Novel Compounds, Pharmaceutical Compositions Containing Same, Methods of Use for Same, and Methods for Preparing Same

The present invention relates to novel pharmaceutical compositions containing the same, and methods of use for a variety of therapeutically valuable uses including, but not limited to, treating obesity by inhibiting the activity of Glycerol 3-phosphate acyltransferase (GPAT).

NOVEL SPECIFIC CASPASE-10 INHIBITORS

The invention relates to compounds of the general formula (I) wherein R1, R2, R3, R4, R5, R6, i and j have the meanings given in claim 1, and to the use thereof as caspase-10 inhibitors, especially for the treatment of diabetic retinopathy. 128.-. (canceled)301. A method according to Claim , in which R1 represents a phenyl group optionally substituted by one or more groups , which may be identical or different , chosen from a halogen atom and an -alkyl , —O-alkyl , —CO-alkyl , —NO , —O-perhaloalkyl , —S(O)-alkyl or -perhaloalkyl group , or two substituents together form a phenyl or pyridyl group fused to the phenyl nucleus to which they are attached; or R1 represents a cycloalkyl , heteroaryl or alkyl group.311. A method according to Claim , in which R1 represents a phenyl group substituted by at least one halogen atom.321. A method according to Claim , in which R2 and R3 together form a cycloalkyl group , optionally substituted by one or more alkyl groups; or R2 and R3 together form a heterocyclyl group.331. A method according to Claim , in which R5 represents a hydrogen atom or an alkyl group , optionally substituted by one or more cycloalkyl groups.341. A method according to Claim , in which R and R′ , which may be identical or different , independently represent a hydrogen atom or an alkyl group.351. A method according to Claim , in which i=2.361. A method according to Claim , in which j=0.371. A method according to Claim , in which the group —(CH)R4 is in the para position.391. A method according to Claim , wherein the compound is administered to a newly diagnosed diabetic patient and/or a patient suffering from early retinopathy and which comprises specifically inhibiting caspase-10 in the patient.4140. A compound of the formula (I) according to Claim , for which R1 represents a phenyl group optionally substituted by one or more groups , which may be identical or different , chosen from a halogen atom and an -alkyl , —O-alkyl , —CO-alkyl , —NO , —S(O)-alkyl , ...

Use of Compounds for Inducing Differentiation of Mesenchymal Stem Cells to Chondrocytes

Use of a compound of Formula 1 for inducing differentiation of mesenchymal stem cells to chondrocytes, and a pharmaceutical composition for treating a cartilage disease, which includes chondrocytes in which differentiation from mesenchymal stem cells is induced by the compound of Formula 1, are provided. Differentiation of the mesenchymal stem cells treated with the compound of Formula 1 to chondrocytes is specifically induced, and thus the compound can be used to effectively treat a cartilage disease such as arthritis, cartilage damage, and a cartilage defect. 2. The method of claim 1 , wherein Rto Rare each independently hydrogen claim 1 , phenyl claim 1 , Calkyl claim 1 , or halogen claim 1 , or Rand Ror Rand Rare joined together to form a pyridine or benzene ring;{'sub': 4', '5', '1-4, 'Rand Rare each independently hydrogen, Calkyl, or halogen;'}{'sub': 6', '3-12', '1-4, 'Ris phenyl, naphthalyl, Ccycloalkyl, or Calkyl substituted with phenyl;'}{'sub': 7', '1-4, 'Ris hydrogen or Calkyl, and'}{'sub': 1', '6', '1-4', '1-4, 'Rto Ris each independently unsubstituted, or further substituted with at least one substituent selected from the group consisting of Calkyl, hydroxyl, hydroxyl Calkyl, nitro, carboxyl, and halogen.'}3. The method of claim 1 , wherein Rand Rare each independently hydrogen claim 1 , or are joined together to form a pyridine ring;{'sub': 3', '1-4', '2, 'Ris hydrogen, phenyl, or Calkyl, or is joined together with Rto form a benzene ring;'}{'sub': 4', '5, 'Rand Rare each independently hydrogen,'}{'sub': 6', '5-10', '1-4, 'Ris phenyl, naphthalyl, Ccycloalkyl, or Calkyl group substituted with phenyl,'}{'sub': 7', '1-4, 'Ris hydrogen or Calkyl, and'}{'sub': 1', '6', '1-4', '1-4, 'Rto Ris each independently unsubstituted, or further substituted with at least one substituent selected from the group consisting of Calkyl, hydroxyl, hydroxyl Calkyl, nitro, carboxyl, and halogen.'}4. The method of claim 1 , wherein the compound of Formula 1 is at least one ...

ARYLOXY PHENOXY ACRYLIC COMPOUND HAVING HIF-1 INHIBITION ACTIVITY, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS AN ACTIVE INGREDIENT

The present invention relates to a compound inhibiting HF-1 activity, a preparation method of the same, and a pharmaceutical composition comprising the same as an active ingredient. The compound of the present invention demonstrates anticancer activity not by non-selective cytotoxicity but by inhibiting the activity of HIF-1, the transcription factor playing an important role in cancer cell growth and metastasis. Accordingly, the compound or the pharmaceutically acceptable salt thereof according to the present invention inhibits HIF-1 activity, and therefore can be used as a therapeutic agent for solid tumors such as colon cancer, liver cancer, stomach cancer and breast cancer. In addition, the compound or the pharmaceutically acceptable salt thereof according to the present invention can be used as an active ingredient for a therapeutic agent for diabetic retinopathy or arthritis which may become worse when hypoxia-induced VEGF expression by HIF-1 increases. 5. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound represented by formula 1 is selected from the group consisting of(E)-3-[3-(4-adamantan-1-yl-phenoxy)-acryloylamino]-benzoic acid methylester,(E)-3-(3-(4-t-butylphenoxy)acrylamido)benzoic acid methylester,(E)-3-(3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)acrylamido)benzoic acid methylester,(E)-3-(3-(4-adamantan-1-yl-2-methylphenoxy) acrylamido)benzoic acid methylester,(E)-4-(3-(4-adamantan-1-yl-phenoxy)acrylamido)benzoic acid methylester,(E)-3-(4-adamantan-1-yl-phenoxy)-N-(3-sulfamoylphenyl) acrylamide,(E)-3-(4-adamantan-1-ylphenoxy)-N-(3-(methylsulfonyl)phenyl)acrylamide,(E)-5-[3-(4-adamantan-1-yl-phenoxy)-acryloamino]-2-hydroxy-benzoic acid methylester,(E)-3-[3-(4-adamantan-1-yl-phenoxy)-acryloylamino]-benzoic acid,(E)-3-(3-(4-adamantan-1-yl-phenoxy)acrylamido)benzoic acid ethylester,(E)-3-(3-(4-adamantan-1-ylphenoxy)acrylamido)benzoic acid 2-methoxyethylester,(E)-3-(3-(4-adamantan-1-yl-phenoxy)acrylamido) ...

