Cross-Coupled Peptide Nucleic Acids for Detection of Nucleic Acids of Pathogens

The present invention concerns methods for detecting a nucleic acid comprising (i) contacting a solution comprising a first PNA having a first cross-reactive functional group with a substrate having a second PNA affixed thereto, the second PNA having a second first cross-reactive functional group, wherein the first PNA has a reporter molecule attached thereto and the first and second PNAs being complementary to different portions of a target DNA; (ii) contacting a sample suspected of containing the nucleic acid with the first and second PNAs; and (iii) determining the presence of the reporter molecule on the substrate.

ENANTIOMERICALLY PURE AMINES

A compound of formula 3. A compound according to claim 1 , wherein PROT and PROT′ together with the nitrogen atom to which are attached form phthalimido-N-yl.4. A compound according to claim 1 ,wherein PROT″ is benzoyl or trityl.7. A compound according to claim 1 , selected from the group consisting of:{(1R,2R,4R)-4-[(tert-Butoxycarbonyl)-amino]-2-hydroxy-cyclohexyl}-benzene-carbothioate,{(1R,2R,4R)-4-[(2,2,2-Trifluoro-acetyl)-amino]-2-hydroxy-cyclohexyl}-benzene-carbothioate,tert-Butyl [(1R,3R,4R)-3-hydroxy-4-tritylsulfanyl-cyclohexyl]-carbamate, and2,2,2-Trifluoro-N-((1R,3R,4R)-3-hydroxy-4-tritylsulfanyl-cyclohexyl)-acetamide.10. A compound of formula II claim 9 , II claim 9 , IIor IIaccording to claim 9 , selected from the group consisting oftert-Butyl (1R,3R,6R)-(7-oxa-bicyclo[4.1.0]hept-3-yl)-carbamate, and2,2,2-Trifluoro-N-(1R,3R,6S)-(7-oxa-bicyclo[4.1.0]hept-3-yl)-acetamide.12. A process according to claim 11 , wherein none of the intermediates obtained in a) to d) is isolated.13. A process according to claim 11 , wherein the reaction a) to e) is performed in a single solvent (system).14. (canceled) The present invention relates to enantiomerically pure amines, such as amino and thio protected hydroxy-mercapto-cyclohexyl amines and production processes thereof.Organic compounds, such as cyclohexyl amines containing an asymmetric carbon atom may exist in the form of enantiomers, diastereoisomers and mixtures thereof, e.g. racemates. Such compounds may exist in the (R)-, (S)- or (R,S)-configuration. For pharmaceutical use it is often vital to have an active compound comprising an asymmetric carbon atom in one of the enantiomerically pure forms, since one isomer may differ, e.g. in several aspects from another isomer, e.g. one isomer may be more active than the other isomer. Separation of isomers is often burdensome. Chromatography which, for example, may be useful for isomeric separation, is on technical scale not easy to carry out and often needs sophisticated ...

NOVEL DERIVATIVES OF MESALAZINE, PROCESS OF THEIR PREPARATION AND THEIR USE IN THE TREATMENT OF INTESTINAL INFLAMMATORY DISEASES

The present invention refers to the compounds corresponding to the following general formula (I): 3. 5-amino-2-(butyryloxy)benzoic acid and/or pharmaceutically acceptable salts thereof , preferably hydrochloride salt.4. Method for treating acute or chronic intestinal inflammatory diseases claim 1 , comprising the administration to a patient in need of such treatment a compound according to claim 1 , wherein said acute or chronic intestinal inflammatory diseases are preferably selected from among IBD claim 1 , IBS claim 1 , ulcerative colitis claim 1 , Crohn's disease claim 1 , diverticular disease claim 1 , more preferably IBD.5. Method for treating according to claim 4 , wherein said acute or chronic intestinal inflammatory diseases are acute intestinal inflammatory diseases.6. Method for treating according to claim 4 , wherein said acute or chronic intestinal inflammatory diseases are chronic intestinal inflammatory diseases.7. Method for treating according to claim 6 , wherein said chronic intestinal inflammatory diseases are in a remission phase.8. A compound according to claim 2 , characterised in that it is administered enterally claim 2 , preferably orally and/or rectally claim 2 , or topically claim 2 , preferably through anal application.9. Pharmaceutical composition containing a compound according to claim 2 , and at least one physiologically acceptable excipient.10. Pharmaceutical composition according to selected from among tablet claim 9 , capsule claim 9 , granule claim 9 , microgranule claim 9 , suspension or aqueous solution claim 9 , enema claim 9 , suppository claim 9 , gel and rectal foam.13. Process according to claim 11 , wherein the step a) is conducted in an aprotic polar solvent and/or in a mixture of said solvent with HO preferably in a molar ratio comprised between 1:1 and 3:1 claim 11 , more preferably 2:1.14. Process according to claim 11 , wherein said mixture is constituted by dioxane and water claim 11 , preferably in a 2:1 molar ratio ...

Stabilized phenylcarbamate derivative in solid state

The invention relates to retigabine with improved color quality, and to processes for preparing the same. In addition, the invention relates to a process for drying wet retigabine. Also, the invention relates to stabilized or substantially stabilized retigabine in solid state, or a mixture or pharmaceutical formulation comprising the same. Further, the invention also relates to an improved process for preparing retigabine.

HISTONE DEMETHYLASE INHIBITORS AND METHODS FOR USING THE SAME

The present invention provides compounds, or derivatives or prodrugs thereof, that comprise a methyllysine mimic, and an α-ketoglutarate mimic that are attached through a linker and methods for using and producing the same. In some embodiments, compounds of the invention are of the formula: M-L-K, or a derivative or a prodrug thereof, wherein M is a methyllysine mimic, L is a linker, and K is an α-ketoglutarate mimic. 1. A compound of the formula: M-L-K , or a derivative or a prodrug thereof , wherein M is a methyllysine mimic , L is a linker , and K is an α-ketoglutarate mimic.3. The compound according to claim 2 , wherein Ris phenyl claim 2 , naphthyl claim 2 , benzyl claim 2 , or naphthylalkyl claim 2 , each of which is optionally substituted claim 2 , or fluorescein.4. The compound according to claim 2 , wherein X is NH.5. The compound according to claim 2 , wherein Y is O.6. The compound according to claim 2 , wherein Z is O.7. The compound according to claim 2 , wherein Ris C-Calkylene.8. The compound according to claim 2 , wherein Rand Rare methylene.9. The compound according to claim 2 , wherein Aris phenylene.10. The compound according to claim 2 , wherein Ris H or methyl.11. The compound according to claim 2 , wherein Ris alkyl or absent.13. The compound according to claim 12 , wherein Ris hydrogen or C-Calkyl.14. The compound according to claim 12 , wherein Xand Xare O.15. The compound according to claim 12 , wherein Yis —OR.16. The compound according to claim 12 , wherein Lis C-Calkylene or C-Calkenylene.17. A method for treating a clinic condition associated with activity of Jumonji C Domain-Containing Histone Demethylase comprising administering to the subject in need of such a treatment a therapeutically effective amount of a compound of .18. The method of claim 17 , wherein the clinical condition is a cancer or a mental retardation.19. A method for treating a clinic condition associated with overexpression of Jumonji C Domain-Containing Histone ...

PHENYL ALKYL CARBAMATE DERIVATIVE COMPOUND AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME

A phenyl alkyl carbamate derivative compound and a pharmaceutical composition containing the compound are provided. More specifically, the phenyl alkyl carbamate derivative compound and a pharmaceutically acceptable salt thereof, a composition for muscle relaxation containing the phenyl alkyl carbamate derivative compounds and/or pharmaceutically acceptable salt thereof as an active ingredient, and a method of muscle relaxation comprising administering a pharmaceutically effective amount of the phenyl alkyl carbamate derivative compound and/or a pharmaceutically acceptable salt thereof to a subject in need of to a subject in need of, are provided. 3. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is in the form of racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , a mixture of enantiomer claim 1 , or a mixture of diastereomer.4. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is selected from the group consisting of:1-(2-chlorophenyl)-2-carbamoyloxypropyl-1-carbamate,1-(2-chlorophenyl)-2-carbamoyloxypropyl-1-N-methylcarbamate,1-(2-chlorophenyl)-2-carbamoyloxypropyl-1-N-propylcarbamate1-(2-chlorophenyl)-2-carbamoyloxybutyl-1-carbamate,1-(2-chlorophenyl)-2-carbamoyloxy-3-methyl-butyl-1-carbamate,1-(2-chlorophenyl)-2-carbamoyloxyhexyl-1-carbamate,1-(2-iodophenyl)-2-carbamoyloxypropyl-1-carbamate,1-(2-iodophenyl)-2-carbamoyloxybutyl-1-carbamate,1-(2-iodophenyl)-2-carbamoyloxy-3-methyl-butyl-1-carbamate,1-(2-iodophenyl)-2-carbamoyloxyhexyl-1-carbamate,1-(2-fluorophenyl)-2-carbamoyloxypropyl-1-carbamate,1-(2-fluorophenyl)-2-carbamoyloxybutyl-1-carbamate,1-(2-fluorophenyl)-2-carbamoyloxy-3-methyl-butyl-1-carbamate,1-(2-fluorophenyl)-2-carbamoyloxyhexyl-1-carbamate,1-(2,4-dichlorophenyl)-2-carbamoyloxypropyl-1-carbamate,1-(2,4-dichlorophenyl)-2-carbamoyloxybutyl-1-carbamate,1-(2,4-dichlorophenyl)-2-carbamoyloxy-3-methyl-butyl-1-carbamate,1-(2,4- ...

Unnatural amino acids comprising a cyclooctynyl or trans-cyclooctenyl analog group and uses thereof

The present invention relates to unnatural amino acids comprising a cyclooctynyl or trans-cyclooctenyl analog group and having formula (I) or an acid or base addition salt thereof. The invention also relates to the use of said unnatural amino acids, kits and processes for preparation of polypeptides that comprise one or more than one cyclooctynyl or trans-cyclooctenyl analog group. These polypeptides can be covalently modified by in vitro or in vivo reaction with compounds comprising an azide, nitrile oxide, nitrone, diazocarbonyl or 1,2,4,5-tetrazine group.

FUMARATE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USE

Fumarate compounds, pharmaceutical compositions comprising the fumarate compounds, and methods of using fumarate compounds 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 each Ris independently chosen from hydrogen claim 1 , 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 , n-hexyl claim 1 , cyclohexyl claim 1 , cyclohexylmethyl claim 1 , phenyl claim 1 , benzyl claim 1 , substituted methyl claim 1 , substituted ethyl claim 1 , substituted n-propyl claim 1 , substituted isopropyl claim 1 , substituted n-butyl claim 1 , substituted isobutyl claim 1 , substituted tert-butyl claim 1 , substituted n-pentyl claim 1 , substituted n-hexyl claim 1 , substituted cyclohexyl claim 1 , substituted cyclohexylmethyl claim 1 , substituted phenyl claim 1 , and substituted benzyl.3. The compound according to claim 1 , wherein each Ris independently chosen from hydrogen claim 1 , 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 , n-hexyl claim 1 , cyclohexyl claim 1 , cyclohexylmethyl claim 1 , phenyl claim 1 , and benzyl.4. The compound according to claim 1 , wherein each Ris independently chosen from hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , tert-butyl claim 1 , cyclohexyl claim 1 , phenyl claim 1 , and benzyl.5. The compound according to claim 1 , wherein each Wis independently chosen from —N(R)C(O)O— claim 1 , wherein Ris independently chosen from hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , n- ...

FUMARATE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USE

Fumarate compounds, pharmaceutical compositions comprising the fumarate compounds, and methods of using fumarate compounds 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 Rand Rare independently chosen from hydrogen claim 1 , 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 , n-hexyl claim 1 , cyclohexyl claim 1 , cyclohexylmethyl claim 1 , phenyl claim 1 , benzyl claim 1 , substituted methyl claim 1 , substituted ethyl claim 1 , substituted n-propyl claim 1 , substituted isopropyl claim 1 , substituted n-butyl claim 1 , substituted isobutyl claim 1 , substituted tert-butyl claim 1 , substituted n-pentyl claim 1 , substituted n-hexyl claim 1 , substituted cyclohexyl claim 1 , substituted cyclohexylmethyl claim 1 , substituted phenyl claim 1 , and substituted benzyl.3. The compound according to claim 1 , wherein Rand Rare independently chosen from hydrogen claim 1 , 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 , n-hexyl claim 1 , cyclohexyl claim 1 , cyclohexylmethyl claim 1 , phenyl claim 1 , and benzyl.4. The compound according to claim 1 , wherein Rand Rare independently chosen from hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , tert-butyl claim 1 , cyclohexyl claim 1 , phenyl claim 1 , and benzyl.5. The compound according to claim 1 , wherein Xis chosen from methane-diyl claim 1 , ethane-1 claim 1 ,1-diyl claim 1 , ethane-1 claim 1 ,2-diyl claim 1 , 2-phenylethane-1 claim 1 ,2-diyl claim 1 , ...

Norbornene Modified Peptides and Their Labelling With Tetrazine Compounds

The invention relates to a polypeptide comprising an amino acid having a norbornene group. Suitably said norbornene group is present as an amino acid residue of a norbornene lysine. The invention also relates to a method of producing a polypeptide comprising a norbornene group, said method comprising genetically incorporating an amino acid comprising a norbornene group into a polypeptide. The polypeptide comprising the norbornene group can be specifically labelled by inverse electron demand Diels-Alder reaction with a tetrazine compound. 1. A polypeptide comprising a single amino acid having a norbornene group , wherein said norbornene group is present as an amino acid residue of a norbornene lysine , wherein said single amino acid is not the N-terminal amino acid.2. (canceled)3. A method of producing a polypeptide comprising a norbornene group , said method comprising genetically incorporating an amino acid comprising a norbornene group into a polypeptide.4. A method according to wherein producing the polypeptide comprises (i) providing a nucleic acid encoding the polypeptide which nucleic acid comprises an orthogonal codon encoding the amino acid having a norbornene group; (ii) translating said nucleic acid in the presence of an orthogonal tRNA synthetase/tRNA pair capable of recognising said orthogonal codon and incorporating said amino acid having a norbornene group into the polypeptide chain.5. A method according to wherein said orthogonal codon comprises an amber codon (TAG) claim 4 , said tRNA comprises MbtRNAand said tRNA synthetase comprises MbPyIRS.6. A method according to wherein said amino acid comprising a norbornene group is a norbornene lysine.7. A polypeptide according to claim 1 , wherein said amino acid is Nε-5-norbomene-2-yloxycarbonyl-L-lysine.8. A polypeptide according to claim 1 , wherein said amino acid having a norbornene group is incorporated at a position corresponding to a lysine residue in the wild type polypeptide.9. A polypeptide ...

LOW BY-PRODUCT CONTENT POLYPHENYLENE POLYMETHYLENE POLYISOCYANATES

The invention relates to polyphenyl polymethylene polyisocyanates having an NCO number of at least 29% comprising less than 2% by weight ureas, less than 8% by weight carbodiimides or uretonimines and less than 1000 ppm organic chlorine compounds. 1. A method for preparing a polyphenyl polymethylene polyisocyanate having an NCO number , determined according to DIN EN ISO 14896 , of at least 29% comprising less than 2% by weight ureas , determined by NMR , less than 8% by weight carbodiimides or uretonimines , determined by NMR , and less than 1000 ppm organic chlorine compounds , determined by high-resolution mass spectrometry or according to ASTM D4663-10 , the method comprising:reacting a polyphenyl polymethylene polyamine with an organic carbonate to give a corresponding polyphenyl polymethylene polycarbamate,thermally cleaving the polyphenyl polymethylene polycarbamate to give the polyphenyl polymethylene polyisocyanate; andprior to the thermally cleaving, reacting free amino groups or urea groups present in a carbamate crude mixture comprising the polyphenyl polymethylene polycarbamate with a derivatizing reagent to give amide groups or urethane groups.2. The method according to claim 1 , wherein the derivatizing reagent comprises at least one selected from the group consisting of an ester claim 1 , an acid anhydride claim 1 , and an acyl chloride of an aliphatic carboxylic acid having 1 to 10 carbon atoms or an aromatic carboxylic acid having 7 to 14 carbon atoms.3. The method according to claim 1 , wherein the derivatizing reagent comprises at least one of acetic anhydride and acetyl chloride.4. The method according to claim 1 , wherein the derivatizing reagent comprises at least one of a chloroformic ester and a pyrocarbonate of C-C-alkanols5. The method according to claim 1 , wherein the reacting of the free amino groups or the urea groups with the derivatizing reagent is carried out in a solvent.6. The method according to claim 5 , wherein the solvent is ...

Phenyl Carbamate Compound and a Composition for Preventing or Treating a Memory Loss-Related Disease Comprising the Same

The present invention relates to a composition for preventing or treating a memory loss related disease comprising a phenyl carbamate compound and a method for preventing or treating various diseases related to loss of memory therewith. The present invention ensures the enhancement of neuroprotection, such that it is promising for preventing or treating memory loss-related diseases such as dementia and Alzheimer's disease.

Modulators of Liver Receptor Homologue 1 (LRH-1) and Uses

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein. 2. The compound of claim 1 , wherein Rand Rare hydrogen claim 1 , Ris 1-phenylvinyl or 1-phenylethyl claim 1 , and Ris phenyl.3. The compound of claim 1 , wherein Ris alkyl terminally substituted with a hydroxy claim 1 , carboxy claim 1 , or phosphate claim 1 , wherein the hydroxy claim 1 , carboxy claim 1 , or phosphate are optionally further substituted with R.5. The compound of claim 1 , wherein Ris hydroxyl claim 1 , alkyl claim 1 , amino claim 1 , aminoalkyl claim 1 , carbamoyl claim 1 , sulphate claim 1 , sulfonate claim 1 , aminosulfonyl claim 1 , phosphate claim 1 , phosphonate claim 1 , or heterocyclyl claim 1 , wherein Ris optionally substituted with R.7. The compound of claim 6 , wherein{'sup': '1', 'a) X is O, and Ris alkanoyl;'}{'sup': '1', 'b) X is —NH—, and Ris alkanoyl;'}{'sup': '1', 'c) X is O, and Ris aminosulfonyl;'}{'sup': '1', 'd) X is —NH—, and Ris aminosulfonyl;'}{'sup': '1', 'e) X is —(C═O)—, Ris amino;'}{'sup': '1', 'f) X is O, Y is —(C═O)—, Ris amino;'}{'sup': '1', 'g) X is O, Y is —(C═O)—, Z is —NH—, and Ris sulfonate; and'}{'sup': '1', 'h) X is O, Y is —(C═O)—, Z is —NH—, and Ris aminosulfonyl.'}8. The compound of claim 1 , wherein the compound is 5-hexyl-4-phenyl-3a-(1-phenylvinyl)-1 claim 1 ,2 claim 1 ,3 claim 1 ,3a claim 1 ,6 claim 1 ,6a-hexahydropentalen-1-yl sulfamide or salt thereof.9. The compound of claim 1 , wherein the compound is 5-hexyl-4-phenyl-3a-(1-phenylvinyl)-1 claim 1 ,2 claim 1 ,3 claim 1 ,3a claim 1 ,6 claim 1 ,6a-hexahydropentalen-1-yl)acetamide or salt thereof.10. A pharmaceutical composition ...

