Substituted thieno(2,3-B)(1,4)thiazine-6-sulfonamides as antiglaucoma agents

Cephalosporin derivatives, the process for preparing the same, and antimicrobial composition containing the derivatives

Process for producing 2-hydroxymethylmorpholine salt

The invention relates to a production method of a 2-hydroxymethylmorpholine salt, which includes crystallization from a solution containing 2-hydroxymethylmorpholine of formula (1) 1,4-oxazepane compound of formula (2) and an acid.

Bait chemistries in hydrogel particles for serum biomarker analysis

This invention describes the identification of novel organic dye chemistries that can be used as affinity baits to capture proteins and other biomolecules useful in the fields of medical diagnostics, environmental science, toxicology, and infectious disease. Incorporation of unique affinity dye compounds within hydrogel capture particles improves analyte yield and preanalytical precision, and stabilizes the analyte against degradation, while increasing measurement sensitivity. The particles in this invention can be used for routine clinical testing as well as for discovery of low abundance disease biomarkers. Example hydrogel particles containing new high affinity bait chemistries were used to identify a new set of human serum biomarkers.

Reduction of fused bicyclic impurities in triiodinated x-ray contrast media

The present disclosure generally relates to an improved process for alkylating a triiodo-substituted arylamide to form a compound suitable for use as an X-ray contrast agent. More particularly, the present disclosure is directed to such a process that limits the formation of fused bicyclic impurities, such as Impurity G, in the alkylation reaction mixture.

CONTROLLED RELEASE OF SEED AND SOIL TREATMENTS TRIGGERED BY pH CHANGE OF GROWING MEDIA

The invention features a method of improving the growth of a plant, involving applying to a seed or locus thereof a composition comprising an active ingredient and a pH-dependent film-forming polymer, followed by exposing the composition to an appropriate pH to release said active ingredient. The invention further features a seed including a composition having a) an active ingredient; and b) a pH-dependent film-forming polymer. Additionally, the invention features a seed treatment composition that includes a) an agrochemical; b) a pH-dependent film-forming polymer; and c) a seed coating agent. 1. A method of improving the growth of a plant , said method comprising applying to a seed or locus thereof a composition comprising an active ingredient and a pH-dependent film-forming polymer , followed by exposing said composition to an appropriate pH to release said active ingredient.2. The method of claim 1 , wherein said composition is a microcapsule.3. The method of claim 1 , wherein said active ingredient is an agrochemical claim 1 , an attractant claim 1 , a repellent claim 1 , or a bait.4. The method of claim 3 , wherein said agrochemical is a pesticide claim 3 , insecticide claim 3 , nematicide claim 3 , acaricide claim 3 , miticide claim 3 , bactericide claim 3 , fungicide claim 3 , herbicide claim 3 , plant growth regulator claim 3 , fertilizer or agrochemical with phytotoxic properties.5. The method of claim 4 , wherein said pesticide is abamectin or thiamethoxam.6. The method of claim 4 , wherein said fungicide is mefenoxam claim 4 , fludioxonil claim 4 , a strobularin claim 4 , thiabendazole claim 4 , or a triazole.7. The method of claim 4 , wherein said herbicide is atrazine.8. The method of claim 4 , wherein said plant growth regulator is a triazole selected from the group consisting of uniconazole claim 4 , paclobutazol claim 4 , cyproconazole claim 4 , propiconazole claim 4 , and trinexapac-ethyl.9. The method of claim 1 , wherein said pH-dependent film- ...

USE OF AMINODIHYDROTHIAZINES FOR THE TREATMENT OR PREVENTION OF DIABETES

This invention relates to compounds of formula I, 2. A compound according to claim 1 , wherein Ris halogen.3. A compound according to claim 1 , wherein Ris fluoro.4. A compound according to claim 1 , wherein Ris heteroaryl claim 1 , said heteroaryl being unsubstituted or substituted by one claim 1 , two or three groups selected from the group consisting of C-alkyl claim 1 , halogen claim 1 , halogen-C-alkyl claim 1 , C-alkoxy claim 1 , halogen-C-alkoxy claim 1 , cyano claim 1 , hydroxy-C-alkyl and phenyl.5. A compound according to claim 1 , wherein Ris heteroaryl selected from the group consisting of thienyl claim 1 , oxazolyl claim 1 , thiazolyl claim 1 , pyrazolyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , isoquinolinyl claim 1 , thieno[2 claim 1 ,3-c]pyridyl and benzo[b]thienyl claim 1 , said heteroaryl being unsubstituted or substituted by one claim 1 , two or three groups selected from the group consisting of C-alkyl claim 1 , halogen claim 1 , halogen-C-alkyl and phenyl.6. A compound according to claim 1 , wherein Ris phenyl claim 1 , said phenyl being unsubstituted or substituted by one claim 1 , two or three groups selected from the group consisting of C-alkyl claim 1 , halogen claim 1 , halogen-C-alkyl claim 1 , C-alkoxy claim 1 , halogen-C-alkoxy claim 1 , cyano claim 1 , hydroxy-C-alkyl and phenyl.8. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier and/or adjuvant.10. A method according to wherein:{'sup': '1', 'Ris ethyl; and'}{'sup': '2', 'sub': 1-7', '1-7, 'Ris selected from the group consisting of C-alkyl, halogen, cyano and C-alkoxy.'} This application is a continuation of U.S. application Ser. No. 12/874,336, filed Sep. 2, 2010, and claims the benefit of European Patent Application No. 09170126.8, filed Sep. 11, 2009, and European Patent Application No. 09172068.0, filed Oct. 2, 2009 which are hereby incorporated by reference in their entirety.The present invention is concerned ...

BENZOXAZINE DERIVATIVES AND USES THEREOF

The present invention provides a compound of the formula: 169-. (canceled)71. The compound according to claim 70 , wherein Zis N.74. The compound according to claim 73 , wherein n and p are 2.75. The compound according to claim 74 , wherein Y is —SO—.76. The compound according to claim 75 , wherein Rand Rare hydrogen.77. The compound according to claim 76 , wherein each Ris independently halo or alkyl.78. The compound according to claim 77 , wherein each Ris independently chloro or methyl.79. The compound according to claim 78 , wherein m is 1.80. The compound according to claim 79 , wherein Ris aryl.81. The compound according to claim 80 , wherein Ris optionally substituted phenyl or optionally substituted naphthyl.82. The compound according to claim 81 , wherein Ris phenyl claim 81 , 2-fluorophenyl claim 81 , 2-chlorophenyl claim 81 , 3 claim 81 ,4-dichlorophenyl claim 81 , 4-chlorophenyl claim 81 , 3-chlorophenyl claim 81 , 4-methoxyphenyl claim 81 , 3 claim 81 ,5-dichlorophenyl claim 81 , 2 claim 81 ,6-dichlorophenyl claim 81 , 2 claim 81 ,4-dichlorophenyl claim 81 , 3-methanesulfonylaminophenyl claim 81 , 2-methanesulfonylphenyl claim 81 , 2-carbamoylphenyl claim 81 , 3-methanesulfonylphenyl claim 81 , 4-methanesulfonylphenyl claim 81 , 3-fluorophenyl claim 81 , naphthyl claim 81 , 2 claim 81 ,4-difluorophenyl claim 81 , 2-cyanophenyl claim 81 , 2-chloro-4-fluorophenyl claim 81 , 2-methyl-5-fluorophenyl claim 81 , or 5-chloronaphthyl.83. The compound according to claim 81 , wherein Ris phenyl or halide substituted phenyl.84. The compound according to claim 83 , wherein Ris phenyl claim 83 , 2-chlorophenyl or 2-fluorophenyl.87. A method for treating a CNS disease state in a subject claim 70 , said method comprising administering to said subject a therapeutically effective amount of a compound of . This application is entitled to the benefit of U.S. Provisional Application No. 60/378,003, filed on May 13, 2002, the disclosure of which is incorporated herein by ...

METHOD FOR PRESERVING AQUEOUS SOLUTION CONTAINING LEUCO CHROMOGEN

It is to provide a method for preserving an aqueous solution comprising a leuco chromogen, comprising adding at least one compound selected from the group consisting of polyoxyethylene alkylamine and polyoxyethylene alkenylamine to the aqueous solution containing a leuco chromogen, and a method for stabilizing a leuco chromogen, comprising allowing the leuco chromogen to coexist in an aqueous solution comprising at least one compound selected from the group consisting of polyoxyethylene alkylamine and polyoxyethylene alkenylamine. The present invention provides a method for preserving an aqueous solution comprising a leuco chromogen for stably preserving the leuco chromogen in an aqueous solution and a method for stabilizing a leuco chromogen. 1. A method for preserving an aqueous solution containing a leuco chromogen , comprising adding at least one compound selected from the group consisting of polyoxyethylene alkylamine and polyoxyethylene alkenylamine to the aqueous solution containing a leuco chromogen.2. A method for stabilizing a leuco chromogen , comprising allowing the leuco chromogen to coexist in an aqueous solution comprising at least one compound selected from the group consisting of polyoxyethylene alkylamine and polyoxyethylene alkenylamine.3. The method according to claim 1 , wherein the leuco chromogen is a phenothiazine chromogen.4. The method according to claim 3 , wherein the phenothiazine chromogen is 10-(carboxymethylaminocarbonyl)-3 claim 3 ,7-bis(dimethylamino)phenothiazine.5. A liquid reagent comprising a leuco chromogen and at least one compound selected from the group consisting of polyoxyethylene alkylamine and polyoxyethylene alkenylamine.6. The reagent according to claim 5 , wherein the leuco chromogen is a phenothiazine chromogen.7. The reagent according to claim 6 , wherein the phenothiazine chromogen is 10-(carboxymethylaminocarbonyl)-3 claim 6 ,7-bis(dimethylamino)phenothiazine.8. The method according to claim 2 , wherein the leuco ...

Mediator For Test Sensor

A method of forming a 3-phenylimino-3H-phenothiazine or a 3-phenylimino-3H-phenoxazine mediator includes providing a first reactant including phenothiazine or phenoxazine, providing a first solvent, providing a second reactant and providing a second solvent. The first reactant, first solvent, second reactant and second solvent are combined to form a reactants solution. Sodium persulfate is added to the reactants solution to couple the first and second reactants resulting in a reaction solution including the 3-phenylimino-3H-phenothiazine or the 3-phenylimino-3H-phenoxazine mediator. 125-. (canceled)26. A 3-phenylimino-3H-phenothiazine mediator or 3-phenylimino-3H-phenoxazine mediator wherein the background current is less than 200 nA after being exposed to a temperature of 50° C. for a duration of two weeks.27. The mediator of wherein the mediator is a 3-phenylimino-3H-phenothiazine mediator.28. The mediator of wherein the mediator is a 3-phenylimino-3H-phenoxazine mediator.29. The mediator of wherein the 3-phenylimino-3H-phenothiazine mediator or 3-phenylimino-3H-phenoxazine mediator is in the form of a salt.30. The mediator of wherein the -phenylimino-3H-phenothiazine mediator or 3-phenylimino-3H-phenoxazine mediator is in the form of a acid.31. A test sensor including a base claim 26 , the base including an enzyme adapted to react with an analyte claim 26 , and a mediator claim 26 , the mediator having a background current being less than 200 nA after being exposed to a temperature of 50° C. for a duration of two weeks.32. The test sensor of further including a neutralizing agent.33. The test sensor of wherein the neutralizing agent is sodium hydroxide.34. The test sensor of wherein the neutralizing agent is sodium bicarbonate.35. The test sensor of further including a buffer.36. The test sensor of wherein the buffer is sodium phosphate.37. The test sensor of wherein the test sensor is an electrochemical test sensor.38. The test sensor of wherein the test sensor ...

COMPOUNDS FOR THE REDUCTION OF BETA-AMYLOID PRODUCTION

Compounds of formula (I), including pharmaceutically acceptable salts thereof, are set forth herein: 2. The compound of claim 1 , wherein:{'sub': '2', 'X is selected from CHand O;'}m=0 or 1;n=0 to 3;{'sup': '1', 'sub': 1-4', '1-4', '1-4', '1', '6', '1', '6', '2', '4, 'Rat each instance is selected from the group of halogen, hydroxy, amino, Calkylamino, Cdialkylamino, haloCalkyl, CN, C-Calkyl or cycloalkyl, C-Calkoxy, or C-Calkynyl;'}L is either a bond or is —NHCO—;{'sub': 1-4', '1-4', '1-4', '1', '6', '1', '6', '2', '4, 'Z is a phenyl, pyridyl, pyrimidinyl, or pyrazinyl group which can be further substituted with from 0-3 substituents selected from the group of halogen, hydroxy, amino, Calkylamino, Cdialkylamino, haloCalkyl, CN, C-Calkyl or cycloalkyl, C-Calkoxy, and C-Calkynyl;'}{'sup': 3', '4', '5, 'sub': '1-4', 'and R, Rand Rare independently selected from hydrogen or Calkyl.'}3. The compound of claim 2 , wherein:{'sub': '2', 'X is selected from CHand O;'}m=0 or 1;n=0 to 3;{'sup': '1', 'Rat each instance is selected from halogen,'}L is either a bond or is —NHCO—;{'sub': 2', '4, 'Z is a phenyl, pyridyl, pyrimidinyl, or pyrazinyl group which can be further substituted with from 0-3 substituents selected from halogen, CN, or C-Calkynyl;'}{'sup': '3', 'sub': '1-4', 'Ris selected from hydrogen or Calkyl;'}{'sup': 4', '5, 'and Rand Rare hydrogen.'}4. A compound of any claims of 1 to 3 wherein the configuration of the chiral center adjacent to the nitrogen of the aminothiazine is (S) or a pharmaceutically acceptable salt thereof.5. The compound of claim 4 , which is 5-Chloro-pyridine-2-carboxylic acid ((4aS claim 4 ,11bS)-2-amino-11b-methyl-4 claim 4 ,4a claim 4 ,5 claim 4 ,6 claim 4 ,7 claim 4 ,11b-hexahydro-3-thia-1-aza-dibenzo[a claim 4 ,c]cyclohepten-10-yl)-amide.6. A pharmaceutical composition which comprises one or more of the compounds as claimed in claim 1 , together with one or more pharmaceutically acceptable carriers claim 1 , excipients or diluents.7. A ...

RADICALLY POLYMERIZABLE PHENOTHIAZINE MACROMONOMER FOR USE IN THE COATING OF MEDICAL DEVICES

The present invention is directed to phenothiazine-base macromonomer compounds and methods of making the same. 4. The compound of claim 1 , wherein said Linker is derived from polyethylene glycol.5. The compound of claim 1 , wherein R claim 1 , R claim 1 , and Rare independently selected from H claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , or butyl.6. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , and Ris H.8. The compound of claim 7 , wherein said Linker is derived from polyethylene glycol.10. A polymer comprising at least one unit comprising the compound of .11. A polymer comprising at least two units comprising the compound of .12. The polymer of claim 10 , wherein said polymer is crosslinked to a biological molecule.13. The polymer of claim 10 , wherein said polymer is crosslinked to a different polymer or copolymer.14. A viscous solution comprising the polymer of and a biological molecule.15. The viscous solution of claim 14 , wherein said biological molecule is an enzyme.16. The viscous solution of claim 14 , wherein said biological molecule is flavin adenine dinucleotide.17. The viscous solution of claim 14 , wherein said biological molecule is nicotinamide adenine dinucleotide.18. The viscous solution of claim 14 , wherein said biological molecule is trapped within a matrix of said polymer.19. A film coating comprising the polymer of .20. A medical device comprising a coating comprising the polymer of claim 10 , wherein said coating is at least partially applied to at least one surface of said medical device.21. The medical device of claim 20 , wherein said medical device is a sensor claim 20 , a transducer claim 20 , or an electrode.22. A method of polymerizing or crosslinking said compounds of claim 20 , wherein said method comprises reacting at least two equivalents of the compounds of in the presence of a catalyst to form a polymer claim 20 , said catalyst selected from the group consisting of an initiator claim ...

CRYSTALLINE FORMS OF THE TRI-MESYLATE SALT OF PERPHENAZINE-GABA AND PROCESS OF PRODUCING THE SAME

Novel crystalline form of perphenazine 4-aminobutyrate trimesylate and a process of producing the same are disclosed. The novel crystalline form is characterized by a unique XRPD pattern and a DSC that exhibits an endothermic peak at a relatively high temperature (e.g., higher than 209° C.). Also disclosed are a process of preparing perphenazine 4-aminobutyrate trimesylate by in situ deprotection and salification, in a single-step synthesis, and a highly pure perphenazine 4-aminobutyrate trimesylate obtained thereby. Uses of any of the described perphenazine 4-aminobutyrate trimesylate are also disclosed. 1. A crystalline form of perphenazine 4-aminobutyrate trimesylate , having at least one of:{'figref': {'@idref': 'DRAWINGS', 'FIG. 2'}, '(a) an X-Ray Powder Diffraction (XRPD) pattern exhibiting at least five of the peaks shown in ; and'}(b) a Differential Scanning Calorimetry (DSC) exhibiting an endothermic peak at or higher than about 209° C.2. The crystalline form of perphenazine 4-aminobutyrate trimesylate of claim 1 , wherein said endothermic peak is at about 214° C.3. The crystalline form of perphenazine 4-aminobutyrate trimesylate of claim 1 , having an X-Ray Powder Diffraction (XRPD) pattern exhibiting at least six of the peaks shown in .4. The crystalline form of perphenazine 4-aminobutyrate trimesylate of claim 1 , having an X-Ray Powder Diffraction (XRPD) pattern exhibiting at least seven of the peaks shown in .5. The crystalline form of perphenazine 4-aminobutyrate trimesylate of claim 1 , having an X-Ray Powder Diffraction (XRPD) pattern substantially identical to one or more of the XRPD patterns shown in .6. The crystalline form of perphenazine 4-aminobutyrate trimesylate of claim 1 , having an X-Ray Powder Diffraction (XRPD) pattern substantially identical to one or more of the XRPD patterns shown in .7. A crystalline form of perphenazine 4-aminobutyrate trimesylate having an X-Ray Powder Diffraction (XRPD) pattern exhibiting at least five of the ...

Treatment of Microbial Infections

The invention provides compositions, medicaments and methods of treating microbial infections, and especially respiratory disorders caused by microbial infections. In particular, the invention relates to the treatment of respiratory diseases caused by pathogenic infections using certain either alkyl substituted or un-substituted 2-aryl acetic acid, or 2-aryl, N-hydroxyacetamide derivatives, or pentoxifylline, and to the use of these compounds in methods of treatment. 2. The compound according to claim 1 , wherein Ar is a substituted phenyl group.3. The compound according to claim 1 , wherein Ris hydrogen or a methyl group.4. The compound according to claim 1 , wherein Ris —NHOH.5. The compound according to claim 1 , wherein when Ar is a substituted phenyl group claim 1 , the bond joining it to the remainder of the structure shown in formula I extends directly to a carbon atom in the phenyl ring.6. The compound according to claim 1 , wherein compound (I) is a 2-aryl claim 1 , N-hydroxyacetamide claim 1 , or 2-aryl claim 1 , 2-methyl claim 1 , N-hydroxyacetamide derivative.7. The compound according to claim 1 , wherein compound (I) is ibuproxam claim 1 , oxametacin claim 1 , benoxaprofen claim 1 , or benoxaprofen hydroxamate.1023-. (canceled)24. A pharmaceutical composition comprising a therapeutically effective amount of a compound claim 1 , as defined in claim 1 , and a pharmaceutically acceptable vehicle.25. The pharmaceutical composition according to claim 24 , wherein compound is pentoxifylline claim 24 , ibuproxam claim 24 , oxametacin claim 24 , benoxaprofen claim 24 , benoxaprofen hydroxamate claim 24 , or a pharmaceutically acceptable salt claim 24 , solvate or solvate of a salt thereof.27. A method of treating an infection claim 1 , the method comprising the step of administering claim 1 , to a subject in need of such treatment claim 1 , a therapeutically effective amount of a compound as defined in claim 1 , wherein the infection causes a respiratory ...

2-(R2-THIO)-10-[3-(4-R1-PIPERAZIN-1-YL) PROPYL]-10H-PHENOTHIAZINE FOR TREATING A BETA-AMYLOIDOPATHY OR AN ALPHA-SYNUCLEOPATHY, AND METHOD FOR THE DIAGNOSIS OR PREDIAGNOSIS THEREOF

The invention relates to 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to general formula I, for treating a β-amyloidopathy or an α-synucleinopathy accompanied by a cerebral protein deposit and a reduced activity of the cerebral ABCC1-transporter. The invention also relates to a method for the diagnosis or prediagnosis of a β-amyloidopathy or an α-synucleopathy accompanied by a cerebral protein deposit and a reduced activity of the cerebral ABCC1-transporter, or for determining the risk of a proband suffering from such an illness, the proband already having accumulated substances transported by the cerebral ABCC1 transporter. 2. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to claim 1 , characterized in that wherein the halogen atom/the halogen atoms are selected from the group consisting of fluorine and chlorine.3. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to claim 1 , wherein Rand Rare the same or different and each independently of one another is a C-Calkyl group.4. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to claim 1 , wherein the residues Rand Rare hydrogen.5. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to claim 1 , wherein the residue Ris a methyl group claim 1 , the residue Ris an ethyl group claim 1 , and the residues Rand Rare hydrogen.6. A composition comprising a 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to claim 1 , further comprising a further active substance.7. A composition according to claim 6 , wherein a 1-benzohydrylpiperazine is a further active substance.8. A composition according to claim 7 , wherein 1-benzohydryl-4-cinnamyl piperazine is the 1-benzohydrylpiperazine.9. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazines according to claim 1 , wherein the β-amyloidopathy is Alzheimer's dementia.10. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H- ...

MORPHOLINOALKYL FUMARATE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE

Morpholinoalkyl fumarates, pharmaceutical compositions comprising the morpholinoalkyl fumarates, and methods of using morpholinoalkyl fumarates and pharmaceutical compositions for treating neurodegenerative, inflammatory, and autoimmune disorders including multiple sclerosis, psoriasis, irritable bowel disorder, ulcerative colitis, arthritis, chronic obstructive pulmonary disease, asthma, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are disclosed. 2. The compound according to claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , isobutyl claim 1 , tert-butyl claim 1 , n-pentyl claim 1 , pentyl-2-yl claim 1 , 2-methylbutyl claim 1 , isopentyl claim 1 , 3-methylbutan-2-yl claim 1 , neopentyl claim 1 , tert-pentyl claim 1 , n-hexyl claim 1 , hexan-2-yl claim 1 , 2-methylpentyl claim 1 , 3-methylpentyl claim 1 , 4-methylpentyl claim 1 , 3-methylpentan-2-yl claim 1 , 4-methylpentan-2-yl claim 1 , 2 claim 1 ,3-dimethylbutyl claim 1 , or 3 claim 1 ,3-dimethylbutyl.3. The compound according to claim 1 , wherein Ris methyl.6. The compound according to claim 1 , wherein the compound is a pharmaceutically acceptable salt.7. The compound according to claim 1 , wherein the compound is a HCl salt.8. A compound selected from the compounds listed in Table 1.10. The compound according to claim 9 , wherein the compound is a HCl salt.12. The pharmaceutical composition according to claim 11 , wherein Ris methyl.13. The pharmaceutical composition according to claim 11 , wherein Ris methyl claim 11 , ethyl claim 11 , n-propyl claim 11 , isopropyl claim 11 , n-butyl claim 11 , isobutyl claim 11 , tert-butyl claim 11 , n-pentyl claim 11 , pentyl-2-yl claim 11 , 2-methylbutyl claim 11 , isopentyl claim 11 , 3-methylbutan-2-yl claim 11 , neopentyl claim 11 , tert-pentyl claim 11 , n-hexyl claim 11 , hexan-2-yl claim 11 , 2-methylpentyl claim 11 , 3-methylpentyl claim 11 , 4-methylpentyl claim 11 , 3- ...

