beeswax is not chemically bleached.9. The ointment according to claim 1 , for use in the treatment and/or prevention of eczema and dermatitis. This application is a continuation of U.S. application Ser. No. 16/064,618 filed Jun. 21, 2018 which is a National Stage of International Application No. PCT/JP2016/088843 filed Dec. 27, 2016, claiming priority based on Japanese Patent Application No. 2015-256784 filed Dec. 28, 2015, the entire disclosures of which are incorporated herein by reference.The present invention relates to an ointment comprising an oxazole compound.PTL 1 and 2 report an oxazole compound having specific inhibitory activity against phosphodiesterase 4 (PDE4) and a method for producing the oxazole compound. PDE4 is predominant in inflammatory cells. Inhibition of PDE4 ...

HETEROCYCLIC COMPOUNDS AS IMMUNOMODULATORS

Disclosed are compounds of Formula (I), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections. 335.-. (canceled)36. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof claim 1 , and at least one pharmaceutically acceptable carrier or excipient.37. A method of inhibiting PD-1/PD-L1 interaction claim 1 , said method comprising administering to a patient a compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof.38. A method of treating a disease or disorder associated with inhibition of PD-1/PD-L1 interaction claim 1 , said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof.39. A method of enhancing claim 1 , stimulating and/or increasing the immune response in a patient claim 1 , said method comprising administering to the patient in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof. The present application is concerned with pharmaceutically active compounds. The disclosure provides compounds as well as their compositions and methods of use. The compounds modulate PD-1/PD-L1 protein/protein interaction and are useful in the treatment of various diseases including infectious diseases and cancer.The immune system plays an important role in controlling and eradicating diseases such as cancer. However, cancer cells often develop strategies to evade or to suppress the immune system in order to favor their growth. One such mechanism is altering the expression of co-stimulatory and co-inhibitory molecules expressed on immune cells (Postow et al, J. Clinical Oncology 2015, 1-9). ...

Process for conducting organic reactions in a standalone and affordable laboratory scale solar photo thermochemical reactor

A process conducts organic reactions in a standalone laboratory scale solar photo thermo chemical reactor. For organic reactions require elevated temperature, light and mechanical agitation, all three energy forms can be simultaneously derived from solar radiation. Organic synthesis, such as bromination of toluene derivatives (benzylic bromination), bromination of cyclic acyclic hydrocarbon and oxidative cyclization of N-phenylethyl benzamide through bromination were successfully conducted in such reactors.

PROCESS FOR THE PREPARATION OF FEBUXOSTAT POLYMORPHS

The present invention relates to polymorphic forms of Febuxostat and processes for the preparation of polymorphic forms of Febuxostat. 1. A process for the preparation of crystalline Form-K of Febuxostat comprising the steps of:a) dissolving Febuxostat in an ester solvent,b) removing the solvent,c) adding hydrocarbon solvent, andd) isolating Febuxostat crystalline Form-K.2. The process according to claim 1 , wherein the ester solvent is ethyl acetate.3. The process according to claim 1 , wherein the hydrocarbon solvent is selected from cyclohexane or toluene.4. A process for the preparation of crystalline Form-K of Febuxostat comprising the steps of:a) dissolving Febuxostat in an ester solvent at 50-80° C.,b) filtering the reaction mass,c) maintaining the filtrate for 30-120 minutes at same temperature,d) removing the solvent,e) adding hydrocarbon solvent, andf) isolating Febuxostat crystalline Form-K.5. The process according to claim 4 , wherein the ester solvent is ethyl acetate.6. The process according to claim 4 , wherein the hydrocarbon solvent is selected from cyclohexane or toluene.7. A process for the preparation of crystalline Form-K of Febuxostat comprising the steps of:a) dissolving Febuxostat in a mixture of an ester and hydrocarbon solvent,b) partially removing the solvent, andc) isolating Febuxostat crystalline Form-K.8. The process according to claim 7 , wherein ester solvent is ethyl acetate.9. The process according to claim 7 , wherein hydrocarbon solvent is selected from cyclohexane or toluene.10. The process according to claim 7 , wherein the mixture of solvents is a mixture of ethyl acetate and toluene.11. A process for the preparation of crystalline Form-K of Febuxostat comprising the steps of:a) dissolving Febuxostat in an ester solvent,b) evaporating the solvent by agitated thin film dryer (ATFD), andc) isolating Febuxostat crystalline Form-K.12. The process according to claim 11 , wherein the ester solvent is ethyl acetate.13. A process for ...

HISTONE DEACETYLASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF

Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, compositions thereof, and methods of their use. 4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris fluoro or chloro.5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein Ris fluoro.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —C(O)NH(OH).7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —N(OH)C(O)Rwherein Ris hydrogen.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —N(OH)C(O)Rwherein Ris methyl.9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris chosen from aryl and heteroaryl claim 1 , each of which is optionally substituted with one or two groups independently chosen from lower alkyl claim 1 , halo claim 1 , hydroxyl claim 1 , and lower alkoxy.10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof claim 9 , wherein Ris chosen from aryl optionally substituted with one or two groups independently chosen from lower alkyl claim 9 , halo claim 9 , hydroxyl claim 9 , and lower alkoxy.11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein Ris chosen from phenyl claim 10 , 2-methylphenyl claim 10 , and 3-fluoro-2-methylphenyl.12. The compound of claim 11 , or a pharmaceutically acceptable salt thereof claim 11 , wherein Ris phenyl.13. The compound of claim 9 , or a pharmaceutically acceptable salt thereof claim 9 , wherein Ris chosen from heteroaryl optionally substituted with one or two groups independently chosen from lower alkyl claim 9 , halo claim 9 , hydroxyl claim 9 , and lower alkoxy.14. The compound of claim 13 , or a pharmaceutically acceptable salt thereof claim 13 , wherein Ris chosen from pyridin-3-yl and 6-oxo-1 claim 13 ,6-dihydropyridin-2-yl claim 13 ...

PHOTO-DECOMPOSABLE COMPOUND, PHOTORESIST COMPOSITION INCLUDING THE SAME, AND METHOD OF MANUFACTURING INTEGRATED CIRCUIT DEVICE

A photo-decomposable compound, a photoresist composition, and a method of manufacturing an IC device, the compound generating acid upon exposure and acts as a quenching base that neutralizes acid in an unexposed state and being represented by Formula 1: 2. The photo-decomposable compound as claimed in claim 1 , wherein Ris a monocyclic aromatic hydrocarbon group including the nitrogen atom.4. The photo-decomposable compound as claimed in claim 1 , wherein Ris a condensed aromatic hydrocarbon group including the nitrogen atom.6. The photo-decomposable compound as claimed in claim 1 , wherein Yis a C1 to C5 substituted or unsubstituted alkylene group claim 1 , a C5 to C20 divalent monocyclic or condensed alicyclic hydrocarbon group claim 1 , or a C5 to C20 divalent monocyclic or condensed aromatic hydrocarbon group.7. The photo-decomposable compound as claimed in claim 1 , wherein:{'sup': 'a', 'sub': 2', 'm, 'Yis —(CH)—, and'}m is an integer of 1 to 5.9. The photo-decomposable compound as claimed in claim 1 , wherein A is a sulfonium cation claim 1 , an iodonium cation claim 1 , or an ammonium cation.10. The photo-decomposable compound as claimed in claim 1 , wherein the compound generates acid having an acid dissociation constant (pKa) of 1 to 10 upon exposure.12. The photoresist composition as claimed in claim 11 , wherein:the PAG generates a first acid having a first acid dissociation constant (pKa) upon exposure,the photo-decomposable compound generates a second acid having a second pKa upon exposure, andthe second pKa is higher than the first pKa.13. The photoresist composition as claimed in claim 11 , wherein Ris a monocyclic or condensed aromatic hydrocarbon group including the nitrogen atom.15. The photoresist composition as claimed in claim 11 , wherein:{'sup': 'a', 'sub': 2', 'm, 'Yis a divalent group represented by —(CH)—, and'}m is an integer of 1 to 5.17. The method as claimed in claim 16 , wherein:forming the photoresist film includes coating the feature ...

Biaryl-propionic acid derivatives and their use as pharmaceuticals

The present invention relates to compounds of the formula I, 2. A compound of the formula I claim 1 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein R2 is Hydrogen.4. A compound of the formula I claim 1 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein{'sub': 3', '4', '1', '3, 'Gand Gare —C(R10)= and —C(R11)=, wherein R10 and R11 form a 5 or 6 membered saturated carbocycle or heterocycle with one or two oxygen atoms; which is optionally mono or disubstituted by halogen and or (C-C)-alkyl.'}6. A compound of the formula I as claimed in or a physiologically acceptable salt thereof or a physiologically acceptable solvate of any of them for use as a pharmaceutical.7. A pharmaceutical composition claim 1 , which comprises at least one compound of the formula I as claimed in or a physiologically acceptable salt thereof or a physiologically acceptable solvate of any of them and a pharmaceutically acceptable carrier.8. Use of a compound of the formula I as claimed in or a physiologically acceptable salt thereof or a physiologically acceptable solvate of any of them for the manufacture of a medicament for the treatment of heart failure claim 1 , congestive heart failure claim 1 , cardiomyopathy claim 1 , myocardial infarction claim 1 , left ventricular dysfunction claim 1 , cardiac hypertrophy claim 1 , valvular heart diseases claim 1 , hypertension claim 1 , atherosclerosis claim 1 , peripheral arterial occlusive disease claim 1 , restenosis claim 1 , vasvular permeability disorders claim 1 , treatment of edema claim 1 , thrombosis claim 1 , rheumatoid arthritis claim 1 , ...