PHENYL ALKYL CARBAMATE COMPOUNDS FOR USE IN PREVENTING OR TREATING EPILEPSY OR EPILEPSY-RELATED SYNDROME

The present invention provides a pharmaceutical composition for preventing and/or treating a epilepsy or epilepsy-related syndrome, for example an intractable epilepsy or its related syndrome such as drug-resistant epilepsy, comprising the phenyl alkyl carbamate compound as an active ingredient, and a use of the phenyl alkyl carbamate compound for preventing and/or treating epilepsy or epilepsy-related syndrome. 2. The pharmaceutical composition according to claim 1 , wherein A is a carbamoyl group claim 1 , B is C-Clinear or branched alkyl group or a C-Calkoxy alky ether group.3. The pharmaceutical composition according to claim 1 , wherein B is a carbamoyl group claim 1 , A is C-Clinear or branched alkyl group or a C-Calkoxy alky ether group.4. The pharmaceutical composition according to claim 1 , wherein the substituents of A and B are carbamoyl group at the same time.5. The pharmaceutical composition according to claim 1 , wherein the C2-C8 alkoxy alky ether group is methoxy methy (MOM) claim 1 , methoxyethoxymethyl (MEM) claim 1 , thertahydropyranyl (THP) claim 1 , benzyloxymethyl (BOM) claim 1 , methylthiomethyl (MTM) claim 1 , trimethylsilylethoxymethyl (SEM) or ethoxyethyl (EE) group.6. The pharmaceutical composition according to claim 1 , wherein the C-Clinear or branched alkyl group in the substituents A and B is a linear or branched C-Clower aliphatic alkyl claim 1 , a C-Ccycloaliphatic ring and a C-Caromatic group which may be substituted with at least one selected from the group consisting of hydrogen claim 1 , C-Clower alkyl and C-Calkoxy group.7. The pharmaceutical composition according to claim 1 , wherein claim 1 , X is chlorine claim 1 , fluorine claim 1 , iodine claim 1 , or bromine; n is 1 or 2; and Rand Rare the same as or different from each other claim 1 , and independently selected from the group consisting of hydrogen claim 1 , methyl group claim 1 , propyl group claim 1 , isopropyl group claim 1 , cyclopropyl group claim 1 , cyclohexyl ...

Phenyl Carbamate Compounds for Use in Preventing or Treating a Movement Disorder

The present invention provides a pharmaceutical composition for preventing and/or treating a movement disorder comprising the phenyl carbamate compound as an active ingredient, and a use of the phenyl carbamate compound for preventing and/or treating movement disorder. 2. The pharmaceutical composition according to claim 1 , wherein A is hydrogen and B is carbamoyl group claim 1 , or A is a carbamoyl group and B is hydrogen.3. The pharmaceutical composition according to claim 1 , wherein the phenyl carbamate compound is in the form of racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , a mixture of enantiomer claim 1 , or a mixture of diastereomer.4. The pharmaceutical composition according to claim 1 , wherein X is chlorine claim 1 , fluorine claim 1 , iodine claim 1 , or bromine; n is 1 or 2; and R2 and R3 are the same as or different from each other claim 1 , and independently selected from the group consisting of hydrogen claim 1 , methyl group claim 1 , propyl group claim 1 , isopropyl group claim 1 , cyclopropyl group claim 1 , cyclohexyl group claim 1 , bicycloheptane group claim 1 , and benzyl group.5. The pharmaceutical composition according to claim 1 , wherein the phenyl carbamate compound is selected from the group consisting of:1-(2-chlorophenyl)-1-hydroxypropyl-2-carbamate,1-(2-chlorophenyl)-1-hydroxy-3-methyl-butyl-2-carbamate,1-(2-chlorophenyl)-1-hydroxyhexyl-2-carbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-methylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-propylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-isopropylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-cyclopropylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-cyclohexylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-benzylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-bicyclo[2,2,1]heptanecarbamate,1-(2,4-dichlorophenyl)-1-hydroxypropyl-2-carbamate,1-(2,6-dichlorophenyl)-1-hydroxypropyl-2-carbamate,1-(2,4-dichlorophenyl)-1-hydroxybutyl-2-carbamate,1-(2,4- ...

PROCESS FOR THE PREPARATION OF 6-(7-((1-AMINOCYCLOPROPYL)METHOXY)-6-METHOXYQUINOLIN-4-YLOXY)-N-METHYL-1-NAPHTHAMIDE AND SYNTHETIC INTERMEDIATES THEREOF

A process for the preparation in high yields and purity of the compound 6-(7-((1-aminocyclopropyl)methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide of formula (I) and of the pharmaceutically acceptable salts thereof is described. The process has various advantages over those previously described, in particular it avoids the use of acyl azide intermediates and their Curtius rearrangement. Novel intermediates useful for the preparation of compound (I) are also described. 2. The process of wherein R′ is hydrogen and R is selected from the group consisting of benzyl optionally substituted on the aromatic ring with up to three substituents selected from the group consisting of halogen claim 1 , cyano claim 1 , trifluoromethyl; C-Cacyl claim 1 , C-Caroyl claim 1 , C-Calkylsulfonyl claim 1 , C-Carylsulfonyl claim 1 , C-Calkoxycarbonyl claim 1 , benzyloxycarbonyl optionally substituted on the aromatic ring with up to three substituents selected from the group consisting of halogen claim 1 , cyano claim 1 , trifluoromethyl.3. The process of wherein R is selected from the group consisting of benzyl claim 2 , acetyl claim 2 , benzoyl claim 2 , trifluoromethanesulfonyl claim 2 , benzenesulfonyl claim 2 , p-toluenesulfonyl claim 2 , methoxycarbonyl claim 2 , ethoxycarbonyl claim 2 , tert-butoxycarbonyl claim 2 , allyloxycarbonyl claim 2 , benzyloxycarbonyl.4. The process of wherein R′ is tri (C-Calkyl)silyl and R is C-Calkoxycarbonyl or benzyloxycarbonyl optionally substituted on the aromatic ring with up to three substituents selected from the group consisting of halogen claim 1 , cyano claim 1 , trifluoromethyl.5. The process of wherein R′ is trimethylsilyl and R is tert-butoxycarbonyl.6. The process of wherein R and R′ together with the nitrogen atom they are linked to form a phthalimido group.12. A compound as claimed in claim 7 , wherein said compound is:1-[(4-Acetyl-2-methoxyphenoxy)methyl]-N-benzyloxycarbonyl-1-aminocyclopropane.13. Method of synthesizing a ...

Augmenting Moieties for Anti-Inflammatory Compounds

Augmented or synergized anti-inflammatory constructs are disclosed including terpenes covalently conjugated with other anti-inflammatory molecules such as nonsteroidal anti-inflammatory drugs, vanilloids, amino acids and polyamines; and anti-inflammatory molecules covalently conjugated with specific amino acids. For the latter, further conjugation with a choline bioisostere further augments the anti-inflammatory activity. 2. (canceled)31. The conjugate of (d) or (f) claim 1 , wherein said terpenes are the same terpene.41. The conjugate of (d) or (f) claim 1 , wherein said terpenes are different terpenes.51. The conjugate of (b) or (e) claim 1 , wherein said vanilloids are the same vanilloid.61. The conjugate of (b) or (e) claim 1 , wherein said vanilloids are different vanilloids.7. (canceled)8. A method of increasing the potency of an anti-inflammatory compound claim 1 , comprising conjugating said anti-inflammatory compound with another anti-inflammatory compound via a carbamate linkage claim 1 , wherein said anti-inflammatory compounds are independently selected from the group consisting of anti-inflammatory terpenes claim 1 , anti-inflammatory vanilloids claim 1 , anti-inflammatory polyamines and anti-inflammatory amino acids.9. (canceled)10. The method of claim 8 , wherein said terpenes are independently selected from the group consisting of thymol claim 8 , carvacrol claim 8 , menthol claim 8 , geraniol claim 8 , nerol claim 8 , farnesol and perillyl alcohol.11. The method of claim 10 , comprising two terpenes which are the same.12. The method of claim 10 , comprising two terpenes which are different.13. The method of claim 8 , comprising two vanilloids which are the same.14. The method of claim 8 , comprising two vanilloids which are different.15. The method of claim 8 , wherein the structure of the conjugate is selected from the group consisting of Formulae 1 A claim 8 , 2A claim 8 , 3A claim 8 , 4A claim 8 , 5A claim 8 , 6A claim 8 , and 7A:(a) Formula 1A, ...

Process for making lysine-glutamic acid dipeptide derivatives

The invention relates to compounds of the formula and to a process for making same and to the use of the products in the solid phase peptide synthesis. The compounds of formula I are versatile peptide intermediates for the solid phase peptide synthesis (SPPS) of peptide drugs which comprise a Glu-fatty alkyl side chain building block attached to a Lys-part of the peptide chain.

Compound

The present application relates to a curable composition, a cured product and uses of the curable composition and the cured product. By comprising the curable compound having a certain structure, the present application can provide a curable composition which can increase cohesiveness of the cured product without increasing viscosity of the composition before curing, also minimize the increase of the elastic modulus, and also minimize the ratio of a nonreactive oligomer with an effect of improving the interfacial adhesion. The curable composition can be applied to a variety of optical applications and can be usefully used, for example, for bonding various optical functional members in a display device, for example, for directly bonding a touch panel and a display panel. 2. The compound according to claim 1 , wherein the core (A) and the chain (B) of Formula 1 each comprise at least one polyalkylene oxide unit.3. The compound according to claim 2 , wherein the polyalkylene oxide unit is a polyethylene oxide unit or a polypropylene oxide unit.4. The compound according to claim 1 , wherein the core (A) of Formula 1 is a core derived from polyalkylene polyol.5. The compound according to claim 4 , wherein the polyalkylene polyol has a weight average molecular weight in a range of 1000 to 10 claim 4 ,000.9. The compound according to claim 7 , wherein the structure of -L-Q-L- or the structure of -L-Q-L- in Formulas 2 and 3 is a structure derived from a diisocyanate compound.10. The compound according to claim 9 , wherein the diisocyanate compound is tolylene diisocyanate claim 9 , xylene diisocyanate claim 9 , diphenylmethane diisocyanate claim 9 , hexamethylene diisocyanate claim 9 , isoboron diisocyanate claim 9 , tetramethylxylene diisocyanate or naphthalene diisocyanate.11. The compound according to claim 7 , wherein [O-A]in Formula 7 is a structure derived from polyalkylene glycol.12. The compound according to claim 7 , wherein A in Formula 3 is a core derived from ...

PRODRUGS OF GAMMA-HYDROXYBUTYRIC ACID, COMPOSITIONS AND USES THEREOF

The present disclosure discloses prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof. 2. The composition of claim 1 , wherein the composition is a solid.3. The composition of claim 1 , wherein the composition further comprises a solvent for dissolving or dispersing the compound.4. The composition of claim 3 , wherein the solvent comprises water.5. The composition of claim 1 , wherein the composition is in a liquid dosage form.6. The composition of claim 1 , wherein the composition further comprises a flavoring agent claim 1 , sucrose claim 1 , lactose claim 1 , cellulose sugar claim 1 , mannitol claim 1 , maltitol claim 1 , dextran claim 1 , sorbitol claim 1 , starch claim 1 , agar claim 1 , alginates claim 1 , chitins claim 1 , chitosans claim 1 , pectins claim 1 , tragacanth gum claim 1 , gum arabic claim 1 , gelatins claim 1 , collagens claim 1 , casein claim 1 , albumin claim 1 , synthetic or semi-synthetic polymers or glycerides claim 1 , methyl cellulose claim 1 , hydroxypropylmethyl-cellulose claim 1 , or polyvinylpyrrolidone.7. The composition of claim 1 , wherein the composition further comprises a polymeric excipient.8. The composition of claim 1 , wherein the composition comprises a tablet claim 1 , a caplet claim 1 , a capsule claim 1 , a gel cap claim 1 , granules claim 1 , a pill claim 1 , a powder claim 1 , a lozenge claim 1 , a sachet claim 1 , a cachet claim 1 , a suspension claim 1 , an emulsion claim 1 , a solution claim 1 , a slurry claim 1 , or a syrup.9. The composition of claim 1 , wherein the composition is formulated in a unit dosage form.10. The composition of claim 9 , wherein the unit dosage form has a weight from 0.5 grams to 30 grams.11. The composition of claim 10 , wherein the composition is in a liquid dosage form.12. The composition of claim 11 , further comprising a pH adjusting agent selected from sodium hydroxide claim 11 , hydrochloric acid claim 11 , or malic acid.13. The composition of claim 1 , ...

Modulators of Liver Receptor Homologue 1 (LRH-1) and Uses

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein. 4. The method of claim 3 , wherein{'sup': '1', 'a) X is O, and Ris alkanoyl;'}{'sup': '1', 'b) X is —NH—, and Ris alkanoyl;'}{'sup': '1', 'c) X is O, and Ris aminosulfonyl;'}{'sup': '1', 'd) X is —NH—, and Ris aminosulfonyl;'}{'sup': '1', 'e) X is —(C═O)—, Ris amino;'}{'sup': '1', 'f) X is O, Y is —(C═O)—, Ris amino;'}{'sup': '1', 'g) X is O, Y is —(C═O)—, Z is —NH—, and Ris sulfonate; and'}{'sup': '1', 'h) X is O, Y is —(C═O)—, Z is —NH—, and Ris aminosulfonyl.'}5. The method of claim 1 , wherein the compound is 5-hexyl-4-phenyl-3a-(1-phenylvinyl)-1 claim 1 ,2 claim 1 ,3 claim 1 ,3a claim 1 ,6 claim 1 ,6a-hexahydropentalen-1-yl sulfamide or salt thereof.6. The method of claim 1 , wherein the compound is 5-hexyl-4-phenyl-3a-(1-phenylvinyl)-1 claim 1 ,2 claim 1 ,3 claim 1 ,3a claim 1 ,6 claim 1 ,6a-hexahydropentalen-1-yl)acetamide or salt thereof.7. The method of claim 1 , wherein the cardiovascular disease is cardiovascular disease is selected from coronary artery disease (CAD) claim 1 , angina claim 1 , myocardial infarction claim 1 , stroke claim 1 , hypertensive heart disease claim 1 , rheumatic heart disease claim 1 , cardiomyopathy claim 1 , heart arrhythmia claim 1 , congenital heart disease claim 1 , valvular heart disease claim 1 , carditis claim 1 , aortic aneurysms claim 1 , peripheral artery disease claim 1 , and venous thrombosis.11. The method of claim 10 , wherein{'sup': '1', 'a) X is O, and Ris alkanoyl;'}{'sup': '1', 'b) X is —NH—, and Ris alkanoyl;'}{'sup': '1', 'c) X is O, and Ris aminosulfonyl;'}{'sup': '1', 'd) X is —NH—, ...

HETEROGENEOUS CATALYSTS FOR THE SYNTHESIS OF CARBAMATES

The present invention relates to a catalyst for preparing carbamates, in particular aromatic carbamates, comprising a binary oxide having the formula LMO, wherein L is a metal selected from the lanthanoid series and M is a metal selected from the group consisting of Sc, Y, Ti, Zr, Hf, metals from the lanthanoid series and metals from the actinoid series, and wherein x ranges from 0.01 to 0.05. The present invention also relates to a method for producing said catalysts and a method of utilizing said catalysts in the production of carbamates, in particular aromatic carbamates. 1. A catalyst for preparing carbamates comprising a binary oxide having the formula LMO , wherein L is a metal selected from the lanthanoid series and M is a metal selected from the group consisting of scandium , yttrium , titanium , zirconium , hafnium , a metal from the lanthanoid series and a metal from the actinoid series , and wherein x ranges from 0.01 to 0.05.2. The catalyst of claim 1 , wherein L is cerium.3. The catalyst of claim 1 , wherein M is selected from the group consisting of yttrium claim 1 , zirconium claim 1 , hafnium claim 1 , lanthanum claim 1 , praseodymium claim 1 , samarium claim 1 , europium and terbium.4. The catalyst of claim 3 , wherein M is zirconium.5. The catalyst of claim 1 , wherein x ranges from 0.01 to 0.045.6. A method for preparing the catalyst of claim 1 , comprising:I. precipitating a catalyst precursor by combining an aqueous solution of a salt of the metal L and an aqueous solution of a salt of the metal M in the presence of an oxidizing agent;II. separating off the catalyst precursor precipitated in step I; andIII. calcining the catalyst precursor separated off in step II to yield the catalyst.7. The method of claim 6 , wherein the oxidixing agent is selected from the group consisting of hydrogen peroxide claim 6 , nitric acid claim 6 , perchloric acid claim 6 , peroxydisulphuric acid claim 6 , peroxymonosulphuric acid claim 6 , chlorite claim 6 , ...

Disubstituted amino acids and methods of preparation and use thereof

Provided are crystalline α, α-disubstituted amino acids and their crystalline salts containing a terminal alkene on one of their side chains, as well as optionally crystalline halogenated and deuterated analogs of the α, α-disubstituted amino acids and their salts; methods of making these, and methods of using these.

(PER) FLUOROPOLYETHER BLOCK COPOLYMERS

The invention relates to (per)fluoropolyether block copolymers comprising: A) a fluoropolyoxyalkylene segment (chain R) comprising one or more units of formula (CHXCFCFO)— in which X is hydrogen or fluorine; B) a (per)fluoropolyoxyalkylene segment (chain Rf), that is to say a segment comprising recurring units having at least one catenary ether bond and at least one fluorocarbon moiety, said (per)fluoropolyoxyalkylene segment being different from chain Rand having a molecular weight higher than 400 g/mol. These copolymers are endowed with improves lubricant properties or with improved water and oil-repellence properties. 115-. (canceled)17. The process according to claim 16 , wherein the (per)fluoropolyether block copolymer complies with formula (IA):{'br': None, 'sub': a', 'f', 'a′, 'R—R—R\u2003\u2003(IA)'}{'sub': f', 'a, 'claim-ref': {'@idref': 'CLM-00016', 'claim 16'}, 'claim-text': [ [{'br': None, 'sub': 2', '2', '2', 'n', '2', '2, '(CHCFCFO)CHCFC(O)F\u2003\u2003(II)'}, 'wherein n is an integer equal to or higher than 1;, 'a group (II) of formula, [{'br': None, 'sub': 2', '2', '2', 'n', '2', '2, '(CHCFCFO)CHCFC(O)R\u2003\u2003(III)'}, n is as defined above, and', {'sup': 1', '1', 'A', 'A, 'sub': 1', '36', '5', '14', '5', '14', '1', '10', '1', '4', '6', '14', '1', '10', '6', '14', 'H', '2', 'H', '1', '34, 'claim-text': [{'br': None, 'sup': 'B', '—NH—R—O—CO—;\u2003\u2003(j)'}, {'br': None, 'sup': B', 'B, '—NH—R—NHCOO—R—OCO—; and\u2003\u2003(jj)'}, {'br': None, 'sup': 'B', '—R—O—CO—;\u2003\u2003(jjj)'}], 'R is hydrogen a hydroxy group or a W—Rgroup in which W is a bond or is selected from —O—, —NH—, —OC(O)—, and —NHC(O)—; and Ris selected from: a straight or branched, saturated or unsaturated (C-C)hydrocarbon chain; a (C-C)cycloalkyl or (C-C)cycloalkyl(C-C)alkyl group, the cycloalkyl moiety being optionally substituted with one or more (C-C) straight or branched alkyl chains; a (C-C)aryl or (C-C)alkyl(C-C)aryl group; and a group of formula —R—CR═CHin which Ris ...