USE OF CYANINE DYES FOR THE DETECTION OF TAU FOR DIAGNOSIS OF EARLY-STAGE TAUOPATHIES

Radiolabeled compounds useful as diagnostic imaging agents of Tau pathology in Alzheimer's disease are described. Compositions and methods of making such compounds are also described. 87. A pharmaceutical composition comprising a compound according to any one of - and a pharmaceutically acceptable carrier or excipient.97. A method of making a compound of according to any one of -.107. A method of imaging using a compound according to any one of - or a pharmaceutical composition thereof.117. A method of detecting tau aggregates in vitro and/or in vivo using a compound according to any one of - or a pharmaceutical composition thereof.13. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier or excipient.14. A method of imaging using a compound of or a pharmaceutical composition thereof.15. A method of detecting tau aggregates in vitro and/or in vivo using a compound according to or a pharmaceutical composition thereof.17. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier or excipient. The present invention relates to radiolabeled compounds, compositions thereof, methods of making such compounds and their use as imaging probes of Tau pathology especially as it relates to Alzheimer's Disease. Compounds of the present invention may be used for Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) imaging.Alzheimer's disease (AD) is the most common cause of dementia in the elderly. It is definitively diagnosed and staged on the basis of post-mortem neuropathology. The pathological hallmark of AD is a substantial neuronal loss accompanied by deposition of amyloid plaques and neurofibrillary tangles (NFTs).NFTs consist of filamentous aggregates composed of microtubule-associated protein tau. Much of the literature suggests that tau aggregates (NFTs) or NFT formation correlate more closely with AD progression than amyloid plaques (Braak, H. et al., ...

CHEMICAL LIGATION BY RING OPENING OF OXO-THIOMORPHOLINES

The invention discloses processes for preparing compounds comprising an α-amino acid motif. The compounds are useful in e.g. the chemical ligation of peptides. 2. A process according to wherein compound (IX) is a thioester.4. A process according to wherein Ris an optionally protected peptide.5. A process according to wherein Rcomprises at least a 9H-fluoren-9-ylmethoxycarbonyl (FMOC) protecting group.6. A process according to wherein X is NH.7. A process according to wherein Ris H.8. A process according to wherein Ris H.9. A process according to wherein A is CH.10. A process according to wherein Ris aryl claim 1 , optionally attached to a solid support claim 1 , optionally via a linker.11. A process according to wherein Ris an optionally protected peptide optionally attached to a solid support claim 1 , optionally via a linker.12. A process according to wherein Ris an optionally protected peptide optionally attached to a solid support claim 1 , optionally via a linker.14. A process according to comprising a further deprotection step or steps to give a free peptide.17. (canceled)19. A compound of formula (VI) according to wherein Z is t-butyloxycarbonyl (BOC). The invention relates to processes for the synthesis of molecules comprising an α-amino acid unit, in particular peptides, and to intermediates useful in the synthesis of such compounds.Peptides are of central importance in biological systems. In addition, peptides find use in pharmaceutical, agrochemical and other commercial applications.Chemical synthesis of peptides is a large field of academic endeavour, and many successful approaches to the synthesis of peptides have been developed over the years. The chemical synthesis of peptides allows for the production of the substances on a scale not possible by extraction and purification from natural sources; furthermore, it allows for the incorporation of non-natural amino acids into the peptide structure.Many chemical syntheses of peptides are linear in approach, ...

2-(2-PHENYLETHENYL) 1,3-BENZODIAZEPINE COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER

The present invention provides compounds of formula (1) acting as protein kinase (PK) and receptor kinase (RK) signaling modulators. The invention further provides methods of their preparation, pharmaceutical compositions including such compounds, and methods of using these compounds and compositions, especially as anti-cancer agents for preventions and treatments of PK- and RK-related disorders, in particular cancer. (I) wherein A is H or CN; Z is S, SO or S0; X, X, X, X, X, Yand Yare each independently selected from H, halogen, alkyl, haloalkyl and OR; and Yand Yare each OR, wherein each Ris independently H, C-Calkyl, acyl, —(CHCH0)wherein n is an integer of 1 to 20, or a functional group that gives rise to hydroxyl upon hydrolysis. 150.-. (canceled)52. A compound according to claim 51 , wherein A is H.53. A compound according to claim 51 , wherein A is CN.54. A compound according to claim 51 , wherein Z is S.55. A compound according to claim 51 , wherein Z is SO.56. A compound according to claim 51 , wherein{'sup': 1', '2', '3', '4', '1', '2, 'at least one of X, X, X, X, Yand Yis a halogen: or'}{'sup': 1', '2', '3', '4, 'X, X, X, and Xare each H or a halogen; or'}{'sup': 3', '4, 'Yand Yare each OH; or'}{'sup': 1', '2, 'Yand Yare each OH.'}57. A compound according to claim 51 , wherein{'sup': 3', '4', '1, 'A is H, Z is S, Yand Yare each OH, and Xis a halogen selected from Br and I; or'}{'sup': 3', '4', '1, 'A is CN, Z is S, Yand Yare each OH, and Xis a halogen selected from Br and I; or'}{'sup': 3', '4', '3, 'A is H, Z is S, Yand Yare each OH, and Xis a halogen selected from Br and I; or'}{'sup': 3', '4', '2, 'A is H, Z is S, Yand Yare each OH, and Xis a halogen selected from Br and I; or'}{'sup': 3', '4', '1', '4, 'A is H, Z is S, Yand Yare each OH, and Xand Xare each a halogen selected from Br and I; or'}{'sub': '2', 'sup': 3', '4', '1, 'A is H, Z is SO, Yand Yare each OH, and Xis a halogen selected from Br and I; or'}{'sub': '2', 'sup': 3', '4', '1', '2', '3', ...

CENTRAL NERVOUS SYSTEM TISSUE-LABELING COMPOSITION, METHOD FOR LABELING CENTRAL NERVOUS SYSTEM TISSUE, AND SCREENING METHOD USING CENTRAL NERVOUS SYSTEM TISSUE-LABELING COMPOSITION

To provide a central nervous system tissue-labeling composition labeling the central nervous tissue system. Also, another object of the present invention is to provide a method for non-invasively labeling the central nervous tissue system. Further, another object of the present invention is to provide a screening method using the above central nervous system tissue-labeling composition. A central nervous system tissue-labeling composition containing, as an active ingredient, at least one of compounds represented by the general formula (1) or (7). 16-. (canceled)8. The composition according to claim 7 , wherein the compound is able to label at least any one of optic nerve claim 7 , optic tract claim 7 , superior colliculus (optic tectum) claim 7 , pituitary gland claim 7 , tectospinal (tectobulbar) tract claim 7 , and reticular formation.9. The composition according to claim 7 , wherein the compound is a fluorescent compound.10. The composition according to claim 7 , wherein the compound is labeled with a radionuclide.12. The method according to claim 11 , wherein the ring formed by X and Y is cyclopentane.14. The method according to claim 13 , wherein the ring formed by X and Y is cyclopentane. This application is a continuation of International Application No. PCT/JP2010/007519, filed Dec. 24, 2010, which claims the benefit of Japanese Patent Application No. 2009-296270, filed Dec. 25, 2009.1. Field of the InventionThe present invention relates to a labeling composition capable of clearly labeling a central nervous system tissue, a method for labeling a central nervous system tissue using the central nervous system tissue-labeling composition, and a screening method using the central nervous system tissue-labeling composition.2. Description of the Related ArtRecently, a number of patients with central nervous system diseases has been on the increase along with the aging of society. Representative examples of the diseases include Parkinson's disease, Alzheimer's ...

1-ARYL -1-HYDROXY -2,3-DIAMINO-PROPYL AMIN ES, 1-HETEROARYL-1-HYDROXY-2,3-DIAMINO-PROPYL AMINES AND RELATED COMPOUNDS HAVING ANALGESIC AND/OR IMMUNO STIMULANT ACTIVITY

Compounds of the formula 2. (canceled)3. (canceled)4. (canceled)5. (canceled)10. (canceled)11. (canceled)12. A method of treating a mammal in need of such treatment with a pharmaceutical composition having an analgesic effect claim 1 , the composition including a compound in accordance with .13. (canceled)14. (canceled)15. A method of treating a mammal in need of such treatment with a pharmaceutical composition having an analgesic effect claim 6 , the composition including a compound in accordance with .16. A method of treating a mammal in need of such treatment with a pharmaceutical composition having an analgesic effect claim 7 , the composition including a compound in accordance with .17. A method of treating a mammal in need of such treatment with a pharmaceutical composition having an analgesic effect claim 8 , the composition including a compound in accordance with .18. A method of treating a mammal in need of such treatment with a pharmaceutical composition having an analgesic effect claim 9 , the composition including a compound in accordance with .19. (canceled) This application is a divisional application of Ser. No. 13/196,132, filed Aug. 2, 2011, which is a continuation of Ser. No. 11/814,601, filed Mar. 17, 2008, which is a §371 National Stage of PCT/US2006/002570, filed Jan. 25, 2006, which claims the benefit of U.S. Provisional Application Ser. No. 60/647,271, filed Jan. 26, 2005, each of which is hereby incorporated by reference herein.The present invention relates to derivatives of 1-aryl-1-hydroxy-2,3-diamino-propyl amines, 1-heteroaryl-1-hydroxy-2,3-diamino-propyl amines and to related compounds having analgesic and in some cases immunostimulant activity.The present invention also relates to pharmaceutical compositions containing these compounds as active ingredient for alleviating or eliminating pain in mammals and/or stimulating the immune system in mammals and to methods of using said pharmaceutical compositions as analgesics and/or ...

NOVEL THIAZOLIDIN-4-ONE-DERIVATIVES

The invention relates to pharmaceutical compositions containing at least one thiazolidin-4-one derivative to prevent or treat disorders associated with an activated immune system. Furthermore, the invention relates to novel thiazolidin-4-one derivatives notably for use as pharmaceutically active compounds. Said compounds particularly act also as immunosuppressive agents. 2. The method according to claim 1 , wherein said thiazolidin-4-one derivative is the (Z claim 1 ,Z) isomer.3. The method according to claim 1 , wherein Rrepresents an unsubstituted claim 1 , or a mono- or di-substituted phenyl group.4. The method according to claim 1 , wherein Rrepresents an unsubstituted claim 1 , or a mono- or di-substituted phenyl group claim 1 , substituted with methyl or halogen.5. The method according to claim 1 , wherein Rrepresents lower alkyl.6. The method according to claim 1 , wherein Rrepresents halogen or methyl.7. The method according to claim 1 , wherein m represents the integer 0 claim 1 , and R claim 1 , R claim 1 , Rand Rrepresent hydrogen.8. The method according to claim 1 , wherein m represents the integer 1 claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rrepresent hydrogen claim 1 , and Rrepresents hydroxy.9. The method according to claim 1 , wherein Rrepresents hydrogen.10. The method according to claim 1 , wherein m represents the integer 0 claim 1 , and R claim 1 , R claim 1 , R claim 1 , Rand Rrepresent hydrogen.11. The method according to claim 1 , wherein m represents the integer 1 claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rrepresent hydrogen claim 1 , and Rrepresents hydroxy.12. The method according to claim 1 , wherein Rrepresents an unsubstituted claim 1 , or a mono- or di-substituted phenyl group claim 1 , substituted with methyl or halogen claim 1 , and Rrepresents lower alkyl.13. The method according to claim 1 , wherein Rrepresents an unsubstituted claim 1 , or a mono- or di-substituted phenyl group claim 1 , substituted ...

TRICYCLIC HETEROAROMATIC COMPOUNDS AS ALPHA-SYNUCLEIN LIGANDS

Derivatives of phenothiazine, phenoxazine, and phenazine compounds and their use as α-synuclein ligands are described. Also described are methods of using these compounds and their radiolabeled analogs for the detection, monitoring, and treatment of synucleinopathies, including Parkinson's disease. 2. (canceled)3. (canceled)4. The compound of wherein R is hydrogen claim 1 , C-Calkyl claim 1 , or C-Cacyl.5. The compound of wherein R is hydrogen claim 4 , methyl claim 4 , or acetyl.6. (canceled)7. The compound of wherein one or more of A claim 1 , A claim 1 , A claim 1 , A claim 1 , A claim 1 , A claim 1 , A claim 1 , or Ais nitrogen.8. The compound of wherein either Aor Ais nitrogen and Ais C—R claim 7 , Ais C—R claim 7 , Ais C—R claim 7 , Ais C—R claim 7 , Ais C—R claim 7 , and Ais C—R.9. The compound of claim 1 , wherein Ais C—R claim 1 , Ais C—R claim 1 , Ais C—R claim 1 , Ais C—R claim 1 , Ais C—R claim 1 , Ais C—R claim 1 , Ais C—R claim 1 , and Ais C—R.10. The compound of wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare each independently hydrogen claim 1 , fluoro claim 1 , bromo claim 1 , iodo claim 1 , hydroxy claim 1 , substituted or unsubstituted C-Calkyl claim 1 , substituted or unsubstituted C-Calkoxy claim 1 , cyano claim 1 , nitro claim 1 , amino claim 1 , C-Calkylamino claim 1 , or di-C-Calkylamino.11. The compound of wherein R claim 10 , R claim 10 , R claim 10 , R claim 10 , R claim 10 , R claim 10 , R claim 10 , and Rare each independently hydrogen claim 10 , bromo claim 10 , iodo claim 10 , hydroxy claim 10 , C-Calkyl claim 10 , C-Chaloalkyl claim 10 , substituted or unsubstituted C-Calkoxy claim 10 , cyano claim 10 , nitro claim 10 , amino claim 10 , C-Calkylamino claim 10 , or di-C-Calkylamino.12. (canceled)13. The compound of wherein R claim 11 , R claim 11 , R claim 11 , R claim 11 , R claim 11 , R claim 11 , R claim 11 , and Rare each independently hydrogen claim 11 , bromo claim 11 , iodo ...

PHENOTHIAZINE DIAMINIUM SALTS AND THEIR USE

The invention relates to compounds of general formula (I): wherein: each of Rand Ris independently selected from: —H, Calkyl, Calkenyl, and halogenated Calkyl; each of Rand Ris independently selected from: —H, Calkyl, Calkenyl, and halogenated Calkyl; each of R7NA and R7NB is independently selected from: —H, Calkyl, Calkenyl, and halogenated Calkyl; and wherein: each of Rand Ris independently selected from: Calkyl, halogenated Calkyl, and Caryl; or Rand Rare linked to form a group selected from: Calkylene and Carylene; and pharmaceutically acceptable salts thereof, which are useful in the treatment of, for example, Alzheimer's disease. In other aspects the invention also relates to novel formulations of 3,7-diamino-10H-phenothiazinium salts. 2. A compound according to wherein each of Rand Ris independently Calkyl.3. A compound according to wherein each of Rand Ris independently methyl.4. A compound according to wherein each of Rand Ris independently —H.5. A compound according to wherein each of Rand Rand is independently Calkyl.6. A compound according to wherein each of Rand Ris independently methyl.7. A compound according to wherein each of Rand Ris independently Calkyl.8. A compound according to wherein each of Rand Ris independently methyl.10. A compound according to in crystalline form.11. A compound according to in crystalline form claim 9 , having a crystal structure as represented by .12. A compound according to in substantially purified form.13. A compound according to and a pharmaceutically acceptable carrier or diluent.14. A process for preparing a pharmaceutical composition comprising admixing a compound according to claim 1 , and a pharmaceutically acceptable carrier or diluent.15. A solid dosage form comprising the pharmaceutical composition of and at least one diluent suitable for dry compression.16. A composition according to wherein the solid dosage form is produced by direct compression.17. A composition according to wherein the solid dosage form is ...

METHODS OF SYNTHESIS AND/OR PURIFICATION OF DIAMINOPHENOTHIAZINIUM COMPOUNDS

Described are methods of synthesis and/or purification of certain 3,7-diamino-phenothiazin-5-ium compounds (referred to herein as “diaminophenothiazinium compounds”) including Methylthioninium Chloride (MTC) (also known as Methylene Blue), the resulting (high purity) compounds, compositions comprising such compounds (e.g., tablets, capsules), and the use of such high purity compounds. The compounds are useful in inactivating pathogens, and methods of medical treatment, prophylaxis, and diagnosis of diseases including a tauopathy, related neurological and infectious diseases. 2. A method according to claim 1 , for the synthesis and/or purification of methylthioninium chloride (MTC) claim 1 , which method comprises at least the following steps claim 1 , in order:purifying (PUR) 3,7-di(dimethylamino)-10-acetyl-phenothiazine;deacylating (DAC) said 3,7-di(dimethylamino)-10-acetyl-phenothiazine to give 3,7-di(dimethylamino)-10H-phenothiazine;{'sup': 'DAC-OX', 'optionally purifying (PUR) said 3,7-di(dimethylamino)-10H-phenothiazine;'}oxidizing (OX) said 3,7-di(dimethylamino)-10H-phenothiazine to give said methylthioninium chloride (MTC); and{'sup': 'OX', 'optionally purifying (PUR) said methylthioninium chloride (MTC).'}5. A diaminophenothiazinium compound according to claim 4 , having a purity of greater than 98%.6. A diaminophenothiazinium compound according to any one of claim 4 , having less than 1% Azure B as impurity.7. A diaminophenothiazinium compound according to any one of claim 4 , having less than 0.15% Azure A as impurity.8. A diaminophenothiazinium compound according to any one of claim 4 , having less than 0.15% Azure C as impurity.9. A diaminophenothiazinium compound according to any one of claim 4 , having less than 0.05% Methylene Violet Bernthsen (MVB) as impurity.10. A diaminophenothiazinium compound according to claim 4 , having an elementals purity better than the European Pharmacopoeia (EP) limits as set in Version EP5.4.11. A pharmaceutical tablet ...

2,4-PYRIMIDINEDIAMINE COMPOUNDS AND THEIR USES

The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades. 1. 6-amino-2,2-difluoro-4H-benzo[1,4]oxazin-3-one. This application is a continuation of U.S. patent application Ser. No. 13/759,835, filed Feb. 5, 2013, which is a continuation of U.S. patent application Ser. No. 13/288,813, filed Nov. 3, 2011, now issued as U.S. Pat. No. 8,410,266, which is a continuation of U.S. patent application Ser. No. 12/762,178, filed Apr. 16, 2010, now issued as U.S. Pat. No. 8,148,525, which is a continuation of U.S. patent application Ser. No. 11/539,049, filed Oct. 5, 2006, now issued as U.S. Pat. No. 7,820,819, which is a continuation of U.S. patent application Ser. No. 10/355,543, filed Jan. 31, 2003, now issued as U.S. Pat. No. 7,557,210, which in turn claims benefit under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 60/353,333, filed Feb. 1, 2002; U.S. Provisional Patent Application No. 60/353,267, filed Feb. 1, 2002; U.S. Provisional Patent Application No. 60/399,673, filed Jul. 29, 2002; and U.S. Provisional Patent Application No. 60/434,277, filed Dec. 17, 2002, all of which prior applications are incorporated herein by reference.The present invention relates generally to 2,4-pyrimidinediamine compounds, pharmaceutical compositions comprising the compounds, intermediates and synthetic methods of making the compounds and methods of using the compounds and compositions in a variety of contexts.Crosslinking of Fc receptors, such as the high affinity receptor for IgE (FcεRI) and/or the high ...

EPOTHILONE DERIVATIVES

The present invention relates to compounds of the formula 4. A compound according to claim 3 , wherein G is optionally-substituted benzothiazolyl.5. A compound according to claim 3 , wherein G is optionally-substituted quinolinyl.7. A compound according to claim 6 , wherein{'sub': '8', 'Ris methyl;'}G is selected from optionally-substituted benzothiazolyl, benzoxazolyl, benzothienyl, quinuclidinyl, and quinolinyl;{'sub': '7', 'Ris hydrogen; and'}{'sub': 3', '4', '5, 'R, R, and Rare each alkyl groups containing from one to four carbon atoms.'} This application is a continuation of, and claims the benefit of priority of application Ser. No. 11/763,636, filed Jun. 15, 2007, which is a continuation of application Ser. No. 11/512,623, filed Aug. 30, 2006 (now U.S. Pat. No. 7,241,755), which is a continuation of Ser. No. 10/405,886, filed Apr. 3, 2003 (now U.S. Pat. No. 7,125,899), which is a continuation of, and claims the benefit of priority of application Ser. No. 09/084,542, filed May 26, 1998, (now U.S. Pat. No. 6,650,599), which claims priority to U.S. provisional application Ser. No. 60/067,524, filed Dec. 4, 1997, and provisional application Ser. No. 60/051,951, filed Jul. 8, 1997.The present invention relates to epothilone derivatives, methods for the preparation of the derivatives and intermediates therefor.Epothilones are macrolide compounds which find utility in the pharmaceutical field. For example, Epothilones A and B having the structures:have been found to exert microtubule-stabilizing effects similar to TAXOL and hence cytotoxic activity against rapidly proliferating cells, such as, tumor cells or other hyperproliferative cellular disease, see 1996, 35, No. 13/14.The present invention relates to compounds of the formulawherein,Q is selected from the group consisting ofG is selected from the group consisting of alkyl, substituted alkyl, substituted or unsubstituted aryl, heterocyclo,W is O or NR;X is O or H, H;Y is selected from the group consisting of O; ...