Method of Treating Skin with microRNA Modulators

Methods for preventing, ameliorating, or reducing dermatological signs of aging are provided which employ active agents that suppress or down-regulate microRNA expression in dermal fibroblast, resulting in enhanced production of collagen, elastin and/or fibrillin in the skin. Also provided are methods for screening for activity against specific microRNAs and the methods of using active agents identified by the screening protocol in the treatment of skin. 2. The method according to claim 1 , wherein said active agent suppresses miR-29a.3. The method according to claim 1 , wherein said active agent suppresses miR-29b.4. The method according to claim 1 , wherein said active agent suppresses miR-29a and miR-29b.5. The method according to claim 1 , wherein R claim 1 , when not hydrogen claim 1 , is alkyl claim 1 , aryl claim 1 , arylalkyl claim 1 , or alkylaryl.6. The method according to claim 5 , wherein Ris hydrogen.7. The method according to claim 1 , wherein R claim 1 , Rand Rare independently a group R claim 1 , where R is selected from alkyl claim 1 , aryl claim 1 , arylalkyl claim 1 , and alkylaryl claim 1 , each being optionally substituted with 1-12 heteroatoms selected from halogen claim 1 , O claim 1 , N and S.8. The method according to claim 1 , wherein Ris a Cto Calkyl.9. The method of claim 5 , wherein Rand Rindependently is a C1 to C4 alkyl or phenyl claim 5 , and Ris hydrogen or a Cto Calkyl.11. The method according to claim 1 , wherein said aesthetic improvement of said skin is selected from the group consisting of:(a) treatment, reduction, and/or prevention of fine lines or wrinkles,(b) reduction of skin pore size,(c) improvement in skin thickness, plumpness, and/or tautness;(d) improvement in skin suppleness and/or softness;(e) improvement in skin tone, radiance, and/or clarity;(f) improvement in maintenance and remodeling of elastin;(g) improvement in skin texture and/or promotion of retexturization;(h) improvement in skin barrier repair and/or ...

Sulfonamide-Containing Compounds

This invention relates generally to the discovery of sulfonamide-containing compounds that are inhibitors of γ-secretase. 2. The compound of claim 1 , wherein W claim 1 , W claim 1 , W claim 1 , and Ware defined according to definition (A).3. (canceled)4. The compound according to claim 1 , wherein each of W claim 1 , W claim 1 , W claim 1 , and Wis CH.512-. (canceled)13. The compound according to claim 1 , wherein Ris selected from —COH; —C(O)OR; —NHC(O)OR; —N(CH)C(O)OR; —C(O)N(R)(R); —C(O)R; —CN; and —SO(R).14. The compound according to claim 13 , wherein Ris —COH.15. The compound according to claim 13 , wherein Ris —COR.16. (canceled)17. The compound according to claim 13 , wherein Ris —SO(R).18. (canceled)19. The compound according to claim 13 , wherein Ris —C(O)N(R)(R).2027-. (canceled)28. The compound of claim 1 , wherein Ris C-Caryl claim 1 , which is optionally substituted with from 1-3 independently selected R.29. The compound of claim 28 , wherein Ris phenyl claim 28 , which is optionally substituted with from 1-3 independently selected R.30. The compound of claim 29 , wherein claim 29 , Ris unsubstituted phenyl.31. The compound according to claim 1 , wherein Ris C-Calkyl claim 1 , which is optionally substituted with a substituent selected from —OH and —CN.32. The compound of claim 31 , wherein Ris —CHCHor —CH.3338-. (canceled)39. The compound according to claim 1 , wherein the carbon attached to Rand Rhas the S configuration.40. The compound according to claim 1 , wherein Ris C-Caryl claim 1 , which is optionally substituted with from 1-3 independently selected R.41. (canceled)42. The compound of claim 40 , wherein Ris 4-chloro-phenyl claim 40 , 4-fluoro-phenyl claim 40 , or 2 claim 40 ,4-difluorophenyl.4346-. (canceled)47. The compound according to claim 1 , wherein A is CH.48. A pharmaceutical composition comprising a compound of formula (I) claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , as claimed in claim 1 , and a pharmaceutically ...

POLYMERIZABLE MONOMER, POLYMERIC COMPOUND, CHARGE CONTROL AGENT CONTAINING THE POLYMERIC COMPOUND, AND DEVELOPER BEARING MEMBER AND TONER WHICH CONTAIN THE CHARGE CONTROL AGENT

A polymerizable monomer is provided which is represented by the following formula (1): 4. The polymeric compound according to claim 3 , wherein the unit represented by the formula (4) is a styrene derivative unit or an acrylate derivative unit.5. The polymeric compound according to claim 2 , which has a weight-average molecular weight of from 3 claim 2 ,000 to 100 claim 2 ,000.6. A charge control agent comprising the polymeric compound according to .7. A developer bearing member comprising in a surface layer thereof the charge control agent according to .8. A toner comprising a binder resin claim 6 , a colorant and the charge control agent according to .9. The toner according to claim 8 , which is produced by a suspension polymerization process.10. The toner according to claim 8 , which is produced by a suspension granulation process. The present invention relates to a novel polymerizable monomer having a salicylic acid unit, and a polymeric compound produced by polymerizing the same. The present invention also relates to a charge control agent used in recording methods making use of electrophotography or the like, and a developer bearing member and a toner which contain the same.In image forming methods as typified by an electrophotographic recording method, a developer charged electrostatically (hereinafter “toner”) flies to the surface of a photosensitive member by electrostatic force which accords with potential differences on the photosensitive member surface, and develops electrostatic latent images formed on the photosensitive member surface. Hence, it is necessary and indispensable to control charge characteristics of the toner. Then, as a method for providing the toner with proper charge characteristics, a method is known in which a binder resin of a developer bearing member (hereinafter also “developing roller”) is incorporated with a charge control agent or a method in which a charge control agent capable of providing the toner with positive charges or ...