Biaryl-Propionic Acid Derivatives and their Use as Pharmaceuticals

The present invention relates to compounds of the formula I, 2. A compound of the formula I claim 1 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein R2 is Hydrogen.3. A compound of the formula I claim 1 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , whereinR is Hydrogen, methyl or ethyl;{'sub': 3', '2', '2', '3', '3, 'R1 is H, methyl, ethyl, CF, —CH-cyclopropyl or —CH—C(CH);'}R2 is Hydrogen;R4 is H or O-methyl;{'sub': 3', '1', '6, 'R5 is H F, Cl, CF, (C-C)-alkyl, cyclopropyl;'}{'sub': '3', 'R8 is H, F, Cl, methyl, O-methyl, CF3 or OCF;'}{'sub': 2', '2', '3', '3, 'R9 is H, F, Cl, OH, O-propyl, CHOH, CO—NH, methyl, O-methyl, CFor OCF;'}{'sub': 2', '2', '3', '3, 'R10 is H, F, Cl, OH, i-propyl, t-butyl, CHOH, CO—O-methyl, SO-methyl, CN, methyl, O-methyl, CFor OCF;'}{'sub': 2', '2', '3, 'R11 is H, F, Cl, OH, O-methyl, O-i-propyl, CHOH, CO-methyl, CO—N(methyl), CO-pyrrolidin, CO—O-methyl, CN, methyl or OCF.'}4. A compound of the formula I claim 1 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein{'sub': 3', '4', '1', '3, 'Gand Gare —C(R10)= and —C(R11)=, wherein R10 and R11 form a 5 or 6 membered saturated carbocycle or heterocycle with one or two oxygen atoms; which is optionally mono- or disubstituted by halogen and or (C-C)-alkyl.'}6. A compound of the formula I claim 1 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically ...

MODULATORS OF C3A RECEPTORS

Heterocyclic compounds that modulate C3a receptors and their use in the treatment or prevention of inflammatory diseases, infectious diseases, cancers, metabolic disorders, obesity, type 2 diabetes, metabolic syndrome and associated cardiovascular diseases are described. The use of the compounds in stimulating or suppressing an immune response is also described together with pharmaceutical compositions comprising the compounds or their pharmaceutically acceptable salts. 8. A compound according to wherein Ris COH.9. A compound according to wherein Ris selected from hydrogen claim 1 , —Calkyl claim 1 , —Calkenyl claim 1 , —Ccycloalkyl claim 1 , cycloalkenyl claim 1 , aryl claim 1 , and 5 or 6 membered heterocyclyl and heteroaryl.10. A compound according to wherein Ris hydrogen.11. A compound according to wherein Ris selected from methyl claim 9 , ethyl claim 9 , propyl claim 9 , isopropyl claim 9 , cyclohexyl claim 9 , cyclohexenyl claim 9 , cyclohexadienyl and phenyl.12. A compound according to wherein Ris selected from hydrogen claim 1 , —CH claim 1 , cyclohexyl claim 1 , phenyl claim 1 , —(CH)NHC(═NH)NH claim 1 , —CH—CONH claim 1 , —CHCOH claim 1 , —CHSH claim 1 , —(CH)CONH claim 1 , —(CH)COH claim 1 , —CH(4-imidazolyl) claim 1 , —CH(CH)CHCH claim 1 , —CHCH(CH) claim 1 , —(CH)NH claim 1 , —(CH)SCH claim 1 , —CHPh claim 1 , —CHOH claim 1 , —CH(CH)OH claim 1 , —CH(3-indolyl) claim 1 , —CH(4-hydroxyphenyl) claim 1 , —CH(CH)and —(CH)cyclohexyl.13. A compound according to wherein Ris selected from —CHCH(CH)and —CH(CH)CHCH.14. A compound according to wherein Ris selected from —NHC(O)R claim 1 , —NHC(O)R claim 1 , —NHC(O)NHRand —NHSOR.15. A compound according to wherein Ris selected from Calkyl claim 14 , cycloalkyl claim 14 , cycloalkenyl claim 14 , aryl claim 14 , heterocyclyl claim 14 , heteroaryl claim 14 , —CHcycloalkyl claim 14 , —CHcycloalkenyl claim 14 , —CHaryl claim 14 , —CHheterocyclyl claim 14 , —CHheteroaryl and —CH(CH)aryl claim 14 , wherein each cycloalkyl ...

ANTIVIRALS AGAINST MOLLUSCUM CONTAGIOSUM VIRUS

This invention provides compounds of formulas (I)-(XIV) as defined in the specification, and pharmaceutical compositions comprising the same, and methods of inhibiting, treating, or abrogating a molluscum contagiosum virus infection in a subject using compounds or compositions of the invention: 37-. (canceled)8. The compound of claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , and Rare each independently H claim 2 , halo claim 2 , cyano claim 2 , nitro claim 2 , CF claim 2 , or SONH.9. The compound of claim 1 , wherein Y is pyridine claim 1 , pyrimidine claim 1 , pyrazine claim 1 , indole claim 1 , indolizine claim 1 , benzimidazole claim 1 , 1 claim 1 ,3-dihydrobenzimidazol-2-one claim 1 , or indazole.1118-. (canceled)2023-. (canceled)2527-. (canceled)28. The compound of claim 24 , wherein R claim 24 , R claim 24 , R claim 24 , R claim 24 , R claim 24 , R claim 24 , R claim 24 , R claim 24 , R claim 24 , R claim 24 , R claim 24 , R claim 24 , and Rare each independently H claim 24 , halo claim 24 , cyano claim 24 , nitro claim 24 , CF claim 24 , or SONH.29. (canceled)3137-. (canceled)38. The compound of claim 1 , wherein Ris H or C-Calkyl.39. (canceled)40. The compound of claim 1 , wherein said compond is at least one selected from the group consisting of:5-[(2-benzyloxyphenyl)methylamino]-1,3-dihydrobenzimidazol-2-one,5-[[2-[(4-chlorophenyl)methoxy]phenyl]methylamino]-1,3-dihydrobenzimidazol-2-one,5-[[2-[(2-chlorophenyl)methoxy]phenyl]methylamino]-1,3-dihydrobenzimidazol-2-one,5-[[2-[(4-fluorophenyl)methoxy]phenyl]methylamino]-1,3-dihydrobenzimidazol-2-one,5-[(2-benzyloxy-5-bromo-phenyl)methylamino]-1,3-dihydrobenzimidazol-2-one,5-[[5-chloro-2-[(2-fluorophenyl)methoxy]phenyl]methylamino]-1,3-dihydrobenzimidazol-2-one,N-[(2-benzyloxyphenyl)methyl]-1H-indazol-5-amine,4-[[5-bromo-2-[(4-fluorophenyl)methoxy]phenyl]methylamino]phenol,4-[(2-benzyloxy-5-chloro-phenyl)methyl amino]benzene sulfonamide,4-[[2-[( ...

NONPEPTIDE HIV-1 PROTEASE INHIBITORS

Novel compounds and compositions for treating patients in need of relief from HIV, AIDS and AIDS-related diseases are described. Methods for treating HIV, AIDS, and AIDS-related diseases using the compounds described herein are also described. 171-. (canceled)73. The compound of claim 72 , wherein Rand Xtogether with the attached nitrogen form an optionally substituted heterocycle.74. The compound of claim 72 , wherein Ris C-Calkyl or cycloalkyl.75. The compound of claim 72 , wherein R is an optionally substituted heteroaryl.76. The compound of claim 72 , wherein Ris optionally substituted aryl.77. The compound of wherein Xis SO; and Ris optionally substituted aryl.78. The compound of claim 72 , wherein Ris branched alkyl.79. The compound of claim 72 , wherein Xis optionally substituted alkylene; and Ris optionally substituted aryl.80. The compound of wherein R claim 72 , Rand Xand the attached nitrogen are taken together to form an optionally substituted heterocycle.81. A pharmaceutical composition comprising a compound of ; and one or more pharmaceutically acceptable carriers claim 72 , diluents claim 72 , or excipients claim 72 , or a combination thereof. This application claims priority under 35 U.S.C §119(e) to U.S. Provisional Application Ser. No. 61/077,343, filed on Jul. 1, 2008, the disclosure of which is incorporated by reference in its entirety.This invention pertains to the field of non-peptide inhibitors of HIV protease enzymes and their use in the treatment of HIV infections.The AIDS epidemic is one of the most challenging problems in medicine in the 21st century. A retrovirus designated human immunodeficiency virus (HIV) is the etiological agent of the complex disease that includes progressive destruction of the immune system (acquired immune deficiency syndrome; AIDS) and degeneration of the central and peripheral nervous system. This virus was previously known as LAV, HTLV-III, or ARV. A common feature of retrovirus replication is the extensive post ...

BIS-(ARYL/HETEROARYL)-METHYLENE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND THEIR USE FOR TREATING CANCER

The present disclosure relates to novel compounds having vitamin D receptor agonist and histone deacetylase inhibitory efficacy as well as methods for reducing or inhibiting the proliferation of cancer cells or for treating cancer. 3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A and B are each independently a phenyl claim 1 , a 5-6 membered heteroaryl or a 8 to 10 membered bicyclic heteroaryl.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein X is O and Y is O or NR10(CO).5. The compound claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein W is OH.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R1 is an alkyl or cycloalkyl and R2 is hydrogen claim 1 , an alkyl or cycloalkyl.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R3 and R4 are independently hydrogen claim 1 , an alkyl.9. A method for treating cancer comprising administering to a patient in need thereof an effective amount of at least one compound or a pharmaceutically acceptable salt thereof claim 1 , as defined in .10. (canceled)11. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof claim 1 , as defined in claim 1 , and a pharmaceutically acceptable carrier.12. The method of claim 9 , wherein said cancer is responsive to the inhibition of a histone deacetylase (HDAC).14. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein A and B are both a phenyl.15. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein A is a 5-6 membered heteroaryl and B is a phenyl.16. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein X and Y are both O.17. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein R1 is an alkyl and R2 is hydrogen.18. The compound of or a pharmaceutically ...