CARBAMATE DERIVATIVE COMPOUNDS, PROCESSES FOR PREPARING THEM AND THEIR USES

The present invention relates to a pharmaceutical composition for treating or preventing CNS disorders containing a carbamate derivative compound and/or pharmaceutically acceptable salt thereof as an active ingredient. Furthermore, the present invention relates to a method for treatment or prevention CNS disorders comprising administering a carbamate derivative compound in a pharmaceutically effective amount to a subject in need of treatment or prevention of CNS disorders. 2. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R claim 1 , R claim 1 , Rand Rare each independently selected from the group consisting of hydrogen claim 1 , F claim 1 , Br claim 1 , Cl and I; and if R claim 1 , R claim 1 , Rand Rare hydrogen claim 1 , l+m is not 1.4. The compound or a pharmaceutically acceptable salt thereof according to or claim 1 , wherein Rand Rare each independently selected from the group consisting of hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , iso-propyl claim 1 , t-butyl claim 1 , cyclopropyl claim 1 , cyclohexyl claim 1 , bicycloheptanyl claim 1 , phenyl and benzyl.5. The compound or a pharmaceutically acceptable salt thereof according to or claim 1 , Ris selected from hydrogen claim 1 , trimethyl silyl claim 1 , triethyl silyl claim 1 , triisopropyl silyl claim 1 , t-butyl dimethyl silyl claim 1 , trimethylsilylethoxymethyl (SEM) claim 1 , methoxymethyl (MOM) claim 1 , methoxyethoxymethyl (MEM) claim 1 , ethoxyethyl (EE) claim 1 , therahydropyranyl (THP) methylthiomethyl (MTM) and benzyloxymethyl (BOM).6. The compound or a pharmaceutically acceptable salt thereof according to or claim 1 , wherein Rand Rare each independently selected from the group consisting of hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , iso-propyl and t-butyl; and{'sup': '7', 'Ris selected from hydrogen, methyl, ethyl, propyl, iso-propyl, t-butyl and methoxymethyl (MOM); and'}l and m are independently an ...

Fluorinated 2-Amino-4-(Benzylamino)Phenylcarbamate Derivatives

The invention relates to fluorinated compounds and their use as anti-epileptic, muscle-relaxing, fever-reducing and peripherally analgesically acting medications and as imaging agents. Novel fluorinated 2-amino-4-(benzylamino)phenyl carbamate derivatives of ezogabine and pharmaceutically acceptable salts or solvates thereof and their use are described. 3. The compound of claim 2 , wherein two of X claim 2 , X claim 2 , X claim 2 , X claim 2 , X claim 2 , X claim 2 , Xand Xare F.4. The compound of claim 2 , wherein three of X claim 2 , X claim 2 , X claim 2 , X claim 2 , X claim 2 , X claim 2 , Xand Xare F.6. The compound of claim 5 , wherein at least one of X claim 5 , X claim 5 , and Xis fluorine.7. The compound of claim 5 , wherein Xis fluorine and one of X claim 5 , X claim 5 , and Xis fluorine.9. A pharmaceutical composition comprising at least one compound according to or a pharmaceutically acceptable salt or solvate thereof and one or more pharmaceutically acceptable carrier or excipient.10. A method of treating a subject suffering from or susceptible to conditions ameliorated by KCNQ2/3 potassium channel opening claim 1 , comprising administering to the subject an effective amount of a compound according to or a pharmaceutically acceptable salt or solvate thereof.11. A method of treating or preventing a disease or disorder selected from epilepsy claim 1 , neurodegenerative disorder claim 1 , cognitive disorder claim 1 , cancer claim 1 , inflammatory disease claim 1 , ophthalmic disease claim 1 , migraine claim 1 , bipolar disorder claim 1 , unipolar depression claim 1 , functional bowel disorder claim 1 , or tinnitus in a subject in need thereof claim 1 , comprising administering to the subject an effective amount of a compound according to or a pharmaceutically acceptable salt or solvate thereof.12. The method of claim 11 , wherein the disease is epilepsy.14. The 18F compound of claim 13 , wherein at least one of X claim 13 , X claim 13 , X claim 13 , X ...

FLUORINATED 2-AMINO-4-(BENZYLAMINO)PHENYLCARBAMATE DERIVATIVES

The invention relates to fluorinated compounds and their use as anti-epileptic, muscle-relaxing, fever-reducing and peripherally analgesically acting medications and as imaging agents. Novel fluorinated 2-amino-4-(benzylamino)phenyl carbamate derivatives of ezogabine and pharmaceutically acceptable salts or solvates thereof and their use are described. 3. The compound of claim 2 , wherein two of X claim 2 , X claim 2 , X claim 2 , X claim 2 , X claim 2 , X claim 2 , Xand Xare F.4. The compound of claim 2 , wherein three of X claim 2 , X claim 2 , X claim 2 , X claim 2 , X claim 2 , X claim 2 , Xand Xare F.6. The compound of claim 5 , wherein at least one of X claim 5 , X claim 5 , and Xis fluorine.7. The compound of claim 5 , wherein Xis fluorine and one of X claim 5 , X claim 5 , and Xis fluorine.9. A pharmaceutical composition comprising at least one compound according to or a pharmaceutically acceptable salt or solvate thereof and one or more pharmaceutically acceptable carrier or excipient.10. A method of treating a subject suffering from or susceptible to conditions ameliorated by KCNQ2/3 potassium channel opening claim 1 , comprising administering to the subject an effective amount of a compound according to or a pharmaceutically acceptable salt or solvate thereof.11. A method of treating or preventing a disease or disorder selected from epilepsy claim 1 , neurodegenerative disorder claim 1 , cognitive disorder claim 1 , cancer claim 1 , inflammatory disease claim 1 , ophthalmic disease claim 1 , migraine claim 1 , bipolar disorder claim 1 , unipolar depression claim 1 , functional bowel disorder claim 1 , or tinnitus in a subject in need thereof claim 1 , comprising administering to the subject an effective amount of a compound according to or a pharmaceutically acceptable salt or solvate thereof.12. The method of claim 11 , wherein the disease is epilepsy.14. The 18F compound of claim 13 , wherein at least one of X claim 13 , X claim 13 , X claim 13 , X ...

Novel Super-Resolution Imaging Compositions and Methods Using Same

The invention provides compositions that may be used for imaging intracellular structures. The invention further provides methods of imaging intracellular structures. In certain embodiments, the compositions of the invention include trans-cyclooctene-containing ceramide lipids and tetrazine-containing rhodamine-related dyes. 1. A trans-cyclooctene-containing lipid , or a salt , solvate , stereoisomer , or any mixtures thereof , wherein the lipid comprises TCO-LINK-LIPID , wherein TCO is a trans-cyclooctene group , LINK is a bivalent linker , and LIPID is a lipid.4. The trans-cyclooctene-containing lipid of claim 1 , wherein LIPID comprises at least one selected from the group consisting of a sphingolipid claim 1 , phospholipid claim 1 , sterol lipid and fatty acid.5. The trans-cyclooctene-containing lipid of claim 4 , wherein LIPID comprises at least one selected from the group consisting of sphingosine claim 4 , 1-phosphocholine-sphingosine claim 4 , 1-phosphoethanolamine-sphingosine claim 4 , and a 1-glycosyl-sphingosine.6. The trans-cyclooctene-containing lipid of claim 5 , wherein LIPID comprises sphingosine.7. The trans-cyclooctene-containing lipid of claim 6 , wherein LIPID comprises sphingosine and is covalently conjugated to LINK through the 2-amino group of sphingosine.8. The trans-cyclooctene-containing lipid of claim 1 , wherein LINK comprises:{'br': None, 'sub': 'n', '—X(CR′R″)C(═O)—, wherein'}X is covalently conjugated to TCO and is selected from the group consisting of a covalent bond, —C(═O)—, —C(═O)O— and —C(═O)NR′—;{'sub': 1', '6, 'each occurrence of R′ and R″ is independently selected from the group consisting of H and optionally substituted C-Calkyl; and'}n is an integer ranging from 1 to 20.9. The trans-cyclooctene-containing lipid of claim 8 , wherein n is 5.12. The tetrazine-containing dye of claim 11 , wherein Ris —(CH)—.15. The compound of claim 14 , wherein in (I) Ris —CH—.16. The compound of claim 14 , wherein in (I) Ris S claim 14 , O or ...

Process for preparing {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate having high purity

A process for obtaining {{6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate and/or pharmaceutically acceptable salts thereof having high purity is described. This process allows to obtain a product having an amount of any single unknown impurity equal to or less than 0.10%, as well as a product having a purity greater than 99.5%, preferably equal to or greater than 99.6%. 123-. (canceled)25. The process according to claim 24 , wherein the organic solvent is selected from the group consisting of THF claim 24 , methyl-THF claim 24 , dioxane claim 24 , ethylene glycol dimethyl ether claim 24 , and bis(2-methoxyethyl)ether.26. The process according to claim 24 , wherein the organic solvent is used in an amount between 1 and 100 parts by volume per part by weight of the compound of formula (II).27. The process according to claim 24 , wherein the organic solvent has a water content lower than 0.5%.28. The process according to claim 24 , wherein step ii) is carried out at room temperature.29. The process according to claim 24 , which further comprises a step iii) of isolating {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate as a free base or as a pharmaceutically acceptable salt.30. The process according to claim 29 , wherein the {6-((diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate is isolated as a hydrochloride or hydrochloride monohydrate salt.32. The process according to claim 31 , wherein the aprotic dipolar solvent is selected from the group consisting of DMSO claim 31 , acetonitrile claim 31 , dimethylacetamide claim 31 , anddimethylformamide.33. The process according to claim 31 , wherein the halogenating agent is a chlorinating agent.34. The process according to claim 33 , wherein the chlorinating agent is selected from the group consisting of thionyl chloride (SOCl) claim 33 , phosphorus trichloride (PCl) claim 33 , phosphorus oxychloride (POCl) claim 33 , and ...

AFFINITY ILLUDOFULVENE CONJUGATES

In an embodiment of the invention, a composition for treating a cell population comprises a medicant. The medicant moiety can be an illudofulvene analog. In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The affinity moiety can be an antibody, an antibody fragment, a receptor protein, a peptidic growth factor, an anti-angiogenic protein, a specific binding peptide, protease cleavable peptide, a glycopeptide, a peptide, a peptidic toxin, a protein toxin and an oligonucleotide. The affinity moiety can be covalently bound to the medicant via a linker. 1. A compound , (a) the compound comprising an illudofulvene moiety , or (b) the compound being an illudofulvene analog , where the illudofulvene moiety or the illudofulvene analog is selected from the group consisting of analog 317 (2'S ,3′R ,6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′ ,4′ ,6′-trimethyl-7′-oxo-2′ ,3′ ,6′ ,7′-tetrahydrospiro[cyclopropane-1 ,5′-inden]-3′-yl 4-(fluorosulfonyl)benzoate; analog 318 ((2'S ,3′R ,6′R)-3′-((4-(fluorosulfonyl)benzoyl)oxy)-6′-hydroxy-2′ ,4′ ,6′-trimethyl-7′-oxo-2′ ,3′ ,6′ ,7′-tetrahydrospiro[cyclopropane-1 ,5′-inden]-2′-yl)methyl 4-(fluorosulfonyl)benzoate; analog 333 ((2'S ,3′R ,6′R)-6′-hydroxy-2′ ,4′ ,6′-trimethyl-3′-(((4-nitrophenoxy)carbonyl)oxy)-7′-oxo-2′ ,3′ ,6′ ,7′-tetrahydrospiro[cyclopropane-1 ,5′-inden]-2′-yl)methyl acetate; analog 334 ((2'S ,3′R ,6′R)-3′-(((2-((tert-butoxycarbonyl)(methyl)amino)ethyl)(methyl)carbamoyl)oxy)-6′-hydroxy-2′ ,4′ ,6′-trimethyl-7′-oxo-2′ ,3′ ,6′ ,7′-tetrahydrospiro[cyclopropane-1 ,5′-inden]-2′-yl)methyl acetate; analog 335 tert-butyl ((2'S ,3′R ,6′R)-6′-hydroxy-2′-(hydroxymethyl)-2′ ,4′ ,6′-trimethyl-7′-oxo-2′ ,3′ ,6′ ,7′-tetrahydrospiro[cyclopropane-1 ,5′-inden]-3′-yl) ethane-1 ,2-diylbis(methylcarbamate); analog 339 ((2'S ,3′R ,6′R)-3′ ,6′-dihydroxy-2′ ,4′ ,6′-trimethyl-7′-oxo-2′ ,3′ ,6′ ,7′-tetrahydrospiro[cyclopropane-1 ,5′-inden]-2′-yl)methyl 4-methylbenzenesulfonate; ...

PHENYLCARBAMATE COMPOUND AND MUSCLE RELAXANT CONTAINING THE SAME

A novel phenylcarbamate compound and a pharmaceutical composition containing the same are provided. More specifically, a novel phenylcarbamate compound, a composition for muscle relaxation containing the phenylcarbamate compound as an active ingredient, and a method of muscle relaxation comprising administering a therapeutically effective amount of the phenylcarbamate compound, are provided. 117.-. (canceled)19. The compound or the pharmaceutically acceptable salt thereof according to claim 18 , wherein the compound is in the form of racemate claim 18 , enantiomer claim 18 , diastereomer claim 18 , a mixture of enantiomer claim 18 , or a mixture of diastereomer.23. The pharmaceutical composition according to claim 21 , wherein the compound is in the form of racemate claim 21 , enantiomer claim 21 , diastereomer claim 21 , a mixture of enantiomer claim 21 , or a mixture of diastereomer.26. The method according to claim 24 , wherein the compound is in the form of racemate claim 24 , enantiomer claim 24 , diastereomer claim 24 , a mixture of enantiomer claim 24 , or a mixture of diastereomer.29. The method according to claim 27 , wherein the compound is in the form of racemate claim 27 , enantiomer claim 27 , diastereomer claim 27 , a mixture of enantiomer claim 27 , or a mixture of diastereomer. This application is a continuation of and claims the benefit of priority to U.S. patent application Ser. No. 13/175,025, filed 1 Jul. 2011, which application claims priority to and the benefit of U.S. Provisional Application No. 61/630,952 filed in the United States Patent and Trademark Office on Jul. 2, 2010, which applications are incorporated herein by reference in their entirety.(a) Field of the InventionThe present invention relates to novel phenyl carbamate compounds and pharmaceutical compositions containing the compound. More specifically, the present invention relates to phenyl carbamate compounds and a pharmaceutically acceptable salt thereof, which have a ...

MACROCYCLES

Cyclosporin derivatives, methods of manufacturing the cyclosporin derivatives and methods for treating subjects infected with certain viruses, including hepatitis virus or HIV by administering the cyclosporin derivatives are described. 1. A cyclosporine A derivative in which the 3-Sarcosine position is substituted by a group —S—CHC[CH(CH)]NRR , wherein Ris hydrogen or an alkyl chain having from one to four carbon atoms and , when the alkyl chain has 3 or 4 carbon atoms , the chain is straight or branched; Ris an alkyl chain having from one to four carbon atoms and , when the alkyl chain has 3 or 4 carbon atoms the chain is straight or branched; and n is 1 or 2.3. The compound of claim 2 , where X is hydroxyl.4. The compound of claim 2 , where A is (E) —CH═CHCH claim 2 , B is ethyl claim 2 , and n is 1.5. The compound of claim 2 , where A is (E) —CH═CHCH claim 2 , B is ethyl claim 2 , n is 1 and Rand Rare each methyl.6. The compound of claim 2 , where{'sub': '3', 'A is (E) —CH═CHCH;'}B is ethyl;n is 1 or 2;{'sup': '1', 'Ris hydrogen or benzyl; and'}{'sup': 2', '3, 'sub': 1', '4, 'Rand R, which may be the same or different, each are a C-Calkyl group.'}7. The compound of claim 1 , which is selected from the group consisting of:{'sup': 3', '4, '[(R)-[(1-(N,N-dimethylamino)cyclopropyl)methylthio-Sar][4′hydroxy-N methylleucine]cyclosporine A;'}{'sup': 3', '4, '[(R)-[(1-(N-methyl-N-isopropylamino)cyclopropyl)methylthio-Sar][4′hydroxy-N methylleucine]cyclosporine A;'}{'sup': 3', '4, '[(R)-[(1-(N,N-dimethylamino)cyclobutyl)methylthio-Sar][4′hydroxy-N methylleucine]cyclosporine A;'}{'sup': 3', '4, '[(R)-[(1-(N,N-diethylamino)cyclopropyl)methylthio-Sar][4′hydroxy-N methylleucine]cyclosporine A;'}{'sup': 3', '4, '[(R)-[(1-(N-ethyl-N-methylamino)cyclopropyl)methylthio-Sar][4′hydroxy-N methylleucine]-cyclosporine A; and'}{'sup': 3', '5, '[(R)-[(1-(N,N-dimethylamino)cyclobutyl)methylthio-Sar]-(N-benzyl)-Valcyclosporine A.'}8. A composition comprising a compound of and a ...