SELECTIVE HYDROXAMIC ACID BASED MMP-12 AND MMP-13 INHIBITORS

The present invention provides a compound of formula (I): 1. A compound or salt thereof selected from the group consisting of:(R)—N-Hydroxy-2-[(1-hydroxy-naphthalene-2-sulfonyl)-(3-methyl-butyl)-amino]-3-methyl-butyramide;2-[Benzyl-(7-ethoxy-naphthalene-2-sulfonyl)-amino]-N-hydroxy-3-methyl-butyramide;N-isoamyl-N-(6-ethyl naphthalene-2-sulfonyl)-D-valine hydroxamic acid;N-Hydroxy-2-[(6-hydroxy-naphthalene-2-sulfonyl)-(3-methyl-butyl)-amino]-3-methyl-butyramide;2-[(6-Amino-naphthalene-2-sulfonyl)-(3-phenyl-propyl)-amino]-N-hydroxy-3-methyl-butyramide;2-[(6-Acetylamino-naphthalene-2-sulfonyl)-(3-phenyl-propyl)-amino]-N-hydroxy-3-methyl-butyramide;N-isoamyl-N-(6-methoxy naphthalene-2-sulfonyl)-D-valine hydroxamic acid;N-isoamyl-N-(6-hydroxy naphthalene-2-sulfonyl)-D-valine hydroxamic acid;2-[(7-Amino-naphthalene-2-sulfonyl)-(3-phenyl-propyl)-amino]-N-hydroxy-3-methyl-butyramide;(R)—N-Hydroxy-2-[(7-methoxy-naphthalene-2-sulfonyl)-(3-methyl-butyl)-amino]-3-methyl-butyramide;2-[(6-Ethoxy-naphthalene-2-sulfonyl)-(3-methyl-butyl)-amino]-N-hydroxy-3-methyl-butyramide;2-[Benzyl-(6-p-tolylamino-naphthalene-2-sulfonyl)-amino]-N-hydroxy-3-methyl-butyramide;N-Hydroxy-3-methyl-2-[[6-(3-methyl-butoxy)-naphthalene-2-sulfonyl]-(3-methyl-butyl)-amino]-butyramide;2-[(7-Ethoxy-naphthalene-2-sulfonyl)-(3-methyl-butyl)-amino]-N-hydroxy-3-methyl-butyramide;N-Hydroxy-2-[(6-isobutoxy-naphthalene-2-sulfonyl)-(3-methyl-butyl)-amino]-3-methyl-butyramide;2-[(6-Amino-naphthalene-2-sulfonyl)-(3-methyl-butyl)-amino]-N-hydroxy-3-methyl-butyramide;2-[(6-Benzyloxy-naphthalene-2-sulfonyl)-(3-methyl-butyl)-amino]-N-hydroxy-3-methyl-butyramide;2-[(6-Acetylamino-naphthalene-2-sulfonyl)-(3-methyl-butyl)-amino]-N-hydroxy-3-methyl-butyramide;N-Hydroxy-3-methyl-2-{(3-methyl-butyl)-[7-(3-methyl-butylamino)-naphthalene-2-sulfonyl]-amino}-butyramide;2-[(7-Acetylamino-naphthalene-2-sulfonyl)-(3-methyl-butyl)-amino]-N-hydroxy-3-methyl-butyramide;2-[(6-Allyloxy-naphthalene-2-sulfonyl)-(3-methyl-butyl)-amino]-N- ...

METHOD FOR PRODUCING DIAMINE COMPOUND

The present invention provides a method for producing a compound represented by general formula (1) (wherein R, R, R, R-R, A-A, nand nare as defined in the description), which is characterized by reacting a compound represented by general formula (2) (wherein R-R, A-A, n, nand B are as defined in the description) with a diamine compound represented by general formula (3) (wherein R-Rare as defined in the description). The present invention is a method for producing a diamine compound, which is useful for the formation of a ruthenium-diamine complex, under mild conditions, said method being able to be put in industrial practice. 2. The production method according to claim 1 , whereinthe reaction of the compound represented by the general formula (2) is reacted with the diamine compound represented by the general formula (3) at a temperature of 100° C. to 200° C. This application is a National Stage of International Application No. PCT/JP2012/061445 filed Apr. 27, 2012, claiming priority based on Japanese Patent Application No. 2011-101528 filed Apr. 28, 2011, the contents of all of which are incorporated herein by reference in their entirety.The present invention relates to a method for producing a diamine compound useful for forming a ruthenium-diamine complex important as an asymmetric reduction catalyst.Many asymmetric reactions including asymmetric reduction have been developed, and many asymmetric reactions have been reported in which asymmetric metal complexes having optically active phosphine ligands are used. On the other hand, many reports have shown that complexes in which optically active nitrogen compounds are coordinated to transition metals, such as ruthenium, rhodium, and iridium, for example, have excellent performances as catalysts for asymmetric synthesis reactions. Moreover, to enhance the performances of these catalysts, various optically active nitrogen compounds have been developed (Non Patent Literatures 1, 2, 3, 4, etc.). In particular, M. ...