Method for Producing Oxazole Compound

An object of the present invention is to provide a novel method for producing an oxazole compound. The invention relates to a method for producing a compound represented by formula (1): wherein Ris lower alkyl group or halogen substituted lower alkyl group, Ris lower alkyl group, Ris lower alkyl group, Ris lower alkyl group, halogen substituted lower alkyl group or a group represented by formula: —CYCOOR, wherein Y is a halogen atom, Ris an alkali metal atom or lower alkyl group, Aris phenyl group substituted with lower alkyl group, etc., or pyridyl group substituted with lower alkyl group, etc., X, Xand Xare the same or different and are halogen atoms, Xis a leaving group, and M is an alkali metal atom. 2. The compound according to claim 1 , wherein in formula (12) claim 1 , Ris methyl or difluoromethyl group claim 1 , and Ris methyl claim 1 , isopropyl claim 1 , or isobutyl group. The present invention relates to a novel method for producing an oxazole compound.Patent Literature 1 reports an oxazole compound that exhibits a specific inhibitory activity against phosphodiesterase 4 (PDE4). Patent Literature 1 discloses a method for producing an oxazole compound. It indicates, as a typical method thereof, Reaction Scheme 1 to Reaction Scheme 12.Among these, Reaction Scheme 10 discloses that compound (14) having an oxazole ring is produced by reacting dihaloketone compound (12) (specifically, 1,3-dichloro-2-propanone) with amide compound (13); and that primary amine compound (5a) is produced by reacting compound (16) having a phthalimide group with hydrazine (17).However, because the starting material dihaloketone compound (12) exhibits strong stimulant and tearing properties; and, furthermore, because hydrazine (17) has a risk of explosion during the processes of concentration and dehydration, it is preferable to avoid the use thereof for the health and safety of the people involved in its production.Furthermore, in the method for producing the oxazole compound ...

3-HETEROAROYLAMINO-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PHARMACEUTICALS

The present invention relates to compounds of the formula I, 111-. (canceled)14. A compound of the formula I claim 12 , in any of its stereoisomeric forms claim 12 , or a physiologically acceptable salt thereof claim 12 , or a physiologically acceptable solvate thereof claim 12 , as claimed in claim 12 , wherein{'sup': 30', '32, 'sub': u', '2u, 'Ris R—CH—, wherein u is independently 0 or 1;'}{'sup': 32', '33', '33', '1, 'sub': 1', '6', '3', '7', '1', '6', '1', '4', '2', '2', '1', '6', 'm', '2', '2', '1', '4', '2', '1', '4', '2', '2', '1', '6', '1', '6', '1', '4', '1', '4', '2, 'Ris selected from the group consisting of phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle containing one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and bonded via a ring carbon atom, and wherein the phenyl and the heterocycle are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C-C)-alkyl, (C-C)-cycloalkyl, HO—, (C-C)-alkyl-O—, R—O—, R—(C-C)-alkyl-O—, —O—CH—O—, —O—CF—O—, (C-C)-alkyl-S(O)—, HN—S(O)—, (C-C)-alkyl-NH—S(O)—, di((C-C)-alkyl)N—S(O)—, HN—, (C-C)-alkyl-NH—, di((C-C)-alkyl)N—, Het, (C-C)-alkyl-C(O)—NH—, Ar—C(O)—NH—, (C-C)-alkyl-S(O)—NH— and NC—;'}{'sup': '33', 'sub': 1', '6', '3', '7', '1', '6', '1', '6', 'm', '2', '2', '1', '4', '2', '1', '4', '2, 'Ris selected from the group consisting of phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle containing one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and bonded via a ring carbon atom, and wherein the phenyl and the heterocycle are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C-C)-alkyl, (C-C)-cycloalkyl, HO—, (C-C)-alkyl-O—, (C-C)-alkyl-S(O)—, HN—S(O)—, (C-C)-alkyl-NH—S(O)—, di((C-C)-alkyl)N—S(O)— ...

ORGANIC LUMINOGENS

Small molecule compounds having aggregation-induced emission (AIE) characteristics. The compounds include organic, aromatic salts having anion-π interactions. In some embodiments, the anion-πinteractions can include heavy-atom-anion-π interactions. The heavy atom anions can include bromine or iodide, for example. The compounds can be water-soluble. The compounds can be useful as probes for bioimaging, as room temperature luminogens for electroluminescent devices, and white organic light-emitting applications. 4. The compound of claim 1 , wherein the compound is water soluble.5. The compound of claim 4 , wherein the compound includes at least one charge.6. The compound of claim 1 , wherein the compound has fluorescence properties when in a solid state.7. The compound of claim 1 , wherein X is Br or I.8. The compound of claim 7 , wherein the compound has at least one of fluorescence and phosphorescence properties when in a solid state.9. The compound of claim 8 , wherein the compound provides white light emission in thin films.10. A polymer comprising the compound of 9 as an additive claim 8 , wherein the polymer exhibits white light emission.11. The polymer of claim 10 , wherein the polymer is suitable for use in 3D printing.12. The compound of claim 1 , wherein the compound further comprises a donor group and an acceptor group.13. A fluorescence imaging method claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00012', 'claim 12'}, 'contacting a target cell with the compound of to obtain a contacted target cell; and'}conducting fluorescence imaging of the contacted target cell in far red and near infrared spectral regions.14. A method of cellular imaging comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting a target cell with the compound according to ; and'}detecting a presence or absence of a target of interest in the target cell using an imaging method.15. The method of claim 14 , wherein the target of interest in the target cell comprises at ...

(2R,4R)-5-(5'-CHLORO-2'-FLUOROBIPHENYL-4-YL)-2-HYDROXY-4-[(5-METHYLOXAZOLE-2-CARBONYL)AMINO]PENTANOIC ACID

In one aspect, the invention relates to a compound of the structure: 2. (2R ,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxy-4-[(5-methyl-oxazole-2-carbonyl)amino]pentanoic acid.3. A crystalline form of (2R ,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxy-4-[(5-methyl-oxazole-2-carbonyl)amino]pentanoic acid.4. The crystalline form of claim 3 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 8.48±0.20 claim 3 , 14.19±0.20 claim 3 , 17.03±0.20 claim 3 , 21.15±0.20 claim 3 , and 25.41±0.20.5. The crystalline form of claim 3 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 7.51±0.20 claim 3 , 8.48±0.20 claim 3 , 14.19±0.20 claim 3 , 17.03±0.20 claim 3 , 17.62±0.20 claim 3 , 17.87±0.20 claim 3 , 20.59±0.20 claim 3 , 21.15±0.20 claim 3 , 21.88±0.20 claim 3 , 24.45±0.20 claim 3 , 24.78±0.20 claim 3 , 25.41±0.20 claim 3 , 25.67±0.20 claim 3 , 27.67±0.20 claim 3 , and 28.22±0.20.6. The crystalline form of claim 5 , wherein the crystalline form is further characterized by having one or more additional diffraction peaks at 2θ values selected from 16.09±0.20 claim 5 , 18.70±0.20 claim 5 , 19.21±0.20 claim 5 , 19.40±0.20 claim 5 , 21.64±0.20 claim 5 , 22.25±0.20 claim 5 , 26.43±0.20 claim 5 , 28.55±0.20 claim 5 , 30.73±0.20 claim 5 , 31.10±0.20 claim 5 , 32.64±0.20 claim 5 , 33.14±0.20 claim 5 , and 34.46±0.20.7. The crystalline form of claim 3 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern in which the peak positions are substantially in accordance with the peak positions of the pattern shown in .8. The crystalline form of claim 3 , wherein the crystalline form is characterized by a differential scanning calorimetry trace recorded at a heating rate of 10° C. per minute which shows a maximum in endothermic heat flow at a temperature between about 165° C. and 169° C.9. The ...

PACKAGING SOLUTIONS

A packaging system for the storage of an ophthalmic device is disclosed. The packaging system comprises a sealed container containing one or more unused ophthalmic devices immersed in an aqueous packaging solution comprising one or more hydrophilic polymers or copolymers comprising hydrophilic units and endcapped with a hydrophobic end group and a hydrophilic end group, wherein the solution has an osmolality of at least about 200 mOsm/kg, a pH of about 6 to about 9 and is heat sterilized. 1. A packaging system for the storage of an ophthalmic device comprising a sealed container containing one or more unused ophthalmic devices immersed in an aqueous packaging solution comprising one or more hydrophilic polymers or copolymers comprising hydrophilic units and endcapped with a hydrophobic end group and a hydrophilic end group , wherein the solution has an osmolality of at least about 200 mOsm/kg , a pH of about 6 to about 9 and is heat sterilized.2. The packaging system of claim 1 , wherein the ophthalmic device is a contact lens.3. The packaging system of claim 1 , wherein the hydrophilic units are derived from at least one ethylenically unsaturated polymerizable hydrophilic monomer.4. The packaging system of claim 3 , wherein the at least one ethylenically unsaturated polymerizable hydrophilic monomer is selected from the group consisting of an acrylamide claim 3 , an acetamide claim 3 , a formamide claim 3 , a cyclic lactam claim 3 , a (meth)acrylated alcohol claim 3 , a (meth)acrylated poly(alkyleneoxy) claim 3 , an ethylenically unsaturated carboxylic acid claim 3 , a hydrophilic vinyl carbonate claim 3 , hydrophilic vinyl carbamate claim 3 , hydrophilic oxazolone monomer claim 3 , and mixtures thereof.5. The packaging system of claim 1 , wherein the one or more hydrophilic polymers or copolymers are endcapped with a hydrophilic group selected from the group consisting of an —OH and —CN.6. The packaging system of claim 1 , wherein the one or more hydrophilic ...

THERAPEUTIC OR PROPHYLACTIC AGENT FOR TUMOR LYSIS SYNDROME

The purpose of the present invention is to provide a novel therapeutic or prophylactic agent for tumor lysis syndrome. The present invention is a therapeutic or prophylactic agent for tumor lysis syndrome, which comprises a 2-phenylthiazole compound represented by formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient. 2. The therapeutic or prophylactic agent according to claim 1 , wherein the tumor lysis syndrome is a tumor lysis syndrome in a high-risk patient.3. The therapeutic or prophylactic agent according to claim 1 , wherein the tumor lysis syndrome is a tumor lysis syndrome in an intermediate-risk patient.4. The therapeutic or prophylactic agent according to claim 1 , wherein the tumor lysis syndrome is a tumor lysis syndrome in a low-risk patient.5. The therapeutic or prophylactic agent according to claim 1 , wherein the tumor lysis syndrome is a tumor lysis syndrome involves hyperuricemia caused by chemotherapy or radiotherapy for malignant tumor.6. The therapeutic or prophylactic agent according to claim 1 , wherein the tumor lysis syndrome is a tumor lysis syndrome which occurs without being caused by antitumor therapy and in which hyperuricemia and reduced renal function are occurred.7. The therapeutic or prophylactic agent according to claim 1 , wherein the tumor lysis syndrome is a tumor lysis syndrome in a case where hyperuricemia is presented before implementation of antitumor therapy.8. The therapeutic or prophylactic agent according to claim 1 , wherein the tumor lysis syndrome is a tumor lysis syndrome in a case where renal function is reduced before implementation of antitumor therapy.9. The therapeutic or prophylactic agent according to claim 1 , characterized in that the 2-phenylthiazole compound represented by the formula (I) claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is administered at 0.5 to 1000 mg per day claim 1 , 1 to 7 days/week.10. The therapeutic or prophylactic agent according to ...