BICYCLIC PKM2 ACTIVATORS

Compounds and compositions comprising compounds including formula (I) that activate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that activate PKM2 in the treatment of cancer. 1312. A pharmaceutical composition comprising a compound of - or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.1412. A method of modulating PKM2 activity in a subject in need thereof claims 1 , the method comprising administering to said subject a compound of - or a pharmaceutical composition of .1512. A method of treating a cancer associated with PKM2 activity in a subject in need thereof claims 1 , the method comprising administering to the subject a compound of - or a pharmaceutical composition of .1617-. (canceled) This application claims priority from U.S. Ser. No. 61/425,557, filed Dec. 21, 2010, U.S. Ser. No. 61/425,499, filed Dec. 21, 2010, U.S. Ser. No. 61/425,513 filed Dec. 21, 2010 and U.S. Ser. No. 61/425,528 filed Dec. 21, 2010, each of which is incorporated herein by reference in its entirety.Cancer cells rely primarily on glycolysis to generate cellular energy and biochemical intermediates for biosynthesis of lipids and nucleotides, while the majority of “normal” cells in adult tissues utilize aerobic respiration. This fundamental difference in cellular metabolism between cancer cells and normal cells, termed the Warburg Effect, has been exploited for diagnostic purposes, but has not yet been exploited for therapeutic benefit.Pyruvate kinase (PK) is a metabolic enzyme that converts phosphoenolpyruvate to pyruvate during glycolysis. Four PK isoforms exist in mammals: the L and R isoforms are expressed in liver and red blood cells, the M1 isoform is expressed in most adult tissues, and the M2 isoform is a splice variant of M1 expressed during embryonic development. All tumor cells exclusively express the embryonic M2 isoform. A well-known difference between the M1 and M2 isoforms of ...

BENZO [1,4] OXAZIN DERIVATIVES AS CALCIUM SENSING RECEPTOR MODULATORS

Compounds of Formula (I) along with processes for their preparation that are useful for treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of calcium sensing (CaSR) receptors. Methods of treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of calcium sensing (CaSR) receptors of Formula (I). 4. The compound of claim 1 , wherein L is a bond claim 1 , —(CRR)— claim 1 , —C(O)— claim 1 , —C(O)NR— claim 1 , —C(O)CHand —CHC(O)— claim 1 , where Rand Rare independently selected from hydrogen claim 1 , halogen claim 1 , substituted or unsubstituted alkyl and substituted or unsubstituted haloalkyl; Ris hydrogen or substituted or unsubstituted alkyl; and ‘m’ is 1 to 3.7. The compound of claim 1 , wherein X is selected from a bond claim 1 , —(CRR) claim 1 , —O— claim 1 , —O(CRR)— claim 1 , —(CRR)O— claim 1 , —C(O)(CRR)— claim 1 , —C(O)NR— claim 1 , —C(O)NR(CRR)— claim 1 , -cycloalkylene- claim 1 , and —O-cycloalkylene-; wherein Rand Rmay be same or different and are independently selected from hydrogen claim 1 , halogen claim 1 , hydroxy claim 1 , cyano claim 1 , nitro claim 1 , substituted or unsubstituted alkyl claim 1 , substituted or unsubstituted haloalkyl and substituted or unsubstituted cycloalkyl; or Rand R claim 1 , form a substituted or unsubstituted 3 to 7 membered saturated carbocyclic ring; Ris hydrogen claim 1 , substituted or unsubstituted alkyl claim 1 , substituted or unsubstituted cycloalkyl or substituted or unsubstituted aryl; and‘m’ is 1 or 2.8. The compound of claim 1 , wherein Ris −OR claim 1 , wherein Ris hydrogen or substituted or unsubstituted alkyl.9. The compound of claim 1 , wherein Ris —NRR claim 1 , wherein Rand Rare hydrogen claim 1 , substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.10. The compound of claim 1 , wherein X is selected from a bond claim 1 , —(CRR) claim 1 , —O— claim 1 , —O(CRR ...

Multifunctional Radical Quenchers For The Treatment Of Mitochondrial Dysfunction

The present disclosure provides methods for identifying therapeutic agents that are multifunctional radical quenchers. It also provides compounds of formula (I), (II), or (II-A): and pharmaceutically acceptable salts thereof, compositions comprising these compounds, and methods of using these compounds in a variety of applications, such as treatment or suppression of diseases associated with decreased mitochondrial function resulting in diminished ATP production and/or oxidative stress and/or lipid peroxidation. 2. The compound according to claim 1 , wherein Ris C-Calkyl.3. The compound according to claim 1 , wherein Ris —OR claim 1 , —SR claim 1 , —NHR claim 1 , or —N(R).4. The compound according to claim 1 , wherein Ris hydrogen claim 1 , halogen claim 1 , C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , —OR claim 1 , —SR claim 1 , —NHR claim 1 , or —N(R).516.-. (canceled)17. The compound according to claim 1 , wherein Ris optionally substituted C-Calkyl claim 1 , optionally substituted C-Calkenyl claim 1 , or optionally substituted C-Calkynyl.1819.-. (canceled)20. The compound according to claim 1 , wherein Ris —OR claim 1 , —SR claim 1 , —NHR claim 1 , or —N(R).21. The compound according to claim 1 , wherein Ris optionally substituted C-Calkyl claim 1 , optionally substituted C-Calkenyl claim 1 , or optionally substituted C-Calkynyl.22. (canceled)23. The compound according to claim 1 , wherein Ris optionally substituted C-Calkyl claim 1 , optionally substituted C-Calkenyl claim 1 , or optionally substituted C-Calkynyl.2425.-. (canceled)26. The compound according to claim 1 , wherein Ris —OR claim 1 , —SR claim 1 , —NHR claim 1 , or —N(R).2729.-. (canceled)31. The compound according to claim 30 , wherein X is Br or Cl.32. The compound according to claim 30 , wherein Ris hydrogen claim 30 , optionally substituted C-Calkyl claim 30 , optionally substituted C-Calkenyl claim 30 , optionally substituted C-Calkynyl claim 30 , or —OR.3337.-. (canceled)38. ...

Methods of Use for Monomethyl Fumarate and Prodrugs Thereof

Methods of therapeutic treatment using monomethyl fumarate and prodrugs of monomethyl fumarate are disclosed. 1. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound selected from: (i) monomethyl fumarate , (ii) a prodrug of monomethyl fumarate , and (iii) combinations thereof , wherein the disease is chosen from balo concentric sclerosis , bronchiolitis obliterans organizing pneumonia , central nervous system vasculitis , Charcott-Marie-Tooth Disease , childhood ataxia with central nervous system hypomyelination , diabetic retinopathy , graft versus host disease , monomelic amyotrophy , neurodegeneration with brain iron accumulation , neurosarcoidosis , pareneoplastic syndromes , subacute necrotizing myelopathy , Susac syndrome and transverse myelitis.2. The method of claim 1 , wherein the compound comprises monomethyl fumarate.3. The method of claim 1 , wherein the compound comprises a prodrug of monomethyl fumarate.4. The method of claim 3 , wherein the compound comprises dimethyl fumarate.6. The method of claim 5 , wherein each of Rand Ris hydrogen.7. The method of claim 5 , wherein one of Rand Ris hydrogen and the other of Rand Ris chosen from methyl claim 5 , ethyl claim 5 , n-propyl claim 5 , isopropyl claim 5 , n-butyl claim 5 , isobutyl claim 5 , and sec-butyl.8. The method of claim 5 , wherein Rand Rare independently chosen from hydrogen and Calkyl.9. The method of claim 5 , wherein Rand Rtogether with the nitrogen to which they are bonded form a Cheterocycloalkyl ring.10. The method of claim 5 , wherein one of Rand Ris hydrogen and the other of Rand Ris chosen from hydrogen and Calkyl; and Rand Rtogether with the nitrogen to which they are bonded form a ring chosen from morpholine claim 5 , piperazine claim 5 , and N-substituted piperazine.11. The method of claim 5 , wherein one of Rand Ris hydrogen; and the other of Rand Ris chosen from hydrogen and ...

SUBSTITUTED 2-BENZYLIDENE-2H-BENZO[b][1,4]THIAZIN-3(4H)-ONES, DERIVATIVES THEREOF, AND THERAPEUTIC USES THEREOF

The present invention relates to compounds according to Formula I: 2. A compound according to claim 1 , or a salt thereof claim 1 , wherein n is 0.4. A compound according to claim 3 , or a salt thereof claim 3 , wherein at least one of R claim 3 , R claim 3 , or Ris —OR claim 3 , —NHR claim 3 , —SR claim 3 , —S(═O)R claim 3 , or —S(═O)R.5. A compound according to claim 4 , or a salt thereof claim 4 , wherein at least one of R claim 4 , R claim 4 , or Ris —S(═O)R.6. A compound according to claim 5 , or a salt thereof claim 5 , wherein Ris —(CH)R.7. A compound according to claim 5 , or a salt thereof claim 5 , wherein Ris —S(═O)Rand Ris —(CH)R.8. A compound according to claim 7 , or a salt thereof claim 7 , wherein Ris Ar.9. A compound according to claim 8 , or a salt thereof claim 8 , wherein Aris 2 claim 8 ,3-dichlorophenyl claim 8 , 2 claim 8 ,4-dichlorophenyl claim 8 , 2 claim 8 ,5-dichlorophenyl claim 8 , 2 claim 8 ,6-dichlorophenyl claim 8 , 3 claim 8 ,4-dichlorophenyl claim 8 , 3 claim 8 ,5-dichlorophenyl claim 8 , 2 claim 8 ,3-dibromophenyl claim 8 , 2 claim 8 ,4-dibromophenyl claim 8 , 2 claim 8 ,5-dibromophenyl claim 8 , 2 claim 8 ,6-dibromophenyl claim 8 , 3 claim 8 ,4-dibromophenyl claim 8 , 3 claim 8 ,5-dibromophenyl claim 8 , 2 claim 8 ,3-difluorophenyl claim 8 , 2 claim 8 ,4-difluorophenyl claim 8 , 2 claim 8 ,5-difluorophenyl claim 8 , 2 claim 8 ,6-difluorophenyl claim 8 , 3 claim 8 ,4-difluorophenyl claim 8 , 3 claim 8 ,5-difluorophenyl claim 8 , 2 claim 8 ,3-diiodophenyl claim 8 , 2 claim 8 ,4-diiodophenyl claim 8 , 2 claim 8 ,5-diiodophenyl claim 8 , 2 claim 8 ,6-diiodophenyl claim 8 , 3 claim 8 ,4-diiodophenyl claim 8 , 3 claim 8 ,5-diiodophenyl claim 8 , 2-chloro-3-bromophenyl claim 8 , 2-chloro-4-bromophenyl claim 8 , 2-chloro-5-bromophenyl claim 8 , 2-chloro-6-bromophenyl claim 8 , 3-chloro-4-bromophenyl claim 8 , 3-chloro-5-bromophenyl claim 8 , 4-chloro-5-bromophenyl claim 8 , 2-bromo-3-chlorophenyl claim 8 , 2-bromo-4-chlorophenyl claim 8 , 2 ...

PROCESS AND INTERMEDIATES FOR PREPARATION OF THIAZINE DERIVATIVES

The present invention provides a process for preparation of the compound of formula (VI), wherein each symbol is as defined in the specification, without using any intermediate compound showing mutagenicity. The process comprises salt formation of the intermediate compound of formula (I) with acid to enable optical resolution to isolate the intermediate compound of formula (II) in a stereo-selective manner. 2. The process of wherein the optical resolution is carried out in a mixed solvent comprising water and one or more organic solvent selected from the group consisting of acetonitrile claim 1 , methanol claim 1 , 2-propanol claim 1 , butanol claim 1 , ethyl acetate claim 1 , ethyl formate claim 1 , acetone and methyl ethyl ketone.3. The process of wherein the mixed solvent comprises water claim 2 , 2-propanol and ethyl acetate.10. The process of wherein the base is selected from the group consisting of alkylamine claim 9 , dicyclohexylamine claim 9 , ethanolamine claim 9 , diethanolamine claim 9 , triethanolamine claim 9 , meglumine claim 9 , ethylenediamine claim 9 , and the mixture thereof.11. The process of wherein the base is triethylamine.15. The salt of which is tartrate salt or malate salt.17. The salt of which is acetate salt. The present invention relates to a process for preparation of the compound of formula (VI):The present invention also relates to intermediates for preparation of the compound of formula (VI).The compound of formula (VI) has BACE1 inhibitory activity, and therefore, useful as a therapeutic agent for Alzheimer's disease (Patent Literature 1). The compound has a chiral center, which is assigned as S-configuration, at a carbon on the thiazine ring. Patent Literature 1 discloses a process for preparation of the compound of formula (VI) in a stereo-selective manner using a chiral intermediate compound.Substituted-aminothiazine derivatives having a structure similar to that of formula (VI) were disclosed (Patent Literature 2). Also, ...

DIARYLAMINE-BASED COMPOUND, ANTI-AGING AGENT, AND POLYMER COMPOSITION

The present invention provides a diarylamine-based compound represented by General Formula (1): 5. The diarylamine-based compound according to claim 1 , wherein Aand Aare a 1 claim 1 ,4-phenylene group.8. The composition according to claim 7 , wherein Rand Reach independently represent a linear or branched Cto Calkyl group which may have a substituent claim 7 , or a phenyl group which may have a substituent.10. The composition according to claim 1 , wherein a weight ratio of the diarylamine-based compound to the condensed heterocyclic compound is 30:1 to 1:30 as “diarylamine-based compound:condensed heterocyclic compound”.11. An antioxidant comprising the diarylamine-based compound according to claim 1 , or the composition according to any one of to .12. The antioxidant according to claim 11 , wherein the antioxidant is an antioxidant for a polymer.13. A polymer composition comprising a polymer and the antioxidant according to .14. The polymer composition according to claim 13 , wherein the polymer is a synthetic resin.15. The polymer composition according to claim 13 , wherein the polymer is a rubber.16. The polymer composition according to claim 15 , wherein the rubber is an acrylic rubber.17. The polymer composition according to claim 13 , wherein a content of the antioxidant is 0.05 to 30 parts by weight relative to 100 parts by weight of the polymer.18. An antioxidant comprising the composition according to . The disclosure relates to a novel diarylamine-based compound which has an excellent antioxidant effect on polymer materials required to have high heat resistance (for example, heat resistance in a high temperature range of 190° C. or more) and can be suitably used as an antioxidant, and an antioxidant and a polymer composition comprising such a diarylamine-based compound.With development of petrochemistry, polymers composed of organic compounds have contributed to human development in a variety of forms such as plastics, rubber, fibers, and films. Because ...

Fluorescent Chemical Compounds Having High Selectivity for Double Stranded DNA, and Methods for Their Use

Chemical compounds having a high selectivity for double stranded DNA over RNA and single stranded DNA are disclosed. The chemical compounds are stains that become fluorescent upon illumination and interaction with double stranded DNA, but exhibit reduced or no fluorescence in the absence of double stranded DNA. The compounds can be used in a variety of biological applications to qualitatively or quantitatively assay DNA, even in the presence of RNA. 2. The chemical compound of claim 1 , wherein:{'sup': 1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11, 'R, R, R, R, R, R, R, R, R, R, and Rare independently hydrogen, a hydroxyl group, an alkoxy group, a thiol, a thioalkyl, a thioaryl, a halogen, an alkyl group, an alkenyl group, an alkynyl group, an aromatic group, a primary amine group, a secondary amine group, a tertiary amine group, a reactive group, or combinations thereof.'}3. The chemical compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , and Rcomprises an aromatic group or an alkynyl group.4. The chemical compound of claim 1 , wherein Rcomprises an aromatic group claim 1 , alkyl-aromatic claim 1 , or an alkynyl group.5. The chemical compound of claim 1 , wherein Ris an amine group.6. The chemical compound of claim 1 , wherein:{'sup': 1', '2', '3', '4, 'at least one of R, R, R, and Rcomprises an aromatic group or an alkynyl group; and'}{'sup': '9', 'Rcomprises an aromatic group, alkyl-aromatic group, or an alkynyl group.'}7. The chemical compound of claim 1 , wherein:{'sup': 1', '2', '3', '4, 'at least one of R, R, R, and Rcomprises an aromatic group or an alkynyl group;'}{'sup': '9', 'Rcomprises an aromatic group, alkyl-aromatic group, or an alkynyl group; and'}{'sup': '10', 'Rcomprises an amine group.'}8. The chemical compound of claim 1 , wherein Ris a C-Calkyl group.9. The chemical compound of claim 1 , wherein Ris a methyl group.10. The chemical compound of claim 1 , further comprising one or more cations or anions.13. The ...

ARYLPIPERAZINE DERIVATIVES AND METHODS OF UTILIZING SAME

The present invention provides arylpiperazine derivatives which can be advantageously used for treating schizophrenia and related psychoses such as acute manic, bipolar disorder, autistic disorder, and depression. 3. The compound of claim 2 , wherein A is —O—(CH)— claim 2 , —S—(CH)— claim 2 , —CH—O—(CH)— claim 2 , —(CH)—O—CH—CH— claim 2 , —CH—S—(CH)— claim 2 , or —(CH)—S—CH—CH—.4. The compound of claim 2 , wherein A is —NH—C(O)—(CH)— claim 2 , —CH—NH—C(O)—(CH)— claim 2 , —CH—C(O)—NH—(CH)— or —(CH)—C(O)—NH—CH—CH—.5. The compound of claim 2 , wherein A is —(CH)—.6. The compound of claim 2 , wherein Ris H.7. The compound of claim 2 , wherein Rand Rare independently H claim 2 , halogen claim 2 , or alkoxy.8. The compound of claim 7 , wherein Ris H claim 7 , and Ris methoxy.9. The compound of claim 2 , wherein Rand Rare chloro.10. The compound of claim 7 , wherein A is —O—(CH)—; and R claim 7 , R claim 7 , R claim 7 , R claim 7 , and Rare independently hydrogen or alkyl.11. The compound of claim 7 , wherein R claim 7 , R claim 7 , R claim 7 , R claim 7 , and Rare hydrogen.12. The compound of claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , Rand Rand A are optionally substituted with H (deuterium).13. The compound of claim 1 , wherein the compound is in the form of a hydrochloride salt.14. The compound of claim 1 , wherein the compound is enantiomerically pure and/or diastereomerically pure.15. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier claim 1 , excipient claim 1 , or diluent.16. A method of treating psychosis claim 15 , schizophrenia claim 15 , acute mania claim 15 , bipolar disorder claim 15 , autistic disorder or depression claim 15 , the method comprising administering to a patient in need thereof the pharmaceutical formulation .17. The method of claim 16 , wherein said method treats depression.18. The method of claim 16 , wherein said method treats schizophrenia.19. The ...

Lipophilic Curcumin Analogs And Methods Of Inhibiting HIV-1, Treating Latent HIV In The Brain, And Preventing HIV-Mediated Cognitive Decline And HIV Dementia

Compounds having formulas (I) to (VIII), salts thereof, or combinations thereof and pharmaceutical compositions comprising one or more these compounds are described herein for the treatment of HIV and neurodegenerative effects caused by HIV. Also provided herein are methods and a kit for inhibiting HIV-1, treating latent HIV in the brain, and preventing HIV-mediated cognitive decline and HIV dementia comprising administering the compounds having the formulas (I) to (VIII) and pharmaceutical compositions comprising the compounds having these formulas. The compounds having formulas I through VIII are curcumin analogs which are advantageously characterized as having anti-retroviral, neuroprotective, anti-glucosidase, and anti-HIV integrase properties. In one aspect, the pharmaceutical composition is delivered intranasally. 114-. (canceled)16. The compound according to claim 15 , wherein the compound is of formula (II) or pharmaceutically acceptable salt thereof.17. The compound according to claim 15 , wherein the compound is of formula (III) or pharmaceutically acceptable salt thereof.18. The compound according to claim 15 , wherein the compound is of formula (IV) or pharmaceutically acceptable salt thereof.19. The compound according to claim 15 , wherein the compound is of formula (V) or pharmaceutically acceptable salt thereof.20. The compound according to claim 15 , wherein the compound is of formula (VI) or pharmaceutically acceptable salt thereof.21. The compound according to claim 15 , wherein the compound is of formula (VII) or pharmaceutically acceptable salt thereof.22. The compound according to claim 15 , wherein the compound is of formula (VIII) or pharmaceutically acceptable salt thereof.23. A pharmaceutical composition comprising at least one compound of any of formulas (II) through (VIII) or a pharmaceutically acceptable salt thereof as defined in .24. The pharmaceutical composition according to claim 23 , further comprising a pharmaceutically acceptable ...

UBIQUITIN-SPECIFIC PEPTIDASE 24 INHIBITOR, MEDICINAL COMPOSITION INCLUDING THE SAME AND METHOD OF DELAYING OR REVERSING MULTIDRUG RESISTANCE IN CANCERS USING THE SAME

The present invention relates to a ubiquitin-specific peptidase 24 inhibitor, a medicinal composition including the same and a method of delaying or reversing multidrug resistance in cancers using the same. The USP24 inhibitor, which includes a shUSP24 RNA and/or a carbonyl substituted phenyl compound, can serve as a chemosensitizing agent for inhibiting the drug pump out, cancer sternness and genomic instability of cancer cells, thereby being applied to a medicinal composition and a method for delaying or reversing multidrug resistance in cancers. 6. The USP24 inhibitor of claim 1 , wherein the siRNA is a double-stranded USP24 RNA claim 1 , a short-hairpin USP24 (shUSP24) RNA claim 1 , an isolated ribonucleic acid sequence or a viral siRNA construct claim 1 , and the viral siRNA construct is a lentiviral siRNA construct.12. The medicinal composition of claim 7 , wherein the salt of the carbonyl substituted phenyl compound is selected from the group consisting of oxalate claim 7 , phosphate claim 7 , sulfate and chloride.13. The medicinal composition of claim 7 , wherein the siRNA is a double-stranded USP24 RNA claim 7 , and the siRNA is an isolated ribonucleic acid sequence or a viral siRNA construct.14. The medicinal composition of claim 7 , wherein the viral siRNA construct is a lentiviral siRNA construct claim 7 , and a value of m.o.i. of the lentiviral siRNA is 2.5 to 10.15. The medicinal composition of claim 7 , wherein a dosage of the carbonyl substituted phenyl compound is 12.5 mg/kg to 25 mg/kg of body weight.16. The medicinal composition of claim 7 , wherein the cancer cell is a solid tumor cell or a blood cancer cell claim 7 , and the cancer cell is selected from the group consisting of a lung cancer cell claim 7 , a nasopharyngeal carcinoma cell claim 7 , a brain cancer cell claim 7 , a colorectal carcinoma cell claim 7 , a lymphoma cell claim 7 , a leukemia cell and a multiple myeloma cell. This application is a Continuation-in-part of U.S. application ...

BISHYDRAZONE-BASED ANTIFUNGAL AGENTS

Hydrazone compounds and pharmaceutical compositions including same are disclosed as having antifungal activity. Such compounds are useful for treating or preventing fungal conditions in a subject in need thereof by administering same. 6. The composition of claim 5 , wherein each X is independently selected from the group consisting of fluorine claim 5 , chlorine claim 5 , and bromine.8. The composition of claim 7 , wherein each Xis independently selected from the group consisting of fluorine claim 7 , chlorine claim 7 , and bromine.9. The method of claim 1 , wherein the compound is a pharmaceutically acceptable hydrochloride salt.15. The method of claim 14 , wherein each X is independently selected from the group consisting of fluorine claim 14 , chlorine claim 14 , and bromine.17. The method of claim 16 , wherein each X is independently selected from the group consisting of fluorine claim 16 , chlorine claim 16 , and bromine.18. The method of claim 10 , wherein the compound is a pharmaceutically acceptable hydrochloride salt. This application claims the benefit of U.S. Provisional Application Ser. No. 62/359,487, filed Jul. 7, 2016, the entire disclosure of which is incorporated herein by this reference.This invention was made with government support by NIH grant A1090048 and NIH grants U01 DA013519, UL1TR000117 and T32 DA016176; and NIH grants P20 RR020171, CA172379 and CA187273. The Government has certain rights in the invention.The present disclosure is directed to hydrazone compounds and pharmaceutical compositions including same having antifungal activity and methods for treating or preventing fungal conditions in a subject in need thereof by administering same.The emergence of multidrug-resistant bacteria and fungi as human pathogens warrants a continued focus on the development of new pharmacophores for the treatment of these devastating and often fatal infections. The rise of multidrug-resistant bacteria, such as methicillin-resistant (MRSA) and vancomycin- ...