FLUORESCENT DYE FOR PH SENSOR

The present invention relates to a new type of fluorescent with the following formula (I), its preparation process, and also an optical pH sensor which comprises this fluorescent dye immobilized on an analyte-permeable carrier. 3. The fluorescent dye of claim 2 , where n is an integer from 2 to 4.4. The fluorescent dye of claim 1 , where the fluorescent dye has two different maxima in the fluorescence emission.5. The fluorescent dye of claim 4 , where at least one of the two different maxima in the fluorescence emission has a pH-dependent intensity maximum.6. The fluorescent dye of claim 5 , where the pH-dependent fluorescent maximum is in a range of >420 nm.8. The process of claim 7 , where the compound of the formula (III) is the corresponding disodium salt.10. An optical pH sensor claim 1 , comprising an analyte-permeable carrier and the fluorescent dye of claim 1 , which is immobilized on a carrier.11. The optical pH sensor of claim 10 , where the thickness of the carrier is from 50 μm to 500 μm.12. The optical pH sensor of claim 10 , further comprising at least one coating which is provided on at least one surface of the carrier on which the fluorescent dye is immobilized.13. The optical pH sensor of claim 12 , where the coating is transparent.14. The optical pH sensor of or claim 12 , where an adhesive layer is provided on the coating.15. The optical pH sensor claim 10 , where the dynamic measurement range is in the range from pH 4.0 to pH 8.0. 1. Field of the InventionThe present invention relates to a new type of fluorescent dye, to its preparation process, and to an optical pH sensor comprising this fluorescent dye.2. Description of the Related ArtThe determination of the H+ activity in aqueous media, i.e. the measurement of the pH, using electrochemical sensors, in particular by means of pH glass electrodes, has been known for a long time. Nevertheless, the use of glass electrodes also has disadvantages in several respects, such as, for example, the ...

MODULATORS OF HSP70/DNAK FUNCTION AND METHODS OF USE THEREOF

Compositions and methods for modulating HSP70 function, particularly for the targeted killing of cancer cells, are disclosed. 2. The method of wherein said disease is cancer and said HSP70 function is selected from the group consisting of modulation of protein aggregation claim 1 , chaperone protein binding claim 1 , client protein binding claim 1 , modulation of cellular stress response claim 1 , modulation of autophagy claim 1 , modulation of lysosomal functions claim 1 , modulation of NFκB activity claim 1 , modulation of caspase cleavage claim 1 , modulation of the proteasome system claim 1 , reduced viability claim 1 , modulation of anoikis claim 1 , modulation of formation of detergent-insoluble subcellular complexes claim 1 , and modulation of vacuolization.3. The method of claim 2 , wherein said compound disrupts HSP70 binding to at least one chaperone protein selected from the group consisting of CHIP claim 2 , HSP40 claim 2 , and BAG-1M isoform.4. The method of claim 2 , wherein said compound disrupts HSP70 binding to at least one client protein selected from the group consisting of APAF-1 claim 2 , p53 claim 2 , LAMP-2 claim 2 , integrin α5 claim 2 , integrin β1 claim 2 , SV40 T antigen claim 2 , and HSP90 client proteins.5. The method of claim 1 , wherein Q represents —C≡C— claim 1 , and R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Reach represents hydrogen.6. The method of claim 1 , wherein the compound of formula I is pifithrin-μ.7. The method of claim 1 , wherein said disease is characterized by aberrant cell proliferation.8. The method of claim 7 , wherein said chemotherapeutic agent is an anti-neoplastic agent.9. The method of claim 1 , wherein said chemotherapeutic agent and said compound are administered simultaneously.10. The method of claim 1 , wherein said chemotherapeutic agent and said compound are administered sequentially.11. The method of claim 1 , wherein said chemotherapeutic agent and said compound are administered via a route ...

HEAT SENSITIVE RECORDING MATERIAL AND COLOR DEVELOPER

The presently claimed invention relates to a color developer, a process for its manufacture and its use as a component in heat sensitive recording material. The heat sensitive recording material is useful for thermographic printing. 40. The compound according to claim 3 , wherein the compound is a crystalline polymorph form α that is characterized by an X-ray powder diffraction pattern comprising 2Θ reflections claim 3 , plus or minus 0.2 degrees 2Θ claim 3 , at 5.5 claim 3 , 6.1 claim 3 , 6.4 claim 3 , 12.1 claim 3 , 16.1 claim 3 , 16.8 claim 3 , 17.1 claim 3 , 18.3 claim 3 , 19.1 claim 3 , 19.9 claim 3 , 20.2 claim 3 , 21.4 claim 3 , 22.1 claim 3 , 22.7 claim 3 , 23.3 claim 3 , 24.3 claim 3 , 24.7 claim 3 , 25.0 claim 3 , 26.4 claim 3 , 27.7 and 29.3.5. The compound according to claim 3 , wherein the compound is a crystalline polymorph form β that is characterized by an X-ray powder diffraction pattern comprising 2Θ reflections claim 3 , plus or minus 0.2 degrees 2Θ claim 3 , at 6.2 claim 3 , 8.1 claim 3 , 10.1 claim 3 , 11.8 claim 3 , 12.2 claim 3 ,13.4 claim 3 , 14.1 claim 3 , 15.3 claim 3 , 16.1 claim 3 ,17.2 claim 3 ,18.4 claim 3 , 19.1 claim 3 , 20.6 claim 3 , 21.4 claim 3 , 22.4 claim 3 , 24.5 claim 3 , 25.0 claim 3 , 25.9 claim 3 , 26.2 claim 3 , 26.9 and 28.4.7. The process according to claim 6 , wherein the chlorination agent is selected from the group of thionyl chloride claim 6 , POCl claim 6 , PCland oxalyl chloride.8. The process according to claim 6 , wherein acid chloride (IVb) is 5-sulfonylchloride-isophthalic acid dichloride.10. The process according to claim 6 , wherein step c. comprises reacting the acid chloride of formula (IVb) with an amine RNHto obtain compound of formula (I) claim 6 , wherein Ris identical to R.11. The process according to claim 6 , wherein the amine is m-toluidine.13. (canceled)15. The heat sensitive recording material according to claim 14 , wherein the weight ratio of color developer to color former is in the range of 1. ...