ANTIVIRAL MACROCYCLES

Cyclosporin derivatives, methods of manufacturing the cyclosporin derivatives and methods for treating subjects infected with certain viruses, including hepatitis virus or HIV by administering the cyclosporin derivatives are described. 1. A cyclosporine A derivative in which the 3-Sarcosine position is substituted by a group —S—CHC[CH(CH)]NRR , wherein Ris hydrogen or an alkyl chain having from one to four carbon atoms and , when the alkyl chain has 3 or 4 carbon atoms , the chain is a straight or branched; Ris an alkyl chain having from one to four carbon atoms and , when the alkyl chain has 3 or 4 carbon atoms the chain is a straight or branched; and n is 1 or 2.3. The compound of claim 2 , where X is hydroxyl.4. The compound of claim 2 , where A is (E) —CH═CHCH claim 2 , B is ethyl claim 2 , and n is 1.5. The compound of claim 2 , where A is (E) —CH═CHCH claim 2 , B is ethyl claim 2 , n is 1 and Rand Rare each methyl.6. The compound of claim 2 ,{'sub': '3', 'where A is (E) —CH═CHCH;'}B is ethyl;n is 1 or 2;{'sup': '1', 'Ris hydrogen or benzyl; and'}{'sup': '2', 'sub': 1', '4, 'Ris hydrogen or a C-Calkyl group;'}{'sup': '3', 'sub': 1', '4, 'Ris a C-Calkyl group.'}7. The compound of claim 2 ,{'sub': '3', 'where A is (E) —CH═CHCH;'}B is ethyl;n is 1 or 2;{'sup': '1', 'Ris hydrogen or benzyl; and'}{'sup': 2', '3, 'sub': 1', '4, 'Rand R, which may be the same or different, each are a C-Calkyl group.'}8. The compound of claim 1 , selected from the group consisting of:{'sup': 3', '4, '[(R)-[(1-(N,N-dimethylamino)cyclopropyl]methylthio-Sar][4′ hydroxy-N methylleucine]cyclosporine A;'}{'sup': 3', '4, '[(R)-[(1-(N-methyl-N-isopropylamino)cyclopropyl]methylthio-Sar][4′ hydroxy-N methylleucine]cyclosporine A;'}{'sup': '4', '[(R)-[(1-(N,N-dimethylamino)cyclobutyl]methylthio-Sar]3[4′ hydroxy-N methylleucine]cyclosporine A;'}{'sup': 3', '4, '[(R)-[(1-(N,N-diethylamino)cyclopropyl]methylthio-Sar][4′ hydroxy-N methylleucine]cyclosporine A;'}{'sup': 3', '4, '[(R)-[(1-(N-ethyl-N- ...

CURABLE INKS COMPRISING DIURETHANE GELATORS

The disclosure provides curable inks including a diurethane gelator having the structure of Formula I. 2. The ink according to claim 1 , wherein Rand R′ each claim 1 , independently of the other claim 1 , having from about 10 to about 20 carbon atoms.3. The ink according to claim 1 , wherein each one of Rand R′ is an unsubstituted linear aliphatic group.4. (canceled)5. The ink according to claim 1 , wherein Rand R′ are the same as each other.6. The ink according to claim 1 , wherein Rand R′ are different from each other.7. The ink according to claim 1 , wherein X is an alkylene group selected from the group consisting of (1) linear aliphatic groups claim 1 , (2) branched aliphatic groups claim 1 , (3) cyclic aliphatic groups claim 1 , (4) aliphatic groups containing both cyclic and acyclic portions claim 1 , any carbon atom of the saturated aliphatic hydrocarbon group may be optionally substituted with an alkyl group (cyclic or acyclic).8. The gelator according to wherein X is an aliphatic group containing both cyclic and acyclic portions.9. The ink according to claim 8 , wherein the aliphatic group comprises one or more cyclic portions.10. The ink according to claim 9 , wherein each one of the one or more cyclic portions is independently selected from cyclopropylene claim 9 , 1 claim 9 ,2-cyclobutylene claim 9 , 1 claim 9 ,3-cyclobutylene claim 9 , cyclopentylene claim 9 , 1 claim 9 ,3-cyclopenylene claim 9 , cyclohexylene claim 9 , 1 claim 9 ,3-cyclohexylene claim 9 , and 1 claim 9 ,4-cyclohexylene.11. The ink according to claim 8 , wherein the acyclic portion comprises a C-Calkylene.12. The ink according to claim 1 , wherein the diurethane gelator has a viscosity of from about 10cps to about 10cps at a temperature between 85° C. to 22° C.13. The ink according to claim 1 , wherein the diurethane gelator is present in the ink in from about 1 to about 25 percent by weight of the ink.14. The ink according to further comprising a colorant.15. The ink according to ...

KCNQ2-5 CHANNEL ACTIVATOR

An object of the present invention is to provide a novel compound having a strong opening action with respect to KCNQ2-5 channels. A compound represented by the general formula (1) (wherein the definition of each group is as described in the specification) is provided. The compound represented by the general formula (1) has a strong opening action with respect to KCNQ2-5 channels, and therefore is useful as a prophylactic and/or therapeutic agent for a KCNQ2-5 channel-related disease (for example, dysuria, overactive bladder, or the like). 2. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris a hydrogen atom.3. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Y is —NH— or —O—.4. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Z is a bond or —O—.5. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris a hydrogen atom claim 1 , a methyl group claim 1 , or a trifluoromethyl group.6. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is (1) 1-(4 claim 1 ,6-dichloro-1-hydroxy-1-methyl-2 claim 1 ,3-dihydro-1H-inden-5-yl)-3-{[5-(trifluoromethyl)-2-pyridinyl]methyl}urea claim 1 , (2) 1-[4 claim 1 ,6-dichloro-1-hydroxy-1-(trifluoromethyl)-2 claim 1 ,3-dihydro-1H-inden-5-yl]-3-(4-fluorobenzyl)urea claim 1 , (3) 1-[4 claim 1 ,6-dichloro-1-hydroxy-1-(trifluoromethyl)-2 claim 1 ,3-dihydro-1H-inden-5-yl]-3-{[5-(trifluoromethyl)-2-pyridinyl]methyl}urea claim 1 , (4) 1-[4 claim 1 ,6-dichloro-1-hydroxy-1-(trifluoromethyl)-2 claim 1 ,3-dihydro-1H-inden-5-yl]-3-[(1R)-1-(4-fluorophenyl)ethyl]urea claim 1 , or (5) 1-(4 claim 1 ,6-dichloro-2 claim 1 ,2-difluoro-1-hydroxy-1-methyl-2 claim 1 ,3-dihydro-1H-inden-5-yl)-3-(4-fluorobenzyl)urea.7. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is 1-[(1R)-4 claim 1 ,6-dichloro ...

FLEXIBLE TO RIGID NANOPOROUS POLYURETHANE-ACRYLATE (PUAC) TYPE MATERIALS FOR STRUCTURAL AND THERMAL INSULATION APPLICATIONS

Novel urethane-acrylate (UAC) Star monomers and polyurethane-acrylate (PUAC) aerogel polymers derived therefrom are described herein, along with other novel, related monomers and polymers. Also described herein are processes for preparing the UAC Star monomers, the PUAC aerogel polymers, and the other related monomers and polymers. The PUAC and related polymers herein are useful in various applications including in structural and thermal insulation. 132.-. (canceled)35. The process of claim 34 , wherein the organic solvent is selected from the group consisting of benzene claim 34 , toluene claim 34 , and xylene claim 34 , and combinations thereof.37. A process for preparing the norbornene-containing star monomer of claim 36 , the process comprising the step of mixing a tris(isocyanatophenyl)methane of formula (III) with three molar equivalents of the norbornene-containing hydroxyl compound of formula (IX) in an organic solvent.38. The process of claim 37 , further comprising the addition of a catalyst.39. The process of claim 38 , wherein the catalyst is an organotin compound.40. The process of claim 39 , wherein the organotin compound is dibutyltin dilaurate.41. The process of wherein the organic solvent is selected from the group consisting of a ketone solvent claim 37 , an ester solvent claim 37 , and a combination thereof.42. The process of claim 41 , wherein the organic solvent is acetone claim 41 , ethyl acetate claim 41 , or a combination thereof.46. The polynorbornene-polyurethane polymer of or claim 41 , wherein the polymerization is ring-opening metathesis polymerization.4748.-. (canceled)49. The norbornene-containing hydroxyl compound of claim 33 , wherein R1=R2=R3=H claim 33 , W=CHCH claim 33 , and m=1.50. The norbornene-containing star monomer of claim 36 , wherein claim 36 , in the norbornene-containing hydroxyl compound of formula (IX) claim 36 , R1=R2=R3=H claim 36 , W=CHCH claim 36 , and m=1; and claim 36 , wherein claim 36 , in the tris( ...

REACTION PRODUCTS CONTAINING AMIDOAMINE GROUPS

A reaction product containing amido amine groups, comprising one or more species of the general formula (I) 1. A reaction product containing amido amine groups , comprising one or more species of the general formula (I){'br': None, 'sup': 1', '1, 'sub': p', 'y, '(R—X)—Z—(XH)\u2003\u2003(I)'}where p+y=w andw is an integer from 1 to 10,p is an integer from 1 to 10,y is an integer from 0 to 9, and{'sup': 2', '2, 'sub': '2', 'X is independently O, NH and/or NZand XH is independently a hydroxyl group OH, a primary amino group NHand/or a secondary amino group NHZwhere'}{'sup': '2', 'sub': 'a', 'Zis independently a branched or unbranched, saturated or unsaturated organic radical G(U)where U is independently a hydroxyl group, a primary amino group or a secondary amino group and'}a is an integer from 0 to 9,where p+y+a≤10, andG is a branched or unbranched, saturated or unsaturated radical,{'sup': '1', 'claim-text': {'br': None, 'sup': '2', 'Y—O—CO—NH—R—NH—CO \u2003\u2003(II)'}, 'the p Rradicals are independently a radical of the general formula (II)'}in which the p Y radicals are independently a branched or unbranched, saturated or unsaturated organic radical which has 1 to 1000 carbon atoms and does not contain any hydroxyl groups, any primary amino groups or any secondary amino groups,{'sup': '2', 'the p Rradicals are independently a branched or unbranched, saturated or unsaturated organic radical having 6 to 20 carbon atoms,'}{'sup': '1', 'Zis a branched or unbranched, saturated or unsaturated organic radical containing at least two carbon atoms, having at least one amide group and at least one tertiary amino group.'}2. The reaction product containing amido amine groups as claimed in claim 1 , containing at least 40% by weight of one or more species of the general formula (I).3. The reaction product containing amido amine groups as claimed in claim 1 , wherein the species of the general formula (IV) which is free of urethane groups claim 1 , is reactive toward isocyanate ...

ALKYNES AND METHODS OF REACTING ALKYNES WITH 1,3-DIPOLE-FUNCTIONAL COMPOUNDS

1,3-Dipole-functional compounds (e.g., azide functional compounds) can be reacted with certain alkynes in a cyclization reaction to form heterocyclic compounds. Useful alkynes (e.g., strained, cyclic alkynes) and methods of making such alkynes are also disclosed. The reaction of 1,3-dipole-functional compounds with alkynes can be used for a wide variety of applications including the immobilization of biomolecules on a substrate. 2. The alkyne of wherein each Rrepresents hydrogen.3. The alkyne of wherein each Rrepresents hydrogen.5. The composition of wherein the copolymer is of the formula RO—[CHCHO]—[C(O)(CH)O]—H claim 4 , wherein Rrepresents an alkyl group claim 4 , p=0 to 100 claim 4 , and o=0 to 100.6. The composition of wherein Rrepresents methyl.8. The substrate of wherein the X group of the alkyne represents a point of attachment to the surface of the substrate.10. The substrate of wherein the X group of the alkyne represents a point of attachment to the surface of the substrate.11. A method of immobilizing a biomolecule on a substrate claim 9 , the method comprising:{'claim-ref': {'@idref': 'CLM-00007', 'claim 7'}, 'providing a substrate according to ; and'}contacting the substrate with a 1,3-dipole-functional biomolecule under conditions effective to form a heterocyclic compound.12. The method of wherein the 1 claim 11 ,3-dipole-functional biomolecule is selected from the group consisting of an azide-functional biomolecule claim 11 , a nitrile oxide-functional biomolecule claim 11 , a nitrone-functional biomolecule claim 11 , an azoxy-functional biomolecule claim 11 , an acyl diazo-functional biomolecule claim 11 , and combinations thereof.13. The method of wherein the biomolecule is selected from the group consisting of peptides claim 11 , proteins claim 11 , glycoproteins claim 11 , nucleic acids claim 11 , lipids claim 11 , saccharides claim 11 , oligosaccharides claim 11 , polysaccharides claim 11 , and combinations thereof.14. A method of immobilizing ...

METHODS AND INTERMEDIATES FOR PREPARING MACROLACTAMS

The present invention includes compounds useful as intermediates in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing macrolactams. One use of the methods and intermediates described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. HCV NS3 inhibitory compounds have therapeutic and research applica 11. The method of claim 10 , wherein the reaction uses tri tert-butylphosphine tetra fluoroborate salt in a solvent claim 10 , and Compound 8 is provided as either a dibenzylamine salt or a t-butylamine salt. The present invention relates to process and intermediates that can be used for preparing macrolactams. One use of the methods and intermediates described herein is the production of macrolactam compounds able to inhibit HCV NS3 protease activity. HCV NS3 inhibitory compounds have therapeutic and research applications.Hepatitis C virus (HCV) infection is a major health problem. HCV infection leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals.Several virally-encoded enzymes are putative targets for therapeutic intervention, including a metalloprotease (NS2-3), a serine protease (NS3), a helicase (NS3), and an RNA-dependent RNA polymerase (NS5B). The NS3 protease is located in the N-terminal domain of the NS3 protein. NS4A provides a cofactor for NS3 activity.Potential treatments for HCV infection are discussed in different references including Balsano, 8(4):307-318, 2008, Rönn et al., 8:533-562, 2008, Sheldon et al., 16(8):1171-1181, 2007, and De Francesco et al., 58:1-16, 2003.Examples of publications describing macrolactam compounds able to inhibit HCV protease activity include: Harper et al., WO2010011566; Liverton et al., WO2009134624; McCauley et al., WO2009108507; Liverton et al., WO2009010804; Liverton et al., WO2008057209; Liverton et al., WO2008051477; Liverton et al., WO2008051514; ...

Processes for the Preparation of Edoxaban and Intermediates Thereof

The present invention provides processes for the preparation of Edoxaban (1) and salts thereof, as well as intermediates thereof. In particular, intermediate compounds and/or salts of the Formulae (3), (4), (6-A), (7-A), (8-A), (9-A) and (10-AS) are provided. 2. The process of claim 1 , wherein the deprotection in step (a) occurs by hydrogenolysis.3. The process of claim 2 , wherein the hydrogenolysis is conducted in the presence of a hydrogen source and a palladium catalyst selected from the group consisting of palladium on carbon and palladium hydroxide on carbon.4. The process of claim 3 , wherein the hydrogen source is sodium formate.5. The process of claim 1 , wherein step (b) is conducted without isolation of the compound of Formula (5-A) in step (a).6. The process of claim 1 , wherein the desulfonylation in step (b) occurs in the presence of pyridine.8. The process of claim 7 , wherein HA is selected from the group consisting of sulfuric acid claim 7 , benzoic acid claim 7 , tartaric acid claim 7 , citric acid claim 7 , camphorsulfonic acid and p-toluenesulfonic acid.9. The process of claim 1 , wherein the deprotection in step (d) occurs in the presence of acid.10. The process of claim 1 , wherein{'sup': 1a', '1b', '1c, 'R, Rand Rare independently selected from the group consisting of H, aryl, and substituted aryl;'}{'sup': 1a', '1b', '1c, 'at least one of R, Rand Ris aryl or substituted aryl; and'}{'sup': '2', 'Ris an aliphatic group or a substituted aliphatic group.'}11. The process of claim 1 , wherein{'sup': 1a', '1b, 'Rand Rare both H;'}{'sup': '1c', 'Ris phenyl; and'}{'sup': '2', 'Ris selected from the group consisting of t-butyl, 2-methyl-2-hexanyl, 1-methylcyclohexyl and 2-trimethylsilylethyl.'}13. The compound of claim 12 , wherein Ris an aliphatic group or a substituted aliphatic group.16. The salt of claim 15 , wherein HA is selected from the group consisting of sulfuric acid claim 15 , benzoic acid claim 15 , tartaric acid claim 15 , citric acid ...

Process for the Preparation of 6-(7-((1-Aminocyclopropyl)Methoxy)-6-Methoxyquinolin-4-Yloxy)-N-Methyl-1-Naphthamide and Synthetic Intermediates Thereof

A process for the preparation in high yields and purity of the compound 6-(7-((1-aminocyclopropyl)methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide of formula (I) and of the pharmaceutically acceptable salts thereof is described. The process has various advantages over those previously described, in particular it avoids the use of acyl azide intermediates and their Curtius rearrangement. Novel intermediates useful for the preparation of compound (I) are also described. 6. A compound as claimed in claim 1 , wherein said compound is:1-[(4-Acetyl-2-methoxyphenoxy)methyl]-N-benzyloxycarbonyl-1-aminocyclopropane.7. Method of synthesizing a compound as claimed in as an intermediate in the synthesis of 6-(7-((1-aminocyclopropyl)methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (I) or a pharmaceutically acceptable salt thereof.8. A compound as claimed in claim 2 , wherein the compound is 1-[(4-Acetyl-2-methoxy-5-nitrophenoxy)methyl]-N-benzyloxycarbonyl-1-aminocyclopropane.9. A compound as claimed in claim 3 , wherein the compound is 1-[(4-(3-Dimethylaminopropenoyl)-2-methoxy-5-nitrophenoxy)methyl]-N-benzyloxycarbonyl-1-aminocyclopropane.10. A compound as claimed in claim 4 , wherein the compound is 1-[(4-Hydroxy-6-methoxyquinolin-7-yloxy)methyl]-N-benzyloxycarbonyl-1-aminocyclopropane.11. A compound as claimed in claim 5 , wherein the compound is 1-[(4-Chloro-6-methoxyquinolin-7-yloxy)methyl]-N-benzyloxycarbonyl-1-aminocyclopropane. This application is a divisional of U.S. application Ser. No. 14/138,302, filed Dec. 23, 2013. U.S. application Ser. No. 14/138,302 is a divisional of U.S. application Ser. No. 13/256,722 filed on Sep. 15, 2011, now U.S. Pat. No. 8,642,767. U.S. application Ser. No. 13/256,722 is a 371 U.S. National phase of PCT/EP2010/001519 filed on Mar. 11, 2010, which claims priority to and benefit of Italian Application No. MI2009A000397 filed on Mar. 16, 2009, all of which are incorporated herein by reference in their entireties.The ...