Processes for the preparation of aryl hydrocarbon receptor ligands

The present disclosure relates to the preparation of methyl 2-(1H-indole-3-carbonyl)thiazole-4-carboxylate (ITE) and related compounds with high yield, purity, and scalability. The processes apply the use of a Weinreb amide intermediate as a scaffold for the preparation of ITE and structural analogs.

COMPOSITIONS USEFUL IN THERAPY OF AUTOPHAGY-RELATED PATHOLOGIES, AND METHODS OF MAKING AND USING THE SAME

Lanthionine ketimine phosphonate (LK-P), lanthionine ketimine ester phosphonate (LKE-P), other lanthionine ketimine, lanthionine ketimine phosphonate, and lanthionine ketimine ester derivatives, and methods of making and using the same, are described. 2. (canceled)3. (canceled)4. (canceled)5. (canceled)7. (canceled)8. (canceled)9. (canceled)10. The compound of claim 6 , wherein:{'sub': 2', '1', '15', '2', '15', '2', '15', '1', '15', '2', '15', '1', '15', '1', '15', '2', '15', '2', '15', '1', '15', '2', '15', '1', '15, 'Ris selected from the group consisting of hydrogen, or heteroatom substituted or unsubstituted versions of C-C-alkoxy, C-C-alkenylamino, C-C-alkynylamino, C-C-aryloxy, C-C-aralkoxy, C-C-acyloxy, C-C-alkylamino, C-C-alkenylamino, C-C-alkynylamino, C-C-arylamino, C-C-aralkylamino, and C-C-amido; and'}{'sub': 3', '1', '15', '2', '15', '2', '15', '1', '15', '2', '15', '1', '15', '1', '15', '2', '15', '2', '15', '1', '15', '2', '15', '1', '15, 'Ris selected from the group consisting of heteroatom substituted or unsubstituted versions of C-C-alkoxy, C-C-alkenylamino, C-C-alkynylamino, C-C-aryloxy, C-C-aralkoxy, C-C-acyloxy, C-C-alkylamino, C-C-alkenylamino, C-C-alkynylamino, C-C-arylamino, C-C-aralkylamino, and C-C-amido.'}11. (canceled)12. (canceled)13. (canceled)14. (canceled)18. (canceled)19. (canceled)20. A method of treating a disorder comprising one or more of: an autophagy-related disease claim 6 , inflammatory disease claim 6 , stroke claim 6 , cancer claim 6 , neurodegenerative disease claim 6 , the method comprising{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering an effective amount of an LK, LKE, LKEE, LK-P, LKE-P, LK-PE, or LKE-PE compound of to a subject in need thereof and treating the disorder;'}wherein “LK” refers to lanthionine ketimine, “LKE” refers to a 5-ester of lanthionine ketimine, “LKEE” refers to a 3,5-diester of lanthionine ketimine, “LK-P” refers to a lanthionine ketimine phosphonate compound: “LKE-P” refers to a 5 ...

METHOD FOR PREPARATION OF 3,7-BIS-(DIMETHYLAMINO)-PHENOTHIAZIN-5-IUM CHLORIDE OR BROMIDE

The present invention relates to: a process for preparing 3,7-bis-(dimethylamino)-phenothiazin-5-ium bromide or chloride; a method of converting 3,7-bis-(dimethylamino)-phenothiazin-5-ium bromide to 3,7-bis-(di-methylamino)-phenothiazin-5-ium chloride; and the purification of 7-bis-(di-methylamino)-phenothiazin-5-ium chloride by crystallization from aqueous solution of hydrochloric acid, leading to a pharmaceutically acceptable 3,7-bis-(di-methylamino)-phenothiazin-5-ium chloride (methylthioninium chloride, methylene blue, MTC) of formula I below reported. 1. A process for producing 3 ,7-bis-(dimethylamino)-phenothiazin-5-ium chloride or bromide comprising the steps of:a) reacting chlorine or bromine with phenothiazine, to produce 3,7-dichloro-phenothiazin-5-ium chloride or 3,7-dibromo-phenothiazin-5-ium bromide respectively; 'wherein steps a) and b) are carried out without isolation and/or purification of the intermediate formed in step a).', 'b) adding dimethylamine to the reaction mixture of step a), to produce 3,7-bis-(dimethylamino)-phenothiazin-5-ium chloride or 3,7-bis-(dimethylamino)-phenothiazin-5-ium bromide respectively;'}2. The process of claim 1 , wherein step a) is carried out at a temperature of less than about 10° C. claim 1 , preferably less than about 5° C.; optionally wherein step a) is carried out at a temperature of less than about 0° C. claim 1 , preferably less than about −10° C. claim 1 , more preferably between about −20° C. and about −10° C. claim 1 , much more preferably at about −15° C.; and further optionally wherein step b) is carried out at a temperature of less than about 20° C. claim 1 , preferably less than about 10° C. claim 1 , more preferably between about −20° C. and about 10° C. claim 1 , much more preferably at about −15° C.3. The process of any of the preceding claims claim 1 , wherein step a) is carried out in a suitable solvent system selected from the group of dichloromethane claim 1 , acetic acid claim 1 , methylacetate ...

CONSTRAINED TRICYCLIC SULFONAMIDES

Tricyclic chemical modulators of protein phosphatase 2A are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of the following phenothiazine and dibenzoazepine compounds and similar genera: 3. (canceled)4. (canceled)5. A compound according to claim 1 , wherein B is —(CH—CH)—.6. A compound according to claim 1 , wherein B is —S—.7. A compound according to claim 1 , wherein B is —CH═CH—.8. A compound according to claim 1 , wherein A is N.9. A compound according to claim 8 , wherein B is —(CH—CH)— and A is N.10. A compound according to claim 1 , wherein A is —CH.11. A compound according to claim 1 , wherein n is 1.12. (canceled)13. (canceled)14. A compound according to claim 1 , wherein Xand Xare both H.15. (canceled)16. (canceled)17. A compound according to claim 1 , wherein one instance of Y is H or Cl claim 1 , and another instance of Y is selected from —H claim 1 , —F claim 1 , —(C-C)haloalkyl claim 1 , —(C-C)haloalkoxy claim 1 , —(C-C)alkoxy claim 1 , —C(═O)(C-C)alkyl claim 1 , —C(═O)H claim 1 , —(C-C)hydroxyalkyl claim 1 , —(C-C)haloalkylthio claim 1 , —N claim 1 , and —CN.18. A compound according to claim 17 , wherein one instance of Y is H or Cl claim 17 , and another instance of Y is —OCF.19. (canceled)20. A compound according to claim 11 , wherein B is —(CH—CH)— and n is 1.21. (canceled)23. (canceled)25. (canceled)26. (canceled)2837-. (canceled)38. A method for restoring sensitivity to one or more chemotherapeutic agents in the treatment of cancer claim 1 , the method comprising administering an effective amount of a compound according to .39. A method for treating a disease or disorder in a patient where the disease or disorder involves the dysregulation of the PI3K-AKT-FOXO signaling pathway claim 1 , the method comprising administering to the patient a therapeutically effective amount of a compound according to .40. A pharmaceutical composition comprising a ...

USE OF ARYLALKANOLAMINES AS SIGMA-1 RECEPTOR ANTAGONISTS

The present invention relates to the use of arylalkanolamine compounds with sigma-1 receptor antagonist activity. In particular, the said arylalkanolamine compounds are useful in the treatment of conditions selected from the abuse of psychotropic substances such as cocaine or amphetamines, pain and cancer. 2. The aryl alkanolamine compounds according to claim 1 , wherein R1 and R2 claim 1 , equal to or different from each other claim 1 , are a linear or branched (C-C)alkyl group claim 1 , a benzyl group claim 1 , or R1 and R2 form claim 1 , together with the nitrogen atom to which they are bonded claim 1 , a 6-membered heterocyclic ring claim 1 , optionally comprising another heteroatom selected from N claim 1 , O and S.3. The aryl alkanolamine compounds according to claim 2 , wherein R1 and R2 claim 2 , equal to or different from each other claim 2 , are a methyl group claim 2 , an ethyl group claim 2 , a benzyl group claim 2 , or R1 and R2 form claim 2 , together with the nitrogen atom to which they are bonded claim 2 , a piperidine or morpholine ring.4. The aryl alkanolamine compounds according to claim 3 , wherein R1 and R2 form claim 3 , together with the nitrogen atom to which they are bonded claim 3 , a piperidine ring.5. The aryl alkanolamine compounds according to claim 1 , wherein R3 and R4 claim 1 , equal to or different from each other claim 1 , are hydrogen atom claim 1 , a phenyl group claim 1 , or R3 and R4 form claim 1 , together with the ring to which they are bonded claim 1 , an optionally substituted naphthalene ring.627.-. (canceled)28. The aryl alkanolamine compounds according to claim 5 , wherein said naphthalene ring formed by R3 and R4 is substituted with a hydroxy) group claim 5 , an alkoxy group having from 1 to 3 carbon atoms claim 5 , or a halogen atom.29. The aryl alkanolamine compounds according to claim 5 , wherein R3 is a hydrogen atom and R4 is a phenyl group.30. The aryl alkanolamine compounds according to claim 1 , wherein n is an ...

S-IMINO-S-OXO-IMINOTHIAZINE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain S-imino-S-oxo iminothiazine compounds, including compounds Formula (I): or a tautomers and/or stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein R, R, R, R, R, R, ring A, R, m, L-, and Rare as defined herein. The novel compounds of the invention are useful as BACE inhibitors and may be useful for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed. 2. A compound of claim 1 , or a tautomer thereof claim 1 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 1 , wherein:{'sup': '4', 'sub': '2', 'Ris selected from the group consisting of methyl and —CHF;'}{'sup': '2', 'Ris selected from the group consisting of H and methyl; and'}{'sup': '3', 'Ris H.'}3. A compound of claim 2 , or a tautomer thereof claim 2 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 2 , wherein:{'sup': '1A', 'sub': 2', '2', '3, 'Ris H, H fluorine, methyl —CHF, —CHF, and —CF; and'}{'sup': '1B', 'sub': 3', '2', '2', '2', '3', '2', '3', '2', '3', '2', '3', '2', '2, 'Ris selected from the group consisting of H, fluoro, methyl, ethyl, —CF, —CHF, —CHF, —CHCF, —CFCH, —CHOCH, —CHN(CH), cyclopropyl, —CH-cyclopropyl, and fluorophenyl.'}4. A compound of claim 1 , or a tautomer thereof claim 1 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 1 , wherein:{'sup': '1A', 'Ris methyl; and'}{'sup': '1B', 'sub': '2', 'Ris selected from the group consisting of methyl, ethyl, cyclopropyl, —CH-cyclopropyl, and fluorophenyl.'}5. A compound of claim 2 , or a tautomer thereof claim 2 , or a pharmaceutically acceptable salt of said ...

BLUE FLUORESCENT EMITTERS

The present invention relates to compounds of the formula (I) 8. Use of at least one compound according to in an optoelectronic component from the group comprising: an organic electroluminescent device (OLED) claim 1 , an organic integrated circuit (O-IC) claim 1 , an organic field-effect transistor (O-FET) claim 1 , an organic thin-film transistor (O-TFT) claim 1 , an organic light-emitting transistor (O-LET) claim 1 , an organic solar cell (O-SC) claim 1 , an organic optical detector claim 1 , an organic photoreceptor claim 1 , an organic field-quench device (O-FQD) claim 1 , a light-emitting electrochemical cell (LEC) claim 1 , or an organic laser diode (O-laser).9. An optoelectronic component comprising at least one compound according to . The present application is a national stage entry according to 35 U.S.C. §371 of PCT Application No. PCT/EP2016/052413 filed on Feb. 4, 2016, which claims priority to German Patent Application No. 10 2015 101 767.9, filed on Feb. 6, 2015; both of which are herein incorporated by reference in their entirety.The subject matter herein generally provides compounds of formula (I) as defined herein, as well as their use as emitter or carrier material in an optoelectronic component.The development of novel functional compounds for use in electronic devices is currently the subject of intensive research. The aim here is the development and study of compounds which have not been used to date in electronic devices, and the development of compounds which enable an improved profile of properties of the devices.According to a non-limiting embodiment, the term “optoelectronic component” is understood to mean inter alia organic integrated circuits (OICs), organic field-effect transistors (OFETs), organic thin-film transistors (OTFTs), organic light-emitting transistors (OLETs), organic solar cells (OSCs), organic optical detectors, organic photoreceptors, organic field-quench devices (OFQDs), organic light-emitting electrochemical cells ( ...

Process for manufacturing 4-substituted amino-benzoxazinones

The present invention relates to a process for manufacturing 4-substituted amino-benzoxazinones of formula (I), 110-. (canceled)12. The process according to claim 11 , wherein the base is selected from the group consisting of carbonates claim 11 , hydrogen carbonates claim 11 , hydroxides claim 11 , oxides claim 11 , phosphates and alkoxides.13. The process according to claim 11 , wherein the base is selected from carbonates.14. The process according to claim 11 , wherein Rand Rare halogen.15. The process according to claim 11 , wherein{'sup': '2', 'Ris F; and'}W is O.16. The process according to claim 11 , wherein Ris C-C-alkynyl.17. The process according to claim 11 , wherein a NH-benzoxazinone of formula (II) is employed. The invention relates to 4-substituted amino-benzoxazinones of formula (I), a process for manufacturing the 4-substituted amino-benzoxazinones of formula (I), their use in and a process for manufacturing triazinon-benzoxazinones of formula (IV).WO 2010/145992 discloses a process for the preparation of amino-benzoxazinones by first alkylation of the 4-position of nitro-benzoxazinones and then subsequent reduction of the nitro substituent.EP 170 191 describes the alkylation of benzoxazinones, which are in 2-position of the benzoxazinone ring preferably unsubstituted or substituted by an alkyl group.However, there is still room for improvement, specifically in view of economical and ecological aspects.One task of the invention is to provide an improved process for manufacturing 4-substituted amino-benzoxazinones of formula (I). A further task of the invention is to provide an improved process for manufacturing triazinon-benzoxazinones of formula (IV).Surprisingly, it has been found that benzoxazinones bearing at least one halogen atom in the 2-position and a free amino group in the 6-position can be substituted, particularly alkylated, in the 4-position of the benzoxazinone ring. The corresponding 4-substituted amino-benzoxazinones of formula (I) ...

COMPOUNDS AND METHODS FOR TREATING OCULAR DISEASES

Described herein are compounds of formula I 2. The compound of claim 1 , wherein:X is CH;{'sub': 1', '3, 'Y is C-Calkyl optionally substituted by OH; and'}Z is interarylene.3. The compound of claim 2 , wherein Z is phenylene.4. The compound of claim 2 , wherein:Z is phenylene; and{'sub': 3', '3', '2', '3, 'Q is H, halogen, CF, OCF, or CHOCH.'}5. The compound of claim 4 , wherein Q is CF.6. The compound of claim 1 , wherein Y is C-Calkyl substituted by OH.7. The compound of claim 6 , wherein Y is CH(OH)CH.8. The compound of claim 1 , wherein Ar is a 5 membered heteroaryl containing 1 or 2 heteroatoms selected from the group consisting of O claim 1 , N and S.9. The compound of claim 1 , wherein A is CORand B is H.10. The compound of claim 1 , wherein n is 3.11. The compound of claim 1 , wherein:Ar is a 5 membered heteroaryl containing 1 or 2 heteroatoms selected from the group consisting of O, N and S;n is 1, 2 or 3;X is CH;{'sub': 1', '3, 'Y is C-Calkyl optionally substituted by OH; and'}Z is interarylene.12. The compound of claim 1 , wherein;Ar is a 5 membered heteroaryl containing 1 or 2 heteroatoms selected from the group consisting of O, N and S;n is 1, 2 or 3;X is CH;{'sub': '2', 'Y is CH(OH)CH; and'}Z is phenylene.13. The compound of claim 1 , wherein:Ar is a 5 membered heteroaryl containing 1 or 2 heteroatoms selected from the group consisting of O, N and S;n is 1, 2 or 3;{'sub': '2', 'sup': '3', 'A is COR;'}B is H;X is CH;{'sub': '2', 'Y is CH(OH)CH; and'}Z is phenylene.14. The compound of claim 1 , wherein:Ar is a 5 membered heteroaryl containing 1 or 2 heteroatoms selected from the group consisting of O, N and S;n is 1, 2 or 3;{'sub': '2', 'sup': '3', 'A is COR;'}{'sup': '3', 'Ris H;'}B is H;X is CH;{'sub': '2', 'Y is CH(OH)CH; and'}Z is phenylene.15. The compound of claim 1 , wherein:Ar is a 5 membered heteroaryl containing 1 heteroatom selected from the O and S;n is 1, 2 or 3;{'sub': '2', 'sup': '3', 'A is COR;'}B is H;X is CH;{'sub': '2', 'Y is CH(OH)CH; ...

ORGANIC MOLECULES FOR USE IN OPTOELECTRONIC DEVICES

The invention relates to an organic molecule having precisely two units of formula I linked to one another via a single bond or a bridge Y 119-. (canceled)21. The organic molecule according to claim 20 , wherein{'sup': 4', '4', '4', '4, 'sub': '2', 'R′=the attachment position for the second unit of the formula I or selected from the group consisting of Y, H, N(R), OR, a linear alkyl or alkoxy group having 1 to 40 carbon atoms or a branched or cyclic alkyl or alkoxy group having 3 to 40 carbon atoms wherein this group is optionally substituted in each case by one or more radicals R, and an aromatic or heteroaromatic ring system having 5 to 60 aromatic ring atoms wherein this ring system is optionally substituted in each case by one or more radicals R; and'}{'sup': 4', '4', '4', '4, 'sub': '2', 'R″=the attachment position for the second unit of the formula I or selected from the group consisting of Y, N(R), OR, a linear alkyl or alkoxy group having 1 to 40 carbon atoms or a branched or cyclic alkyl or alkoxy group having 3 to 40 carbon atoms wherein this group is optionally to be substituted in each case by one or more radicals R, and an aromatic or heteroaromatic ring system having 5 to 60 aromatic ring atoms wherein this ring system is optionally substituted in each case by one or more radicals R;'}wherein the heteroaromatic ring system is not an N-heteroaromatic;wherein, if R′ is Y, R″ is not Y, and, if R″ is Y, R′ is not Y;wherein if R′ is the attachment position for the second unit of the formula I, then R″ is not the attachment position for the second unit of the formula I, and, if R″ is the attachment position for the second unit of the formula I, then R′ is not the attachment position for the second unit of the formula I; and{'sup': '4', 'wherein Y and Rhave the aforestated meanings.'}22. The organic molecule according to claim 20 , wherein{'sup': 4', '4', '4', '4', '4, 'sub': '2', 'R′=the attachment position for the second unit of the formula I or selected ...

LIGHT EMITTING DEVICES AND COMPOUNDS

Thermally Activated Delayed Fluorescence (TADF) compounds wherein two aromatic heterocyclic moieties are provided as acceptor groups, spaced apart from two donor moieties by an aromatic spacer ring, are described. Charged organic TADF species having a similar structure are also described. The TADF compounds and charged organic TADF species may be employed as emitter material in light emitting devices such as OLEDs and LEECs. Also described TADF compounds wherein at least one donor moiety is substituted by at least one substituent that is a phosphine oxide or a phosphine sulphide. 137-. (canceled)44. A light emitting device comprising a TADF compound according to .45. The light emitting device of claim 44 , wherein said light emitting device is an OLED.492. The TADF compound according to claim 46 , wherein the acceptor moieties Acc are claim 46 , independently for each occurrence selected from the group consisting of -Het as defined in claim claim 46 , —CN claim 46 , sulfone claim 46 , sulfoxide claim 46 , imine claim 46 , amide claim 46 , acridine claim 46 , acridinium claim 46 , carboxylate ester claim 46 , phosphine oxide claim 46 , phosphine sulfide claim 46 , ketone and aldehyde.52. A light emitting device comprising a TADF compound according to .53. The light emitting device of claim 52 , wherein said light emitting device is an OLED.57. The charged organic species according to claim 56 , wherein at least one linking group L is present and is independently for each occurrence claim 56 , a hydrocarbylene chain claim 56 , that may be substituted or unsubstituted claim 56 , hydrocarbylene or unsaturated hydrocarbylene.58. The charged organic species according to claim 57 , wherein the at least one linking group L is selected from substituted or unsubstituted cyclopentane-1 claim 57 ,3-diyl claim 57 , cyclohexane-1 claim 57 ,4-diyl claim 57 , 1 claim 57 ,4-phenylene and 4 claim 57 ,4′-biphenylene.60. The charged organic species according to claim 56 , wherein ...

FLUOROGENIC WATER SOLUBLE HYDRAZINE SENSORS

Water soluble fluorogenic sensors for detecting a hydrazine analyte are provided. Aspects of the fluorogenic sensors include at least one water soluble group and a hydrazine reactive group. Methods of evaluating a sample for the presence of a hydrazine analyte and methods of detecting hydrazine diffusion across a phospholipid membrane are provided. Kits for practicing the subject methods are also provided. 2. The water soluble compound according to claim 1 , wherein at least one of R claim 1 , R claim 1 , Rand Ris —SOH.3. The water soluble compound according to claim 1 , wherein Ris —SOH.4. The water soluble compound according to claim 1 , wherein Ror R is —C═C(R)(R) or an aldehyde claim 1 , wherein Rand Rare each independently selected from the group consisting of CN claim 1 , C(O)OR claim 1 , C(O)NRand C(O)R claim 1 , wherein Ris alkyl claim 1 , substituted alkyl claim 1 , aryl or substituted aryl and Rare each independently H claim 1 , alkyl claim 1 , substituted alkyl claim 1 , aryl or substituted aryl.5. The water soluble compound according to claim 1 , wherein R is ethyl.7. The water soluble compound according to claim 6 , wherein the alkene is the E isomer.8. The water soluble compound according to claim 6 , wherein the alkene is the Z isomer.10. A method of detecting a hydrazine analyte in a sample claim 6 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting a sample with the water soluble compound according to under conditions sufficient to react the hydrazine analyte, if present, with the compound to produce a fluorescent adduct;'}detecting the fluorescence of the adduct.11. The method according to claim 10 , wherein the detecting comprises detecting a change in intensity of fluorescence emitted from the sample.12. The method according to claim 11 , wherein the change in intensity of fluorescence emitted is detected at 525 nm.13. The method according to claim 10 , wherein the hydrazine analyte is detected at neutral pH.14. The method ...