BENZENDE SULFONAMIDE DERIVATIVES AS HIV INTEGRASE INHIBITORS

Methods for treating retroviral infection or inhibiting HIV integrase in target cells or in a patient involve administering to target cells or to a patient in need of treatment an effective amount of at least one having a disulfonamide scaffold which is represented by the formula: 2. A method for inhibiting HIV integrase according to claim 1 , wherein X and Y independently represent lower alkyl.3. A method for inhibiting a HIV integrase according to claim 2 , wherein X and Y independently represent C-Calkyl.4. A method for inhibiting a HIV integrase according to claim 1 , wherein one of X and Y is lower alkyl and the other is halogeno claim 1 , amine or substituted amine.5. A method for inhibiting HIV integrase according to claim 1 , wherein n is 1 and m is 1 claim 1 , X and Y are independent of one another and represent para-substitutents.6. A method for inhibiting HIV integrase according to claim 1 , wherein R represents alkylene.7. A method for inhibiting HIV integrase according to claim 1 , wherein R represents an alkylene group having one to seven carbon atoms.8. A method for inhibiting HIV integrase according to claim 1 , wherein X and Y are independent of one another and represent para-substitutents and R represents an alkylene group having one to seven carbon atoms.9. A method for inhibiting HIV integrase according to claim 8 , wherein R represents —(CH)—.10. A method for inhibiting a HIV integrase according to claim 8 , wherein one of X and Y is lower alkyl and the other is halogeno.11. A method for inhibiting a HIV integrase according to claim 8 , wherein at least one X and Y is halogeno.12. A method for inhibiting a HIV integrase according to claim 1 , wherein at least one of X and Y is amine.13. A method for inhibiting a HIV integrase according to claim 1 , wherein when n is 1 and m is 2 claim 1 , one Y is substituted amino and the other Y is amino. For this application priority is claimed to U.S. Provisional Application 61/944990, filed Feb. 26, 2014, ...

COVALENT PEPTIDE BINDERS

There are provided, inter alia, compositions and methods for covalently binding peptides to proteins. 2. The compound according to claim 1 , wherein said Lis substituted or unsubstituted alkyl.3. The compound according to claim 2 , wherein said Lis substituted or unsubstituted C-Calkyl.4. The compound according to claim 3 , wherein said Lis unsubstituted C-Calkyl.5. The compound according to claim 4 , wherein said Lis methylene.6. The compound according to claim 1 , wherein said Lis substituted or unsubstituted heteroalkyl.7. The compound according to claim 6 , wherein said Lis substituted or unsubstituted 2 to 10 membered heteroalkyl.8. The compound according to claim 7 , wherein said Lis unsubstituted 2 to 10 membered heteroalkyl.9. The compound according to claim 7 , wherein said Lis oxo substituted 2 to 10 membered heteroalkyl.10. The compound according to claim 9 , wherein said Lis —(CH)—NH—C(O)— claim 9 , wherein n is an integer in the range 1-10.11. The compound according to claim 10 , wherein n is 1.13. The compound according to claim 1 , wherein Ris hydrogen.14. The compound according to claim 1 , wherein Ris an amino protecting group.15. The composition according to claim 14 , wherein said amino protecting group is tert-butyloxycarbonyl (tBoc) claim 14 , 9H-fluoren-9-ylmethoxycarbonyl (Fmoc) claim 14 , benzyloxy-carbonyl (Z) claim 14 , allyloxycarbonyl (Alloc) claim 14 , 4-methyltrityl (Mtt) claim 14 , 1-(4 claim 14 ,4-Dimethyl-2 claim 14 ,6-dioxocyclohex-1-ylidene)-3-ethyl (Dde) claim 14 , or 1-(4 claim 14 ,4-Dimethyl-2 claim 14 ,6-dioxocyclohex-1-ylidene)-3-methylbutyl (ivDde).16. The composition according to claim 15 , wherein said amino protecting group is Fmoc.18. The compound according to claim 17 , wherein said Lis substituted or unsubstituted alkyl.19. The compound according to claim 18 , wherein said Lis substituted or unsubstituted C-Calkyl.20. The compound according to claim 19 , wherein said Lis unsubstituted C-Calkyl.21. The compound according ...

SUBSTITUTED BIARYL SULFONAMIDES AND THE USE THEREOF

Provided herein are substituted biaryl sulfonamide compounds, pharmaceutical compositions comprising the compounds, methods of their preparation, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or amelioration of various disorders, including cancer and proliferative disorders. In one embodiment, the compounds provided herein modulate initiation of protein translation. In one embodiment, the compounds provided herein are used in combination with surgery, radiation therapy, immuno therapy and/or one or more additional anticancer drugs for the treatment, prevention, and/or amelioration of cancer and proliferative disorders.

Methods and compositions for treatment of muscle wasting, muscle weakness, and/or cachexia

Embodiments of the invention include methods of treating, preventing, and/or reduce the risk or severity of a condition selected from the group consisting of muscle wasting, muscle weakness, cachexia, and a combination thereof in an individual in need thereof. In some embodiments, particular small molecules are employed for treatment, prevention, and/or reduction in the risk of muscle wasting. In at least particular cases, the small molecules are inhibitors of STAT3.

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 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.3. The compound according to claim 1 , wherein each Ris independently chosen from methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , isobutyl claim 1 , tert-butyl claim 1 , and phenyl.4. The compound according to claim 1 , wherein each Ris independently chosen from methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , and phenyl.5. The compound according to claim 1 , wherein each Wis independently chosen from —S(O)N(R)— claim 1 , wherein Ris 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 , and tert-butyl.6. The compound according to claim 1 , wherein each Wis —S(O)NH—.7. The compound according to claim 1 , wherein each Xis independently chosen from methane-diyl claim 1 , ethane-1 claim 1 ,1-diyl claim 1 , ethane-1 claim 1 ,2-diyl claim 1 , propane-1 claim 1 ,2-diyl claim 1 , propane-1 claim 1 ,3-diyl claim 1 , 2-methylpropane-1 claim 1 ,1-diyl claim 1 , 2-methylpropane-1 claim 1 ,2-diyl claim 1 , 2 claim 1 ,2-dimethylpropane-1 claim 1 ,3-diyl claim 1 , butane-1 claim 1 ,2-diyl claim 1 , butane-1 claim 1 ,3-diyl claim 1 , butane-1 claim 1 ,4-diyl ...