PHENYL CARBAMATE COMPOUNDS FOR USE IN PREVENTING OR TREATING PEDIATRIC EPILESY AND EPILESY-RELATED SYNDROMES

The present invention provides a pharmaceutical composition for preventing and/or treating a pediatric epilepsy or epilepsy-related syndrome comprising the phenyl carbamate compound as an active ingredient, and a use of the phenyl carbamate compound for preventing and/or treating pediatric epilepsy or pediatric epilepsy-related syndromes. 2. The pharmaceutical composition according to claim 1 , wherein A is hydrogen and B is carbamoyl group claim 1 , or A is a carbamoyl group and B is hydrogen.3. The pharmaceutical composition according to claim 1 , wherein the phenyl carbamate compound is in the form of racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , a mixture of enantiomer claim 1 , or a mixture of diastereomer.4. The pharmaceutical composition according to claim 1 , wherein X is chlorine claim 1 , fluorine claim 1 , iodine claim 1 , or bromine; n is 1 or 2; and Rand Rare the same as or different from each other claim 1 , and independently selected from the group consisting of hydrogen claim 1 , methyl group claim 1 , propyl group claim 1 , isopropyl group claim 1 , cyclopropyl group claim 1 , cyclohexyl group claim 1 , bicycloheptane group claim 1 , and benzyl group.5. The pharmaceutical composition according to claim 1 , wherein the phenyl carbamate compound is selected from the group consisting of:1-(2-chlorophenyl)-1-hydroxypropyl-2-carbamate,1-(2-chlorophenyl)-1-hydroxy-3-methyl-butyl-2-carbamate,1-(2-chlorophenyl)-1-hydroxyhexyl-2-carbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-methylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-propylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-isopropylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-cyclopropylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-cyclohexylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-benzylcarbamate,1-(2-chlorophenyl)-1-hydroxypropyl-2-N-bicyclo [2,2,1]heptanecarbamate,1-(2,4-dichlorophenyl)-1-hydroxypropyl-2-carbamate,1-(2,6-dichlorophenyl)-1-hydroxypropyl-2- ...

POLYMERIC STRUCTURES CONTAINING STRAINED CYCLOALKYNE FUNCTIONALITY FOR POST-FABRICATION AZIDEALKYNE CYCLOADDITION FUNCTIONALIZATION

A method of creating biocompatible polymeric structures includes the steps of: providing a biocompatible polymer including a strained cycloalkyne end group; forming a polymeric structure from the biocompatible polymer such that the strained cycloalkyne end group remains on the biocompatible polymer; providing an azide tethered molecule; and, after forming the polymeric structure, reacting the azide tethered molecule with the cycloalkyne in an azide alkyne cycloaddition reaction to further functionalize the polymeric structure. 1. A method of creating biocompatible polymeric structures comprising the steps of:providing a biocompatible polymer including a strained cycloalkyne end group;forming a polymeric structure from the biocompatible polymer such that the strained cycloalkyne end group remains on the biocompatible polymer;providing an azide tethered molecule; and, after said step of forming,reacting the azide tethered molecule with the cycloalkyne in an azide alkyne cycloaddition reaction to further functionalize the polymeric structure.2. The method of claim 1 , wherein said step of providing a biocompatible polymer includes the step of polymerizing monomers through a ring-opening polymerization employing a ROP initiator having a strained cycloalkyne to create the biocompatible polymer including a strained cycloalkyne end group.3. The method of claim 2 , wherein the ROP initiator includes a five to nine member strained cycloalkyne.4. The method of claim 3 , wherein the ROP initiator further includes a reactive group selected from an hydroxyl group or amine group.5. The method of claim 4 , wherein the reactive group is an hydroxyl group claim 4 , and the monomers polymerized in said step of polymerizing are cyclic esters.6. The method of claim 4 , wherein the reactive group is an hydroxyl group claim 4 , and the monomers polymerized in said step of polymerizing are selected from lactones claim 4 , lactides and glycolides.7. The method of claim 4 , wherein the ...

PRODUCTION METHOD OF CARBAMIC ACID ESTER

A method of production of carbamic acid ester has a high yield and high selectivity and is superior in economy. The method of production of a carbamic acid ester includes reacting an amine, carbon dioxide, and an alkoxysilane compound in the presence of a catalyst containing a zinc compound or an alkali metal compound or in the presence of an ionic liquid. A carbamic acid ester is produced, for example by reacting aniline, carbon dioxide, and tetramethoxysilane at a temperature of 150 to 180° C. in the presence of zinc acetate and 2,2′-bipyridine. 1. A method of producing a carbamic acid ester , comprising:reacting an amine, carbon dioxide, and an alkoxysilane compound in the presence of a catalyst containing a zinc compound.2. The method according to claim 1 , wherein the zinc compound is at least one of zinc oxide claim 1 , a zinc halide claim 1 , zinc trifluoromethanesulfonate and zinc acetate.3. The method according to claim 1 , wherein the catalyst further contains a ligand.4. The method of according to claim 3 , wherein the zinc compound is zinc acetate claim 3 , and the ligand is at least one of 1 claim 3 ,10-phenanthroline claim 3 , 2 claim 3 ,2′-bipyridine claim 3 , N claim 3 ,N′-bis(2-pyridylmethyl)ethylenediamine claim 3 , and 1 claim 3 ,4 claim 3 ,8 claim 3 ,11-tetraazacyclotetradecane.5. The method according to claim 1 , wherein the amine claim 1 , the carbon dioxide claim 1 , and the alkoxysilane compound are reacted at a pressure of the carbon dioxide of 3 to 10 MPa.6. A method of producing a carbamic acid ester claim 1 , comprising:reacting an amine, carbon dioxide, and an alkoxysilane compound in the presence of an ionic liquid.7. The method according to claim 6 , wherein an anion of the ionic liquid is at least one of an acetate ion claim 6 , a trifluoroacetate ion claim 6 , and a 2 claim 6 ,2 claim 6 ,2-trifluoroethanol ion.9. The method according to claim 8 , wherein the cation of the ionic liquid is at least one of the compounds represented by ...

DIFLUOROALKYLCYCLOPROPYL AMINO ACIDS AND ESTERS, AND SYNTHESES THEREOF

The invention provides methods of synthesizing compounds in an asymmetric or enantioenriched fashion, wherein the compounds are useful intermediates in the synthesis of viral protease inhibitors. 117-. (canceled)19. The method of claim 18 , wherein the fifth base comprises KOH claim 18 , NaOH claim 18 , or LiOH.20. The method of claim 18 , wherein the eighth solvent comprises EtOH claim 18 , n-PrOH claim 18 , i-PrOH claim 18 , ethyl acetate claim 18 , dioxane claim 18 , DMF claim 18 , acetonitrile claim 18 , water claim 18 , or DMSO.23. The method of claim 22 , wherein the fourth base comprises i-PrN claim 22 , (i-Pr)EtN claim 22 , EtN claim 22 , EtNH claim 22 , EtNH claim 22 , or (iPr)NH.24. The method of claim 22 , wherein the seventh solvent is heptane claim 22 , toluene claim 22 , methyl t-butyl ether claim 22 , or dioxane.25. The method of claim 22 , wherein the N source is diphenylphosphorylazide (DPPA) or tosylazide.27. The method of claim 26 , wherein the selective hydrolysis of the 2S-enantiomer of a compound of formula D takes place in a first buffer.28. The method of claim 27 , wherein the first buffer comprises sodium phosphate.29Mucor miehei. The method of claim 26 , wherein the first enzyme is lipase (RML claim 26 , enzyme).30Bacillus subtilis. The method of claim 26 , wherein the first enzyme is esterase (yvaK enzyme).32. The method of claim 31 , wherein the third base comprises BnMeNOH claim 31 , CsOH claim 31 , ammonium hydroxide claim 31 , tetraalkylammonium hydroxide claim 31 , KOH claim 31 , NaOH claim 31 , or LiOH.33. The method of claim 31 , wherein the third solvent comprises t-BuOH claim 31 , n-BuOH claim 31 , n-PrOH claim 31 , i-PrOH claim 31 , EtOH claim 31 , MeOH claim 31 , or water.34. The method of claim 31 , wherein the fifth temperature is from about 15° C. to about 40° C. and the fifth period of time is from about 1 hour to about 18 hours.36. The method of claim 35 , wherein the second base comprises NaH claim 35 , LiH claim 35 , ...

SYNTHESIS OF AN ANTIVIRAL COMPOUND

The present disclosure provides processes for the preparation of a compound of formula I: 115-. (canceled) This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 61/920,446 filed on Dec. 23, 2013, the entirety of which is incorporated herein by reference.The present disclosure relates generally to the field of organic synthetic methodology for the preparation of Flaviviridae virus inhibitor compounds and their synthetic intermediates.The hepatitis C virus (HCV), a member of the hepacivirus genera within the Flaviviridae family, is the leading cause of chronic liver disease worldwide (Boyer, N. et al. J Hepatol. 2000, 32, 98-112). Consequently, a significant focus of current antiviral research is directed toward the development of improved methods for the treatment of chronic HCV infections in humans (Ciesek, S., von Hahn T., and Manns, M P., Clin. Liver Dis., 2011, 15, 597-609; Soriano, V. et al, J. Antimicrob. Chemother., 2011, 66, 1573-1686; Brody, H., Nature Outlook, 2011, 474, S1-S7; Gordon, C. P., et al., J. Med. Chem. 2005, 48, 1-20; Maradpour, D., et al., Nat. Rev. Micro. 2007, 5, 453-463).Virologic cures of patients with chronic HCV infection are difficult to achieve because of the prodigious amount of daily virus production in chronically infected patients and the high spontaneous mutability of HCV (Neumann, et al., Science 1998, 282, 103-7; Fukimoto, et al., Hepatology, 1996, 24, 1351-4; Domingo, et al., Gene 1985, 40, 1-8; Martell, et al., J. Virol. 1992, 66, 3225-9). HCV treatment is further complicated by the fact that HCV is genetically diverse and expressed as several different genotypes and numerous subtypes. For example, HCV is currently classified into six major genotypes (designated 1-6), many subtypes (designated a, b, c, and so on), and about 100 different strains (numbered 1, 2, 3, and so on).HCV is distributed worldwide with genotypes 1, 2, and 3 predominate within the United States, Europe, Australia ...

Method for the stereoselective preparation of amino acid derivatives

The invention relates to a process for the stereoselective preparation of amino acid derivatives, comprising a hydrogenation reaction of the compound of formula (III), alternatively its enantiomer, wherein R is (C 1 -C 8 )-alkyl; followed by a hydrolysis reaction to obtain L-mesityl alanine, alternatively its enantiomer D-mesityl alanine and, optionally, subjecting said compound to an amino group protection reaction, particularly as Fmoc. It also comprises Fmoc-L- or Fmoc-D- mesityl alanine as products per se, useful as intermediates in preparing peptides or peptide analogs with therapeutic or biological activity.

URETHANE ACRYLATE, AND REACTIVE COMPOSITION CONTAINING SAME

The present invention is directed to a urethane acrylate containing a reaction product of an alkylene oxide-modified dipentaerythritol (meth)acrylate. 2. A reactive composition comprising the urethane acrylate described in . The present invention relates to a reaction composition containing a urethane acrylate, and to a urethane acrylate for the same. In particular, the invention relates to a reaction composition which exhibits, after cured, high pencil hardness, scratch resistance, abrasion resistance, adhesiveness to substrate, transparency and contamination resistance, and to a urethane acrylate for the same.A reaction composition containing a urethane acrylate can be made to have excellent characteristics of toughness, flexibility, scratch resistance, weather resistance, chemical resistance, and the like. Further, the composition has a characteristic of curing within a short period of time through heating or active energy ray irradiation, and is favorable for production of components for optical use, resist compositions, hard coat compositions, and ink compositions for inkjet.In these latter days, in mobile electronic appliances such as notebook-size personal computers and mobile telephones, components having a fine patterned indented surface (for example, a key sheet) formed of a reactive resin composition on a sheet-like transparent plastic substrate, and housings with high-quality design are used in some cases and high pencil hardness and scratch resistance are required therefor. Consequently, attention has become paid to reactive compositions containing a urethane acrylate.The cured product using the reactive composition described in Patent Literature 1 is excellent in scratch resistance, but in fact, the composition contains a solvent as described in Examples therein, and is therefore unfavorable for use in shaping applications. On the other hand, the cured product using the reactive composition described in Patent Literature 2 is disclosed to have ...

PRODRUGS OF GAMMA-HYDROXYBUTYRIC ACID, COMPOSITIONS AND USES THEREOF

The present disclosure discloses prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof. 2. The pharmaceutical formulation of claim 1 , wherein the pharmaceutical formulation is a solid.3. The pharmaceutical formulation of claim 1 , wherein the pharmaceutically acceptable carrier comprises a solvent for dissolving or dispersing the compound.4. The pharmaceutical formulation of claim 3 , wherein the solvent comprises water.5. The pharmaceutical formulation of claim 1 , wherein the formulation is in a liquid dosage form.6. The pharmaceutical formulation of claim 1 , wherein the pharmaceutically acceptable carrier comprises a flavoring agent claim 1 , sucrose claim 1 , lactose claim 1 , cellulose sugar claim 1 , mannitol claim 1 , maltitol claim 1 , dextran claim 1 , sorbitol claim 1 , starch claim 1 , agar claim 1 , alginates claim 1 , chitins claim 1 , chitosans claim 1 , pectins claim 1 , tragacanth gum claim 1 , gum arabic claim 1 , gelatins claim 1 , collagens claim 1 , casein claim 1 , albumin claim 1 , synthetic or semi-synthetic polymers or glycerides claim 1 , methyl cellulose claim 1 , hydroxypropylmethyl-cellulose claim 1 , or polyvinylpyrrolidone.7. The pharmaceutical formulation of claim 1 , wherein the pharmaceutically acceptable carrier comprises a polymeric excipient.8. The pharmaceutical formulation of claim 1 , wherein the formulation comprises a tablet claim 1 , a caplet claim 1 , a capsule claim 1 , a gel cap claim 1 , granules claim 1 , a pill claim 1 , a powder claim 1 , a lozenge claim 1 , a sachet claim 1 , a cachet claim 1 , a suspension claim 1 , an emulsion claim 1 , a solution claim 1 , a slurry claim 1 , or a syrup.9. The pharmaceutical formulation of claim 1 , wherein the pharmaceutical formulation is formulated in a unit dosage form.10. The pharmaceutical formulation of claim 9 , wherein the unit dosage form has a weight from 0.5 grams to 30 grams.11. The pharmaceutical formulation of claim 10 , wherein the ...

PRODRUGS OF GAMMA-HYDROXYBUTYRIC ACID, COMPOSITIONS AND USES THEREOF

The present disclosure discloses prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof. 2. The method of claim 1 , wherein Ris selected from hydrogen and Calkyl.3. The method of claim 1 , wherein at least one of Rand Ris selected from hydrogen and Calkyl.4. The method of claim 1 , wherein each of Rand Ris selected from hydrogen and Calkyl.5. The method of claim 1 , wherein claim 1 ,{'sub': h', '1-3, 'Ris selected from hydrogen and Calkyl; and'}{'sub': f', '1-3', '5-6, 'sup': 5', '5, 'Ris —COR, wherein Ris selected from Calkoxyl and Ccycloalkyloxyl.'}6. The method of claim 1 , wherein claim 1 ,{'sub': h', 'f, 'each of Rand Ris hydrogen; and'}{'sub': g', '1-3, 'Ris selected from hydrogen and Calkyl.'}7. The method of claim 1 , wherein the carbon atom to which Ris bonded is in the (R)-configuration.8. The method of claim 1 , wherein the carbon atom to which Ris bonded is in the (S)-configuration.9. The method of claim 1 , wherein the compound is selected from:4-(((tert-butoxycarbonyl)glycyl)oxy)butanoic acid;4-(glycyloxy)butanoic acid;4-((D-valyl)oxy)butanoic acid;4-((L-alanyl)oxy)butanoic acid;4-(((ethoxycarbonyl)glycyl)oxy)butanoic acid;4-(((isopropoxycarbonyl)glycyl)oxy)butanoic acid;4-((((cyclohexyloxy)carbonyl)glycyl)oxy)butanoic acid;4-(((ethoxycarbonyl)-D-valyl)oxy)butanoic acid;4-((L-valyl)oxy)butanoic acid;a pharmaceutically acceptable salt of any of the foregoing;and a combination of any of the foregoing.13. The method of claim 1 , wherein administering comprises orally administering.14. The method of claim 1 , wherein administering comprises administering a pharmaceutical composition comprising the compound of Formula (IA) or a pharmaceutically acceptable salt thereof.15. The method of claim 1 , wherein the pharmaceutical composition comprises an oral formulation.16. The method of claim 1 , wherein the pharmaceutical composition comprises an oral dosage form.17. The method of claim 1 , wherein the pharmaceutical composition comprises ...

MULTIPLE CYCLOADDITION REACTIONS FOR LABELING OF MOLECULES

The present invention relates to methods for linking tetrazines with dienophiles to establish at least two linkages by sequentially performing at least two cycloaddition reactions. The methods in particular allow establishing multi-labeling strategies. In particular, the invention relates to methods for forming linkages by cycloaddition reactions, wherein the method comprises reacting a first alkyl-substituted tetrazine with a first dienophile comprising a irans-cyclooctenyl group followed by reacting a second tetrazine with a second dienophile comprising a cyclooctynyl group, wherein the reaction of the first tetrazine with the first dienophile proceeds in the presence of the second dienophile. 2. The method of claim 1 , wherein the first tetrazine preferentially reacts with the first dienophile in the presence of the second dienophile.3. The method of claim 1 , wherein the rate constant k of the first tetrazine with the first dienophile is usually at least 10-times higher than the rate constant k of the reaction of the first tetrazine with the second dienophile.4. The method of claim 1 , wherein the rate constant k of the first tetrazine with the first dienophile is allowed to proceed for 30 minutes or less at a temperature of about 37° C.7. The method of claim 1 , wherein the first dienophile or the target molecule or target molecule composition is reacted with the first tetrazine or labeling agent under conditions that allow for substantially all trans-cyclooctenyl groups to react prior to reacting the second dienophile or the target molecule or target molecule composition with the second tetrazine or labeling agent.9. The cell of claim 8 , wherein the cyclooctynyl group is attached to a first polypeptide and the trans-cyclooctenyl group is attached to a second polypeptide claim 8 , the first and the second polypeptide being different polypeptides. This application is a continuation of U.S. application Ser. No. 15/111,138, which is a 35 U.S.C. § 371 U.S. ...

METHODS AND INTERMEDIATES FOR PREPARING MACROLACTAMS

The present invention includes compounds useful as intermediates in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing macrolactams. One use of the methods and intermediates described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. HCV NS3 inhibitory compounds have therapeutic and research applications. 4. The method of claim 3 , wherein X is Br.6. The method of claim 1 , wherein Ris acetyl.8. The method of claim 1 , wherein Ris selected from the group consisting of C-Calkyl groups.9. The method of claim 2 , wherein Ris tert-butyl.10. The method of claim 1 , wherein LG is Cl.11. The method of claim 1 , wherein claim 1 , in step (1) claim 1 , the chiral alcohol is chlorohydrin.14. The method of claim 1 , wherein step (iii) is conducted in the presence of a promoter.15. The method of claim 14 , wherein the promoter is selected from the group consisting of 2-hydroxypyridine-N-oxide claim 14 , hydroxyl succinimide claim 14 , imidazole and imidazole HCl salt.16. The method of claim 5 , wherein step (iv) comprises forming a salt of the compound claim 5 , wherein the salt is selected from tert-butylamine salt claim 5 , dibenzylamine salt claim 5 , and dicyclohexyl amine salt. The present invention relates to process and intermediates that can be used for preparing macrolactams. One use of the methods and intermediates described herein is the production of macrolactam compounds able to inhibit HCV NS3 protease activity. HCV NS3 inhibitory compounds have therapeutic and research applications.Hepatitis C virus (HCV) infection is a major health problem. HCV infection leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals.Several virally-encoded enzymes are putative targets for therapeutic intervention, including a metalloprotease (NS2-3), a serine protease (NS3), a helicase (NS3), and an RNA-dependent RNA ...