Bicyclic Compound as a Caspase Inhibitor

A compound represented by formula (I), a pharmaceutically acceptable salt or tautomer thereof, and an application of the compound as a caspase inhibitor. 2. The Compound claim 1 , the pharmaceutically acceptable salt or tautomer thereof according to claim 1 , wherein a heteroatom of ring A is independently selected from 0 claim 1 , S or N claim 1 , and number of the heteroatom of ring A is selected from 1 claim 1 , 2 or 3.3. The compound claim 1 , the pharmaceutically acceptable salt or tautomer thereof according to claim 1 , wherein ring A is selected from oxazolyl claim 1 , isoxazolyl claim 1 , imidazolyl claim 1 , thiazolyl claim 1 , 1 claim 1 ,2 claim 1 ,4-oxadiazolyl claim 1 , 1 claim 1 ,3 claim 1 ,4-oxadiazolyl or pyrazolyl.5. The compound claim 1 , the pharmaceutically acceptable salt or tautomer thereof according to claim 1 , wherein ring B is selected from phenyl or cyclohexyl claim 1 , which is optionally substituted with R.6. The compound claim 1 , the pharmaceutically acceptable salt or tautomer thereof according to claim 1 , wherein R is selected from F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , OH claim 1 , NH claim 1 , or Me or Et optionally substituted with 1 claim 1 , 2 or 3 R.7. The compound claim 6 , the pharmaceutically acceptable salt or tautomer thereof according to claim 6 , wherein R is selected from F claim 6 , Cl claim 6 , Br claim 6 , I claim 6 , OH claim 6 , NH or CF.14. A pharmaceutical composition comprising a therapeutically effective amount of the compound claim 1 , the pharmaceutically acceptable salt or tautomer thereof according to claim 1 , and a pharmaceutically acceptable carrier or excipient.15. (canceled)16. A method of preventing or treating caspase receptor related diseases in a mammal claim 1 , comprising administering a therapeutically effective amount of the compound claim 1 , the pharmaceutically acceptable salt or tautomer thereof according to to the mammal in need thereof.17. The compound claim 6 , the ...

NOVEL COMPOUNDS FOR REGENERATION OF TERMINALLY-DIFFERENTIATED CELLS AND TISSUES

The present invention discloses novel compounds and their use in medicine. Preferably the compounds are applicable in the therapy of disorders associated with damaged post-mitotic tissues in mammals. The novel compounds are compounds according to formula I (I) wherein—X is O (oxygen) or S (sulphur),—R1 is a substituent selected from the group consisting of straight-chain (unbranched) or branched, unsubstituted or substituted alkyl groups, cycloalkyl groups, alkylcycloalkyl groups, aryl groups, alkylaryl groups, arylalkyl groups, cycloalkylaryl groups and arylcycloalkyl groups, which optionally contain heteroatoms,—R2 is a substituent selected from the group consisting of straight-chain (unbranched) or branched, unsubstituted or substituted C1-C6 alkyl groups, C1-C6 alkoxy groups, C1-C6 alkoxy alkyl groups and C2-C6 alkenyl groups,—R3 is a substituent selected from the group consisting of straight-chain (unbranched) or branched, unsubstituted or substituted alkyl groups, cycloalkyl groups, alkylcycloalkyl groups, aryl groups, alkylaryl groups, arylalkyl groups, cycloalkylaryl groups and arylcycloalkyl groups, which optionally contain heteroatoms,—or a stereoisomer, a tautomer, a prodrug or a pharmaceutically acceptable salt thereof. 2. The compound according to claim 1 , wherein X is O (oxygen).3. The compound according to claim 1 , wherein R1 is a substituent selected from the group consisting of straight-chain or branched claim 1 , unsubstituted or substituted aryl groups claim 1 , alkylaryl groups claim 1 , and arylalkyl groups claim 1 , which optionally contain heteroatoms.4. The compound according to claim 3 , wherein R1 is a substituent selected from the group consisting of straight-chain or branched claim 3 , unsubstituted or substituted heteroaryl groups claim 3 , alkylheteroaryl groups claim 3 , and heteroarylalkyl groups claim 3 , in particular indolyl groups claim 3 , alkylindolyl groups claim 3 , and indolylalkyl groups.5. The compound according to claim ...

METHODS OF TREATING OR PREVENTING COGNITIVE IMPAIRMENT USING INDANE ACETIC ACID DERIVATIVES

The present invention provides indane acetic acid and their derivatives and methods for the treating and/or preventing of cognitive disorders. 3. The method according to wherein:R is H,{'sup': '1', 'Ris H,'}{'sup': '2', 'Ris H,'}{'sup': '3', 'sub': 1', '6, 'Ris C-Calkyl,'}X is O, and{'sup': 4', '6', '6, 'sub': 1', '6', '1', '6, 'Ris a phenyl substituted with R, wherein Ris C-Calkoxyl or C-Calkyl.'}5. The method according to wherein the compound is a pharmaceutically acceptable salt thereof claim 1 , wherein the pharmaceutically acceptable salt is selected from the group consisting of alkali metal salts claim 1 , alkaline earth metal salts claim 1 , ammonium salts with organic bases claim 1 , and basic nitrogen containing groups in the conjugate base that is quaternized with agents selected from the group consisting of alkyl halides and aralkyl.6. The method according to wherein the compound is a meglumine claim 5 , potassium or sodium salt thereof.7. The method according to wherein said compound is administered intravenously claim 1 , orally claim 1 , buccally claim 1 , transdermally claim 1 , rectally claim 1 , nasally claim 1 , otically claim 1 , intrathecally or intra-cranially8. The method according to further comprising administration of one or more additional therapeutic agent.9. The method according to wherein said one or more additional therapeutic agent is used to treat or prevent Alzheimer's disease.10. The method according to wherein said one or more additional therapeutic agents is at least one of acetylcholinesterase inhibitor claim 9 , and a NMDA receptor antagonist.11. The method according to wherein said additional therapeutic agent is selected from the group consisting of tacrine claim 10 , galantamine claim 10 , rivastigamine claim 10 , donepezil and memantine.12. The method according to wherein said one or more additional therapeutic agents reglates beta amyloid plaque disease is selected from the group consisting of an antioxidant claim 9 , an ...

TRPM8 ANTAGONISTS

The invention relates to compounds acting as selective antagonists of Transient Receptor Potential cation channel subfamily M member 8 (TRPM8), and having formula (I). Said compounds are useful in the treatment of diseases associated with activity of TRPM8 such as pain, inflammation, ischaemia, neurodegeneration, stroke, psychiatric disorders, itch, irritable bowel diseases, cold induced and/or exhacerbated respiratory disorders and urological disorders. 117-. (canceled)19. The method of claim 18 , wherein{'sub': 3', '3', '4, 'when Ris F, Ris in position ortho of the aromatic ring and Ris F in position para of the aromatic ring.'}20. The method of claim 18 , wherein{'sub': 3', '4, 'when Ris H, Ris in position para or meta on the aromatic ring.'}21. The method of claim 18 , wherein{'sub': 5', '1', '4', '1', '3', '2', '2', '6, 'claim-text': {'sub': '6', 'wherein Ris selected from H and (furan-2-yl)methyl.'}, 'Ris selected from H; C-Calkyl; trifluoromethanesulfonyl; benzyl; (trifluoromethyl)benzyl, (chloro)benzyl; (trifluoromethyl)benzoyl, N-benzylcarbamoyl, cyclohexyloxyacetoyl substituted with at least one C-Calkyl group, (methoxy)methyl, propanoyl and —CHCHNHR;'}22. The method of claim 18 , wherein{'sub': 7', '2', '8, 'claim-text': {'sub': 8', '2', '9, 'claim-text': {'sub': 9', '1', '3, 'Ris selected from H, C-Calkyl and cyclopentyl.'}, 'Ris selected from phenyl, benzo[d][1,3]dioxole, pyridin-3-yl, (pyrrolidin-1-yl)methyl, —CHNHRwherein'}, 'Ris selected from H, tert-butoxycarbonyl, acetyl, (4-trifluoromethyl)benzoyl; N-phenylaminoacarbonyl, CHR, wherein'}23. The method of claim 18 , wherein{'sub': 10', '1', '3, 'Ris selected from H; C-Calkyl and 2-isopropyl-5-methyl-cyclohexyl.'}24. The method of claim 18 , wherein:{'sub': 4', '3, 'Ris selected from H; CH; F; Cl; dimethylamino; pyridin-4-yl; phenyl, 2-F-phenyl, 2-trifluoromethylphenyl; 2- or 4-halobenzyloxy.'}26. The method of claim 18 , wherein Ris COORwherein{'sub': 10', '1', '3, 'Ris selected from H, C-Calkyl.'} ...