CRYSTALLINE MODIFICATION OF N-(2-(3-PHENYLUREIDO)PHENYL)BENZENESULFONAMIDE AND RECORDING MATERIAL USING SAME

The disclosure provides a novel crystal form of N-(2-(3-phenylureido)phenyl)benzenesulfonamide, which is crystalline modification thereof specified by an X-ray diffraction diagram having peaks at diffraction angles (2θ±0.1°) of 23.60°, 20.80°, 12.24° and 13.80° in a powder X-ray diffractometry using Cu-Kα ray. 1. A crystalline modification of N-(2-(3-phenylureido)phenyl)benzenesulfonamide specified by an X-ray diffraction diagram having peaks at diffraction angles (2θ±0.1°) of 23.60° , 20.80° , 12.24° and 13.80° in a powder X-ray diffractometry using Cu-Kα ray.2. The crystalline modification of N-(2-(3-phenylureido)phenyl)benzenesulfonamide according to claim 1 , wherein a melting point is 160-162° C.3. A recording material comprising a color former claim 1 , wherein the recording material comprises the crystalline modification of N-(2-(3-phenylureido)phenyl)benzenesulfonamide according to .4. A recording sheet having a recording material layer formed from the recording material according to .5. A recording material comprising a color former claim 2 , wherein the recording material comprises the crystalline modification of N-(2-(3-phenylureido)phenyl)benzenesulfonamide according to .6. A recording sheet having a recording material layer formed from the recording material according to . The present invention relates to a novel crystal form of N-(2-(3-phenylureido)phenyl)benzenesulfonamide. The present application claims priority of Japanese Patent Application No. 2015-035568 filed on Feb. 25, 2015 and priority of Japanese Patent Application No. 2015-065613 filed on Mar. 27, 2015, the contents of which are incorporated herein by reference.The recording material employing color development through a reaction between a color former and a color-developing agent, since record may be made by a relatively simple apparatus in a short time without applying a complicated treatment such as development and fixation, are widely used in e.g., thermal recording paper for output- ...

COMPOUND HAVING ENHANCING ACTIVITY FOR GLUCAGON-LIKE PEPTIDE-1 RECEPTOR ACTIONS

Compounds represented by formula (I): 2. The compound or salt according to claim 1 , wherein{'sub': '6-14', 'A is a Caryl group or a 5- or 6-membered monocyclic aromatic heterocyclic group, each of which is optionally further substituted,'}L is a bond or a methylene group,Q is an oxygen atom,{'sup': 4', '5, 'sub': '1-6', 'Rand Rare the same or different and are each independently a hydrogen atom or an optionally substituted Calkyl group, and'}n is 1 or 2.3. The compound or salt according to claim 1 , wherein{'sub': 1-6', '1-6', '1-6', '1-3', '1-6', '1-6', '1-6', '1-3, 'A is a phenyl group optionally further substituted by the same or different 1 to 5 substituents selected from the group consisting of a halogen atom, a hydroxy group, a carboxy group, a sulfanyl group, an optionally substituted Calkyl group, an optionally substituted Calkoxy group, an optionally substituted amino group, a Calkylthio group optionally substituted by a halogen atom, and a Calkylenedioxy group, or a pyridyl group optionally further substituted by the same or different 1 to 4 substituents selected from the group consisting of a halogen atom, a hydroxy group, a carboxy group, a sulfanyl group, an optionally substituted Calkyl group, an optionally substituted Calkoxy group, an optionally substituted amino group, a 4- to 7-membered monocyclic non-aromatic heterocyclic group, a Calkylthio group optionally substituted by a halogen atom, and a Calkylenedioxy group,'}{'sub': 1-6', '1-6', '1-6', '1-3, 'B is a benzene ring optionally further substituted by the same or different 1 to 4 substituents selected from the group consisting of a halogen atom, a hydroxy group, a sulfanyl group, an optionally substituted Calkyl group, an optionally substituted Calkoxy group, an optionally substituted amino group, a Calkylthio group optionally substituted by a halogen atom, a Calkylenedioxy group, and a 4- to 7-membered monocyclic non-aromatic heterocyclic group,'}L is a bond or a methylene group,{'sup': '1', ...

CCR9 INHIBITORS AND METHODS OF USE THEREOF

The invention relates to compounds represented by Structural Formula I, which can bind to CCR9 receptors and block the binding of a ligand (e.g., TECK) to the receptors. The invention also relates to a method of inhibiting a function of CCR9, and to the use compounds represented by Structural Formula I in research, therapeutic, prophylactic and diagnostic methods. 2. The compound of claim 1 , wherein Aris a substituted or unsubstituted group selected from pyrid-4-yl claim 1 , N-oxido pyrid-4-yl claim 1 , pyrimidinyl claim 1 , and pyrazinyl.4. The compound of claim 3 , wherein Aris a substituted or unsubstituted group selected from phenyl claim 3 , naphthyl claim 3 , thienyl claim 3 , and thianaphthenyl.5. The compound of claim 3 , wherein Aris a substituted or unsubstituted group selected from phenyl and pyridyl.6. The compound of claim 3 , wherein Aris a substituted or unsubstituted group selected from phenyl and thienyl.7. The compound of claim 3 , wherein Aris unsubstituted or is substituted with one or more substituents selected from substituted aliphatic claim 3 , unsubstituted aliphatic claim 3 , aryl claim 3 , arylalkyl claim 3 , substituted alkoxy claim 3 , unsubstituted alkoxy claim 3 , aryloxy claim 3 , arylalkoxy claim 3 , alkylthio claim 3 , halo claim 3 , nitro claim 3 , cyano claim 3 , S(O)-(aliphatic) claim 3 , S(O)-(aliphatic) claim 3 , NRS(O)-(aliphatic) claim 3 , C(O)N(R) claim 3 , C(O)R claim 3 , N(R) claim 3 , NRC(O)R claim 3 , and NRC(O)R claim 3 , wherein Rfor each occurrence is independently H or an aliphatic group claim 3 , and Ris an aliphatic group.8. The compound of claim 3 , wherein Aris unsubstituted or is substituted with one or more substituents selected from aliphatic claim 3 , alkoxy claim 3 , and haloalkoxy.9. The compound of claim 3 , wherein one or both rings A and B are unsubstituted or are independently substituted with a substituent selected from halo claim 3 , aliphatic claim 3 , alkoxy claim 3 , and haloalkyl.10. The compound ...