NOVEL COMPOUND AS KCNQ POTASSIUM CHANNEL AGONIST, PREPARATION METHOD THEREFOR AND USE THEREOF

The present invention provides compounds having the structure represented by general formula I, pharmaceutically acceptable salts thereofagonist, preparation methods therefor and a use thereof in the preparation of a medicine for the treatment of nervous system diseases. The compounds or pharmaceutical compositions thereof can be used as the KCNQ potassium channel agonist for treating nervous system diseases. Compared to retigabine, a compound in the prior art, the compound of the present invention have the same or better therapeutic effect, are easier for synthesis and storage, and less prone to oxidate deterioration. 5. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the pharmaceutically acceptable salt of the compound is a salt formed by the compound with an acid claim 1 , and the acid is selected from the group consisting of maleic acid claim 1 , succinic acid claim 1 , citric acid claim 1 , tartaric acid claim 1 , fumaric acid claim 1 , formic acid claim 1 , acetic acid claim 1 , propanoic acid claim 1 , propandioic acid claim 1 , oxalic acid claim 1 , benzoic acid claim 1 , phthalic acid claim 1 , methanesulfonic acid claim 1 , benzenesulfonic acid claim 1 , toluenesulfonic acid claim 1 , naphthalenesulfonic acid claim 1 , 1 claim 1 ,5-naphthalenedisulfonic acid claim 1 , camphoric acid claim 1 , camphor sulfonic acid claim 1 , salicylic acid claim 1 , acetyl salicylic acid claim 1 , aspartic acid claim 1 , glutamic acid claim 1 , lactic acid claim 1 , gluconic acid claim 1 , ascorbic acid claim 1 , gallic acid claim 1 , amygdalic acid claim 1 , malic acid claim 1 , sorbic acid claim 1 , trifluoroacetic acid claim 1 , taurine claim 1 , homotaurine claim 1 , isethionic acid claim 1 , cinnamic acid claim 1 , hydrochloric acid claim 1 , hydrobromic acid claim 1 , hydroiodic acid claim 1 , sulfuric acid claim 1 , nitric acid claim 1 , phosphoric acid and perchloric acid.7. A pharmaceutical composition claim 1 , wherein ...

NOVEL INTERMEDIATE OF TAPENTADOL

The present invention relates to novel carbamate intermediate of formula (II), process for its preparation and process for its conversion into 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol, tapentadol and its pharmaceutically acceptable salts. 2. The process as in wherein R in compound of Formula IV and II is selected from phenyl claim 1 , ethyl or cyclohexyl.3. The process as in wherein step a carried out in presence of a base.4. The process as in claim 1 , wherein in step ‘a’ the compound of Formula II is converted into its salt.5. The process as in claim 1 , wherein step ‘b’ involves converting the salt of compound of Formula II to the compound of Formula V or salt thereof.7. The compound as in wherein R is selected from phenyl claim 6 , ethyl or cyclohexyl.8. The compound of wherein the salt is citrate or hydrochloride.10. The process as in wherein R is selected from phenyl claim 9 , ethyl or cyclohexyl. The present invention relates to novel intermediate of Formula II, process for its preparation and process for its conversion into 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol, tapentadol of Formula I and its pharmaceutically acceptable salts.3-[(1R,2R)-3-(Dimethylamino)-1-ethyl-2-methylpropyl]phenol is the IUPAC name for Tapentadol (Formula I). It is a centrally acting analgesic with a dual mode of action as an agonist of μ-opioid receptor and as a norepinephrine reuptake inhibitor.U.S. Pat. No. 6,248,737 reissued as U.S. RE39593 discloses a variety of 1-phenyl-3-dimethylaminopropane compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and methods of use thereof. Among them, Tapentadol hydrochloride, is a one compound which has analgesic activity.As per the process exemplified in U.S. RE39593 (hereinafter referred to as the '593 patent), (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride is prepared by the reaction of (-)-(2S,3 S)-1-dimethylamino-3-(3-methoxyphenyl ...

NOVEL POLYMORPHS OF N-[2-AMINO-4-(4-FLUOROBENZYLAMINO)-PHENYL] CARBAMIC ACID ETHYL ESTER AND PROCESSES THEREOF

The present invention relates to novel polymorphs of N-[2-amino-4-(4-fluorobenzylamino)-phenyl]carbamic acid ethyl ester, processes for preparing them, and pharmaceutical composition comprising them. In one aspect, the present invention relates to a novel crystalline polymorph of retigabine designated as crystalline Form I, characterized by XRPD having characteristic peaks at about 4.87, 5.04, 7.03, 9.74, 10.02, 11.6, 18.03, 19.9 and 28.5±0.2 degrees two-theta, which is substantially same as depicted in FIG. 114-. (canceled)15. Crystalline Form II of retigabine characterized by an X-ray powder diffraction (XRPD) pattern having characteristic 2-theta peaks at about 5.07 , 10.09 , 14.86 , 15.1 and 30.4±0.2 degrees substantially in accordance with .16. (canceled)17. The crystalline Form II of claim 15 , which is further characterized by an FT-IR spectrum having main bands at about 694 claim 15 , 734 claim 15 , 765 claim 15 , 789 claim 15 , 827 claim 15 , 837 claim 15 , 860 claim 15 , 907 claim 15 , 937 claim 15 , 979 claim 15 , 1014 claim 15 , 1066 claim 15 , 1096 claim 15 , 1155 claim 15 , 1173 claim 15 , 1223 claim 15 , 1259 claim 15 , 1295 claim 15 , 1345 claim 15 , 1367 claim 15 , 1391 claim 15 , 1428 claim 15 , 1474 claim 15 , 1509 claim 15 , 1536 claim 15 , 1600 claim 15 , 1628 claim 15 , 1679 claim 15 , 1709 claim 15 , 1890 claim 15 , 2850 claim 15 , 2873 claim 15 , 2906 claim 15 , 2959 claim 15 , 2985 claim 15 , 3040 claim 15 , 3283 claim 15 , 3346 claim 15 , 3395 and 3442±2 cmsubstantially in accordance with .18. The crystalline Form II of claim 15 , which is further characterized by differential scanning calorimetric (DSC) thermogram having an endotherm curve at about 141.23° C. with an onset at about 140.48° C. substantially in accordance with .19. The crystalline Form II of claim 15 , which is further characterized by FT-RAMAN spectra having peaks at about 60 claim 15 , 139 claim 15 , 243 claim 15 , 338 claim 15 , 369 claim 15 , 400 claim 15 , 466 claim 15 ...

DISUBSTITUTED AMINO ACIDS AND METHODS OF PREPARATION AND USE THEREOF

Provided are crystalline α, α-disubstituted amino acids and their crystalline salts containing a terminal alkene on one of their side chains, as well as optionally crystalline halogenated and deuterated analogs of the α, α-disubstituted amino acids and their salts; methods of making these, and methods of using these. 29.-. (canceled)10. The crystalline salt of claim 1 , wherein n is an integer from 3 to 11.11. The crystalline salt of claim 1 , wherein n is 3 or 6.12. (canceled)13. (canceled)14. The crystalline salt of claim 1 , having a chemical purity ranging from about 90% to 100%.15. The crystalline salt of claim 1 , having an optical purity ranging from about 90% to 100%.16. (canceled)17. The crystalline salt of claim 1 , having an enantiomeric excess ranging from about 90% to 100%.18. (canceled)2022.-. (canceled)23. A method of preparing the crystalline salt of claim 1 , comprising precipitating the compound of Formula (I) as a HCl salt.2430.-. (canceled)31. The method of claim 23 , wherein the HCl salt is further crystallized with a solvent comprising acetonitrile claim 23 , methyl tertiary-butyl ether claim 23 , isopropyl acetate claim 23 , or a mixture thereof.3235.-. (canceled)36. The crystalline salt of claim 1 , wherein the salt is a salt with an acid salt.37. The crystalline salt of claim 36 , wherein the acid is selected from the group consisting of nitric acid claim 36 , phosphoric acid claim 36 , sulfuric acid claim 36 , boric acid claim 36 , hydrofluoric acid claim 36 , hydrobromic acid claim 36 , perchloric acid or hydrochloric acid.38. The crystalline salt of claim 36 , wherein the acid is hydrochloric acid.40. The crystalline composition of claim 39 , wherein Ris C-Calkyl.41. The crystalline composition of claim 39 , wherein n is 3 or 6.42. The crystalline composition of claim 39 , wherein the crystalline compound has a chemical purity ranging from about 90% to 100%.43. The crystalline composition of claim 39 , wherein the crystalline compound has ...

COMPOSITIONS AND METHODS OF MAKING EXPANDED HEMATOPOIETIC STEM CELLS USING DERIVATIVES OF FLUORENE

This invention is directed to, inter alia, compounds, methods, systems, and compositions for the maintenance, enhancement, and expansion of hematopoietic stem cells derived from one or more sources of CD34+ cells. Sources of CD34+ cells include bone marrow, cord blood, mobilized peripheral blood, and non-mobilized peripheral blood. Also provided herein are compounds of Formula I 3. The compound of or , wherein{'sub': '3-6', 'A is a fused cyclic moiety selected from the group consisting of a Ccycloalkyl, heterocycloalkyl, and phenyl,'}wherein each heterocycloalkyl comprises from 3 to 6 ring members having 1 to 3 nitrogen atom ring members.4. The compound of or , wherein{'sub': '3-6', 'A is a fused cyclic moiety selected from the group consisting of a Ccycloalkyl and phenyl.'}5. The compound of or , wherein{'sub': '3-6', 'A is a fused Ccycloalkyl.'}6. The compound of any one of to , wherein{'sup': 4a', 'a', '4b', '4a', '4b, 'Ris —OR; Ris H; or Rand Rare combined to form an oxo moiety'}7. The compound of any one of to , wherein{'sup': 4a', 'a', '4b, 'Ris —OR; and Ris H.'}8. The compound of any one of to , wherein{'sup': 4a', 'a', 'b', '4b, 'Ris —NRR; and Ris H.'}9. The compound of any one of to , wherein{'sup': 1', 'b', '1a', 'b', '1a', 'b', '1', 'a', '1', 'b', 'a', '1', 'b', 'a', '1', 'b', '1a', 'b', '1', '1b', 'b', '1', '1b', 'b', '1a', 'b', '1a', 'b', '1a', '1a, 'Ris selected from the group consisting of —C(O)—NR—R, —NR—C(O)—R, —NR—X—C(O)—R, —C(O)—X—NR—R, —X—C(O)—NR—R, —X—NR—C(O)—R, —NR—C(O)—X—C(O)—R, —C(O)—NR—X—C(O)—R, —NR—C(O)—O—R, —O—C(O)—NR—R, —NR—R, and —C(O)—R.'}10. The compound any one of to , wherein{'sup': 1', '1a', '1a', 'a', 'a', 'a', '1a, 'Ris selected from the group consisting of —C(O)—NH—R, —NH—C(O)—R, —NH—C(O)—O—R, —O—C(O)—NH—R, —NH—R, and —C(O)—R.'}11. The compound any one of to , wherein{'sup': 1', '1a', '1b', '1a', 'b', '1a, 'Ris selected from the group consisting of —NH—C(O)—R, —NH—C(O)—R, —NH—C(O)—O—R, and —NR—R.'}12. The compound any one of to , ...

TRIPTYCENE DERIVATIVES FOR NUCLEIC ACID JUNCTION STABILIZATION

The present invention is directed to compositions and methods using triptycene derivatives (TCDs) for three way junctions (TWJs). 1. A method of screening for triptycene derivative (TCD) compounds that stabilize a target nucleic acid three way junction (TWJ) structures comprising:a) providing an array comprising a solid support comprising a plurality of assay locations each comprising a covalently attached different TCD; i) a nucleic acid substrate with an attached fluorophore donor and an attached fluorophore acceptor; and', 'ii) a nucleic acid inhibitor that hybridizes to said substrate to form an inhibitor complex such that said donor and acceptor are separated and FRET does not occur, wherein said contacting is done under conditions wherein one of said TCDs binds to said TWJ such that said inhibitor is released and that FRET occurs; and, 'b) contacting said array with a target TWJ comprisingd) determining the binding of said TCD to said TWJ by detecting the presence or absence of FRET.2. A method of screening for triptycene derivative (TCD) compounds that stabilize a target nucleic acid three way junction (TWJ) structures comprising:a) providing a target nucleic acid substrate with an attached fluorophore donor and an attached fluorophore acceptor, said substrate forming a TWJ such that said donor and acceptor undergo fluorescence resonance energy transfer (FRET);b) contacting said substrate with a nucleic acid inhibitor that hybridizes to said substrate to form an inhibitor complex such that said donor and acceptor are separated and FRET does not occur;c) contacting said inhibited complex with a triptycene derivative (TCD) under conditions wherein said inhibitor is released and said TCD binds to said TWJ such that FRET reoccurs; andd) determining the binding of said TCD to said TWJ by detecting the presence or absence of FRET.3. A method of screening for triptycene derivative (TCD) compounds that stabilize nucleic acid three way junction (TWJ) structures ...

Fluoro-Containing Ether Monomer For Fabricating Contact Lenses, Contact Lenses Materials And Contact Lenses Obtained Therefrom

The invention provides a fluoro-containing ether monomer for fabricating contact lenses represented by following formula (I): 2. The fluoro-containing ether monomer according to claim 1 , wherein the molar ratio of fluorine to carbon in fluorine-containing ether monomer is in the range of 0.032 to 0.88.3. The fluoro-containing ether monomer according to claim 1 , wherein in formula (I) claim 1 , Ris CFH claim 1 , Ris oxygen and Ris CHCH.4. The fluoro-containing ether monomer according to claim 1 , wherein in formula (I) claim 1 , Ris CFH claim 1 , Ris oxygen and Ris CHCH.5. The fluoro-containing ether monomer according to claim 1 , wherein in formula (I) claim 1 , Ris CFH claim 1 , Ris sulfur and Ris CHCH.6. The fluoro-containing ether monomer according to claim 1 , wherein the fluoro-containing ether monomer is present at an amount of 0.07 to 0.4 weight percent based on the total amount of the contact lenses.9. The composition for fabricating contact lenses according to claim 8 , wherein the first siloxane macromer is present at an amount of 30 to 60 parts by weight claim 8 , the second siloxane macromer of is present at an amount of 1 to 15 parts by weight claim 8 , the hydrophilic monomer is present at an amount of 30 to 65 parts by weight claim 8 , the hydrophilic fluorine-containing ether monomer is present at an amount of 0.1 to 0.3 parts by weight claim 8 , and the initiator is present at an amount of 0.1 to 1 parts by weight based on the total amount of the composition.10. A composition for fabricating contact lenses according to claim 7 , wherein the hydrophilic monomer is selected from the group consisting of N-vinylpyrrolidone (NVP) claim 7 , 2-hydroxyethyl methacrylate (HEMA) claim 7 , N claim 7 ,N-dimethylacrylamide (DMA) claim 7 , methyl acrylic acid claim 7 , acrylic acid claim 7 , glycidyl methacrylate (GMA) claim 7 , (methyl)acrylamide claim 7 , 2-(N claim 7 ,N-dimethylamino) ethyl methacrylate (DMAEMA) claim 7 , vinyl acetate claim 7 , 2-( ...

PHOTO-CROSSLINKER

Described herein is a linking agent that includes a polymeric or non-polymeric core molecule and one or more photoreactive groups covalently attached to the core molecule by one or more linking elements that include a urea linkage, a carbamate linkage, or a combination thereof. 1. A medical device comprisinga substrate comprising a substrate surface;a coating layer disposed over the substrate surface, the coating layer comprising a linking agent disposed within the coating in an unbound state; a core molecule; and', 'one or more photoreactive groups covalently attached to the core molecule by one or more linking elements that include a linkage selected from urea, carbamate, or a combination thereof., 'the linking agent comprising'}2. The medical device of claim 1 , the core molecule comprising a non-polymeric core molecule.3. The medical device of claim 2 , wherein the non-polymeric core molecule comprises a hydrocarbon.4. The medical device of claim 2 , wherein the non-polymeric core molecule is selected from a hydrocarbon that is linear claim 2 , branched claim 2 , cyclic claim 2 , or a combination thereof.5. The medical device of claim 2 , wherein the non-polymeric core molecule comprises a linear hydrocarbon.6. The medical device of claim 2 , wherein the non-polymeric core molecule is selected from a hydrocarbon that is aromatic claim 2 , non-aromatic claim 2 , or a combination thereof.7. The medical device of claim 2 , wherein the non-polymeric core molecule is selected from a hydrocarbon that is non-aromatic.8. The medical device of claim 1 , the core molecule comprising a molecular weight of 100 to 1000 Daltons.9. The medical device of claim 1 , wherein the one or more photoreactive groups comprise an aryl ketone.10. The medical device of claim 9 , wherein each aryl ketone is independently selected from acetophenone claim 9 , benzophenone claim 9 , anthraquinone claim 9 , anthrone claim 9 , anthrone-like heterocycles claim 9 , substituted derivatives thereof ...

USE OF ARYL CARBAMATES IN AGRICULTURE AND OTHER PLANT-RELATED AREAS

Disclosure is provided for methods of preventing, removing or inhibiting microbial biofilm formation or microbial infection in a plant or plant part thereof, including applying thereto a treatment effective amount of an aryl carbamate as described herein, or an agriculturally acceptable salt thereof. Methods of enhancing a microbicide (e.g., including a copper, antibiotic, bacteriophage, etc.) and/or plant defense activator are also provided, including applying an active compound as described herein. Compositions comprising an aryl carbamate compound as described herein in an agriculturally acceptable carrier are also provided, and in some embodiments the compositions further include a microbicide (e.g., including copper, antibiotic, bacteriophage, etc.) and/or a plant defense activator.