(2R,4R)-5-(5'-CHLORO-2'-FLUOROBIPHENYL-4-YL)-2-HYDROXY-4-[(5-METHYLOXAZOLE-2-CARBONYL)AMINO]PENTANOIC ACID

In one aspect, the invention relates to a compound of the structure: 128-. (canceled)30. The method of claim 29 , wherein the disease is selected from hypertension claim 29 , heart failure claim 29 , and renal disease.31. The method of claim 30 , wherein the hypertension is selected from primary hypertension claim 30 , secondary hypertension claim 30 , hypertension with accompanying renal disease claim 30 , severe hypertension with or without accompanying renal disease claim 30 , pulmonary hypertension claim 30 , and resistant hypertension.32. The method of claim 31 , wherein the hypertension is resistant hypertension.33. The method of claim 29 , wherein the disease is portal hypertension.34. The method of claim 29 , further comprising administering a therapeutic agent selected from an ATreceptor antagonist claim 29 , an angiotensin-converting enzyme inhibitor claim 29 , a phosphodiesterase inhibitor claim 29 , a renin inhibitor claim 29 , and a diuretic claim 29 , or a combination thereof.35. The method of claim 29 , further comprising administering an ATreceptor antagonist.36. The method of claim 35 , wherein the ATreceptor antagonist is selected from abitesartan claim 35 , azilsartan claim 35 , azilsartan medoxomil claim 35 , benzyllosartan claim 35 , candesartan claim 35 , candesartan cilexetil claim 35 , elisartan claim 35 , embusartan claim 35 , enoltasosartan claim 35 , eprosartan claim 35 , EXP3174 claim 35 , fonsartan claim 35 , forasartan claim 35 , glycyllosartan claim 35 , irbesartan claim 35 , isoteoline claim 35 , losartan claim 35 , medoxomil claim 35 , milfasartan claim 35 , olmesartan claim 35 , olmesartan medoxomil claim 35 , opomisartan claim 35 , pratosartan claim 35 , ripisartan claim 35 , saprisartan claim 35 , saralasin claim 35 , sarmesin claim 35 , TAK-591 claim 35 , tasosartan claim 35 , telmisartan claim 35 , valsartan claim 35 , and zolasartan.37. The method of claim 35 , wherein the ATreceptor antagonist is selected from azilsartan ...

NOVEL SUBSTITUTED CYCLOBUTYLBENZENE COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) INHIBITORS

Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof: (Formula (I)). Also disclosed herein are uses of a compound disclosed herein in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising a compound disclosed herein. Further disclosed herein are uses of a composition in the potential treatment or prevention of an IDO-associated disease or disorder. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 ,wherein:L is selected from (1) —NHC(O)— and (2) —C(O)NH—; and{'sup': '3', 'sub': 1-4', '1-4, 'Ris selected from (1) H, (2) halogen, (3) Calkyl, optionally substituted with —OH, and (4) —C═N—Calkyl.'}3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from (1) H claim 1 , (2) fluoro claim 1 , (3) methyl claim 1 , (4) ethyl claim 1 , (5) —CH—OH claim 1 , and (6) —C═N—C(CH).4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Rand Ris independently selected from (1) H claim 1 , (2) halogen claim 1 , (3) methyl claim 1 , and (4) —OH.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from:{'sub': 3-6', '1-6', '1-6, '(1) Ccycloalkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen, (b) —O—Calkyl, and (c) Calkyl optionally substituted with 1-3 halogens,'}{'sub': 1-6', '1-6', '2, '(2) phenyl, optionally substituted with 1-3 substituents independently selected from (a) halogen, (b) —CN, (c) —O—Calkyl, and (d) Calkyl optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) —NH,'}{'sub': 4-7', '1-6, '(3) a bicyclic ring comprising a phenyl fused to a Ccycloalkyl, wherein the bicyclic ring is optionally substituted with halogen or Calkyl, and'}{'sub': '1-6', '(4) a heterocyclyl selected from (a) a saturated 4-7 ...

(2R,4R)-5-(5'-CHLORO-2'-FLUOROBIPHENYL-4-YL)-2-HYDROXY-4-[(5-METHYLOXAZOLE-2-CARBONYL)AMINO]PENTANOIC ACID

In one aspect, the invention relates to a compound of the structure: 128-. (canceled)30. The composition of claim 29 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern comprising peaks at 14.19±0.2 and 21.15±0.2 degrees 2θ.31. The composition of claim 29 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern comprising peaks at 8.48±0.2 claim 29 , 17.03±0.2 claim 29 , and 25.41±0.2 degrees 2θ.32. The composition of claim 30 , wherein the powder x-ray diffraction pattern further comprises at least one peak selected from 8.48±0.2 claim 30 , 17.03±0.2 claim 30 , and 25.41±0.2 degrees 2θ.33. The composition of claim 30 , wherein the powder x-ray diffraction pattern further comprises peaks at 8.48±0.2 claim 30 , 17.03±0.2 claim 30 , and 25.41±0.2 degrees 2θ.34. The composition of claim 30 , wherein the powder x-ray diffraction pattern further comprises at least one peak selected from 20.59±0.2 claim 30 , 24.45±0.2 claim 30 , 24.78±0.2 claim 30 , 25.67±0.2 claim 30 , 27.67±0.2 claim 30 , and 30.73±0.2 degrees 2θ.35. The composition of claim 30 , wherein the powder x-ray diffraction pattern further comprises peaks at 20.59±0.2 claim 30 , 24.45±0.2 claim 30 , 24.78±0.2 claim 30 , 25.67±0.2 claim 30 , 27.67±0.2 claim 30 , and 30.73±0.2 degrees 2θ.36. The composition of claim 33 , wherein the powder x-ray diffraction pattern further comprises peaks at 20.59±0.2 claim 33 , 24.45±0.2 claim 33 , 24.78±0.2 claim 33 , 25.67±0.2 claim 33 , 27.67±0.2 claim 33 , and 30.73±0.2 degrees 2θ.37. The composition of claim 29 , wherein the crystalline form is characterized by a differential scanning calorimetry thermogram comprising an endotherm in the range of about 165 to 169° C.38. The composition of claim 33 , wherein the crystalline form is further characterized by a differential scanning calorimetry thermogram comprising an endotherm in the range of about 165 to 169° C.39. The composition of claim 36 , wherein the ...

PROCESS FOR THE PREPARATION OF ROXADUSTAT AND ITS INTERMEDIATES

The present invention provides the process for the preparation of Roxadustat and its intermediates. Another aspect of the present invention provides a process for preparation of ethyl-5-(2-butoxycarbonyl)-4-phenoxyphenyl) oxazole-4-carboxylate of the formula (X) and its use in the preparation of Roxadustat. Another aspect of the present invention provides a process for the preparation of ethyl-4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxylate of the formula (XIII) and its use in the preparation of Roxadustat. 2) The process according to claim 1 , wherein base used in step c) is carried out in presence of a base selected from pyridine claim 1 , piperidine claim 1 , pyrimidine claim 1 , triethylamine claim 1 , tributylamine claim 1 , N-methylmorpholine claim 1 , N claim 1 ,N-diisopropylethylamine claim 1 , diethylamine claim 1 , 1 claim 1 ,1 claim 1 ,3 claim 1 ,3-tetramethylguanidine claim 1 , DBU claim 1 , DABCO.3) The process according to claim 1 , wherein acid used in step d) is carried out in presence of acid selected from hydrochloric acid claim 1 , sulphuric acid claim 1 , hydrobromic acid claim 1 , orthophosphoric acid claim 1 , Lewis acids claim 1 , AlCl claim 1 , FeCl claim 1 , acetic acid claim 1 , citric acid claim 1 , oxalic acid claim 1 , trifluoroacetic acid.5) The process according to claim 4 , wherein base used in step b) is carried out in presence of a base selected from pyridine claim 4 , piperidine claim 4 , pyrimidine claim 4 , triethylamine claim 4 , tributylamine claim 4 , N-methylmorpholine claim 4 , N claim 4 ,N-diisopropylethylamine claim 4 , diethylamine claim 4 , 2 claim 4 ,2-bipyridine claim 4 , 1 claim 4 ,1 claim 4 ,3 claim 4 ,3-tetramethylguanidine claim 4 , DBU claim 4 , DABCO.7) The process according to claim 6 , wherein the methylating reagent used in step a) is selected from trimethyl boroxine claim 6 , methylmagnesium chloride claim 6 , methyl magnesium bromide claim 6 , methyl lithium claim 6 , trimethyl silyl halides.8) The ...

BENZYLHYDROXIDE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF

The invention relates to benzylhydroxyde derivatives of formula (I): The invention also relates to the preparation and the therapeutic use of the compounds of formula (I). 2. The compound of claim 1 , in the form of a base claim 1 , an enantiomer claim 1 , a diastereomer claim 1 , or an acid addition salt claim 1 , wherein A is an oxazolyl claim 1 , thiazol claim 1 , thienyl claim 1 , oxadiazolyl claim 1 , thiadiazolyl or imidazolyl group.3. The compound of claim 1 , in the form of a base claim 1 , an enantiomer claim 1 , a diastereomer claim 1 , or an acid addition salt claim 1 , wherein A is unsubstituted.4. The compound of claim 1 , in the form of a base claim 1 , an enantiomer claim 1 , a diastereomer claim 1 , or an acid addition salt claim 1 , wherein A is substituted with one or more methyl groups.5. The compound of claim 1 , in the form of a base claim 1 , an enantiomer claim 1 , a diastereomer claim 1 , or an acid addition salt claim 1 , wherein each of R1 claim 1 , R2 claim 1 , R′ and R′ is a hydrogen atom or a methyl group.6. The compound of claim 5 , in the form of a base claim 5 , an enantiomer claim 5 , a diastereomer claim 5 , or an acid addition salt claim 5 , wherein each of R1 claim 5 , R2 claim 5 , R′ and R′ is a hydrogen atom.7. The compound of claim 1 , in the form of a base claim 1 , an enantiomer claim 1 , a diastereomer claim 1 , or an acid addition salt claim 1 , wherein at least two of R3 claim 1 , R4 and R5 are —OCHand at least two of R′ claim 1 , R′ and R′ are —OCH.8. The compound of claim 7 , in the form of a base claim 7 , an enantiomer claim 7 , a diastereomer claim 7 , or an acid addition salt claim 7 , wherein two of R3 claim 7 , R4 and R5 are —OCHand two of R′ claim 7 , R′ and R′ are —OCH.9. The compound of claim 1 , in the form of a base claim 1 , an enantiomer claim 1 , a diastereomer claim 1 , or an acid addition salt claim 1 , wherein at least one of R3 claim 1 , R4 claim 1 , R5 claim 1 , R′ claim 1 , R′ and R′ is —OCHF.10. The ...