Pharmaceutical Formulations of HDAC Inhibitors

This invention pertains to pharmaceutical compositions comprising certain carbamic acid compounds (e.g., which inhibit HDAC (histone deacetylase) activity) (e.g., PXD-101, N hydroxyl-3-(3-phenylsulfamoyl-phenyl)-acrylamide)) and one or more additional ingredients selected from cyclodextrin, arginine, and meglumine. The present invention also pertains to the use of such compositions, for example, in the inhibition of HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc. 4. A pharmaceutical composition according to claim 1 , further comprising meglumine.5. A pharmaceutical composition according to claim 1 , wherein said cyclodextrin is selected from:α-cyclodextrin; β-cyclodextrin; γ-cyclodextrin;(C1-4alkyl)-α-cyclodextrin; (C1-4alkyl)-β-cyclodextrin; (C1-4alkyl)-γ-cyclodextrin;(hydroxy-C1-4alkyl)-α-cyclodextrin; (hydroxy-C1-4alkyl)-β-cyclodextrin; (hydroxy C1 4alkyl)-γ-cyclodextrin;(carboxy-C1-4alkyl)-α-cyclodextrin; (carboxy-C1-4alkyl)-β-cyclodextrin; (carboxy C1 4alkyl)-γ-cyclodextrin;saccharide ethers of α-cyclodextrin; saccharide ethers of β-cyclodextrin; saccharide ethers of γ-cyclodextrin;sulfobutyl ethers of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin.6. A pharmaceutical composition according to claim 1 , wherein said cyclodextrin is hydroxypropyl-β-cyclodextrin.7. A pharmaceutical composition according to claim 1 , wherein the molar ratio of cyclodextrin to said HDAC inhibitor is from 0.5 to 5.8. A pharmaceutical composition according to claim 1 , which is a liquid.9. A pharmaceutical composition according to claim 1 , which comprises said HDAC inhibitor at a concentration of 0.1-1000 mg/mL.10. A pharmaceutical composition according to claim 1 , which comprises said HDAC inhibitor at a concentration of 30-300 mg/mL.11. A pharmaceutical composition according to claim 1 , which comprises said HDAC inhibitor at a concentration of 0.3-3000 mM.12. A pharmaceutical composition according to claim 1 , which ...

Transcription Factor Inhibitors and Related Compositions, Formulations and Methods

The present invention provides small molecules useful to affect cancer cells, along with related methods. The present compounds, formulations, kits and methods are useful for a variety of research, diagnostic and therapeutic purposes. STAT3 inhibitors, particularly LLL12, are disclosed. The STAT3 inhibitors are useful to treat breast cancer in general and breast cancer initiating cells in particular. 2. A composition of matter claim 1 , comprising a compound of and a pharmaceutically-acceptable excipient claim 1 , carrier claim 1 , diluents claim 1 , or salt.3. A method to synthesize a compound of claim 1 , comprising:i) reacting an unsubstituted or substituted naphthalene sulfonyl chloride compound with a nitrogen containing compound to form an unsubstituted or substituted naphthalene sulfonyl amine;ii) oxidizing the unsubstituted or substituted naphthalene sulfonyl amine of step i) to yield an unsubstituted or substituted naphthoquinone compound; andiii) catalyzing via a Diels-Alder reaction of 3-hydroxy-2-pyrone with the unsubstituted or substituted naphthoquinone compound of step ii) to yield a compound of formula I.4. The method of claim 3 , wherein the nitrogen containing compound of step i) comprises ammonium hydroxide and the naphthalene sulfonyl chloride is unsubstituted.5. A method to inhibit STAT3 activation in a cell claim 1 , comprising introducing a compound of to a STAT3-expressing cell claim 1 , and measuring STAT3 activation inhibition.6. The method of claim 5 , wherein said inhibition is measured by observing cell apoptosis.7. The method of claim 5 , wherein said inhibition is measured by observing prevention of STAT3 SH2 dimerization.8. The method of claim 5 , wherein said inhibition is measured by observing a decrease in the levels of expression of STAT3 phosphorylation.9. The method of claim 5 , wherein said inhibition is measured by observing inhibition of downstream targets of STAT3.10. The method of claim 9 , wherein said downstream targets ...

SULFINYLAMINOBENZAMIDE AND SULFONYLAMINOBENZAMIDE DERIVATIVES

Provided is a compound of Formula (I): 25-. (canceled)6. The method of claim 1 , wherein Ris selected from the group consisting of: Calkyl claim 1 , —NRR claim 1 , 6-10 membered aryl claim 1 , 5-10 membered heteroaryl claim 1 , Ccycloalkyl claim 1 , and 4-12 membered heterocyclyl claim 1 , wherein each Calkyl claim 1 , 6-10 membered aryl claim 1 , 5-10 membered heteroaryl claim 1 , Ccycloalkyl claim 1 , and 4-12 membered heterocyclyl is further substituted with one or more Rgroups.7. The method of claim 1 , wherein Ris selected from the group consisting of: —H claim 1 , —CN claim 1 , —F claim 1 , methyl claim 1 , methoxy and Chaloalkoxy.8. The method of claim 7 , wherein Ris selected from the group consisting of: —H and —F.9. The method of claim 1 , wherein Ris selected from the group consisting of: —H claim 1 , halo claim 1 , —OH claim 1 , —CN claim 1 , Calkyl claim 1 , Calkoxy claim 1 , Chydroxyalkyl claim 1 , Cheteroalkyl claim 1 , —SF claim 1 , —S(O)R claim 1 , —S(O)(NH)R claim 1 , —S(O)(NR)R claim 1 , —S(O)(NH)NRR claim 1 , —S(O)(NR)NRR claim 1 , —NRSOR claim 1 , —NRS(O)NRR claim 1 , —NRC(O)NRR claim 1 , —NRC(O)OR claim 1 , —C(O)R claim 1 , —C(O)OR claim 1 , —C(O)NRR claim 1 , and —NO claim 1 , wherein each of the Calkyl claim 1 , Calkoxy claim 1 , Chydroxyalkyl claim 1 , and Cheteroalkyl claim 1 , is further substituted with one or more Rgroups.10. The method of claim 9 , wherein Ris selected from the group consisting of: —H claim 9 , —F claim 9 , —Cl claim 9 , —OH claim 9 , —CN claim 9 , —S(O)R claim 9 , —C(O)R claim 9 , —SF claim 9 , —NO claim 9 , Calkyl claim 9 , and Calkoxy claim 9 , and wherein said Calkyl or Calkoxy is optionally substituted with one or more —F claim 9 , and Ris selected from the group consisting of Calkyl claim 9 , Ccycloalkyl claim 9 , Chydroxyalkyl claim 9 , Cheteroalkyl claim 9 , wherein the Calkyl claim 9 , Ccycloalkyl claim 9 , Chydroxyalkyl claim 9 , and Cheteroalkyl claim 9 , are optionally substituted with one or more Rgroups ...