RESORUFIN DERIVATIVES FOR TREATMENT OF OXIDATIVE STRESS DISORDERS

Disclosed herein are resorufin derivative compounds and methods of using such compounds for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging. 2. The compound of claim 1 , wherein R claim 1 , R claim 1 , and Rare —CH.3. The compound of claim 1 , wherein Rand Rare —OCH claim 1 , and Ris —CH.4. The compound of claim 1 , wherein Rand Rare —CH claim 1 , and Ris —H.5. The compound of claim 1 , wherein Rand Rare —CH claim 1 , and wherein Ris -n-C-Calkyl.6. The compound of claim 1 , wherein Rand Rare —OCH claim 1 , and wherein Ris -n-C-Calkyl.9. The compound of claim 1 , wherein R claim 1 , R claim 1 , and Rare —H.10. The compound of claim 1 , wherein three of R claim 1 , R claim 1 , R claim 1 , and Rare —H.1110. The compound of any one of - claims 1 , wherein at least one of R claims 1 , R claims 1 , R claims 1 , and Ris —C-Chaloalkyl.1210. The compound of any one of - claims 1 , wherein at least one of R claims 1 , R claims 1 , R claims 1 , and Ris —C(O)—N(R)(R).1310. The compound of any one of - claims 1 , wherein at least one of R claims 1 , R claims 1 , R claims 1 , and Ris —C-Calkyl.149. The compound of any one of - claims 1 , wherein R claims 1 , R claims 1 , R claims 1 , and Rare —H.2221. A pharmaceutical formulation comprising a compound according to any one of - and a pharmaceutically acceptable excipient.24. The method of claim 23 , wherein the method is a method of treating an oxidative stress disorder selected from the group consisting of: a mitochondrial disorder; an inherited mitochondrial disease; Alpers Disease; Barth syndrome; a Beta-oxidation Defect; Carnitine-Acyl-Carnitine Deficiency; Carnitine Deficiency; a Creatine Deficiency Syndrome; Co-Enzyme Q10 Deficiency; Complex I Deficiency; Complex II Deficiency; Complex III Deficiency; Complex IV Deficiency; Complex V Deficiency; COX Deficiency; chronic progressive external ...

PHENAZINE-3-ONE AND PHENOTHIAZINE-3-ONE DERIVATIVES FOR TREATMENT OF OXIDATIVE STRESS DISORDERS

Disclosed herein are phenazine-3-one and phenothiazine-3-one derivative compounds and methods of using such compounds for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging. 2. The compound of claim 1 , wherein R claim 1 , R claim 1 , and Rare —CH.3. The compound of claim 1 , wherein Rand Rare —OCH claim 1 , and Ris —CH.4. The compound of claim 1 , wherein Rand Rare —CH claim 1 , and Ris —H.5. The compound of claim 1 , wherein Rand Rare —CH claim 1 , and wherein Ris -n-C-Calkyl.6. The compound of claim 1 , wherein Rand Rare —OCH claim 1 , and wherein Ris -n-C-Calkyl.9. The compound of claim 1 , wherein R claim 1 , R claim 1 , and Rare —H.109. The compound of any one of - claims 1 , wherein three of R claims 1 , R claims 1 , R claims 1 , and Rare —H.1110. The compound of any one of - claims 1 , wherein at least one of R claims 1 , R claims 1 , R claims 1 , and Ris —C-Chaloalkyl.1210. The compound of any one of - claims 1 , wherein at least one of R claims 1 , R claims 1 , R claims 1 , and Ris —C(O)—N(R)(R).1310. The compound of any one of - claims 1 , wherein at least one of R claims 1 , R claims 1 , R claims 1 , and Ris —C-Calkyl.149. The compound of any one of - claims 1 , wherein R claims 1 , R claims 1 , R claims 1 , and Rare —H.1716. The compound of any one of - claims 1 , wherein Ris S.2322. A pharmaceutical formulation comprising a compound according to any one of - and a pharmaceutically acceptable excipient.25. The method of claim 24 , wherein the method is a method of treating an oxidative stress disorder selected from the group consisting of: a mitochondrial disorder; an inherited mitochondrial disease; Alpers Disease; Barth syndrome; a Beta-oxidation Defect; Carnitine-Acyl-Carnitine Deficiency; Carnitine Deficiency; a Creatine Deficiency Syndrome; Co-Enzyme Q10 Deficiency; Complex I Deficiency; Complex II Deficiency; Complex III ...

AMINE-CONTAINING ACYCLIC HYDROFLUOROETHERS AND METHODS OF USING THE SAME

An acyclic fluorinated compound of formula (I) is amine-containing acyclic hydrofluoroethers. The acyclic fluorinated compound is useful as heat transfer, solvent cleaning, fire extinguishing agents and electrolyte solvents and additives. 2. The acyclic fluorinated compound of claim 1 , wherein Q=N(R).3. The acyclic fluorinated compound of claim 2 , wherein N(R)is a perfluorinated morpholine group.4. The acyclic fluorinated compound of claim 1 , wherein Q is a perfluorinated alkyl group comprising less than 4 carbon atoms.5. The acyclic fluorinated compound of claim 1 , wherein X and Y are both F.6. The acyclic fluorinated compound of claim 1 , wherein A and Z are both F.8. A working fluid comprising the acyclic fluorinated compound according to claim 1 , wherein the acyclic fluorinated compound is present in the working fluid in an amount of at least 25% by weight based on the total weight of the working fluid.912.-. (canceled)13. A composition comprising a purified form of the acyclic fluorinated compound according to .14. The acyclic fluorinated compound of claim 1 , wherein the acyclic fluorinated compound has a global warming potential of less than 100.15. A working fluid comprising the acyclic fluorinated compound according to claim 1 , wherein the acyclic fluorinated compound is present in the working fluid in an amount of at least 25% by weight based on the total weight of the working fluid.16. The working fluid of claim 15 , wherein the working fluid further comprises a co-solvent.18. An apparatus for heat transfer according to claim 17 , wherein the device is selected from a microprocessor claim 17 , a semiconductor wafer used to manufacture a semiconductor device claim 17 , a power control semiconductor claim 17 , an electrochemical cell claim 17 , an electrical distribution switch gear claim 17 , a power transformer claim 17 , a circuit board claim 17 , a multi-chip module claim 17 , a packaged or unpackaged semiconductor device claim 17 , a fuel cell ...

PVC Plasticizers and Methods for Making Thereof

A plasticized PVC composition free of phthalate and having low color is disclosed. The composition comprises a morpholide plasticizer prepared from a fatty acid selected from a tall oil fatty acid, a tall oil fatty acid monomer derived therefrom, and mixtures thereof. The fatty acid has a total carbon footprint of <95% of the total carbon footprint of a fatty acid obtained from a vegetable oil. The morpholide is prepared from the reaction of a tall oil fatty acid with morpholine in the presence of a catalyst. 1. A morpholide composition , comprising a reaction product of a morpholine compound and a fatty acid selected from a tall oil fatty acid , a tall oil fatty acid monomer derived therefrom , and mixtures thereof;wherein the fatty acid comprises 20-55 wt. % of oleic acid and 20-55 wt. % of linoleic acid, and optionally 0-15 wt. % of linolenic acid;wherein the fatty acid has a total carbon footprint of <95% of the total carbon footprint of a fatty acid obtained from a vegetable oil; andwherein the morpholide composition has a Gardner color (neat) of less than 3.2. The morpholide composition of claim 1 , wherein the fatty acid has an average carbon footprint of less than 500 gram COequivalents per kg of the fatty acid3. The morpholide composition of claim 1 , wherein the morpholide composition has an acid number of less than 12 mg KOH/g.4. The morpholide composition of claim 1 , wherein the morpholide composition has an amine value of less than 1 mg KOH/g.5. The morpholide composition of claim 1 , wherein the fatty acid is a tall oil fatty acid monomer claim 1 , and wherein the tall oil fatty acid monomer comprises iso-oleic acid.6. A plasticizer composition comprising the morpholide composition of .7. A plasticized polyvinyl chloride (PVC) composition comprising the plasticizer composition of .8. The plasticized PVC composition of claim 7 , having a weight loss after 48 hours of less than 1% in an exudation test.9. The plasticized PVC composition of claim 7 , ...

PHENOTHIAZINE DIAMINIUM SALTS AND THEIR USE

Disclosed are compounds of general formula (I): 2. The method of claim 1 , wherein the administering is oral.3. The method of claim 2 , wherein the administering is selected from:(a) about 100 mg of compound, 3 times daily;(b) about 150 mg of compound, 2 times daily; and(c) about 200 mg of compound, 2 times daily.4. The method of claim 1 , wherein the disease is skin cancer or melanoma.5. The method of claim 1 , wherein the disease is a viral disease.6. The method of claim 5 , wherein the viral disease is selected from the list consisting of: Hepatitis C; HIV; and West Nile Virus.7. The method of claim 1 , wherein the disease is a bacterial disease.8. The method of claim 1 , wherein the disease is a protozoal disease.9. The method of claim 7 , wherein the protozoal disease is malaria.11. A compound according to claim 10 , wherein each of Rand Ris independently Calkyl.12. A compound according to claim 10 , wherein each of Rand Ris independently methyl.13. A compound according to claim 10 , wherein each of Rand Ris independently —H.14. A compound according to claim 10 , wherein each of Rand Rand is independently Calkyl.15. A compound according to wherein each of Rand Ris independently methyl.16. A compound according to claim 10 , wherein each of Rand Ris independently Calkyl.17. A compound according to claim 16 , wherein each of Rand Ris independently methyl.19. A compound according to claim 10 , in crystalline form.20. A compound according to in crystalline form claim 18 , having a crystal structure as represented by .21. A compound according to in substantially purified form. This application is a divisional of U.S. application Ser. No. 15/056,610, filed Feb. 29, 2016, which is a divisional of U.S. application Ser. No. 13/984,841, which issued on Mar. 15, 2016, as U.S. Pat. No. 9,283,230; which entered U.S. National Phase on Aug. 9, 2013, from International Application No. PCT/GB2011/001221, filed Aug. 15, 2011, and which was published in English on Sep. 19, 2013 as ...

Two-Electron Donating Phenothiazines and Use Thereof

Compounds for use as electrolyte in a non-aqueous redox battery are provided, including an N-substituted phenothiazine compound according to the formula: 5. The compound according to claim 1 , wherein the structure is arranged and disposed to form a stable doubly oxidized species.6. The compound according to claim 1 , wherein the structure is arranged and disposed to form a stable dication in a non-aqueous electrolyte.7. The compound according to claim 6 , wherein the structure provides increased atom economy as compared to single electron-donor compounds.8. A method of making an N-substituted phenothiazine derivative claim 6 , the method comprising:synthesizing an N-substituted phenothiazine;forming a 3,7-dibromophenothiazine derivative; andforming a 3,7-dimethoxyphenothiazine derivative from the 3,7-dibromophenothiazine derivative.9. The method according to claim 8 , wherein the step of forming a 3 claim 8 ,7-dimethoxyphenothiazine derivative comprises treating the 3 claim 8 , 7-dibromophenothiazine derivative with sodium methoxide and copper (I) iodide in refluxing pyridine.11. A non-aqueous redox flow battery claim 8 , comprising:a negative electrode immersed in a first non-aqueous liquid electrolyte solution;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a positive electrode immersed in a second non-aqueous liquid electrolyte solution, the second non-aqueous liquid electrolyte solution including at least one compound according to ; and'}a semi-permeable separator interposed between the negative and positive electrodes.13. The non-aqueous flow-battery according to wherein the at least one compound has a solubility of greater than 0.5M in the second non-aqueous liquid electrolyte solution. This invention claims priority to U.S. Provisional Application Ser. No. 62/378,443, filed Aug. 23, 2016.This invention was made with government support under grant numbers 1300653 and 1355438 awarded by the National Science Foundation. The government has certain rights in ...

ARYL DIHYDRO-2H BENZO[B][1,4]OXAZINE SULFONAMIDE AND RELATED COMPOUNDS FOR USE AS AGONISTS OF RORY AND THE TREATMENT OF DISEASE

The invention provides aryl dihydro-2H-benzo[b][1,4]oxazine sulfonamide and related compounds, pharmaceutical compositions, methods of promoting RORγ activity, methods of increasing the amount of IL-17 in a subject, and methods of treating cancer and other medical disorders using such compounds. 138-. (canceled)40. The compound of claim 39 , wherein X is phenyl substituted by 1 claim 39 , 2 claim 39 , or 3 substituents independently selected from the group consisting of chloro claim 39 , fluoro claim 39 , Cfluoroalkyl claim 39 , Calkoxy claim 39 , and Cfluoroalkoxy claim 39 , where at least 1 substituent is located at a meta-position on the phenyl group.41. The compound of claim 39 , wherein Ris —(CH)—COH or —CHC(CH)—COH.42. The compound of claim 39 , wherein Ris —CF claim 39 , which is attached at a meta-position on the phenyl group.4358-. (canceled)59. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.60. A method of treating a disorder selected from the group consisting of cancer claim 39 , bacterial infection claim 39 , fungal infection claim 39 , and immune deficiency disorder claim 39 , comprising administering a therapeutically effective amount of a compound of to a subject in need thereof to treat the disorder.61. The method of claim 60 , wherein the disorder is cancer.62. The method of claim 60 , wherein the disorder is colon cancer claim 60 , pancreatic cancer claim 60 , breast cancer claim 60 , ovarian cancer claim 60 , prostate cancer claim 60 , squamous cell carcinoma claim 60 , basal cell carcinoma claim 60 , adenocarcinoma claim 60 , sweat gland carcinoma claim 60 , sebaceous gland carcinoma claim 60 , lung cancer claim 60 , leukemia claim 60 , bladder cancer claim 60 , stomach cancer claim 60 , cervical cancer claim 60 , testicular cancer claim 60 , skin cancer claim 60 , rectal cancer claim 60 , thyroid cancer claim 60 , kidney cancer claim 60 , uterus cancer claim 60 , esophagus cancer claim 60 , liver ...

PHENOTHIAZINE DERIVATIVES AND USES THEREOF

The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA). 2. The compound of claim 1 , wherein Ris hydrogen.3. (canceled)4. The compound of claim 1 , wherein Ris Calkylene-NRRand Ris hydrogen.520. -. (cancelled)22. The pharmaceutical composition of claim 21 , wherein Ris hydrogen.23. (canceled)24. The pharmaceutical composition of claim 21 , wherein Ris Calkylene-NRRand Ris hydrogen.25128-. (canceled)129. The compound of claim 2 , wherein Ris Calkylene-NRRand Ris hydrogen.130. The pharmaceutical composition of claim 22 , wherein Ris Calkylene-NRRand Ris hydrogen. The present application claims priority to, and the benefits of U.S. Provisional Patent application Ser. No. 62/653,741, filed Apr. 6, 2018, and U.S. Provisional Patent Application Ser. No. 62/653,752, filed Apr. 6, 2018, both of which are incorporated herein by reference in their entireties.The invention relates generally to novel phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of such compounds and/or compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies.Mutations in ribosomal protein (RP) genes or transcription factor GATA1 can result in the loss of erythrocyte progenitor cells and cause severe anemia. This is seen in patients with Diamond-Blackfan anemia (DBA), a rare blood disorder that is almost exclusively linked to RP gene haploinsufficiency. DBA, also known as Blackfan-Diamond anemia or inherited erythroblastopenia, affects approximately seven per million live births and is usually diagnosed during the first year of life (Vlachos et al., Br J Haematol. 2008 September; 142(6): 859-876). ...

PHENOTHIAZINE ANALOGUES AS MITOCHONDRIAL THERAPEUTIC AGENTS

The present disclosure provides phenothiazine derivative compounds and salts thereof, compositions comprising these compounds, and methods of using these compounds in a variety of applications, such as treatment or suppression of diseases associated with decreased mitochondrial function resulting in diminished ATP production and/or oxidative stress and/or lipid peroxidation. 1107-. (canceled)115. The method of claim 114 , wherein Ris C-Calkyl claim 114 , wherein the C-Calkyl is optionally substituted with 1 claim 114 , 2 claim 114 , 3 claim 114 , or 4 substituents independently selected from the group consisting of C-Ccycloalkyl claim 114 , C-Ccycloalkenyl claim 114 , and aryl claim 114 , wherein each cycloalkyl claim 114 , cycloalkenyl claim 114 , and aryl is optionally and independently substituted with 1 or more independently selected Rsubstituents.116. The method of claim 114 , wherein:{'sup': 1', '7, 'Ris OR; and'}{'sup': '7', 'sub': 1', '6, 'Ris C-Calkyl.'}117. The method of claim 114 , wherein Ris pyrrolidin-1-yl claim 114 , piperidin-1-yl claim 114 , azepan-1-yl claim 114 , piperazin-1-yl claim 114 , morpholin-4-yl claim 114 , or diazepan-1-yl claim 114 , each optionally substituted with 1 or more independently selected Rsubstituents.118. The method of claim 114 , wherein Ris C-Calkyl claim 114 , C-Calkenyl claim 114 , C-Calkynyl claim 114 , or OR claim 114 , wherein the C-Calkyl claim 114 , C-Calkenyl claim 114 , and C-Calkynyl are each optionally substituted with 1 claim 114 , 2 claim 114 , 3 claim 114 , or 4 substituents independently selected from the group consisting of halogen claim 114 , CN claim 114 , NO claim 114 , C-Calkyl claim 114 , C-Chaloalkyl claim 114 , C(O)N(R) claim 114 , C(O)OR claim 114 , N(R) claim 114 , OR claim 114 , C-Ccycloalkyl claim 114 , C-Ccycloalkenyl claim 114 , heterocyclyl claim 114 , aryl claim 114 , and heteroaryl claim 114 , wherein each cycloalkyl claim 114 , cycloalkenyl claim 114 , heterocyclyl claim 114 , aryl claim ...

IMPROVED PROCESS FOR THE MANUFACTURE OF R-6-HYDROXY-8-[1-HYDROXY-2-[2-(4-METHOXYPHENYL)-1,1-DIMETHYLETHYLAMINOETHYL]-2H-1,4-BENZOXAZIN-3(4H)-ONE HYDROCHLORIDE

The present invention provides an improved process for the manufacture (R)-6-hydroxy-8-[1-hydroxy-2-[2-(4-methoxyphenyl)-1,1-dimethyl-ethylamino-ethyl]-2H-1,4-benzoxazin-3(4H)-one, in high purity and high yield, through the use of 1,1-dimethyl-2-(4-methoxyphenyl)ethyl amine L-tartrate salt, 1,1-dimethyl-2-(4-methoxyphenyl)ethyl amine maletate salt or the camphorsulfonate salt of intermediate (4). The invention also relates to said salts, to processes for preparing them and to their use for the manufacture of (R)-6-hydroxy-8-[1-hydroxy-2-[2-(4-methoxyphenyl)-1,1-dimethyl-ethylamino-ethyl]-2H-1,4-benzoxazin-3(4H)-one or a pharmaceutically acceptable salt thereof. 2. The camphorsulfonate salt according to claim 1 , of (R)-(−)-camphorsulfonic acid.3. The camphorsulfonate salt according to claim 1 , of (S)-(+)-camphorsulfonic acid.4. The camphorsulfonate salt according to any one of to claim 1 , wherein molar ratio of intermediate (4) to camphorsulfonic acid is 1:1.5. The camphorsulfonate salt according to claim 1 , wherein the hydroxyl protecting group PG is benzyl.6. The camphorsulfonate salt according to claim 1 , which is in crystalline solid form.7. A crystalline solid form of the camphorsulfonate salt according to claim 6 , characterized by at least one of the following:a) a DSC thermogram showing an endothermic peak with an onset at 163-166° C., or{'sup': '−1', 'b) an IR spectrum showing bands at 2955, 1745, 1702, 1617, 1513, 1470, 1369, 1329, 1250, 1162, 1051, 1038, 852, 746, 700 cm.'}8. The camphorsulfonate salt according to claim 1 , which is in non-crystalline solid form.1235.-. (canceled)36. The camphorsulfonate salt according to claim 1 , wherein PG is an aralkyl group.37. The camphorsulfonate salt according to claim 1 , wherein PG is C-Calkyl substituted by a C-Caryl group.38. The camphorsulfonate salt according to claim 1 , wherein PG is p-methoxybenzyl.39. The process according to claim 10 , wherein step b) is carried out and comprises the additional ...

PHENOTHIAZINE ANALOGUES AS MITOCHONDRIAL THERAPEUTIC AGENTS

The present disclosure provides phenothiazine derivative compounds and salts thereof, compositions comprising these compounds, and methods of using these compounds in a variety of applications, such as treatment or suppression of diseases associated with decreased mitochondrial function resulting in diminished ATP production and/or oxidative stress and/or lipid peroxidation. 2. The compound according to claim 1 , wherein Ris hydrogen claim 1 , optionally substituted C-Calkyl claim 1 , optionally substituted C-Calkenyl claim 1 , optionally substituted C-Calkynyl claim 1 , or —OR.3. The compound according to claim 2 , wherein Ris hydrogen.4. The compound according to claim 2 , wherein Ris optionally substituted C-Calkyl.5. The compound according to claim 4 , wherein Ris C-Calkyl optionally substituted with —OR claim 4 , C-Ccycloalkyl claim 4 , C-Ccycloalkenyl claim 4 , or aryl claim 4 , wherein each cycloalkyl claim 4 , cycloalkenyl claim 4 , and aryl are optionally substituted with R.6. The compound according to claim 5 , wherein Ris C-Calkyl optionally substituted with C-Ccycloalkyl claim 5 , C-Ccycloalkenyl claim 5 , or aryl claim 5 , wherein each cycloalkyl claim 5 , cycloalkenyl claim 5 , and aryl are optionally substituted with R.7. The compound according to claim 2 , wherein Ris —ORand Ris C-Calkyl.8. The compound according to any one of - claim 2 , wherein Ris piperazinyl claim 2 , piperidinyl claim 2 , morpholinyl claim 2 , pyrrolidinyl claim 2 , azepanyl claim 2 , or diazepanyl claim 2 , each optionally substituted with one or more R.9. The compound according to any one of - claim 2 , wherein Ris piperidinyl optionally substituted with one or more R.10. The compound according to claim 9 , wherein Ris unsubstituted piperidinyl.11. The compound according to any one of - claim 9 , wherein Ris morpholinyl optionally substituted with one or more R.12. The compound according to claim 11 , wherein Ris unsubstituted morpholinyl.13. The compound according to any one ...