HISTONE DEACETYLASE INHIBITORS AND USES THEREOF

Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of cancer. Additionally, provided is a method for treating cancer, comprising the step of administering a therapeutically effective amount of a compound according to formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier to a patient in need thereof. 2. The compound according to claim 1 , wherein Ris a bond.3. The compound according to claim 1 , wherein Ris lower alkyl.4. The compound according to claim 1 , wherein Ris phenyl.5. The compound according to claim 1 , wherein Ris phenyl substituted independently with —C(O)NH-phenyl claim 1 , —C(O)OCH claim 1 , —C(O)OH or phenyl.6. The compound according to claim 1 , wherein Ris —CH(phenyl).7. The compound according to claim 1 , wherein Ris naphthalenyl claim 1 , 1H-indolyl or dioxoisoindolinyl.8. The compound according to claim 1 , wherein Ris —NHC(O)CH(phenyl) claim 1 , —NHC(S)NHCHCHCH(phenyl) claim 1 , —NHCHCHCH(phenyl)or —C(O)NH-phenyl.9. The compound according to claim 1 , wherein Ris a bond and Ris phenyl claim 1 , optionally substituted independently with —C(O)NH-phenyl claim 1 , —C(O)OCH claim 1 , —C(O)OH or phenyl.10. The compound according to claim 1 , wherein Ris a bond and Ris —CH(phenyl).11. The compound according to claim 1 , wherein Ris lower alkyl and Ris —CH(phenyl) claim 1 ,-naphthalenyl claim 1 , -1H-indolyl claim 1 , -dioxoisoindolinyl claim 1 , —NHC(O)CH(phenyl) claim 1 , —NHC(S)NHCHCHCH(phenyl) claim 1 , —NHCHCHCH(phenyl)or —C(O)NH-phenyl.12. The compound according to claim 1 , wherein said lower alkyl is methyl claim 1 , ethyl claim 1 , propyl or butyl.13. The compound according to claim 1 , wherein said lower alkyl is methyl or ethyl.14. The compound according to claim 1 , wherein ...

SUBSTITUTED BENZAMIDES AND THEIR USES

Provided herein are Substituted Benzamides, compositions, and method of their manufacture and use.

OXAZOLE OREXIN RECEPTOR ANTAGONISTS

The present invention is directed to oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the oxazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A is phenyl claim 1 , pyridyl claim 1 , or thiophenyl.3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein RR claim 2 , and Rare independently selected from the group consisting of:(1) hydrogen,(2) halogen,{'sub': '1-3', '(3) C(═O)OCalkyl,'}{'sub': '1-3', '(4) Calkyl, which is unsubstituted or substituted with 1-5 groups which are independently selected from halogen, hydroxyl and phenyl,'}{'sub': '1-3', '(5) —OCalkyl, which is unsubstituted or substituted with 1-5 groups which are independently selected from halogen, hydroxyl and phenyl,'}(6) —C(═O)OH,{'sub': 1-3', '1-3', '2', '1-3', '1-3, '(7) heteroaryl, wherein heteroaryl is triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, indolyl, pyridyl, or pyrimidinyl, and is unsubstituted or substituted with 1-3 groups which are independently selected from halogen, hydroxy, —Calkyl, —OCalkyl, —CN, and —NO, wherein —Calkyl and —OCalkyl are optionally substituted with 1-3 halogens,'}{'sub': 3', '3', '3', '3, '(8) phenyl, which is unsubstituted or substituted with 1-3 groups which are independently selected from halogen, hydroxy, —CN, —CH, —CF, —OCH, and —OCF, and'}{'sub': 3-6', '1-3', '1-3', '1-3', '1-3, '(9) Ccycloalkyl, which is unsubstituted or substituted with 1-3 groups ...

NOVEL OXAZOLE COMPOUNDS AS BETA CATENIN MODULATORS AND USES THEREOF

Oxazole compounds according to formula I: 3. The method of or the compound of , wherein A is -L-X-L-C(O)—NRR.4. The method of or the compound of , wherein A is -L-X-L—C(O)—OR.8. The method or the compound according to any one of - , wherein Lis methylene , ethylene , propylene , or butylene , each of which unsubstituted or substituted with one or more groups selected from C-Calkyl , halo , and hydroxyl.9. The method or the compound according to any one of - , wherein Lis —CH— , —CH—CH— , —CH—CH—CH— , or —CH—CH—CH—CH—.10. The method or the compound according to any one of - , wherein Lis —CH—11. The method or the compound according to any one of - , wherein Lis methylene , ethylene , propylene , or butylene , each of which unsubstituted or substituted with one or more groups selected from C-Calkyl , halo , and hydroxyl.12. The method or the compound according to any one of - , wherein Lis —CH— , —CH—CH— , —CH—CH—CH— , or —CH—CH—CH—CH—.13. The method or the compound according to any one of - , wherein Lis —CH—.14. The method or the compound according to any one of - , wherein Cy is substituted or unsubstituted aryl.15. The method or the compound according to any one of - , wherein Cy is substituted or unsubstituted phenyl.16. The method or the compound according to any one of - , wherein Cy is substituted or unsubstituted naphthyl.17. The method or the compound according to any one of - , wherein Cy is substituted or unsubstituted heteroaryl.18. The method or the compound according to any one of - , wherein Cy is substituted or unsubstituted pyridyl.19. The method or the compound according to any one of - , wherein Cy is substituted or unsubstituted pyrimidinyl.20. The method or the compound according to any one of - , wherein X is —O—.22. The method or the compound according to any one of - , wherein Ris H or substituted or unsubstituted C-Calkyl.23. The method or the compound according to any one of - , wherein Ris halo.24. The method or the compound according to ...

Ribosome-Mediated Incorporation of Peptides and Peptidomimetics

Modified ribosomes that were selected using a dipeptidyl-puromycin aminonucleoside are used to mediate site-specific incorporation of one or more peptides and peptidomimetics into protein in a cell free translation system. In addition, new fluorescent dipeptidomimetics have been synthesized and incorporated into proteins, as well as modified proteins containing one or more non-naturally occurring dipeptides. 111-. (canceled)13E. coli. The system of claim 12 , wherein said materials comprise an S-30 extract.15. The method of claim 14 , wherein said materials include a mRNA encoding the protein(s) of interest and containing one or more stop codons claim 14 , and one or more suppressor tRNA(s) activated with the modified dipeptidomimetic recognized by the selected ribosomes. This application is a divisional application of U.S. application Ser. No. 15/545,275, filed Jul. 20, 2017, which is a 371 application of PCT/US2016/014548 filed Jan. 22, 2016, which claims priority to U.S. provisional patent application 62/106,958 filed on Jan. 23, 2015, which are incorporated herein by reference as if set forth in their entirety.This invention was made with government support under R01 GM103861 awarded by the National Institutes of Health. The government has certain rights in the invention.This disclosure relates to modified ribosomes used to mediate site-specific incorporation of peptides and peptidomimetics into protein in a cell free translation system, as well as to the creation of novel fluorescent dipeptidomimetics and novel fluorescent proteins having a fluorescent peptidomimetic.Peptide and protein engineering have long been desired. Irrespective of the approach, the engineered chemical structure is designed to advantageously adjust the molecular properties such as, stability or biological activity. This can have a role in the development of drug-like compounds from existing peptides and peptidomimetics.Embodiments disclosed herein relate to a genetically modified ribosome ...

Heterocyclocarboxamide derivatives

The invention relates to a fungicidally active compound of formula (I): where Het is a 5- or 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur, provided that the ring is not 1,2,3-triazole, the ring being substituted by groups R8, R9 and R10; X is a single or double bond; Y is O, S, N(R11) or (CR12R13)(CR14R15)m(CR16R17)n; m is 0 or 1; n is 0 or 1; and R1 to R17 each, independently, have a range of values; to the preparation of these compounds, to novel intermediates used in the preparation of these compounds, to agrochemical compositions which comprise at least one of the novel compounds as active ingredient, to the preparation of the compositions mentioned and to the use of the active ingredients or compositions in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.

Alpha substituted carboxylic acids

Alpha substituted carboxylic acids of formula (I): wherein R 1 and R 2 are as defined in the specification and R 3 is wherein Y, Ar 1 , Ar 2 , Ar 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 9a , R 10 , R 11 , R 12 , R 17 , ring A, and p are as defined in the specification; pharmaceutical compositions containing effective amounts of said compounds or their salts are useful for treating PPAR, specifically PPAR α/γ related disorders, such as diabetes, dyslipidemia, obesity and inflammatory disorders.

Organic compounds

OXYGEN OR SULFUR CONTAINING 5-MEMBERED HETEROAROMATICS AS FACTOR Xa INHIBITORS

The present application describes oxygen and sulfur containing heteroaromatics and derivatives thereof of formula (I), or pharmaceutically acceptable salt or prodrug forms thereof, wherein J is O or S and D may be C(=NH)NH2, which are useful as inhibitors of factor Xa.

4-Halogeno-5-(halogenomethyl-phenyl)-oxazole derivatives, a process for the preparation thereof, and radiation-sensitive compositions containing these derivatives

This invention relates to a novel 4-halogeno-5-(halogenomethyl-phenyl)-oxazole derivative; to a radiation-sensitive composition which, as the radiation-sensitive compound, contains a 4-halogeno-5-(halogenomethyl-phenyl)-oxazole derivative; and to a process for the preparation of the novel 4-halogeno-5-(halogenomethyl-phenyl)-oxazole derivatives.

2-(Halogenomethyl-phenyl)-4-halogeno-oxaxole derivatives, a process for the preparation thereof, and radiation-sensitive compositions containing these derivatives

This invention relates to a novel 2-(halogenomethyl-phenyl)-4-halogeno-oxazole derivative; to a radiation-sensitive composition which, as the radiation-sensitive compound, contains a 2-halogenomethyl-phenyl)-4-halogeno-oxazole derivative; and to a process for the preparation of the novel 2-(halogenomethyl-phenyl)-4-halogeno-oxazole derivatives.