SOLID FORMS OF AN ADAMANTYL COMPOUND, COMPOSITIONS AND USES THEREOF

Provided herein are crystalline forms of (((((1r, 3R, 5S, 7r)-3, 5-dimethyladamantan-1-yl)carbamoyl) oxy) methyl benzoate (Compound (I)): Also provided are compositions comprising the crystalline forms of Compound (I), processes of manufacture and methods of using the crystalline forms of Compound (I). 2. The crystalline form of Compound (I) according to claim 1 , wherein the crystalline form exists in substantially anhydrous form.3. The crystalline form of Compound (I) according to claim 1 , wherein the crystalline form is crystalline Form I characterized by an X-ray powder diffraction pattern comprising at least one group of peaks expressed as 2θ selected from the groups consisting of: (A) 7.7±0.2° claim 1 , 8.9±0.2° claim 1 , and 10.7±0.2°; (B) 13.1±0.2° claim 1 , 15.4±0.2° claim 1 , and 18.0±0.2°; (C) 21.6±0.2° claim 1 , 22.8±0.2° claim 1 , and 23.9±0.2°; and (D) 25.5±0.2° claim 1 , 26.5±0.2° claim 1 , and 27.0±0.2°.4. The crystalline form of Compound (I) according to claim 1 , wherein the crystalline form is crystalline Form I characterized an X-ray powder diffraction pattern comprising peaks expressed as 2θ at 14.2±0.2° claim 1 , 15.4±0.2° claim 1 , 18.0±0.2° claim 1 , and 18.7±0.2°.5. The crystalline form of Compound (I) according to claim 1 , wherein the crystalline form is crystalline Form I characterized by an X-ray powder diffraction pattern comprising peaks expressed as 2θ at 14.2±0.2° claim 1 , 15.4±0.2° claim 1 , 18.0±0.2° claim 1 , 18.7±0.2° claim 1 , 21.4±0.2° claim 1 , 21.6±0.2° and 22.4±0.2°.6. The crystalline form of Compound (I) according to claim 1 , wherein the crystalline form is crystalline Form I characterized by an X-ray powder diffraction pattern comprising peaks expressed as 2θ at 7.7±0.2° claim 1 , 8.9±0.2° claim 1 , 14.2±0.2° claim 1 , 15.4±0.2° claim 1 , 16.7±0.2° claim 1 , 17.7±0.2° claim 1 , 18.0±0.2° claim 1 , 18.7±0.2° claim 1 , 19.2±0.2° claim 1 , 21.4±0.2° claim 1 , 21.6±0.2° claim 1 , 22.4±0.2° claim 1 , and 22.8±0.2°.7. ( ...

MULTIPLE CYCLOADDITION REACTIONS FOR LABELING OF MOLECULES

The present invention relates to methods for linking tetrazines with dienophiles to establish at least two linkages by sequentially performing at least two cycloaddition reactions. The methods in particular allow establishing multi-labeling strategies. In particular, the invention relates to methods for forming linkages by cycloaddition reactions, wherein the method comprises reacting a first alkyl-substituted tetrazine with a first dienophile comprising a irans-cyclooctenyl group followed by reacting a second tetrazine with a second dienophile comprising a cyclooctynyl group, wherein the reaction of the first tetrazine with the first dienophile proceeds in the presence of the second dienophile. 2. The method of claim 1 , wherein the first tetrazine preferentially reacts with the first dienophile in the presence of the second dienophile.3. The method of claim 1 , wherein the rate constant k of the first tetrazine with the first dienophile is usually at least 10-times higher than the rate constant k of the reaction of the first tetrazine with the second dienophile.4. The method of claim 1 , wherein the rate constant k of the first tetrazine with the first dienophile is allowed to proceed for 30 minutes or less at a temperature of about 37° C.7. The method of claim 1 , wherein the first dienophile or the target molecule or target molecule composition is reacted with the first tetrazine or labeling agent under conditions that allow for substantially all trans-cyclooctenyl groups to react prior to reacting the second dienophile or the target molecule or target molecule composition with the second tetrazine or labeling agent.9. The cell of claim 8 , wherein the cyclooctynyl group is attached to a first polypeptide and the trans-cyclooctenyl group is attached to a second polypeptide claim 8 , the first and the second polypeptide being different polypeptides. The invention relates to methods for linking tetrazines with dienophiles to establish at least two linkages by ...

Process for preparing the anti-tumor agent 6-(7-((1-aminocyclopropyl)methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide and its crystalline

The present invention relates a new process to synthesize 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (AL3810) by deprotection of substituted benzyl 1-((6-methoxy-4-(5-(methylcarbamoyl)naphthalen-2-yloxy)quinolin-7-yloxy)-methyl)cyc-lopropylcarbamate (Formula I) under a diluted or weak acidic condition. A stable crystalline form of 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide has also been prepared. 8. A method of preparing a compound having Formula II of comprising to react formula 17 with 4-methoxybenzylalcohol in a refluxing toluene condition.15. A crystalline form of 6-(7-((1-aminocyclopropyl)methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide exhibiting at least one ofa melting point at 185° C.-205° C.;a no observable endotherm DSC from about 40° C. to about 185° C.;an observable endotherm DSC from about 185° C. to about 210° C.;a TGA themogram that doesn't exhibit significant weight loss until at 210° C. to 250° C.;a XRPD graph having 20-40 characteristic peaks.18. A crystalline form of 6-(7-((1-aminocyclopropyl)methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide according is recrystallized from isopropanol. This application claims the benefit of U.S. Provisional Applications 61/754,516 filed on Jan. 18, 2013The present invention relates a new process to synthesize 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (AL3810) by deprotection of substituted benzyl 1-((6-methoxy-4-(5-(methylcarbamoyl)naphthalen-2-yloxy)quinolin-7-yloxy)-methyl)cyclopropylcarbamate (Formula I) under a diluted or weak acidic condition. A stable crystalline form of 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide has also been prepared.6-(7-((1-Aminocyclopropyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (AL3810), or a pharmaceutically acceptable salt (such as hydrochloride salt) thereof, has been ...

Naphthyl acrylates as writing monomers for photopolymers

The invention relates to naphthyl urethane acrylates particularly useful as writing monomers in photopolymer formulations for holographic media. The invention further relates to a photopolymer formulation comprising matrix polymers, writing monomers and photoinitiators, wherein the writing monomers comprise a naphthyl urethane acrylate according to the invention, to a holographic medium comprising matrix polymers, writing monomers and photoinitiators, wherein the writing monomers comprise a naphthyl urethane acrylate according to the invention, and also to a display comprising a holographic medium according to the invention.

PRODRUGS OF GAMMA-HYDROXYBUTYRIC ACID, COMPOSITIONS AND USES THEREOF

Provided are prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof. 3. The compound of claim 2 , wherein Ris hydrogen or Calkyl.4. The compound of claim 2 , wherein at least one of Rand Ris hydrogen or Calkyl.5. The compound of claim 4 , wherein both Rand Rare hydrogen or Calkyl.6. The compound of claim 2 , wherein Ris hydrogen or Calkyl and Ris —COR claim 2 , and Ris Calkyl claim 2 , Calkoxyl claim 2 , or Ccycloalkyloxyl.7. The compound of claim 2 , wherein when Ror Ris an amino protecting group claim 2 , Ris not isopropyl or benzyl.15. The compound of claim 14 , wherein R claim 14 , R claim 14 , Rare all hydrogen claim 14 , and Rand Rare independently hydrogen claim 14 , halogen claim 14 , Calkyl claim 14 , Calkoxy claim 14 , cyano claim 14 , Calkylsulfonyl claim 14 , Calkylcarbonyloxyl claim 14 , Calkyloxycarbonyl claim 14 , or mono- claim 14 , di- or tri-halo-Calkyl.16. The compound of claim 14 , wherein one of Rand Ris hydrogen.21. The compound of claim 1 , wherein B is:{'sub': 1-8', '2-6, 'Calkyl substituted with Calkyl, aryl or amino group and B is not linear alkyl; or'}{'sub': 2-6', '1-6, 'Calkenyl substituted with Calkyl, aryl or amino group; or'}{'sub': 3-8', '1-6, 'substituted or unsubstituted Ccycloalkyl, wherein the substituent is selected from the group consisting of halogen, hydroxyl, Calkyl; or'}{'sub': '1-6', 'substituted or unsubstituted 3-8 membered heterocyclic alkyl, wherein the substituent is selected from the group consisting of halogen, hydroxyl, Calkyl; or'}{'sub': '1-6', 'substituted or unsubstituted 5-8 membered heterocyclic aryl, wherein the substituent is selected from the group consisting of halogen, hydroxyl, Calkyl.'}22. The compound of claim 21 , wherein B is —CHRR claim 21 , wherein Rand Rare independently selected from the group consisting of Calkyl claim 21 , aryl and amino group claim 21 ,{'sup': 13', '14, 'wherein Rand Rcannot be methyl at the same time,'}{'sup': 13', '14', '13', '14, 'sub': '3-8', ' ...

Compositions and methods of the use thereof achiral analogues of CC-1065 and the duocarmycins

The present invention relates to novel achiral seco-analogues of the DNA minor groove and sequence-selective alkylating agents (+)-CC1065 and the duocarmycins, depicted as general class I, II III, IV and V: wherein X is a good leaving group, such as a chloride, a bromide, an iodide, a mesylate, a tosylate, an acetate, a quaternary ammonium moiety, a mercaptan, an alkylsulfoxyl, or an alkylsulfonyl group, preferably either a chloride, a bromide, or an iodide group. R 1 is a suitable minor groove binding agent to enhance the interactions of the achiral seco-cyclopropaneindole (CI) or an achiral seco-duocarmycin with specific sequences of DNA. Examples of the DNA binders are given in Table 4. The preferred DNA binders are groups A, C, D, E, F, G. H and I. R 1 can also include the following: t-butoxy, benzyloxy, 9-fluorenylmethyloxy or other common protecting groups for amines wherein X is a good leaving group, such as a chloride, a bromide, an iodide, a mesylate, a tosylate, an acetate, a quaternary ammonium moiety, a mercaptan, an alkylsulfoxyl, or an alkylsulfonyl group, preferably either a chloride, a bromide, or an iodide group. R 1 is a suitable minor groove binding agent to enhance the interactions of the covalently reactive achiral seco-pharmacophore with specific sequences of DNA. Examples of the DNA binders are given in Table 4. The preferred DNA binders are groups A, C, D, E, F, G, H, I, J, K and L. R 2 and R 3 can be hydrogen or short chain alkyl (C1-C5) groups, preferably both being hydrogen atoms. The alkyl groups may be straight chain or branched and include such groups as ethyl, propyl, butyl, pentyl and hexyl. R 4 and R 5 can be hydrogen atoms, short alkyl groups, trifluoromethyl moieties, and alkyloxycarbonyl groups. The preferred R 4 and R 5 groups are methoxycarbonyl and trifluoromethyl. R can be either a benzyl, a benzyloxycarbonyl, a hydrogen atom, a 4-nitrobenzyloxycarbonyl, or a N′-methylpiperazinyl-N-carbonyl group wherein X is a good leaving ...

Compositions and methods of the use thereof achiral analogues of CC-1065 and the duocarmycins

The present invention relates to novel achiral seco-analogues of DNA minor groove and sequence-selective alkylating agents (+)-CC1065 and the duocarmycins, depicted as general class I, II, III, IV and V: wherein X is a good leaving group, such as a chloride, a bromide, an iodide, a mesylate, a tosylate, an acetate, a quaternary ammonium moiety, a mercaptan, an alkylsulfoxyl, or an alkylsulfonyl group, preferably either a chloride, a bromide, or an iodide group. R 1 is a suitable minor groove binding agent to enhance the interactions of the achiral seco-cyclopropaneindole (Cl) or an achiral seco-duocarmycin with specific sequences of DNA.

Compositions and methods of the use thereof achiral analogues of cc-1065 and the duocarmycins

The present invention relates to novel achiral seco-analogues of the DNA minor groove and sequence-selective alkylating agents (+)-CC1065 and the duocarmycins, depicted as general class (I), (II), (III), (IV) and (V) wherein X is a good leaving group, such as chloride, a bromide, an iodide, a mesylate, a tosylate, an acetate, a quaternary ammonium moiety, a mercaptan, an alkylsulfoxyl, or an alkylsulfonyl group, preferably either a chloride, a bromide, or an iodide group. R1 is a suitable minor groove binding agent to enhance the interactions of the achiral seco-cyclopropaneindole (CI) or an achiral seco-duocarmycin with specific sequences of DNA. R and R2-R5 are defined in claim 1.

Hydrolytic enzyme-activatible pro-drugs

Antineoplastic agents are rendered tumor-specific by derivatization with a peptide specifier so as to convert the antineoplastic agent into a pharmacologically inactive pro-drug which is selectively activatible at the tumor site. The peptide specifier has an amino acid residue sequence such that it will be selectively enzymatically cleaved from the antineoplastic agent by tumor-associated fibrinolytic and/or blood-coagulating proteases, such as plasmin and plasminogen activator, so as to effect release of the antineoplastic agent in pharmacologically active form in the vicinity of the tumor. These and other similar hydrolytic enzyme-activatible pro-drugs may be formed with their specifier moiety and their drug moiety covalently linked together through an intermediate self-immolative connector moiety having a molecular structure such that enzymatic cleavage of the bond covalently linking it to the specifier moiety will initiate spontaneous cleavage of the bond covalently linking it to the drug moiety to thereby effect release of the drug in pharmacologically active form.

Compositions and methods of the use thereof achiral analogues of cc-1065 and the duocarmycins

The present invention relates to novel achiral seco-analogues of the DNA minor groove and sequence-selective alkylating agents (+)-CC1065 and the duocarmycins, depicted as general class (I), (II), (III), (IV) and (V) wherein X is a good leaving group, such as chloride, a bromide, an iodide, a mesylate, a tosylate, an acetate, a quaternary ammonium moiety, a mercaptan, an alkylsulfoxyl, or an alkylsulfonyl group, preferably either a chloride, a bromide, or an iodide group. R1 is a suitable minor groove binding agent to enhance the interactions of the achiral seco-cyclopropaneindole (CI) or an achiral seco-duocarmycin with specific sequences of DNA. R and R2-R5 are defined in claim 1.

Cc－1065和多卡米新的非手性类似物的组合物及其使用方法

本发明涉及新的 DNA小沟和序列选择性烷化剂(+)-CC1065和多卡米新的非手性seco-类似物，如通式(I)、(II)、(III)、(IV)和(V)所示，其中X为良好的离去基团，如氯化物、溴化物、碘化物、甲磷酸酯、甲苯磺酸酯、乙酸酯、季铵部分、硫醇、烷基次硫酸基或烷基磺酰基，优选为氯化物、溴化物或碘化物基团，R 1 为增强非手性seco-环丙烷吲哚(CI)或非手性seco-多卡米新与特定的DNA序列的相互作用的适宜的小沟结合剂，R和R 2 -R 5 在权利要求1中定义。

A practical synthesis of benzoxazinones useful as hiv reverse transcriptase inhibitors

The present invention describes novel methods for the synthesis of benzoxazinone compounds which are useful as human immunodeficiency virus (HIV) reverse transcriptase inhibitors. The benzoxazinone of formula (VI-a) is particularly effective in the treatment of HIV.

间二取代苯酚化合物及其制备方法与抗结核菌应用

本发明提供了一类通式为(Ⅰ)的间二取代苯酚化合物、其制备方法与应用。所述的间二取代苯酚化合物具有新的抗结核菌药母核结构和优秀的抗结核菌活性，特别是对耐药的变异结核菌株也具有很强的抑制活性。本发明还提供了所述的间二取代苯酚化合物的制备方法，该制备方法的原料廉价易得，无需使用高毒性和高污染试剂，反应步骤简单，可实现工业化生产；具有良好的药用前景。

High refractive oligomer, resin composition for prism sheet containing the same and prism sheet using the same

본 발명은 고굴절 올리고머, 그를 함유한 프리즘 시트성형용 레진 조성물 및 그를 이용한 프리즘 시트에 관한 것이다. 본 발명은 양 말단에 아크릴 관능기를 포함하고 분자 구조 내 우레탄 관능기가 적어도 2개 이상 포함하고, 굴절률 1.61 이상을 충족하는 저점도 및 저황변 타입의 고굴절 올리고머를 제공하며, 상기 고굴절 올리고머를 함유하거나, 상기 고굴절 올리고머와 고굴절 모노머간의 배합비율을 최적화한 프리즘 시트성형용 레진 조성물을 통해, 경화전 액상의 고굴절률과 저점도를 구현하고, 투명성과 내황변성의 양호할 뿐 아니라, 경화 후 우수한 접착력과 연필경도를 충족하여 프리즘 시트를 제공할 수 있다. 이에, 본 발명의 프리즘 시트는 동일 휘도를 구현하기 위해 적용되는 시트의 개수를 줄여 슬림화 및 성능의 향상과 원가 절감에 기여함으로써, 백라이트 유닛에 사용되는 LED 램프의 개수를 줄일 수 있으므로 에너지 절감 효과를 제공한다. The present invention relates to a high refractive index oligomer, a resin composition for molding a prism sheet containing the same and a prism sheet using the same. The present invention provides a high-refractive-index oligomer having a low viscosity and a low yellowing type which contains acrylic functional groups at both ends and contains at least two urethane functional groups in the molecular structure and satisfies a refractive index of 1.61 or more, It is possible to realize a high refractive index and a low viscosity in a liquid phase before curing by means of a resin composition for forming a prism sheet by optimizing a blending ratio between the high refractive index oligomer and a high refractive index monomer and to provide a resin composition which is excellent in transparency and vulcanization resistance, It is possible to provide a prism sheet satisfying the hardness. Accordingly, the prism sheet of the present invention can reduce the number of sheets to be applied for realizing the same luminance, thereby contributing to slimness, improvement in performance, and cost reduction. Thus, the number of LED lamps used in the backlight unit can be reduced, to provide.

Lysine-glutamic acid dipeptide derivatives

FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula I, as well as their enantiomers, diastereomers and salts, which can be used in the solid-phase synthesis of peptides. In formula I, Ris C-alkyl, Ris hydrogen or C-alkenyl, Ris 9H-fluoren-9-ylmethoxycarbonyl (Fmoc) and Ris C-alkyl. The invention also relates to application of formula I compounds in the solid-phase synthesis of peptides that contain a block of glutamic acid (Glu)-fatty alkyl in the side chain attached to the lysine residue (Lys) of the peptide chain.EFFECT: effective treatment.9 cl, 5 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 640 812 C2 (51) МПК C07C 271/22 (2006.01) C07C 269/06 (2006.01) C07K 5/072 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07C 271/22 (2006.01); C07C 269/06 (2006.01) (21)(22) Заявка: 2014148530, 13.05.2013 (24) Дата начала отсчета срока действия патента: (73) Патентообладатель(и): Ф. ХОФФМАНН-ЛЯ РОШ АГ (CH) Дата регистрации: 12.01.2018 R U 13.05.2013 (72) Автор(ы): ПЮНТЕНЕР Курт (CH) (56) Список документов, цитированных в отчете о поиске: JP 2006-233405 A, 07.09.2006. JP 2008-290987 A, 04.12.2008. JP 2009-4590 A, 08.01.2009. US 2006/258580 A1, 16.11.2006. RU 2439075 C2, 10.01.2012. 15.05.2012 EP 12168119.1 (43) Дата публикации заявки: 10.07.2016 Бюл. № 19 (45) Опубликовано: 12.01.2018 Бюл. № 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 15.12.2014 2 6 4 0 8 1 2 Приоритет(ы): (30) Конвенционный приоритет: EP 2013/059759 (13.05.2013) C 2 C 2 (86) Заявка PCT: (87) Публикация заявки PCT: R U 2 6 4 0 8 1 2 WO 2013/171135 (21.11.2013) Адрес для переписки: 197101, Санкт-Петербург, а/я 128, "АРСПАТЕНТ", М.В. Хмара (54) ПРОИЗВОДНЫЕ ДИПЕПТИДА ЛИЗИН-ГЛУТАМИНОВАЯ КИСЛОТА (57) Реферат: Изобретение относится к соединениям твердофазном синтезе пептидов, которые формулы I, а также их энантиомерам, содержат структурный блок глутаминовая диастереомерам и солям, которые могут найти кислота (Glu ...