[6,6] FUSED BICYCLIC HDAC8 INHIBITORS

The present invention is directed to compounds of Formula I: 2. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare CR.3. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare CR.4. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare CR.5. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare CR.6. The compound of claim 1 , wherein one of Y claim 1 , Y claim 1 , Yand Yis N.7. The compound of claim 1 , wherein X is S(O) claim 1 , O claim 1 , or C(R)(R).8. The compound of claim 1 , wherein Ris —(CH)—R.9. The compound of claim 8 , wherein Ris optionally substituted aryl.10. The compound of claim 8 , wherein n is 1.11. The compound of claim 1 , wherein Rand R can combine with the carbon to form an oxo.12. The compound of claim 1 , wherein W is CH.13. The compound of claim 1 , wherein Ris H and Ris —C(O)N(R)(R).1619.-. (canceled)2123.-. (canceled)2527.-. (canceled)2931.-. (canceled)3437.-. (canceled)3941.-. (canceled)4345.-. (canceled)4758.-. (canceled)59. The compound of claim 8 , wherein n is 1 and Ris optionally substituted aryl claim 8 , optionally substituted heteroaryl claim 8 , or optionally substituted 3- to 8-membered heterocycle.60. The compound of claim 8 , wherein n is 1 and Ris aryl optionally substituted with one or more —OH claim 8 , R claim 8 , R claim 8 , halogen claim 8 , oxo claim 8 , (CH)OR claim 8 , —NO claim 8 , —OR claim 8 , N(R)(R) claim 8 , C(O)OR claim 8 , —C(O)N(R)(R) claim 8 , —S(O)R claim 8 , —S(O)R claim 8 , —S(R) claim 8 , —C(O)R claim 8 , —S(O)N(R)(R) claim 8 , —CN claim 8 , —C-Calkyl claim 8 , —C-Chaloalkyl claim 8 , —C-Calkoxy claim 8 , C-Calkylamino claim 8 , C-Cdialkylamino claim 8 , C-Chydroxyalkyl claim 8 , C-Ccycloalkyl claim 8 , C-Ccycloalkylalkyl claim 8 , arylalkyl claim 8 , heterocycle claim 8 , aryl claim 8 , or heteroaryl.61. The compound of claim 8 , wherein n is 1 and Ris heteroaryl optionally substituted with one or more —OH claim 8 , R claim 8 , R claim 8 , halogen ...

Method for Producing Benzoxazine Compounds

The present disclosure provides a method for producing a benzoxazine compound by reacting a phenolic compound with an aldehyde compound and an amine compound in the presence of a solvent system containing a apolar solvent and a polar aprotic solvent. The benzoxazine compound may be easily recovered from the solvent system to provide a benzoxazine compound in powder form that is substantially solvent-free.

Modified Nucleic Acid Binding Cyanine Dyes for the Detection of Reactive Oxygen Species

Disclosed herein are compounds, compositions, methods, and kits for detecting reactive oxygen species (ROS) by conventional fluorescence microscopy, fluorescence spectroscopy, flow cytometry, and/or high content imaging. The compounds disclosed herein are novel reduced nucleic acid binding cyanine dyes, which dyes are probes for detecting ROS and measuring oxidative stress in cells either in vitro and/or in vivo. Also described herein are processes for preparing novel reduced dyes, i.e., ROS probes, for use in the disclosed compositions, methods and kits. 7. The compound according to claim 2 , wherein:{'sup': '2', 'Ris methyl or ethyl;'}{'sup': '4', 'sub': 1', '6, 'Ris C-Calkyl;'}{'sup': '5', 'Ris phenyl;'}X is S; andn is 0.8. A reduced dye compound selected from the group consisting of:(Z)-2-((2-butyl-1-phenylquinolin-4(1H)-ylidene)methyl)-3-methyl-2,3-dihydrobenzo[d]thiazole;(Z)-2-((2-butyl-1-phenylquinolin-4(1H)-ylidene)methyl)-3-methyl-2-dueterio-3-hydrobenzo[d]thiazole;(Z)-3-methyl-2-((1-propylquinolin-4(1H)-ylidene)methyl)-2,3-dihydrobenzo[d]thiazole;(Z)-2-((2-methoxy-1-phenylquinolin-4(1H)-ylidene)methyl)-3-methyl-2,3-dihydrobenzo[d]thiazole;(Z)—N1,N1-dimethyl-N3-(4-((3-methyl-2,3-dihydrobenzo[d]thiazol-2-yl)methylene)-1-phenyl-1,4-dihydroquinolin-2-yl)-N3-propylpropane-1,3-diamine;N-ethyl-N-(4-((Z)-4-((E)-3-(2-methyl-2,3-dihydrobenzo[d]thiazol-2-yl)allylidene)-1-phenyl-1,4-dihydroquinolin-2-yl)benzyl)ethanamine; andN-ethyl-N-(4-((Z)-1-methyl-4-((E)-3-(3-methyl-2,3-dihydrobenzo[d]thiazol-2-yl)allylidene)-1,4-dihydroquinolin-2-yl)benzyl)ethanamine.9. A composition for the detection of reactive oxygen species (ROS) claim 2 , the composition comprising:a) one or more reduced dyes; andb) a carrier,{'claim-ref': {'@idref': 'CLM-00001', 'claims 1'}, 'b': '8', 'wherein said reduced dyes are compounds according to any one of - and are present in an amount effective to detect the presence of ROS upon reaction with ROS.'}10. The composition according to claim 9 , ...

EPOTHILONE DERIVATIVES

The present invention relates to compounds of the formula 4. A compound according to claim 3 , wherein G is optionally-substituted benzothiazolyl.5. A compound according to claim 3 , wherein G is optionally-substituted quinolinyl.7. A compound according to claim 6 , wherein{'sub': '8', 'Ris methyl;'}G is selected from optionally-substituted benzothiazolyl, benzoxazolyl, benzothienyl, quinuclidinyl, and quinolinyl;{'sub': '7', 'Ris hydrogen; and'}{'sub': 3', '4', '5, 'R, R, and Rare each alkyl groups containing from one to four carbon atoms.'}8. A pharmaceutical composition comprising one or more compounds according to any one of and a pharmaceutically acceptable carrier or diluent.9. A method of treating cancer in a patient which comprises providing an effective amount of a compound of to said patient.10. A method of treating a hyperproliferative cellular disease in a patient which comprises providing an effective amount of a compound of to said patient.11. A method of providing an antiangiogenic effect in a patient in need of said treatment which comprises providing an effective amount of a compound of to said patient. This application is a continuation of, and claims the benefit of priority of application Ser. No. 13/966,613, filed Aug. 14, 2013, which is a continuation of application Ser. No. 11/763,636, filed Jun. 15, 2007, (now U.S. Pat. No. 8,536,327) which is a continuation of application Ser. No. 11/512,623, filed Aug. 30, 2006 (now U.S. Pat. No. 7,241,755), which is a continuation of Ser. No. 10/405,886, filed Apr. 3, 2003 (now U.S. Pat. No. 7,125,899), which is a continuation of, and claims the benefit of priority of application Ser. No. 09/084,542, filed May 26, 1998, (now U.S. Pat. No. 6,650,599), which claims priority to U.S. provisional application Ser. No. 60/067,524, filed Dec. 4, 1997, and provisional application Ser. No. 60/051,951, filed Jul. 8, 1997.The present invention relates to epothilone derivatives, methods for the preparation of the ...

COLORING MATTER COMPOUND, INK, RESIST COMPOSITION FOR COLOR FILTER, AND HEAT-SENSITIVE TRANSFER RECORDING SHEET

The coloring matter compound is represented by the following general formula (1): 2. The coloring matter compound according to claim 1 , wherein one of Rand Rof the general formula (1) is an alkyl group.3. An ink comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the coloring matter compound according to ; and'}a medium for dissolving or dispersing the coloring matter compound therein.4. The ink according to claim 3 , wherein a content of the coloring matter compound is 1.0 to 30.0 parts by mass based on 100.0 parts by mass of the medium.5. A resist composition for a color filter comprising the coloring matter compound according to .6. A heat-sensitive transfer recording sheet claim 1 , comprising: a substrate; and a coloring material layer formed on the substrate and containing the coloring matter compound according to . This application is a continuation of International Application No. PCT/JP2013/005043, filed Aug. 27, 2013, which claims the benefit of Japanese Patent Application No. 2012-188151, filed Aug. 29, 2012.1. Field of the InventionThe present invention relates to a coloring matter compound, and an ink, a resist composition for a color filter and a heat-sensitive transfer recording sheet all containing the coloring matter compound.2. Description of the Related ArtRecently, there have been increasing demands for image quality improvement for color images in a color liquid crystal display and the like. A color filter is indispensable for color display in a liquid crystal display and is a significant component that affects the performance of the liquid crystal display. As a conventional method for producing a color filter, a dyeing method, a printing method, an inkjet method, and a photoresist method, are known. Among these methods, production by the photoresist method is principally employed because in this method, spectral properties and color reproducibility can be easily controlled and resolution is so high that high resolution patterning can ...

COLORING MATTER COMPOUND, INK, RESIST COMPOSITION FOR COLOR FILTER, AND HEAT-SENSITIVE TRANSFER RECORDING SHEET

The coloring matter compound is represented by the following general formula (1): 2. The coloring matter compound according to claim 1 , wherein one of Rand Rof the general formula (1) is an alkyl group.3. The coloring matter compound according to claim 1 , wherein Rto Rof the general formula (1) each represent a methyl group.4. An ink comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the coloring matter compound according to ; and'}a medium for dissolving or dispersing the coloring matter compound therein.5. The ink according to claim 4 , wherein a content of the coloring matter compound is 1.0 to 30.0 parts by mass based on 100.0 parts by mass of the medium.6. A resist composition for a color filter comprising the coloring matter compound according to .7. A heat-sensitive transfer recording sheet claim 1 , comprising: a substrate; and a coloring material layer formed on the substrate and containing the coloring matter compound according to . This application is a continuation of International Application No. PCT/JP2013/005046, filed Aug. 27, 2013, which claims the benefit of Japanese Patent Application No. 2012-188149, filed Aug. 29, 2012.1. Field of the InventionThe present invention relates to a coloring matter compound, and an ink, a resist composition for a color filter and a heat-sensitive transfer recording sheet all containing the coloring matter compound.2. Description of the Related ArtRecently, there have been increasing demands for image quality improvement for color images in a color liquid crystal display and the like. A color filter is indispensable for color display in a liquid crystal display and is a significant component that affects the performance of the liquid crystal display. As a conventional method for producing a color filter, a dyeing method, a printing method, an inkjet method, and a photoresist method are known. Among these methods, production by the photoresist method is principally employed because in this method, spectral ...

MEDICAL METHODS UTILISING HIGH PURITY DIAMINOPHENOTHIAZINIUM COMPOUNDS

This disclosure pertains generally to the field of chemical synthesis and purification, and more specifically to methods of synthesizing and purifying certain 3,7 diamino-phenothiazin-5-ium compounds (referred to herein as “diaminophenothiaziniumcompounds”) including Methythioninium Chloride (MTC) (also known as Methylene Blue). In one embodiment, the method comprises the steps of, in order: nitrosylation (NOS); nitrosyl reduction (NR); thiosulfonic acid formation (TSAF); oxidative coupling (OC); Cr(VI) reduction (CR); isolation and purification of zwitterionic intermediate (IAPOZI); ring closure (RC); chloride salt-formation (CSF); one of: sulphide treatment (ST); dimethyldithiocarbamate treatment (DT); carbonate treatment (CT); ethylenediaminetetraacetic acid treatment (EDTAT); organic extraction (OE); and recrystallisation (RX). Also disclosed resulting (high purity) compounds, compositions comprising them (e.g., tablets, capsules), and their use in methods of inactivating pathogens, and methods of medical treatment and diagnosis, etc., for example, for tauopathies, Alzheimer's disease (AD), skin cancer, melanoma, viral diseases, bacterial diseases, or protozoal diseases. 110-. (canceled)13. A high purity diaminophenothiazinium compound according to claim 12 , wherein:{'sub': 2', '2', '7, 'said oxidizing agent for said oxidative coupling (OC) step is NaCrO;'}said oxidative coupling (OC) step is performed under acidic conditions;said ring closure (RC) step is achieved by treatment with Cu(II) sulfate; andsaid ring closure (RC) step is performed under acidic conditions.16. A high purity diaminophenothiazinium compound according to claim 14 , wherein:said treatment to convert residual Cr(VI) to Cr(III) is treatment with a reducing agent selected from sodium hydrosulfite, ethanol, and sodium iodide;{'sub': 2', '2', '3, 'said thiosulfate is or comprises NaSO;'}{'sub': 2', '2, 'said oxidation in said thiosulfonic acid formation (TSAF) step is by reaction with an ...

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. 4. (canceled)7. The compound of claim 2 , wherein ring B is substituted with 1-3: halo claim 2 , C-Calkyl claim 2 , COR claim 2 , or COOR; and{'sup': '15', 'sub': 1', '6', '6', '10', '1', '6', '6', '10, 'Ris C-Calkyl, C-Caryl, 5-10 membered heteroaryl or a 4-10 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N, S, and oxidized forms of N and S, wherein the C-Calkyl, C-Caryl, 5-10 membered heteroaryl or 4-10 membered heterocyclyl is optionally substituted.'}8. (canceled)10. A composition comprising a compound of and at least one pharmaceutically acceptable excipient.11. A method for increasing oxygen affinity of hemoglobin S in a subject claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .12. A method for treating oxygen deficiency associated with sickle cell anemia or acute respiratory distress syndrome claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .13. A composition comprising a compound of and at least one pharmaceutically acceptable excipient.14. A method for increasing oxygen affinity of hemoglobin S in a subject claim 9 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .15. A method for treating oxygen deficiency associated with sickle cell anemia or acute respiratory distress syndrome claim 9 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .16. A method for increasing oxygen affinity of hemoglobin S in a ...

COMPOSITIONS AND METHODS FOR TREATING FRIEDREICH'S ATAXIA

The invention provides compositions and methods useful for the treatment of Friedreich's ataxia. In some embodiments, the invention provides compositions and methods useful for inhibiting the ubiquitination of frataxin. 2. The method of claim 1 , wherein X is —S(O)—.3. The method of claim 1 , wherein X is —C(O)—.4. The method of claim 3 , wherein R claim 3 , R claim 3 , R claim 3 , R claim 3 , and Rare each independently selected from the group consisting of hydrogen claim 3 , C-Calkyl claim 3 , and aryl.5. The method of claim 1 , wherein Ris selected from those that are listed in Table 2.6. The method of claim 1 , wherein Ris a phenyl group substituted with from 0 to 3 Rsubstituents.7. The method of claim 6 , wherein the Rsubstituents for the Rgroups are independently selected from the group consisting of halo claim 6 , C-Calkyl claim 6 , hydroxyl claim 6 , and C-Calkoxy.8. The method of claim 1 , wherein Ris a naphthyl group substituted with from 0 to 3 Rsubstituents.9. The method of claim 1 , wherein Ris selected from those that are listed in Table 2.10. The method of claim 3 , wherein Ris an aryl group substituted with from 0 to 3 Rsubstituents.11. The method of claim 1 , wherein Ris a heteroaryl group substituted with from 0 to 3 Rsubstituents.12. The method of claim 11 , wherein Ris a phenothiazinyl group with from 0 to 3 Rsubstituents.13. The method of claim 12 , wherein Ris C-Calkyl;{'sup': 2', '4, 'wherein Ris phenyl with 0 to 3 Rsubstituents; and'}{'sup': 4', '3, 'sub': 1', '6', '1', '6, 'wherein the Rsubstituents for the Rgroups are independently selected from the group consisting of halo, C-Calkyl, hydroxyl, and C-Calkoxy.'}15. The method of claim 1 , wherein the Rsubstituents for the Rgroups are independently selected from those that are listed in Table 2.16. The method of claim 1 , wherein each R claim 1 , R claim 1 , R claim 1 , R claim 1 , or Ris independently H claim 1 , C-Calkyl claim 1 , halo claim 1 , —NO claim 1 , —CF claim 1 , —CN claim 1 , or ...

Polymer Comprising A Plurality Of Phenothiazine Groups And Methods Of Making The Same

A non-leaching mediator may include a polymer having a polymeric backbone, and a plurality of phenothiazine groups bonded to the polymeric backbone. The plurality of phenothiazine groups may include at least one of a phenothiazine group having the general formula (IV): 2. The polymer of claim 1 , where the phenothiazine group is bonded to the polymeric backbone through a carbon-heteroatom bond.3. The polymer of claim 1 , where the phenothiazine group is bonded to the polymeric backbone through a group selected from the group consisting of an ether group claim 1 , an ester group claim 1 , a carbonate group claim 1 , a urea group claim 1 , a urethane group claim 1 , an amine group claim 1 , an amide group claim 1 , a thioether group claim 1 , a thiourea group and a sulfonamide group.5. The polymer of claim 4 , where m is 1 claim 4 , and R′ is an alkyl group having from 1 to 10 carbon atoms.7. The polymer of claim 6 , where the mole fraction of x and y is from 0.05 to 0.9 claim 6 , from 0.07 to 0.7 claim 6 , or from 0.1 to 0.5.9. The polymer of claim 8 , where the mole fraction of x and y is from 0.05 to 0.9 claim 8 , from 0.07 to 0.7 claim 8 , or from 0.1 to 0.5.10. A method of making the polymer of claim 1 , comprising: a polymer comprising a precursor polymeric backbone and a plurality of nucleophilic side groups bonded to the precursor polymeric backbone, and', 'a mixture of 2-(8-(ω-haloalkyl)-3H-phenothiazin-3-ylideneamino)benzene-1,4-disulfonic acid and 2-(2-(ω-haloalkyl)-3H-phenothiazin-3-ylideneamino)benzene-1,4-disulfonic acid., 'forming the polymer from'}11. The method of claim 10 , further comprising:forming the mixture of 2-(8-(ω-haloalkyl)-3H-phenothiazin-3-ylideneamino)-benzene-1,4-disulfonic acid and 2-(2-(ω-haloalkyl)-3H-phenothiazin-3-ylideneamino)-benzene-1,4-disulfonic acid.12. A method of making the polymer of claim 1 , comprising: a compound comprising a plurality of epoxide groups, and', 'a mixture of 2-(8-(ω-(bis(ω-hydroxyalkyl)amino)alkyl)-3H- ...

CONDENSED HETEROCYCLIC COMPOUND AND COMPOSITION

A condensed heterocyclic compound which is shown by the following formula (I) and a composition containing an (a) organic material and (b) at least one type of the condensed heterocyclic compound are provided. 2. The antiaging agent as set forth in claim 1 , wherein in said formula (I) claim 1 , Rand Rrespectively independently indicate substitutable linear or branched Cto Calkyl groups or substitutable phenyl groups.3. The antiaging agent set forth in claim 2 , wherein in said formula (I) claim 2 , Rand Rrespectively independently indicate α-methylbenzyl groups claim 2 , α claim 2 ,α-dimethylbenzyl groups claim 2 , t-butyl groups claim 2 , phenyl groups claim 2 , or 4-methylphenyl groups.4. A composition which contains (a) an organic material and (b) the antiaging agent as set forth in .5. A composition which contains (a) an organic material and (b) the antiaging agent as set forth in .6. A composition which contains (a) an organic material and (b) the antiaging agent as set forth in .7. The composition as set forth in claim 4 , wherein said ingredient (a) is a synthetic polymer.8. The composition as set forth in claim 4 , wherein said ingredient (a) is a synthetic rubber.9. The composition as set forth in claim 4 , wherein said ingredient (a) is acrylic rubber or hydrogenated nitrile rubber.10. The composition as set forth in claim 4 , wherein said ingredient (a) is acrylic rubber. This application is a Divisional of application Ser. No. 13/575,853 filed on Jul. 27, 2012, which is the national phase of PCT International Application No. PCT/JP2011/051740 filed on Jan. 28, 2011, and which claims priority to Application No. 2010-019346 filed in Japan on Jan. 29, 2010. The entire contents of all of the above applications are hereby incorporated by reference.The present invention relates to a novel condensed heterocyclic compound which can impart high processing stability and heat resistance, and long life to a polymer or other organic material which is susceptible to ...

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. 2. (canceled)3. The compound of claim 1 ,{'sub': 2', '2', '2, 'wherein Y—Z is —CHO— or —CHCH—.'}4. The compound of claim 3 , wherein Ris C-Calkoxy.6. (canceled)7. The compound of claim 1 , wherein ring B is substituted with 1-3substituents selected from halo claim 1 , C-Calkyl claim 1 , COR claim 1 , and COOR; and{'sup': '15', 'sub': 1', '6', '6', '10, 'Ris C-Calkyl, C-Caryl, 5-10 membered heteroaryl or a 4-10 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N, S, and oxidized forms of N and S, wherein the alkyl, aryl, heteroaryl or heterocyclyl is optionally substituted.'}8. (canceled)9. (canceled)10. A composition comprising a compound of claim 1 , and at least one pharmaceutically acceptable excipient.11. A method for increasing oxygen affinity of hemoglobin S in a subject claim 1 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .12. A method for treating sickle cell disease claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of . This application is a continuation of U.S. application Ser. No. 15/688,185, filed Aug. 28, 2017, which is a continuation of U.S. application Ser. No. 14/836,869, filed Aug. 26, 2015, now U.S. Pat. No. 9,776,960, which is a continuation of U.S. application Ser. No. 14/599,341, filed Jan. 16, 2015, which is a continuation of U.S. application Ser. No. 13/815,735, filed Mar. 15, 2013, now U.S. Pat. No. 8,952,171, which are incorporated herein by reference in their entirety.This invention provides compounds and pharmaceutical compositions ...

METHOD OF INHIBITING TAU PHOSPHORYLATION

A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. - 168.-. (canceled)70. The method according to claim 69 , wherein said compound or a pharmaceutically acceptable salt thereof is present dissolved or dispersed in a pharmaceutically acceptable diluent as a pharmaceutical composition when administered.85. The method according to claim 69 , wherein said administration is carried out a plurality of times.86. The method according to claim 85 , wherein said administration is carried out daily.87. The method according to claim 85 , wherein said administration is carried out multiple times daily.88. The method according to claim 70 , wherein said pharmaceutical composition is in liquid form.89. The method according to claim 70 , wherein said pharmaceutical composition is in solid form. This application is a continuation of application Ser. No. 16/030,494 of the same title filed on Jul. 9, 2018 that is now U.S. Pat. No. 10,760,052, that itself was a division of application Ser. No. 13/940,016 of the same title filed on Jul. 11, 2013 and is now U.S. Pat. No. 10,017,736, which claims priority from application Ser. No. 61/789,180 that was filed on Mar. 15, 2013, and application Ser. No. 61/671,235 that was filed on Jul. 13, 2012, whose disclosures are incorporated herein by reference.The present invention contemplates a method of central nervous system (CNS) treatment to inhibit the formation of hyperphosphorylated tau protein and the use of a contemplated compound in the manufacture of a medicament for inhibiting tau protein hyperphosphorylation that can lead to pathological formation of ...