OXAZOLE COMPOUND CRYSTAL

Provided is a crystal of a specific oxazole compound that has specific inhibitory activity against PDE4, and that shows excellent stability. Specifically, provided is a crystal of an oxazole compound represented by formula (5) 111.-. (canceled)13. The production method according to claim 12 , wherein the crystal further has a peak at diffraction angle 2θ(°) of 26.0±0.2 in the X-ray powder diffraction pattern measured using CuKα characteristic X-rays.14. The production method according to claim 13 , wherein the crystal further has one or more peaks at one or more diffraction angles 2θ(°) selected from the group consisting of 10.4±0.2 claim 13 , 11.9±0.2 claim 13 , 15.0±0.2 claim 13 , 15.9±0.2 claim 13 , 19.7±0.2 claim 13 , 24.7±0.2 claim 13 , and 27.6±0.2 in the X-ray powder diffraction pattern measured using CuKα characteristic X-rays.15. The production method according to claim 12 , wherein the crystal has infrared absorption bands at wavenumbers (cm) of 3380±5 claim 12 , 2980±5 claim 12 , 1651±2 claim 12 , 1501±2 claim 12 , 1258±2 claim 12 , 1121±2 claim 12 , and 754±2 in an infrared absorption spectrum measured by a potassium bromide disk method.16. The production method according to claim 12 , wherein the crystal has a melting point of 75 to 90° C.17. The production method according to claim 12 , comprising dissolving the crystal in a solvent by heating at a temperature equal to or higher than the melting point of the crystal.18. The production method according to claim 17 , comprising dissolving the crystal in a solvent by heating at a temperature of 85° C. or higher and 91° C. or lower.19. The production method according to claim 12 , comprisingdissolving the crystal in a solvent, andmixing the solvent containing dissolved crystal with an ointment base.20. The production method according to claim 19 , wherein the solvent containing dissolved crystal in the pharmaceutical composition is dissolved or dispersed in the form of droplets in the ointment base.21. The ...

Heterocyclocarboxamide derivatives

본 발명은 살진균작용을 갖는 화학식 I의 화합물, 당해 화합물의 제조방법, 당해 화합물의 제조에 사용되는 신규한 중간생성물, 유효 성분으로서 하나 이상의 신규한 화합물을 포함하는 농약 조성물, 전술한 조성물의 제조방법, 및 식물병원성 미생물, 바람직하게는 진균에 의한 식물의 감염을 방제 또는 예방하기 위한 농업 또는 원예업에 있어서의 당해 유효성분 또는 조성물의 용도에 관한 것이다. The present invention provides a compound of formula (I) having fungicidal action, a process for preparing the compound, novel intermediates used in the preparation of the compound, pesticide compositions comprising at least one novel compound as an active ingredient, the preparation of the compositions described above A method and the use of said active ingredient or composition in agriculture or horticulture for controlling or preventing plant infection by phytopathogenic microorganisms, preferably fungi. 화학식 I Formula I 상기식에서, In the above formula, Het는 산소, 질소 및 황에서 각각 독립적으로 선택된 1 내지 3개의 헤테로원자를 포함하는 5 내지 6원 헤테로사이클 환인데, 단, 당해 환은 1,2,3-트리아졸환이 아니고, 환은 R 8 , R 9 및 R 10 그룹으로 치환되고, Het is a 5-6 membered heterocycle ring containing 1 to 3 heteroatoms each independently selected from oxygen, nitrogen and sulfur, provided that the ring is not a 1,2,3-triazole ring and the ring is R 8 , R 9 and Substituted with R 10 groups, X는 단일 또는 이중 결합이고; X is a single or double bond; Y는 O, S, N(R 11 ) 또는 (CR 12 R 13 )(CR 14 R 15 ) m (CR 16 R 17 ) n 이고; m은 0 또는 1이고; Y is O, S, N (R 11 ) or (CR 12 R 13 ) (CR 14 R 15 ) m (CR 16 R 17 ) n ; m is 0 or 1; n은 0 또는 1이고; n is 0 or 1; R 1 내지 R 17 은 각각 독립적으로 범위 값을 갖는다. R 1 to R 17 each independently have a range value. 헤테로사이클로카복스아미드, 중간생성물, 농약 조성물, 조성물의 제조, 살진균제 Heterocyclocarboxamides, Intermediates, Agrochemical Compositions, Preparation of Compositions, Fungicides

用作Nurr1激活剂的杂环化合物

本发明涉及式I化合物及其盐、它们的制备、用途以及含有它们的药物组合物：其中，R 1 为羟基、C 1－4 烷氧基、氨基、C 1－4 烷基氨基、二C 1－4 烷基氨基、苄氧基或C 2 －C 7 烷酰基；R 2 为C 1－4 烷基、C 1－4 烷氧基、C 1－4 烷氧基C 1－4 烷氧基、CF 3 、卤素、C 1－4 烷基氨基、二C 1－4 烷基氨基、二C 1－4 烷基氨基C 1－4 烷氧基或N－C 1－4 烷氧基C 1－4 烷基－N－C 1－4 烷基氨基、N－C 1－4 烷基－哌嗪基、吗啉基或吡咯烷基－C 1－4 烷氧基，其中R 2 中的C 1－4 烷基任选进一步被C 1－4 烷基、卤素、氰基、氨基、烷氧基或烷硫基取代；X为N或O；Y为N、O或CH；Z为N或CH；且W为N或CH；条件是(a)当R 2 为CF 3 、X为O、Y为CH、Z为N且W为CH时，R 1 不是羟基或C 1－4 烷氧基；(b)当R 2 为CF 3 或氯、X为N、Y为O、Z为CH且W为CH时，R 1 不是羟基或C 1－4 烷氧基；(c)当R 2 为CF 3 、X为O、Y为N、Z为CH且W为CH时，R 1 不是羟基；(d)X与Y不同时为O。

一种非布索坦中间体及其制备方法

本发明提供了一种非布索坦中间体及其制备方法。本发明的非布索坦中间体为式IV所示的化合物：

一种非布司他中间体的“一锅法”合成方法

本发明属于药物合成领域，具体涉及一种非布司他中间体2‑(3‑氰基‑4‑异丁氧基苯基)‑4‑甲基噻唑‑5‑甲酸乙酯的“一锅法”合成方法，以2‑(4‑羟基苯基)‑4‑甲基噻唑‑5‑甲酸乙酯为起始原料，将其在碱的催化下与溴代异丁烷进行醚化反应，随后经固液分离，得滤液；向滤液中滴加三氯氧磷，搅拌反应后再加入氨水和单质碘继续搅拌，反应结束后淬灭反应，随后经萃取、有机相浓缩，即得。本发明方法可一锅串联合成非布司他关键中间体，工艺无需多次纯化，即可满足纯度的要求，不仅如此，还具有良好的收率；适用于工业大规模生产。

Fungicidal n-cycloalkylbenzylamide derivatives

FIELD: chemistry. SUBSTANCE: invention describes N-cycloalkylbenzylamide derivatives of formula , where A denotes a saturated 5-member heterocyclic group, Z 1 denotes a substituted C 3 -C 7 -cycloalkyl; Z 2 and Z 3 , which can be identical or different from each other, denote a hydrogen atom; C 1 -C 8 -alkyl; cyano; C 1 -C 8 -alkoxycarbonyl; a method of producing said compounds, use thereof as fungicidal active substances, particularly in form of fungicidal compositions, and method of controlling phytopathogenic fungi, mainly in plants, using said compounds or compositions. EFFECT: higher activity, low amount of active substance while maintaining efficiency at least equivalent to that of existing compounds. 11 cl, 5 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 419 616 (51) МПК C07D C07D C07D C07D C07D C07D ФЕДЕРАЛЬНАЯ СЛУЖБА C07D ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, C07D ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ C07D C07D (12) ОПИСАНИЕ 333/38 307/46 277/56 275/02 263/34 261/18 249/04 233/90 231/14 207/04 (24) Дата начала отсчета срока действия патента: 15.11.2006 (43) Дата публикации заявки: 10.03.2010 Бюл. № 7 C 2 (73) Патентообладатель(и): БАЙЕР КРОПСАЙЕНС АГ (DE) C 2 (56) Список документов, цитированных в отчете о поиске: US 4314839, 09.02.1982. JP 4128275, 28.04.1992. US 4177054, 04.12.1979. NICOLAOU К С; ЕТ AL. Natural Product-like Combinatorial Libraries Based on Privileged Structures. 2. Construction of a 10000-Membered Benzopyran Library by Directed Split-and-Pool Chemistry Using NanoKans and Optical Encoding. Journal of the American Chemical Society, 2000 (см. прод.) (72) Автор(ы): МАНСФИЛЬД Даррен (DE), КОКЕРОН Пьер-Ив (FR), ДЕСБОРД Филипп (FR), ВИЛЛЬЕ Ален (FR), ГРОСЖАН-КУРНУАЕ Мари-Клер (FR), ГАРИ Стефани (FR), КАРБОНН Стефан (FR), ДУНКЕЛЬ Ральф (FR), ТЮК Арунарит (FR), ВОР Жан-Пьер (FR) (85) Дата начала рассмотрения заявки PCT на национальной фазе: 01.09.2008 (86) Заявка PCT: EP 2006/068478 (15.11.2006) (87) Публикация заявки РСТ: WO 2007/087906 (09.08.2007) Адрес для ...