우레탄기를 함유하는 (메트)아클릴레이트

우레탄기 및 동일한 한 분자내에 기타 종합성기도 포함하는 신규(메트)아크릴레이트는 자유 라디칼 및/또는 양이온적으로 중합될 수 있으며 피복물, 접착제, 포토레지스트, 땜납 마스크 제조용으로 또는 스테레오리소그래피에서 사용될 수 있다. 이로부터 제조된 성형물은 응집성의 균일한 망상구조를 가지며 고도의 강도 특성, 특히 기계적 특성을 갖는다.

(Meth) acrylate containing urethane group

우레탄기 및 동일한 한 분자내에 기타 중합성기도 포함하는 신규(매트)아크릴 레이트는 자유 라디칼 및/또는 양이온적으로 중합될 수 있으며 피복물, 접착제, 포토레지스트, 땜납 마스크 제조용으로 또는 스테레오리소그래피에서 사용될 수 있다. 이로부터 제조된 성형물은 응집성의 균일한 망상구조를 가지며 고도의 강도 특성, 특히 기계적 특성을 갖는다. The novel (mat) acrylates comprising urethane groups and other polymerizable groups in the same molecule can be free radically and / or cationicly polymerized and can be used for the preparation of coatings, adhesives, photoresists, solder masks or in stereolithography. . The moldings produced therefrom have a coherent uniform network structure and have high strength properties, in particular mechanical properties.

Phenyl isocyanate-based urethane acrylates, processes for producing and methods of using the same

Urethane acrylates of the general Formula (I), corresponding salts, solvates or solvates of a salt thereof: wherein R 1 , R 2 , R 3 , R 4 and R 5 each independently represent a substituent selected from the group consisting of hydrogen, halogens, C 1-6 -alkyls, trifluoromethyl, C 1-6 -alkylthios, C 1-6 -alkylselenos, C 1-6 -alkyltelluros, and nitro groups, with the proviso that at least one of R 1 , R 2 , R 3 , R 4 and R 5 is not hydrogen; R 6 and R 7 each independently represent a substituent selected from the group consisting of hydrogen and C 1-6 -alkyls; and A represents a saturated or unsaturated or linear or branched C 1-6 -alkyl radical or a polyalkylene oxide radical having 2-6 ethylene oxide or propylene oxide units; processes for producing and methods of using the same.

Phenylisocyanate based urethanacrylates with high refraction index

An urethane acrylate compound, or its corresponding salt, solvate or a solvate of a salt, is new. An urethane acrylate compound of formula (I), or its corresponding salt, solvate or a solvate of a salt, is new. R 1-R 5 : H, halo, 1-6C alkyls, trifluoromethyl, 1-6C alkylthios, 1-6C alkylselenos, 1-6C alkyltelluros or nitro; R 6 and R 7 : H or 1-6C alkyl;and A : optionally saturated or linear or branched 1-6C alkyl radical or a polyalkylene oxide radical having 2-6 ethylene oxide or propylene oxide units. Provided that least one of R 1-R 5 is not H. Independent claims are included for the following: (1) preparation of the urethane acrylates (I); (2) a process (P1) involving: providing a polymer matrix comprising the urethane acrylate (I); and subjecting the polymer matrix to electromagnetic radiation such that the urethane acrylate is selectively polymerized; and (3) a holographic optical element/image prepared by the process (P1). [Image].

Phenyl isocyanate-based urethane acrylates, processes for producing and methods of using the same

Urethane acrylates of the general Formula (I), corresponding salts, solvates or solvates of a salt thereof: wherein R 1 , R 2 , R 3 , R 4 and R 5 each independently represent a substituent selected from the group consisting of hydrogen, halogens, C 1-6 -alkyls, trifluoromethyl, C 1-6 -alkylthios, C 1-6 -alkylselenos, C 1-6 -alkyltelluros, and nitro groups, with the proviso that at least one of R 1 , R 2 , R 3 , R 4 and R 5 is not hydrogen; R 6 and R 7 each independently represent a substituent selected from the group consisting of hydrogen and C 1-6 -alkyls; and A represents a saturated or unsaturated or linear or branched C 1-6 -alkyl radical or a polyalkylene oxide radical having 2-6 ethylene oxide or propylene oxide units; processes for producing and methods of using the same.

Phenylisocyanate based urethanacrylate with high refraction index

An urethane acrylate compound, or its corresponding salt, solvate or a solvate of a salt, is new. An urethane acrylate compound of formula (I), or its corresponding salt, solvate or a solvate of a salt, is new. R 1-R 5 : H, halo, 1-6C alkyls, trifluoromethyl, 1-6C alkylthios, 1-6C alkylselenos, 1-6C alkyltelluros or nitro; R 6 and R 7 : H or 1-6C alkyl;and A : optionally saturated or linear or branched 1-6C alkyl radical or a polyalkylene oxide radical having 2-6 ethylene oxide or propylene oxide units. Provided that least one of R 1-R 5 is not H. Independent claims are included for the following: (1) preparation of the urethane acrylates (I); (2) a process (P1) involving: providing a polymer matrix comprising the urethane acrylate (I); and subjecting the polymer matrix to electromagnetic radiation such that the urethane acrylate is selectively polymerized; and (3) a holographic optical element/image prepared by the process (P1). [Image].

Phenylisocyanate based urethane acrylates with high refraction index

Amino acid amide derivative, agrohorticultural bactericide, and production process

本发明提供了包括有效量的式[I]代表的氨基酸酰胺衍生物的农业或园艺杀真菌剂。本发明的杀真菌剂是无害的化学品，且具有优良的内吸作用、残留活性和雨后存留等特性。 式中R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、Z 1 、Z 2 、Z 3 、Q、m和n的定义同说明书中定义。

リシン−グルタミン酸ジペプチド誘導体

Anthraquinone derivative monomer and polymer for volume Bragg grating

本公开提供了用于体布拉格光栅中的包含蒽醌衍生单体和聚合物的记录材料，所述体布拉格光栅包括但不限于用于全息术应用的体布拉格光栅。公开了用于布拉格光栅应用中的蒽醌衍生单体和聚合物的若干结构，从而产生具有更高折射率、低双折射和高透明度的材料。所公开的蒽醌衍生单体及其聚合物可用于任何体布拉格光栅材料中，包括两级聚合物材料，其中在第一步中固化基质，然后通过第二单体固化步骤写入体布拉格光栅。

Vinyl ether compounds having additional functional groups other than vinyl ether groups and the use thereof in the formulation of curable compositions

The invention relates to compounds having at least one vinyl ether group which also contain in the molecule at least one further functional group selected from acrylate, methacrylate, epoxy, alkenyl, cycloalkenyl and vinylaryl groups, to compositions, especially for stereolithography, comprising those vinyl ether compounds, and to a method of producing three-dimensional objects using those compositions.

HCV CRYSTAL FORMS OF PROTEASIC INHIBITOR

1. Соединение A, имеющее форму, выбранную из группы, состоящей из:a) гидрата III, где гидрат III характеризуется или (i) порошковой рентгеновской дифрактограммой, полученной, применяя медь Kизлучение, которая содержит 2θ величины в градусах приблизительно 20,5, 5,0 и 18,2; или (ii) твердофазным углерод-13 CPMAS ЯМР, содержащим пики при приблизительно 5,14, 6,31, 12,49, 18,35, 26,81, 28,03, 30,33, 31,27, 34,95, 35,99, 38,68, 42,01, 54,93, 56,39, 60,14, 74,20, 107,02, 120,11, 121,60, 129,73, 134,35, 135,95, 142,89, 148,47, 155,37, 157,32, 160,90, 168,32, 172,17 и 175,53 м.д.;b) гидрата II, где гидрат II характеризуется порошковой рентгеновской дифрактограммой, полученной, применяя медь Kизлучение, которая содержит 2θ величины в градусах приблизительно 11,7, 16,6 и 11,2;c) кристаллической Na соли, характеризующейся порошковой рентгеновской дифрактограммой, полученной, применяя медь Kизлучение, которая содержит 2θ величины в градусах приблизительно 18,4, 9,1 и 9,8;d) кристаллической K соли, характеризующейся порошковой рентгеновской дифрактограммой, полученной, применяя медь Kизлучение, которая содержит 2θ величины в градусах приблизительно 18,2, 8,9 и 20,3;e) гидрата I, где гидрат I характеризуется или (i) порошковой рентгеновской дифрактограммой, полученной, применяя медь Kизлучение, которая содержит 2θ величины в градусах приблизительно 8,6, 20,6 и 26,6; или (ii) твердофазным углерод-13 CPMAS ЯМР, содержащим пики при приблизительно 4,22, 7,23, 11,45, 17,79, 24,04, 26,95, 28,29, 31,15, 32,47, 32,47, 33,46, 34,03, 35,74, 42,32, 53,50, 56,05, 56,96, 77,49, 108,95, 119,65, 122,55, 131,05, 133,13, 135,38, 142,28, 150,78, 156,03, 157,99, 161,36, 171,40, 173,42, 174,30 м.д.;f) гидрата IV, где гидрат IV характеризуется или (i) порошковой рентгеновской дифрактограммой, полученной, применяя медь Kизлучение, которая содержит 2θ величины в градусах приблизительно 14,7, 11,5 и 7,1; или (ii) твердо� РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2014 110 399 A (51) МПК A61K 38/12 (2006.01 ...

Writing monomer and preparation method thereof, and photopolymer composition and grating thereof

本发明涉及一种书写单体及其制备方法以及光致聚合物组合物及其光栅。书写单体为含有芴基的氨基甲酸酯丙烯酸酯单体，其具有如下通式结构：Fl‑[Ar‑NH‑C(O)‑O‑R 0 ‑O‑C(O)‑C(R 1 )＝C(R 2 ) 2 ] m ；其中，Fl表示可以被苯基、C1～C6的烷基或烷氧基、或卤素取代的芴基，苯基、烷基或烷氧基可以被卤素任意取代；Ar表示可以被苯基、C1～C6的烷基或烷氧基或卤素取代的苯基、联苯基或萘基，苯基、烷基或烷氧基可以被卤素任意取代；当存在多个Ar时，它们之间可以键合；R 0 表示碳原子数为1～10的直链或支链的烷基，R 0 可以进行取代或没有取代；m表示1或2的整数；R 1 为H或CH 3 ；R 2 每次出现时相同或不同，独立地表示氢或卤原子。

Fluorene derived monomers and polymers for volume bragg gratings

本公开内容提供了用于体布拉格光栅的包括芴衍生的单体和聚合物的记录材料，所述体布拉格光栅包括但不限于用于全息术应用的体布拉格光栅。公开了若干种芴结构：简单取代的芴、cardo芴和螺芴。芴衍生的聚合物在布拉格光栅应用中导致材料具有较高的折射率、低的双折射率和高透明度。芴衍生的单体/聚合物可以用于任何体布拉格光栅材料，包括两级聚合物材料，其中在第一步骤中固化基质，并且然后通过单体的第二固化步骤写入体布拉格光栅。

Cure accelerators for anaerobic curable compositions

The present invention provides a compound represented by the formula (III), a reaction product of a compound of the formula (III) with an isocyanate, a use of the compound and a reaction product as an anaerobic curing accelerator, a process for their preparation and a composition comprising the compound : (III) Wherein X, R 1 , R 2 and R 4 are as defined above.

Amino acid amide derivatives, method of preparing fungicidal composition for agriculture or horticulture

FIELD: agriculture. SUBSTANCE: present invention describes amino acid amide derivatives of formula I: ЭзЕзстс ПЧ Го (19) РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ ВИ” 2128 186 ' (51) МПК 13) СЛ С 07К 5/00, 5/103, 1/107, А 01 М 37/46, 47/12, 47/24 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 94046335/04, 21.04.1994 (30) Приоритет: 28.04.1993 УР 5-125455 (46) Дата публикации: 27.03.1999 (56) Ссылки: ЗИ 1836381 АЗ, 1989. КЦ 2043025 СЛ, 1989. 4$ 4284628 А, 1981. СВ 2096897 А, 1982. СВ 2106389 А, 1983. ЕР 0398072 АР, 1992. ЕР 0493683 АЛ, 1992. ЕР 0502718 А, 1992. 4Р 01301657 А, 1989. Шредер Э., Любке К. Пептиды. - М.: М ир, 1967, ч.1, с. 116. Шевченко Л.И. и др. Физиологически активные вещества. - Киев: 1985, М 17, с.55 - 57. (85) Дата перевода заявки РСТ на национальную фазу: 27.12.94 (86) Заявка РСТ: УР 9400708 (27.04.94) (87) Публикация РСТ: М/О 94/25432 (10.11.94) (98) Адрес для переписки: 103735, Москва, ул.Ильинка, 5/2, Союзпатент (71) Заявитель: Кумиай Кемикал Индастри Ко., Лтд. (Р), Ихара Кемикал Индастри Ко., Лтд. (УР) (72) Изобретатель: Масару Сибата (/Р), Казухико Сугияма (.Р), Норихиса Енекура (УР), Дзунетсу Сакаи (/Р), Есиюки Кодзима (УР), Сигеру Хаяси (Р) (73) Патентообладатель: Кумиай Кемикал Индастри Ко., Лтд. (Р), Ихара Кемикал Индастри Ко., Лтд. (4Р) (54) ПРОИЗВОДНЫЕ АМИДОВ АМИНОКИСЛОТ, СПОСОБ ПОЛУЧЕНИЯ, ФУНГИЦИДНАЯ КОМПОЗИЦИЯ ДЛЯ СЕЛЬСКОГО ХОЗЯЙСТВА И САДОВОДСТВА (57) Реферат: Производное амида аминокислоты формулы |, 2. 3 _5 т 2; о в = Е гаи | | з | в 2 е-мн-сн-с-мн-с-сс> 7 -6С> = ст» м п г. Га Ц: Ц: Е Е Е Е в которой радикалы принимают значения, указанные в п. 1 формулы изобретения, проявляют широкий спектр противогрибковой активности, особенно против — Ложной мучнистой росы огурцов, против ложной мучнистой росы винограда и фитофтороза томата. 4 с. и 7 з.п. ф-лы, 20 табл. 2128186 С1 КО ЭзЕзстс ПЧ Го (19) КУЗЗАМ АСЕМСУ ГОК РАТЕМТ$ АМО ТКАОЕМАКК$ 12) АВЗТКАСТ ОЕ 1МУЕМТОМ ВИ” 2128 186 ' (51) 1пЕ. С1.6 13) СЛ 01 М ...

Functional photoinitiators and their manufacture

Lefamulin intermediate compound and application thereof in preparation of Lefamulin

本发明公开了一种Lefamulin的中间体化合物及其在Lefamulin制备中的应用，以期解决现有技术中Lefamulin制备成本高、收率低的技术问题。本发明提供一种中间体化合物 及其制备方法，并将上述中间体化合物在制备Lefamulin或Lefamulin相关的医药中间体中的应用。本发明克服了现有技术的生产过程中碰到的手性氧化缺乏手性诱导，造成目标化合物转化率非常低、成本非常高、工业化生产困难的缺陷；工业化应用时能够有效降低生产成本，且可以有效控制三废的产生，具有显著的经济效益和社会效益。

Process for the preparation of 2-fluorocyclopropylamine and new cyclopropylamine derivatives

Functionalized photoinitiators, macromers thereof, and the use thereof

Compounds of formula I: ##STR1## are disclosed. The compounds are photoinitiators which can be functionalized by means of ethylenic groups or can be bonded to H-active substances, in order, for example, to modify surfaces by means of photopolymerizable substances. The compounds are especially useful in the manufacture of contact lenses.

Functionalized photoinitiators, macromers thereof, and the use thereof

Compounds of formula I: ##STR1## are disclosed. The compounds are photoinitiators which can be functionalized by means of ethylenic groups or can be bonded to H-active substances, in order, for example, to modify surfaces by means of photopolymerizable substances. The compounds are especially useful in the manufacture of contact lenses.

Functionalized photoinitiators, macromers thereof, and the use thereof for contact lens

Contact lenses formed from compounds of formula I: ##STR1## are disclosed. The compounds are photoinitiators which can be functionalized by means of ethylenic groups or can be bonded to H-active substances, in order, for example, to modify surfaces by means of photopolymerizable substances. The compounds are especially useful in the manufacture of contact lenses.

Amino-benzocycloalkane derivatives

Compounds of the formula I wherein R 2 —C, R 3 —C, R 4 —C or R 5 —C may be replaced by N; and wherein n is 1, 2 or 3; R 1 is aryl, cycloalkyl or heterocyclyl; R 2 , R 3 , R 4 and R 5 are independently hydrogen, optionally substituted alkyl, halo, amino, substituted amino, trifluoromethyl, cyano, carboxyl, alkoxycarbonyl, aralkoxycarbonyl, (alkyl, aryl or aralkyl)-thio, (alkyl, aryl or aralkyl)-oxy, acyloxy, (alkyl, aryl or aralkyl)-aminocarbonyloxy; or any two of R 2 , R 3 , R 4 and R 5 at adjacent positions are alkylenedioxy; R 6 is hydrogen, optionally substituted alkyl, amino, substituted amino, acylamino, wherein R a is hydrogen or optionally substituted alkyl, R b and R c are independently hydrogen, optionally substituted alkyl, cycloalkyl, aryl or heterocyclyl; or R b and R c together represent lower alkylene or lower alkylene interrupted by O, S, or N—(H, alkyl or aralkyl); R d is optionally substituted alkyl, cycloalkyl, aryl or heterocyclyl; and R e is optionally substituted alkyl, aryl, heterocyclyl, cycloalkyl, amino or substituted amino; and pharmaceutically acceptable salts thereof; and enantiomers thereof; which are useful as inhibitors of microsomal triglyceride transfer protein (MTP) and of apolipoprotein B (ApoB) secretion.

Compositions containing and methods of using N-acyl-1H-aminoindenes

The present invention provides novel aminoindenes having the structure:wherein n is 1 or 2, R<1 >is hydrogen, linear or branched chain C1-C8 alkyl or linear or branched chain C1-C8 alkoxy and R<2 >is hydrogen or a halogen. Such compounds may be used to treat neurodegenerative conditions such as Alzheimer's disease, head trauma, stroke, hypoxia, anoxia, epilepsy, convulsions, seizures.