NON-ATP DEPENDENT INHIBITORS OF EXTRACELLULAR SIGNAL-REGULATED KINASE (ERK)

A compound, having the formula A-1: 2. A composition claim 1 , comprising the compound of and a pharmaceutically acceptable carrier.5. A composition claim 3 , comprising the compound of and a pharmaceutically acceptable carrier. This application claims the benefit of U.S. Provisional Appl. Nos. 61/740,156 and 61/740,172, both filed Dec. 20, 2012; the entire contents of each of which are hereby incorporated by reference.This invention was made with government support under Grant No. R01 CA120215 awarded by the National Institutes of Health. The government has certain rights in the invention.1. Field of the ApplicationThe present application relates to inhibitors of extracellular signal-regulated kinase (ERK), compositions containing and methods for making same, and their use.2. Discussion of the BackgroundOver the past decade, the inhibition of protein kinases has emerged as one of the most promising therapeutic approaches for treating cancer. Significant efforts in developing anti-cancer therapies have focused on the targeted inhibition of the extracellular signal-regulated kinase (ERK) pathway in cancers that contain activating mutations in upstream RTK, Ras and BRaf proteins. The usefulness of many of these targeted compounds has been limited, however, because of toxicity, lack of efficacy, and development of drug resistance through mutations or activation of alternate survival pathways. The identification of an activating point mutation (primarily V600E) in the BRaf kinase in melanoma patients led to the discovery of PLX4032 (vemurafenib), a drug which selectively inhibits the mutated and constitutively active form of BRaf. While patients showed remarkable initial responses to PLX4032, they invariably developed a resistance to the drug and consequently poor survival outcomes. A major contributor to PLX4032 drug resistance and poor prognosis is the re-activation of the extracellular signal-regulated kinases (ERK). Currently, all small molecule kinase inhibitors in ...

SULFUR-CONTAINING HETEROCYCLIC DERIVATIVE HAVING BETA SECRETASE INHIBITORY ACTIVITY

The following compound is provided as an agent for treating a disease induced by production, secretion and/or deposition of amyloid β protein, for example, 1. (canceled)2. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. The compound according to claim 3 , wherein R claim 3 , R claim 3 , Rand Rare all hydrogen claim 3 , or its pharmaceutically acceptable salt claim 3 , or a solvate thereof.10. The compound according to claim 3 , wherein Rand Rare both hydrogen claim 3 , or its pharmaceutically acceptable salt claim 3 , or a solvate thereof.12. The compound according to claim 11 , wherein ring A′ is phenyl or a nitrogen-containing aromatic heterocyclic group claim 11 , or its pharmaceutically acceptable salt claim 11 , or a solvate thereof.13. The compound according to claim 11 , wherein ring A′ is a nitrogen-containing aromatic heteromonocyclic group claim 11 , or its pharmaceutically acceptable salt claim 11 , or a solvate thereof.14. The compound according to claim 11 , wherein ring B is a nitrogen-containing aromatic heteromonocyclic group claim 11 , or its pharmaceutically acceptable salt claim 11 , or a solvate thereof.15. A pharmaceutical composition comprising claim 3 , as an active ingredient claim 3 , the compound according to claim 3 , or its pharmaceutically acceptable salt claim 3 , or a solvate thereof.16. A pharmaceutical composition having β secretase inhibitory activity claim 3 , comprising claim 3 , as an active ingredient claim 3 , the compound according to claim 3 , or its pharmaceutically acceptable salt claim 3 , or a solvate thereof.17. A method for inhibiting β secretase activity claim 3 , comprising administering the compound according to claim 3 , or its pharmaceutically acceptable salt claim 3 , or a solvate thereof.18. (canceled)19. (canceled)20. The compound according to claim 9 , wherein Rand Rare both hydrogen claim 9 , or its pharmaceutically acceptable salt claim 9 , or a solvate thereof.21. A ...

SULFUR-CONTAINING HETEROCYCLIC DERIVATIVE HAVING BETA SECRETASE INHIBITORY ACTIVITY

The following compound is provided as an agent for treating a disease induced by production, secretion and/or deposition of amyloid β protein, for example, a compound represented by the formula (I): 5. The compound according to claim 1 , wherein Rand Rare both hydrogen claim 1 , or its pharmaceutically acceptable salt claim 1 , or a solvate thereof.6. The compound according to claim 1 , wherein Ris alkyl of a carbon number of 1 to 3 claim 1 , or its pharmaceutically acceptable salt claim 1 , or a solvate thereof.7. The compound according to claim 2 , wherein Ris optionally substituted cycloalkyl claim 2 , optionally substituted phenyl claim 2 , or an optionally substituted nitrogen-containing aromatic heterocyclic group claim 2 , or its pharmaceutically acceptable salt claim 2 , or a solvate thereof.8. The compound according to claim 2 , wherein Rand Rare both hydrogen claim 2 , or its pharmaceutically acceptable salt claim 2 , or a solvate thereof.9. The compound according to claim 3 , wherein R claim 3 , R claim 3 , Rand Rare all hydrogen claim 3 , or its pharmaceutically acceptable salt claim 3 , or a solvate thereof.10. The compound according to claim 1 , wherein Rand Rare both hydrogen claim 1 , or its pharmaceutically acceptable salt claim 1 , or a solvate thereof.12. The compound according to claim 11 , wherein ring A′ is phenyl or a nitrogen-containing aromatic heterocyclic group claim 11 , or its pharmaceutically acceptable salt claim 11 , or a solvate thereof.13. The compound according to claim 11 , wherein ring A′ is a nitrogen-containing aromatic heteromonocyclic group claim 11 , or its pharmaceutically acceptable salt claim 11 , or a solvate thereof.14. The compound according to claim 11 , wherein ring B is a nitrogen-containing aromatic heteromonocyclic group claim 11 , or its pharmaceutically acceptable salt claim 11 , or a solvate thereof.15. A pharmaceutical composition comprising claim 1 , as an active ingredient claim 1 , the compound according to ...

SUBSTITUTED BENZOXAZINE AND RELATED COMPOUNDS

The present invention relates to compounds including but not limited to of any one of formulas Ia, Ib, IIa, IIb, IIIa, IIIb, and IV to VI, VIIa, VIIb, VIIIa, VIIIb and VIIIc as described herein and their tautomers and/or pharmaceutically acceptable salts, compositions, and methods of uses thereof. 116.-. (canceled)18. The compound of claim 17 , or a pharmaceutically acceptable salt thereof claim 17 , wherein Xis O.19. The compound of claim 17 , or a pharmaceutically acceptable salt thereof claim 17 , wherein Ris H.20. A pharmaceutical composition comprising a compound of claim 17 , or a pharmaceutically acceptable salt thereof claim 17 , and a pharmaceutically acceptable excipient.21. A method for inducing neuronal autophagy which method comprises contacting a cell with an effective amount of a compound of claim 17 , or a pharmaceutically acceptable salt thereof claim 17 , wherein the cell is selected from the group consisting of a neuron claim 17 , microglia claim 17 , macrophages claim 17 , and astrocytes.22. A method for treating a disease which method comprises administering to a patient an effective amount of a compound of claim 17 , or a pharmaceutically acceptable salt thereof claim 17 , wherein the disease is selected from the group consisting of Huntington's disease claim 17 , spinocerebellar ataxias claim 17 , Alzheimer's disease claim 17 , Parkinson's disease claim 17 , frontotemporal dementia claim 17 , high-pressure neurological syndrome claim 17 , dystonia claim 17 , olivopontocerebellar atrophy claim 17 , amyotrophic lateral sclerosis claim 17 , multiple sclerosis claim 17 , epilepsy claim 17 , stroke claim 17 , cerebral ischemia claim 17 , hypoxia claim 17 , multi-infarct dementia claim 17 , cerebral trauma or damage claim 17 , damage to the spinal cord claim 17 , AIDS-dementia complex claim 17 , viral or bacterial meningitis claim 17 , poliomyelitis claim 17 , Lyme disease claim 17 , malaria claim 17 , cancers with cerebral localization claim 17 , ...

[6,6] FUSED BICYCLIC HDAC8 INHIBITORS

The present invention is directed to compounds of Formula I: 2. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare CR.3. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare CR.4. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare CR.5. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare CR.6. The compound of claim 1 , wherein Ris heteroaryl claim 1 , 3- to 8-membered heterocycle claim 1 , or —C(O)Rwherein each heteroaryl or heterocycle is optionally substituted with one or more —OH claim 1 , halogen claim 1 , oxo claim 1 , —NO claim 1 , —NH claim 1 , —CN claim 1 , —C-Calkyl claim 1 , —C-Calkoxy claim 1 , heterocycle claim 1 , aryl claim 1 , heteroaryl claim 1 , or R.79-. (canceled)10. The compound of claim 1 , wherein W is CH.11. (canceled)1316-. (canceled)18. The compound of claim 1 , having the formula:19. (canceled)20. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.21. The compound of claim 18 , wherein Rand R′ are each hydrogen.22. The compound of claim 21 , wherein Ris heteroaryl optionally substituted with one or more —C-Calkoxy.23. The compound of claim 21 , wherein Ris 3- to 8-membered heterocycle optionally substituted with one or more —C-Calkoxy.26. The compound of claim 25 , wherein Rand R′ are each hydrogen.27. The compound of claim 26 , wherein Ris heteroaryl optionally substituted with one or more —C-Calkoxy.28. The compound of claim 26 , wherein Ris 3- to 8-membered heterocycle optionally substituted with one or more —C-Calkoxy.29. A compound of claim 1 , wherein the compound is selected from:1-(1H-benzo[d]imidazol-2-yl)-N-hydroxy-1,2,3,4-tetrahydroquinoline-7-carboxamide (I-106);1-(1H-benzo[d]imidazol-2-yl)-N-hydroxy-1,2,3,4-tetrahydroquinoline-6-carboxamide (I-107);N-hydroxy-1-(1-(2-methoxyethyl)-1H-benzo[d]imidazol-2-yl)-1,2,3,4-tetrahydroquinoline-7-carboxamide (I-110);N- ...

Salts

The present invention relates to new crystalline salt forms of flibanserine which have valuable pharmacological properties, to a process for their manufacture, to pharmaceutical formulations containing them and to their use as medicament. 2. (canceled)3. A pharmaceutical composition comprising the crystalline salt form according to and a pharmaceutically acceptable excipients.4. A process for preparing a crystalline salt according to claim 1 , comprising:i) dissolving the free base of flibanserin and the acid providing the anion for salt formation in a suitable solvent;ii) mixing the free base of flibanserin with the acid at a predetermined base/acid molar ratio, which is selected from 1:1 or 2:1 depending on the acid;iii) removing the solvent;iv) adding a suitable crystallization solvent to the residue obtained by step iii), and heating the reaction mixture slowly up to about 50° C. and leaving it to stand for a further period of time;v) slowly cooling down the reaction mixture to a suitable crystallization temperature and leaving it to stand until enough crystals are formed; andvi) isolating the precipitated crystals.5. A method a treating a disorder in a patient in need thereof claim 1 , the method comprising administering an effective amount of a compound according to to the patient.6. The method according to claim 5 , wherein the disorder is Hypoactive Sexual Desire Disorder.7. The method according to claim 5 , wherein the disorder is selected from a central nervous system disorder claim 5 , including an affective disorder (e.g. claim 5 , depression like major depressive disorder claim 5 , childhood depression claim 5 , dysthymia claim 5 , seasonal affective disorder claim 5 , dysthymic disorder and minor depressive disorder; bipolar disorders) claim 5 , anxiety (e.g. claim 5 , panic disorder with or without agoraphobia claim 5 , agoraphobia without history of panic disorder claim 5 , specific phobia (simple phobia) claim 5 , social phobia (social anxiety ...

METHODS FOR PRODUCING VILOXAZINE SALTS AND NOVEL POLYMORPHS THEREOF

Provided here are methods of manufacture of viloxazine and its various salts, as well as viloxazine-related compounds, such as novel intermediate reaction products and polymorphs thereof. In particular, the methods provide a substantially pure API of viloxazine HCl while avoiding undesirable impurities. The methods further provide for separating, identifying, and characterizing novel polymorphs of viloxazine. Further provided are methods for synthesis and identification and characterization of novel intermediates of viloxazine, as well as for some important metabolites and precursors of metabolites of viloxazine. 1. A substantially pure composition consisting essentially of viloxazine or a pharmaceutically acceptable salt thereof , said composition comprising less than about 1.5 μg of any genotoxic impurity per expected human daily dosage.2. The composition according to claim 1 , said composition comprising less than about 2.5 ppm of epichlorohydrin and less than about 2.5 ppm of 1-(2-ethoxyphenoxy)-2 claim 1 ,3-epoxypropane.3. The composition according to claim 1 , said composition comprising less than about 5 ppm of 2-aminoethyl hydrogen sulfate.4. The composition of comprising no esters of 2-aminoethyl hydrogen sulfate.6. The compound according to claim 5 , wherein Ris ortho-ethoxy.7. The compound according to claim 5 , wherein said nitrogen-protecting group is a benzyl group.8. A method of manufacturing viloxazine comprising reacting said compound according to in a solvent system with a base and a cyclization agent to produce viloxazine claim 6 , and thereafter isolating viloxazine or a pharmaceutically acceptable salt thereof.9. The method according to claim 12 , wherein said cyclization agent is toluene sulfonyl chloride.10. The method according to claim 8 , wherein Ris a nitrogen-protecting group claim 8 , said nitrogen-protecting group being a benzyl group claim 8 , and wherein said method further comprises removing said nitrogen-protecting group by ...

THIAZOLIDINONE COMPOUNDS AND THEIR USE IN THE TREATMENT OF PSYCHIATRIC OR NEUROLOGICAL DISORDERS AND INFLAMMATION, IN PARTICULAR NEUROINFLAMMATION

The invention relates to a compound comprising the following general formula (1): 2. The compound according to claim 1 , wherein R2 selected froma substituted or unsubstituted alkyl,a substituted or unsubstituted alkenyl,a substituted or unsubstituted alkynyl,a substituted or unsubstituted cycloalkyl,a substituted or unsubstituted aryl, ora substituted or unsubstituted heteroaryl.3. The compound according to claim 1 , wherein R2 is selected from an alkyl,', 'an alkenyl,', 'an alkynyl, and', 'Ar being a substituted or unsubstituted C5-C6— aryl or a substituted or unsubstituted C5-C6— heteroaryl, or', 'a substituted or unsubstituted C6— aryl or a substituted or unsubstituted C5-C6— heteroaryl., 'with L being'}, 'a substituted alkyl, alkenyl or alkynyl, wherein the substituted alkyl, alkenyl or alkynyl comprises the formula -L-Ar,'}5. The compound according to claim 4 , wherein o of Zo is 0 claim 4 , 1 claim 4 , 2 claim 4 , 3 claim 4 , 4 or 5 claim 4 , and each Zis selected independently from any other Zfrom —F claim 4 , —Cl claim 4 , —Br claim 4 , —I claim 4 , CN claim 4 , —Rb claim 4 , —ORb claim 4 , CH2ORb or —NRb2 claim 4 , with each Rb being selected independently from each other from H claim 4 , a substituted or unsubstituted C1-C12 alkyl claim 4 , a substituted or unsubstituted C2-C12 alkenyl or a substituted or unsubstituted C2-C12 alkynyl.6. The compound according to claim 5 , wherein o of Zo is 0 claim 5 , 1 claim 5 , 2 claim 5 , 3 claim 5 , 4 or 5 claim 5 , and each Zis selected independently from any other Zfrom —F claim 5 , —Cl claim 5 , —Br claim 5 , —I claim 5 , CN claim 5 , —Rb claim 5 , —ORb claim 5 , CH2ORb or —NRb2 claim 5 , with each Rb being selected independently from each other from H claim 5 , a substituted or unsubstituted C1-C12 alkyl claim 5 , a substituted or unsubstituted C2-C12 alkenyl or a substituted or unsubstituted C2-C12 alkynyl.7. A method for administering to a subject in need thereof the compound of claim 1 , inhibiting N- ...

SYNTHESIS OF A THIOSULFONIC ACID BY A STEP OF PERIODATE MEDIATED OXIDATIVE COUPLING OF A THIOSULFONIC ACID WITH AN ANILINE

The present invention pertains generally to the field of chemical synthesis, and more particularly to methods for the chemical synthesis of a thiosulfonic acid of Formula (1) by a step of periodate mediated oxidative coupling of a thiosulfonic acid of Formula (2) with an aniline of Formula (3), as described herein. The present invention also relates to such methods which incorporate one or more additional (subsequent and/or preceding) steps, for example, to prepare compounds of Formula (5) from compounds of Formula (1); to prepare compounds of Formula (6) from compounds of Formula (5); and to prepare compounds of Formula (2) from compounds of Formula (4), as described herein. 1126-. (canceled)128. A method according to claim 127 , wherein each —Ris independently Calkyl; Calkenyl; or halogenated Calkyl preferably wherein —Ris independently —Me or —Et.129. A method according to claim 127 , wherein —Ris independently Calkyl; Calkenyl; or halogenated Calkyl preferably wherein —Ris independently —Me or —Et.130. A method according to claim 127 , wherein —Ris independently Calkyl; Calkenyl; or halogenated Calkyl preferably wherein —Ris independently —Me or —Et.131. A method according to claim 127 , wherein —Ris independently Calkyl; Calkenyl; or halogenated Calkyl preferably wherein —Ris independently —Me or —Et.132. A method according to claim 127 , wherein —R claim 127 , if present claim 127 , is independently Calkyl; Calkenyl; or halogenated Calkyl claim 127 , preferably wherein —R claim 127 , if present claim 127 , is independently —Me or —Et.133. A method according to claim 127 , wherein —R claim 127 , if present claim 127 , is independently Calkyl; Calkenyl; or halogenated Calkyl preferably wherein —R claim 127 , if present claim 127 , is independently —Me or —Et.134. A method according to claim 127 , wherein —R claim 127 , if present claim 127 , is independently Calkyl; Calkenyl; or halogenated Calkyl preferably wherein —R claim 127 , if present claim 127 , is ...

PHENOTHIAZINE ANALOGUES AS MITOCHONDRIAL THERAPEUTIC AGENTS

The present disclosure provides phenothiazine derivative compounds and salts thereof, compositions comprising these compounds, and methods of using these compounds in a variety of applications, such as treatment or suppression of diseases associated with decreased mitochondrial function resulting in diminished ATP production and/or oxidative stress and/or lipid peroxidation. 23-. (canceled)4. The compound according to claim 1 , wherein Ris C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , —OR claim 1 , —SR claim 1 , or —N(R) claim 1 , each optionally substituted with one to four substituents selected from halogen claim 1 , —CN claim 1 , —NO claim 1 , C-Calkyl claim 1 , halo(C-Calkyl) claim 1 , —OR claim 1 , —NR claim 1 , —COR claim 1 , —CONR claim 1 , C-Ccycloalkyl claim 1 , C-Ccycloalkenyl claim 1 , aryl claim 1 , heteroaryl claim 1 , and heterocycle claim 1 , wherein each cycloalkyl claim 1 , cycloalkenyl claim 1 , aryl claim 1 , heteroaryl claim 1 , and heterocycle are optionally substituted with one or more R.5. The compound according to claim 1 , wherein Ris C-Calkyl optionally substituted with —OR claim 1 , C-Ccycloalkyl claim 1 , C-Ccycloalkenyl claim 1 , or aryl claim 1 , wherein each cycloalkyl claim 1 , cycloalkenyl claim 1 , and aryl are optionally substituted with R.6. The compound according to claim 1 , wherein Ris C-Calkyl optionally substituted with C-Ccycloalkyl claim 1 , C-Ccycloalkenyl claim 1 , or aryl claim 1 , wherein each cycloalkyl claim 1 , cycloalkenyl claim 1 , and aryl are optionally substituted with R.7. The compound according to claim 1 , wherein Ris —ORand Ris C-Calkyl.8. The compound according to claim 1 , wherein Ris piperazinyl claim 1 , piperidinyl claim 1 , morpholinyl claim 1 , pyrrolidinyl claim 1 , azepanyl claim 1 , or diazepanyl claim 1 , each optionally substituted with one or more R.915-. (canceled)16. The compound according to claim 1 , wherein Ris C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , or — ...

LIGHT EMITTING DEVICES AND COMPOUNDS

Thermally Activated Delayed Fluorescence (TADF) compounds wherein two aromatic heterocyclic moieties are provided as acceptor groups, spaced apart from two donor moieties by an aromatic spacer ring, are described. Charged organic TADF species having a similar structure are also described. The TADF compounds and charged organic TADF species may be employed as emitter material in light emitting devices such as OLEDs and LEECs. Also described TADF compounds wherein at least one donor moiety is substituted by at least one substituent that is a phosphine oxide or a phosphine sulphide. 137-. (canceled)44. A light emitting device comprising a TADF compound according to .45. The light emitting device of claim 44 , wherein said light emitting device is an OLED.492. The TADF compound according to claim 46 , wherein the acceptor moieties Acc are claim 46 , independently for each occurrence selected from the group consisting of -Het as defined in claim claim 46 , —CN claim 46 , sulfone claim 46 , sulfoxide claim 46 , imine claim 46 , amide claim 46 , acridine claim 46 , acridinium claim 46 , carboxylate ester claim 46 , phosphine oxide claim 46 , phosphine sulfide claim 46 , ketone and aldehyde.52. A light emitting device comprising a TADF compound according to .53. The light emitting device of claim 52 , wherein said light emitting device is an OLED.57. The charged organic species according to claim 56 , wherein at least one linking group L is present and is independently for each occurrence claim 56 , a hydrocarbylene chain claim 56 , that may be substituted or unsubstituted claim 56 , hydrocarbylene or unsaturated hydrocarbylene.58. The charged organic species according to claim 57 , wherein the at least one linking group L is selected from substituted or unsubstituted cyclopentane-1 claim 57 ,3-diyl claim 57 , cyclohexane-1 claim 57 ,4-diyl claim 57 , 1 claim 57 ,4-phenylene and 4 claim 57 ,4′-biphenylene.59. The charged organic species according to claim 57 , wherein the ...

Compounds and uses thereof for the modulation of hemoglobin

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

Process for Manufacturing 4-Propargylated Amino-Benzoxazinones

The present invention relates to a process for manufacturing 4-propargylated amino-benzoxazinones of formula (I), 114.-. (canceled)16. The process of claim 15 , wherein the propargyl chloride prepared in step (a) is used directly in step (b) without further purification.17. The process of claim 15 , wherein in step (a) the thionyl chloride and optionally the catalyst are initially charged in a reaction vessel claim 15 , if appropriate with the desired solvent claim 15 , and subsequently the propargyl alcohol is added.18. The process of claim 15 , wherein step (a) is carried out in the presence of a catalyst.19. The process of claim 15 , wherein in step (a) the catalyst is selected from the group consisting of phosphine oxides claim 15 , guanidinium salts claim 15 , open-chain and cyclic alkylureas claim 15 , alkylacetamides and N claim 15 ,N-dialkylformamides.22. The process of claim 15 , wherein step (b) is carried out in the presence of a base.23. The process of claim 15 , wherein the base used in step (b) is selected from the group consisting of carbonates claim 15 , hydrogen carbonates claim 15 , hydroxides claim 15 , oxides claim 15 , phosphates and alkoxides.24. The process of claim 23 , wherein the base used in step (b) is selected from carbonates.25. The process of claim 15 , wherein Rand Rare halogen.26. The process of claim 15 , wherein{'sup': '2', 'Ris F; and'}W is O. The invention relates a process for manufacturing 4-propargylated amino-benzoxazinones of formula (I), their use in and a process for manufacturing triazinon-benzoxazinones of formula (IV).Propargyl chloride (3-chloropropyne) is a valuable intermediate which is required for preparing a series of intermediates and electrolysis auxiliaries, but also as a reagent for introducing a propargyl radical in the preparation of active compounds for pharmaceuticals and crop protection.WO 99/46226 discloses a continuous method for producing propargyl chloride, wherein phosgene is used as chlorinating ...