FUNGICIDE COMPOSITION CONTAINING DERIVATIVES OF ACID AMIDA

Reivindicacion 1: Una composicion funguicida que contiene un derivado de amina ácida de la formula (1) o una sal del mismo como ingrediente activo: en la que A es fenilo que puede estar sustituido con X, bencilo que puede estar sustituido con X, naftilo que puede estar sustituido con X, un anillo heterocíclico que puede estar sustituido con X, un anillo heterocíclico fusionado que puede estar sustituido con X, indanilo (el indanilo puede estar sustituido con halogeno, alquilo o alcoxi) o tetrahidronaftilo (el tetrahidronaftilo puede estar sustituido con halogeno, alquilo o alcoxi); B es un anillo heterocíclico (con exclusion de piridilo) que puede estar sustituido con Y, un anillo heterocíclico fusionado que puede estar sustituido con Y o naftilo que puede estar sustituido con Y; X es halogeno, alquilo que puede estar sustituido con E1, alquenilo que puede estar sustituido con E1, alquinilo que puede estar sustituido con E1, hidroxi, cianooxi, alcoxi que puede estar sustituido con E1, alqueniloxi que puede estar sustituido con E1, alquiniloxi que puede estar sustituido con E1, mercapto, cianotio, alquiltio que puede estar sustituido con E1, alqueniltio que puede estar sustituido con E1, alquiniltio que puede estar sustituido con E1, alquilsulfinilo que puede estar sustituido con E2, alquilsulfonilo que puede estar sustituido con E2, cicloalquilo que puede estar sustituido con J, cicloalquiloxi que puede estar sustituido con J, cicloalquiltio que puede estar sustituido con J, ciano, nitro, formilo, fenilo que puede estar sustituido con Y, fenoxi que puede estar sustituido con Y, feniltio que puede estar sustituido con Y, fenilalquilo que puede estar sustituido con Y, fenilalquenilo que puede estar sustituido con Y, fenilalquinilo que puede estar sustituido con Y, fenilalquiloxi que puede estar sustituido con Y, fenilalqueniloxi que puede estar sustituido con Y, fenilalquiniloxi que puede estar sustituido con Y, fenilalquiltio que puede estar sustituido con Y, ...

杀真菌剂n-环烷基-苄基-酰胺衍生物

本发明涉及取代基如说明书中所定义的通式(I)的N－环烷基－苄基－酰胺衍生物及其制备方法，以及它们作为杀真菌活性剂的用途，特别是以杀真菌组合物的形式，以及用这些化合物或它们的组合物来控制植物病原真菌，特别是植物中的植物病原真菌的方法。

Heterocyclic amide derivatives useful as microbiocides

본 발명은 살진균 활성 화학식 I의 화합물, 이들 화합물의 제조방법, 이들 화합물의 제조에 사용되는 신규한 중간체, 하나 이상의 신규한 화합물을 활성 성분으로서 포함하는 농약 조성물, 언급된 조성물의 제조방법 및 농업 또는 원예에서 식물병원성 미생물, 바람직하게는 진균이 식물에 침입하는 것을 방제하거나 예방하기 위한 상기 활성 성분 또는 조성물의 용도에 관한 것이다. The present invention provides fungicidal active compounds of formula (I), methods of preparing these compounds, novel intermediates used in the preparation of these compounds, pesticide compositions comprising at least one novel compound as active ingredient, methods of preparing the mentioned compositions and agriculture Or in the horticulture, the use of said active ingredient or composition for controlling or preventing phytopathogenic microorganisms, preferably fungi, from invading the plant. 화학식 I Formula I 상기 화학식 I에서, In the formula (I) Het는 산소, 질소 및 황으로부터 각각 독립적으로 선택된 1 내지 3개의 헤테로원자를 포함하는 5- 또는 6-원 헤테로사이클릭 환이고, 당해 환은 그룹 R 6 , R 7 및 R 8 에 의해 치환되고, R 1 은 수소, C 1-4 알킬, C 1-4 할로알킬, C 1-4 알콕시, C 1-4 할로알콕시, CH 2 C≡CR 9 , CH 2 CR 10 =CHR 11 , CH=C=CH 2 또는 COR 12 이고; R 2 및 R 3 은 각각 독립적으로 수소, 할로, C 1-4 알킬, C 1-4 알콕시, C 1-4 할로알킬 또는 C 1-4 할로알콕시이고; R 4 및 R 5 는 각각 독립적으로 할로, 시아노 및 니트로로부터 선택되거나; R 4 및 R 5 중 하나는 수소이고, 나머지 하나는 할로, 시아노 및 니트로로부터 선택되고; Het is a 5- or 6-membered heterocyclic ring comprising 1 to 3 heteroatoms each independently selected from oxygen, nitrogen and sulfur, which ring is substituted by groups R 6 , R 7 and R 8 , and R 1 is hydrogen, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, CH 2 C≡CR 9 , CH 2 CR 10 = CHR 11 , CH = C = CH 2 or COR 12 ; R 2 and R 3 are each independently hydrogen, halo, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl or C 1-4 haloalkoxy; R 4 and R 5 are each independently selected from halo, cyano and nitro; One of R 4 and R 5 is hydrogen and the other is selected from halo, cyano and nitro; R 6 , R 7 및 R 8 은 각각 독립적으로 수소, 할로, 시아노, 니트로, C 1-4 알킬, C 1-4 할로알킬, C 1-4 알콕시(C 1-4 )알킬, C 1-4 할로알콕시(C 1-4 )알킬 또는 C 1-4 할로알콕시이고, 단, R 6 , R 7 및 R 8 중 적어도 하나는 수소가 아니고; R 9 , R 10 및 R 11 은 각각 독립적으로 수소, 할로, C 1-4 알킬, C 1-4 할로알킬 또는 C ...

Способ получения производного оксазола

1. Соединение, представленное формулой (12),в которой Rпредставляет собой низшую алкильную группу или галогензамещенную низшую алкильную группу, и Rпредставляет собой низшую алкильную группу.2. Соединение по п. 1, у которого в формуле (12) Rпредставляет собой метильную или дифторметильную группу, и Rпредставляет собойметильную, изопропильную или изобутильную группу.3. Способ получения соединения, представленного формулой (12),где Rпредставляет собой низшую алкильную группу или галогензамещенную низшую алкильную группу, Rпредставляет собой низшую алкильную группу, Rпредставляет собой низшую алкильную группу, Rпредставляет собой низшую алкильную группу, галогензамещенную низшую алкильную группу или группу, представленную формулой -CYCOOR, где Y представляет собой атом галогена, Rпредставляет собой атом щелочного металла или низшую алкильную группу, и Хи Хявляются одинаковыми или разными и представляют собой атомы галогена,причем способ включает следующие стадии:(а) реакцию соединения, представленного формулой (6), с соединением, представленным формулой (7), или с галогенирующим агентом и соединением, представленным формулой (21), сполучением соединения, представленного формулой (8);(b) дебензилирование соединения, представленного формулой (8), для получения соединения, представленного формулой (9);(с) реакцию соединения, представленного формулой (9), с соединением, представленным формулой (10), в присутствии основания с получением соединения, представленного формулой (11); и(d) восстановление соединения, представленного формулой (11), с получением соединения, представленного формулой (12).4. Способ получения соединения, представленного формулой (12), по п. 3,где Хпредставляет собой РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07D 263/32 (13) 2015 111 236 A (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2015111236, 29.08.2013 (71) Заявитель(и): ОЦУКА ФАРМАСЬЮТИКАЛ КО., ЛТД. (JP) Приоритет(ы): (30) Конвенционный ...

Novel heterocyclic alkanol derivatives

본 발명은 신규 헤테로사이클릭 알칸올 유도체, 그의 제조방법, 이들 화합물을 포함하는 조성물, 및 특히 작물 보호 및 재료 보호에 있어 유해 미생물을 구제하기 위한 생물학적 활성 화합물 및 식물 생장 조절제로서의 그의 용도에 관한 것이다.

METHOD OF OBTAINING OXAZOLES

Process for producing n-carboxi-anhidrides

Method for producing oxazole compound

本发明的目的是提供用于制造噁唑化合物的新方法。本发明涉及用于制造式(1)所示的化合物的方法。式中，R 1 是低级烷基或被卤素取代的低级烷基；R 2 是低级烷基；R 5 是低级烷基；R 11 是低级烷基、被卤素取代的低级烷基或式-CY 2 COOR 12 所示的基团，其中Y是卤原子，R 12 是碱金属原子或低级烷基；Ar 1 是被低级烷基等取代的苯基或被低级烷基等取代的吡啶基；X 2 、X 3 和X 9 相同或不同，并为卤原子；X 4 是离去基团；M是碱金属原子。(1)

A kind of preparation method of polysubstituted oxazole derivatives

本发明公开了属于有机合成技术领域的一种多取代噁唑衍生物的制备方法。所述方法为：向反应容器中，先后加入取代N‑苯氧基酰胺，取代苯乙炔基碘鎓盐和碳酸钾，加入溶剂1,2‑二氯乙烷，水浴20℃搅拌至反应4小时完毕后，使用旋转蒸发仪浓缩滤液得到粗产物，粗产物用硅胶柱层析分离得到目标化合物。本发明提供的多取代噁唑衍生物的合成方法具有科学合理，合成方法简单，目标化合物产率较高，产物易于纯化等特点。其反应方程式如下：

Preparation method of febuxostat

本发明提供了一种非布司他的制备方法，属于医药合成技术领域。本发明采用2‑(3‑甲酰基‑4‑羟基苯基)‑4‑甲基‑噻唑‑5‑羧酸乙酯为原料，经过异丁基化反应，氰基化反应和水解反应合成非布司他。本发明合成路线简单，且通过对每一步反应的产物进行后处理，及对粗产物进行精制除杂、调晶等处理，极大程度地提高产品纯度和收率、降低了成本，使操作更加简单合理，并且本发明提供的制备方法反应条件温和，能耗更低，更适合工业化生产。

Thiazol-(bi)cycloalkyl-carboxanilides

The invention concerns novel thiazol-(bi)cycloalkyl-carboxanilides of formula (I), wherein Q and R1 are such as defined in the description. The invention also concerns a method for producing said substances and their use for fighting against undesirable micro-organisms.

Anilide derivatives and their use to combat Botrytis

Use of nicotinanilide derivatives of the general formula <IMAGE> in which the substituents have the following meanings: R<1> represents halogen, methyl, trifluoromethyl, methoxy, methylthio, methylsulphinyl, methylsulphonyl and R<2> represents alkyl which is optionally substituted by halogen, alkenyl which is optionally substituted by halogen, alkynyl, alkoxy which is optionally substituted by halogen, alkenyloxy which is optionally substituted by halogen, or alkynyloxy, cycloalkyl, cycloalkenyl, cycloalkyloxy or cycloalkenyloxy for combating botrytis, and nicotin anilides of the formula I.

Thiazol-(bi)cycloalkyl-carboxanilides

This invention relates to novel thiazole(bi)cycloalkylcarboxanilides of the formula (I) in which Q and R 1 are as defined in the disclosure, to a process for preparing these compounds and to their use for controlling unwanted microorganisms.