NEW EMITTER MATERIALS AND MATRIX MATERIALS FOR OPTOELECTRONIC AND ELECTRONIC COMPONENTS, IN PARTICULAR ORGANIC LIGHT-EMITTING DIODES (OLEDS)

The invention relates to compounds, comprising at least one donor group and at least one acceptor group, in which the transition energy of the lowest excited triplet hack into the ground state both of the corresponding donor molecule and of the corresponding acceptor molecule being at least 2.2 eV, and the use thereof as an emitter or a carrier material in an optoelectronic component. 1. A compound comprising at least one donor group and at least one acceptor group , in which the vertical transition energy of the lowest excited triplet back to the electronic ground state both for the individual corresponding donor molecule and for the individual corresponding acceptor molecule is at least 2.2 eV , and wherein the dihedral angle between the at least one donor group and the at least one acceptor group is at least 70°.4. The compound as claimed in claim 1 , wherein the compound claim 1 , in addition to the at least one donor molecule and the at least one acceptor molecule claim 1 , comprises at least one further donor molecule or acceptor molecule in which the vertical transition energy of the lowest excited triplet is at least 2.2 eV.5. The compound as claimed in claim 1 , wherein the at least one further donor group or acceptor group is a compound of the formula (I) or (11) as defined in .6. The compound as claimed in claim 1 , wherein the compound is a compound of the formula (III) or a compound of the formula (IV):{'br': None, 'A-B-A \u2003\u2003(III)'}{'br': None, 'A-B \u2003\u2003(IV)'}wherein, in the compounds of the formula (III) or (IV),components A and B are each either a donor group or an acceptor group, where at least one A or B is, preferably all A and more preferably all A and B are, a compound having a vertical transition energy of the lowest excited triplet back to the electronic ground state of at least 2.2 eV, and wherein the dihedral angle between at least one donor group and at least one acceptor group, preferably between (each) A and B, is at least ...

3,7-DIAMINO-10H-PHENOTHIAZINE SALTS AND THEIR USE

Described are methods of prepraing reduced 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of formula: 6. A method according to claim 5 , wherein nitration is performed using a nitrite.7. A method according to claim 4 , wherein in said ring amino protection (AP) step claim 4 , ring amino protection is achieved as an acetate.8. A method according to claim 7 , wherein ring amino protection is achieved using acetic anhydride.9. A method according to claim 3 , wherein said nitro reduction (NR) is performed using tin (II) chloride.10. A method according to claim 2 , wherein said amine substitution (AS) is performed using an alkyl halide.11. A method according to claim 1 , wherein the steps of ring amino deprotection (DP) and salt formation (SF) are performed simultaneously.13. A method according to claim 12 , wherein the combined reduction (RED) step and ring amino protection (AP) step is achieved using phenylhydrazine and acetic anhydride.14. A method according to or wherein Ris acetate.15. A method according to or wherein salt formation is performed using acid.16. A method according to claim 15 , wherein the acid is concentrated aqueous hydrochloric acid.17. A method according to claim 11 , wherein in the combined ring amino deprotection (DP) and salt formation (SF) step claim 11 , the protecting group of the protected 3 claim 11 ,7-di(disubstituted amino)-10H-phenothiazine is removed to give a 3 claim 11 ,7-di(disubstituted amino)-10H-phenothiazine and the corresponding salt is simultaneously formed.18. A method according to claim 1 , wherein each of Rand Ris independently —H claim 1 , -Me claim 1 , or -Et.19. A method according to claim 18 , wherein each of Rand Ris —H.20. A method according to claim 1 , wherein the groups —N(R)(R) and —N(R)(R) are the same claim 1 , and are selected from: —NMeand —NEt.21. A method according to claim 1 , wherein each of the groups —N(R)(R) and —N(R)(R) is: —NMe.22. A method according to claim 1 , wherein each of HXand HXis ...

USE OF AMINODIHYDROTHIAZINES FOR THE TREATMENT OR PREVENTION OF DIABETES

This invention relates to compounds of formula I, 2. A compound according to claim 1 , wherein Ris halogen.3. A compound according to claim 1 , wherein Ris fluoro.4. A compound according to claim 1 , wherein Ris heteroaryl claim 1 , said heteroaryl being unsubstituted or substituted by one claim 1 , two or three groups selected from the group consisting of C-alkyl claim 1 , halogen claim 1 , halogen-C-alkyl claim 1 , C-alkoxy claim 1 , halogen-C-alkoxy claim 1 , cyano claim 1 , hydroxy-C-alkyl and phenyl.5. A compound according to claim 1 , wherein Ris heteroaryl selected from the group consisting of thienyl claim 1 , oxazolyl claim 1 , thiazolyl claim 1 , pyrazolyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , isoquinolinyl claim 1 , thieno[2 claim 1 ,3-c]pyridyl and benzo[b]thienyl claim 1 , said heteroaryl being unsubstituted or substituted by one claim 1 , two or three groups selected from the group consisting of C-alkyl claim 1 , halogen claim 1 , halogen-C-alkyl and phenyl.6. A compound according to claim 1 , wherein Ris phenyl claim 1 , said phenyl being unsubstituted or substituted by one claim 1 , two or three groups selected from the group consisting of C-alkyl claim 1 , halogen claim 1 , halogen-C-alkyl claim 1 , C-alkoxy claim 1 , halogen-C-alkoxy claim 1 , cyano claim 1 , hydroxy-C-alkyl and phenyl.7. A compound according to claim 1 , selected from the group consisting of5-chloro-pyridine-2-carboxylic acid [3-((S)-2-amino-4-ethyl-5,6-dihydro-4H-[1,3]thiazin-4-yl)-4-fluoro-phenyl]-amide,pyridine-2-carboxylic acid [3-((S)-2-amino-4-ethyl-5,6-dihydro-4H-[1,3]thiazin-4-yl)-4-fluoro-phenyl]-amide,N-[3-((S)-2-amino-4-ethyl-5,6-dihydro-4H-[1,3]thiazin-4-yl)-4-fluoro-phenyl]-4-chloro-benzamide,5-chloro-pyrazine-2-carboxylic acid [3-((S)-2-amino-4-ethyl-5,6-dihydro-4H-[1,3]thiazin-4-yl)-4-fluoro-phenyl]-amide,5-chloro-pyrimidine-2-carboxylic acid [3-((S)-2-amino-4-ethyl-5,6-dihydro-4H-[1,3]thiazin-4-yl)-4-fluoro-phenyl]-amide,3- ...

METHOD OF INHIBITING TAU PHOSPHORYLATION

A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. - 134.-. (canceled)35. A method of inhibiting a TLR4-mediated immune response that comprises administering to TLR4-containing cells in recognized need thereof an effective amount of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1 , inhibits at least about 60 percent and more preferably about 70 percent of the FITC-labeled naloxone binding when present at a 10 μM concentration and using unlabeled naloxone as the control inhibitor at the same concentration , and contains at least four of the six pharmacophores of , said administration being carried out in the absence of a mu opioid receptor- (MOR-) binding effective amount of a separate MOR agonist or antagonist.36. The method according to claim 35 , wherein said compound contains at least five of the six pharmacophores of .37. The method according to claim 35 , wherein said compound or a pharmaceutically acceptable salt thereof is present dissolved or dispersed in a pharmaceutically acceptable diluent as a pharmaceutical composition when administered.38. The method according to claim 35 , wherein said compound exhibits less than about 80 percent the MOR stimulation provided by DAMGO at the same concentration.47. The method according to claim 46 , wherein said anion claim 46 , X claim 46 , is selected from the group consisting of phosphate claim 46 , hydrogenphosphate claim 46 , dihydrogenphosphate claim 46 , sulfate claim 46 , bisulfate claim 46 , chloride claim 46 , bromide claim 46 , iodide claim 46 , acetate ...

CYTOCHROME P450 INHIBITORS AND USES THEREOF

The present invention provides compounds having the general structural formula (I) 2. The compound of wherein X is imidazolyl claim 1 , triazolyl claim 1 , 3-pyridinyl or 4-pyridinyl.3. The compound of wherein X is Gis hydrogen claim 2 , di(Calkyl)amino or saturated heterocycle.4. The compound of wherein Ris Calkyl and Ris hydrogen.5. The compound of wherein Rand Rare Calkyl.6. The compound of wherein Qis —COOH or —COOR.7. The compound of selected from the group consisting of:3-(((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoic acid; 3-((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)-2,2-dimethylpropanoic acid; 3-((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)benzoic acid; 4-(((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoic acid; 4-((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)benzoic acid; Isopropyl 3-(((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoate; Isopropyl 4-(((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoate; Ethyl 3-(((6-(2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoate; Methyl 3-(((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoate; Isopropyl 3-((6-(2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)-2,2-dimethylpropanoate; Methyl 3-((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)benzoate; Methyl 4-(((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoate; Methyl 4-((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)benzoate; 1-((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)carbamoyl)cyclobutanecarboxylic acid; 1-((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)carbamoyl) ...

IMINO COMPOUNDS AS PROTECTING AGENTS AGAINTS ULTRAVIOLET RADIATIONS

The present invention relates to compounds having the general Formula I: which absorb UV radiations and protect biological materials as well as non-biological materials from damaging exposure to UV radiations. The present invention also relates to formulations and compositions comprising such compounds for use in absorbing UV radiations and in protecting biological materials as well as non-biological materials against UV radiations. 196-. (canceled)98. The compound of claim 97 , wherein Ris selected from the group consisting of alkyl claim 97 , alkoxy claim 97 , and —CHCOOH.99. The compound of claim 97 , wherein X is selected from the group consisting of carbon claim 97 , nitrogen or oxygen.100. The compound of claim 97 , wherein Ris selected from the group consisting of alkoxy claim 97 , —OCH claim 97 , halogen claim 97 , fluorine claim 97 , alkanoyl claim 97 , —CONC(CH) claim 97 , amine claim 97 , and —N(CHCH).101. The compound of claim 97 , wherein n is 1.103. The compound of claim 102 , wherein:{'sub': '3', 'Ris selected from the group consisting of —CH3 and hydrogen;'}{'sub': 4', '3, 'Ris selected from the group consisting of —CHand hydrogen;'}{'sub': '5', 'Ris —COOH;'}Y is selected from the group consisting of O, S, and NH;{'sub': '6', 'Ris selected from the group consisting of hydrogen and —COOH; or'}n is 1.106. The compound of claim 105 , wherein:{'sub': '5', 'Ris selected from the group consisting of carboxyl and —COOH;'}Y is selected from the group consisting of S, O, and N;{'sub': '6', 'Ris hydrogen;'}X is selected from the group consisting of O and N; orn is 1.109. The compound of claim 108 , wherein:{'sub': '6', 'Ris hydrogen;'}{'sub': 7', '3, 'Ris selected from the group consisting of hydrogen, alkoxy, and —OCH;'}X is selected from the group consisting of N and O; orn is 1.112. The compound of claim 111 , wherein:{'sub': '3', 'Rand R4 are each independently selected from the group consisting of hydrogen and alkyl;'}{'sub': 3', '3, 'Ris —CH;'}{'sub': 4 ...

STING AGONISTS AND METHODS OF SELECTING STING AGONISTS

Disclosed are small molecules capable of activating the type I interferon (IFN) response by way of the transcription factor IFN regulatory factor 3 (IRF3) were identified. A high throughput in vitro screen yielded 4-(2-chloro-6-fluorobenzyl)-N-(furan-2-ylmethyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (referred to herein as G10), which was found to trigger IRF3/IFN-associated transcription in human fibroblasts. To define cellular proteins essential to elicitation of the antiviral activity by the compound a reverse genetics approach that utilized genome editing via CRISPR/Cas9 technology was employed. This allowed the identification of IRF3, the IRF3-activating adaptor molecule STING, and the IFN-associated transcription factor STAT1 as required for observed gene induction and antiviral effects. 1. A method of identifying a test compound that is likely to act as an agonist of one or more proteins in the STING pathway , the method comprising:contacting a first transfected human cell with the test compound, where the first transfected human cell comprises an expression vector, the expression vector comprising,a first polynucleotide operably linked to a first promoter, the first polynucleotide encoding a human telomerase reverse transcriptase and where the first promoter is a constitutively active promotera second polynucleotide operably linked to a second promoter, the second polynucleotide encoding a bioluminescent protein or fluorescent protein and where the second promoter promotes the expression of the bioluminescent protein or fluorescent protein in the presence of interferon regulatory factor 3;contacting a second transfected human cell with the test compound where the second transfected cell comprises the first polynucleotide operably linked to the first promoter and the second polynucleotide operably linked to the second promoter and where the first transfected human cell expresses STING and where the second transfected human cell does not ...

SMALL MOLECULE MODULATORS OF HUMAN STING

The present invention relates to compounds of formula (I). The compounds may be used to modulate the Stimulator of Interferon Genes (STING) protein and thereby treat diseases such as cancer and microbial infections. 2. A compound according to claim 1 , wherein Xis CR claim 1 , Xis CRand Xis CR.3. A compound according to claim 1 , wherein one or two of X claim 1 , Xand Xis N.4. A compound according to any preceding claim claim 1 , wherein R claim 1 , Rand Rare each H.5. A compound according to any preceding claim claim 1 , wherein X is O claim 1 , S or CRR.6. A compound according to claim 5 , wherein X is S or CRR.7. A compound according to any preceding claim claim 5 , wherein at least one of Rand Ris an optionally substituted C-Calkyl claim 5 , halogen claim 5 , H claim 5 , a C-Ccycloalkyl or C-Cpolyfluoroalkyl.8. A compound according to claim 7 , wherein both Rand Rare H.9. A compound according to any preceding claim claim 7 , wherein n is 1.10. A compound according to any preceding claim claim 7 , wherein at least one of Rand Ris H.11. A compound according to claim 10 , wherein both Rand Ris H.12. A compound according to claim 10 , wherein one of Rand Ris H and the other is an optionally substituted C-Calkyl or an optionally substituted C-Calkenyl.13. A compound according to any preceding claim claim 10 , wherein Q is C═O claim 10 , SOor CRR.14. A compound according to claim 13 , wherein Q is C═O.15. A compound according to any preceding claim claim 13 , wherein L is C═O or SO claim 13 , an optionally substituted C-Calkyl claim 13 , —CHC(O)— or —CHCONH—.16. A compound according to claim 15 , wherein L is —CH— claim 15 , —CHCH— claim 15 , —CHCHCH— claim 15 , C(Me)H claim 15 , CFor C(H)F.17. A compound according to any preceding claim claim 15 , wherein Ris a mono or bicyclic optionally substituted C-Caryl claim 15 , a mono or bicyclic optionally substituted 5 to 10 membered heteroaryl claim 15 , an optionally substituted C-Ccycloalkyl or an optionally substituted ...

MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

CYTOCHROME P450 INHIBITORS AND USES THEREOF

The present invention provides compounds having the general structural formula (I) 185-. (canceled)87. The method of wherein X is imidazolyl claim 86 , triazolyl claim 86 , 3-pyridinyl or 4-pyridinyl claim 86 ,88. The method of wherein Gis hydrogen claim 86 , di(Calkyl)amino or saturated heterocycle.89. The method of wherein Rand Rare independently Calkyl.90. The method of wherein Qis —COOH or —COOR.92. The method of claim 91 , wherein the compound is selected irom the group consisting of: 3-(((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoic acid; 3-((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)-2 claim 91 ,2-dimethylpropanoic acid; 3-((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)benzoic acid; 4-(((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoic acid; 4-((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)benzoic acid; Isopropyl 3-(((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoate; Isopropyl 4-(((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoate; Ethyl 3-(((6-(2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoate; Methyl 3-(((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoate; Isopropyl 3-((6-(2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)-2 claim 91 ,2-dimethylpropanoate; Methyl 3-((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)benzoate; Methyl 4-(((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)methyl)benzoate; and Methyl 4-((6-(-2-(dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d]thiazol-2-yl)amino)benzoate;94. The method of claim 93 , wherein the compound is selected from the group consisting of: 1-((6-(-2-(Dimethylamino)-1-(1H-imidazol-1-yl)butyl)benzo[d] ...

MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating diseases using such CFTR modulators. 158-. (canceled)60. The compound according to claim 59 , wherein Ris halo claim 59 , CN claim 59 , CH claim 59 , CF claim 59 , OCF claim 59 , OCHor SOMe.61. The compound according to claim 59 , wherein Ris hydrogen.62. The compound according to claim 59 , wherein Ris methyl.63. The compound according to claim 59 , wherein Ris hydrogen.64. The compound according to claim 59 , wherein Rand Rare hydrogen.66. The compound according to wherein WRis a C-Cstraight or branched aliphatic claim 65 , or a 3-12 membered cycloaliphatic claim 65 , WRis —OH or OR′ and WRis —C≡CCHN(R′)(R′) claim 65 , —(CH)N(R′)(R′) claim 65 , —(CH)N(R′)(R′) claim 65 , —(CH)N(R′)(R′) or —N(R′)(R′).68. The compound according to wherein WRis a substituted C-Cstraight or branched aliphatic claim 67 , C-Cheterocyclic claim 67 , 3-12 membered cycloaliphatic claim 67 , or 3-12 membered bicyclic and WRis —C≡CCHN(R′)(R′) claim 67 , —(CH)N(R′)(R′) claim 67 , —(CH)N(R′)(R′) claim 67 , —(CH)N(R′)(R′) or —N(R′)(R′).70. The compound according to wherein WRis a substituted C-Cstraight or branched aliphatic claim 69 , C-Cheterocyclic claim 69 , 3-12 membered cycloaliphatic claim 69 , or 3-12 membered bicyclic and WRis —C≡CCHN(R′)(R′) claim 69 , —(CH)N(R′)(R′) claim 69 , —(CH)N(R′)(R′) claim 69 , —(CH)N(R′)(R′) or —N(R′)(R′).71. The compound according to any one of wherein Ris hydrogen.72. The compound according to any one of wherein wherein Ris hydrogen.73. The compound according to any one of wherein wherein Rand Ris hydrogen.75. A pharmaceutical composition comprising a compound of Formula IVD according to and a pharmaceutically acceptable carrier or adjuvant.76. The pharmaceutical composition according ...

Process for Preparing Diaminophenothiazinium Compounds

Process for preparing compounds of the diaminophenothiazinium type of formula (II) below. The products have a high degree of purity and are useful for the preparation of medicaments. 2. The process as claimed in claim 1 , in which R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand R claim 1 , which may be identical or different claim 1 , are chosen from a hydrogen atom and a C-Calkyl.3. The process as claimed in claim 1 , in which one or more of the following requirements are met:{'sub': 5', '8', '9', '10, 'R, R, Rand Rrepresent H,'}X represents Cl or OH,{'sub': 1', '2', '3', '4, 'R, R, Rand R, which may be identical or different, are chosen from a hydrogen atom and methyl,'}{'sub': '6', 'Rrepresents a hydrogen atom,'}{'sub': '7', 'Rrepresents a hydrogen atom,'}Z represents O.4. The process as claimed in claim 1 , in which the compound of formula (I) is methylene blue.5. The process as claimed in claim 1 , in which the compound of formula (I) is chosen from:Azure A,Azure B,Azure C.6. The process as claimed in claim 1 , in which the filtration support is a silica gel.7. The process as claimed in claim 1 , in which claim 1 , for the filtration claim 1 , the compound of formula (II) is solubilized in a solvent chosen from dichloromethane claim 1 , chloroform claim 1 , ethanol claim 1 , isopropanol claim 1 , methanol claim 1 , acetonitrile claim 1 , ethyl acetate claim 1 , tetrahydrofuran claim 1 , or a mixture of these solvents.8. The process as claimed in claim 1 , in which the deprotection is carried out by a means chosen from: quinones claim 1 , HNO claim 1 , HClO claim 1 , I claim 1 , HCl claim 1 , HSO claim 1 , HOand a treatment with ultraviolet radiation.9. The process as claimed in claim 1 , wherein the deprotection is implemented with solvents comprising less than 0.01 ppm metal residues claim 1 , in reactors not comprising any metal parts.10. The process as claimed in claim 1 , wherein the deprotection is implemented in a solvent chosen from: ethyl acetate ...

Liquid phenothiazine catholytes for non-aqueous redox flow batteries

Highly soluble, liquid phenothiazines containing methoxy-terminated ether and oligoether substituents are disclosed with high diffusion coefficients and robust performance in electrochemical measurements, which can be synthesized in one step from commercially-available starting materials, thereby circumventing previous synthetic limitations.

NUCLEATION LAYERS FOR ENHANCING PHOTOCATALYTIC ACTIVITY OF TITANIUM DIOXIDE (TiO2) COATINGS

A photocatalytic system having enhanced photo efficiency/photonic efficacy is provided that includes a thin nucleation material coated on a substrate. The nucleation material enhances lattice matching for a subsequently deposited photocatalytic active material. Such a photocatalytic system may be used as a self-cleaning surface in an application where removal of fingerprints and other residue is desired. In certain aspects, the nucleation material comprises aluminum oxide (AlO) and the photocatalytic material comprises an anatase phase of titanium dioxide (TiO) deposited over the nucleation material. A photocatalytic activity of the system is ≥about 50% above a comparative photocatalytic activity where the photocatalytic active material is disposed directly on the substrate. Methods of making such photocatalytic systems are also provided. 1. A photocatalytic system comprising:a nucleation material coated on a substrate, wherein the nucleation material comprises a metal oxide compound, wherein the metal is selected from the group consisting of: aluminum, zirconium, niobium, cerium, vanadium, lanthanum, titanium, silicon, iron, cobalt, nickel, molybdenum, tungsten, and combinations thereof; and{'sub': '2', 'a photocatalytic active material comprising an anatase phase of titanium dioxide (TiO) deposited over the nucleation material, wherein a photocatalytic activity is greater than or equal to about 50% above a comparative photocatalytic activity where the photocatalytic active material is disposed directly on the substrate.'}2. The photocatalytic system of claim 1 , wherein the nucleation material has an average thickness of less than or equal to about 10 nm.3. The photocatalytic system of claim 1 , wherein the nucleation material is selected from the group consisting of: aluminum oxide (AlO) claim 1 , SrTiO(STO) claim 1 , LaAlO(LAO) claim 1 , Y stabilized ZrO(YSZ) claim 1 , and combinations thereof.4. The photocatalytic system of claim 1 , wherein the nucleation ...