NEW COMPOUNDS FOR THE TREATMENT AND/OR PREVENTION OF PARASITIC DISEASES AND METHOD OF PRODUCTION OF THEREOF

Disclosed are new compounds for treating, preventing or inhibiting a parasitic disease, preferably toxoplasmosis in a subject, the method for preparing thereof. 2. Compound of formula (I′) according to claim 1 , wherein Ar is chosen fromi) a phenyl substituted at the meta-, para-, or ortho-position by a fluor or a thiazolyl, orii) a benzyl substituted at the meta-position by an C1 to C4 alkoxy group.9. A method for treating claim 1 , inhibiting or preventing a parasitic disease in a mammalian subject claim 1 , including human claim 1 , cat or dog claim 1 , comprising applying an effective amount of the compound of formula (I′) of in the form of a pharmaceutical drug.10TrypanosomaLeishmaniaToxoplasma gondii.. The method of claim 9 , wherein the parasitic disease is caused by a protozoan parasite of the family of the Trypanosomatidae selected from the genus or the genus claim 9 , or the parasite11. A method for treating toxoplasmosis claim 4 , comprising applying an effective amount of the compound of formula (Ia1) of in the form of a pharmaceutical drug.12. A pharmaceutical composition comprising a compound of formula (I′) according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutical acceptable excipient.13. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a compound of formula (I′) according , or a pharmaceutically acceptable salt thereof, and'}at least one anti-parasitic compound, selected from the group comprising: miltefosin, antimony based drugs, like meglumine antimoniate or sodium stibogluconate, amphotericin B, benzimidazol, nifurtimox, paromomycin, pentamidin and its derivatives, arsenic derivatives, melarsoprol and difluoromethylornithin.16. The compound of claim 1 , wherein Ar is a phenyl.17. The compound of claim 1 , wherein Ar is a benzyl.18. The compound of claim 1 , wherein the halogen is a fluor atom.19. The compound of claim 1 , wherein the halogen is a thiazolyl.20. The ...

NOVEL STAT3 INHIBITORS

The present disclosure provides pharmaceutical compositions comprising Stat3 inhibitors and certain pharmaceutically acceptable salts thereof, and methods of use. 2. The compound of claim 1 , wherein X1 to X5 are F; and Ris selected from —NH—OH or —OR claim 1 , wherein Ris H claim 1 , or a pharmaceutically acceptable salt claim 1 , crystal or polymorph thereof.43. A pharmaceutical composition comprising a compound claims 1 , salt claims 1 , crystal or polymorph in any one of - claims 1 , and a pharmaceutically acceptable excipient.5. A composition for use in selectively treating tumor cells having a constituitively activated Stat3 claims 1 , comprising an effective amount of a Stat3 inhibitor of Formula I.6. A composition comprising a substantially pure crystalline Stat3 inhibitor of Formula I claims 1 , having alternating layers of GGCI molecules and besylate molecules (besylate salt).73. Use of a compound of any one of - for the preparation of a medicament for the treatment of a condition selected from the group consisting of cancer claims 1 , hyperplasia claims 1 , or neoplasia.8. The use of claim 7 , whereby tumor progression is inhibited claim 7 , or reduced claim 7 , or MDR is inhibited or reduced.9. A method of treating cancer claim 7 , comprising administering to a subject in need thereof claim 7 , a therapeutically effective amount of a pharmaceutical composition comprising a Stat3 inhibitor of Formula I claim 7 , or a pharmaceutically acceptable salt thereof.10. The method of claim 7 , wherein the Stat3 inhibitor has the structure of Formula II or Formula III claim 7 , or a pharmaceutically acceptable salt thereof.11. The method of claim 7 , whereby the expression of Bcl-2 claim 7 , Bcl-xL claim 7 , cyclin D1 claim 7 , c-Myc claim 7 , or survivin is down-regulated.12. The method of claim 7 , wherein the effective dose of the Stat3 inhibitor ranges from about 0.05 mg/kg to about 5 g/kg.13. The method of claim 12 , wherein the effective dose of Stat3 is ...

HETERODIMERS OF GLUTAMIC ACID

Compounds of Formula (Ia) 167-. (canceled)69. The method of claim 68 , wherein the disease claim 68 , disorder claim 68 , or condition is painful and sensory diabetic neuropathy claim 68 , neuronal damage claim 68 , prostate cancer claim 68 , schizophrenia claim 68 , colorectal cancer claim 68 , inflammation claim 68 , amyotrophic lateral sclerosis claim 68 , or diabetic neuropathy.70. The method of claim 69 , wherein the disease claim 69 , disorder claim 69 , or condition is colorectal cancer or prostate cancer.71. The method of claim 70 , wherein the disease claim 70 , disorder claim 70 , or condition is prostate cancer.72. The method of claim 68 , wherein Y is C(O).73. The method of claim 72 , wherein R is pyridinyl substituted with halogen.74. The method of claim 73 , wherein the halogen is a radiohalogen.75. The method of claim 74 , wherein the radiohalogen is selected from the group consisting of: I-123 claim 74 , I-124 claim 74 , I-125 claim 74 , I-131 claim 74 , Br-75 claim 74 , Br-77 claim 74 , and F-18.76. The method of claim 75 , wherein each Z is hydrogen.77. The method of claim 75 , wherein each Z is C-Calkyl.78. The method of claim 77 , wherein each Z is independently selected from t-butyl and methyl.79. The method of claim 75 , wherein the radiohalogen is F-18.80. The method of claim 79 , wherein the radiohalogen is at a position para to variable Y.81. The method of claim 68 , wherein the method comprises obtaining an image of one or more organs or tissues or both in the patient.82. The method of claim 81 , further comprising determining from the image an amount of PSMA which is present in the one or more organs or tissues or both in the patient.83. The method of claim 82 , wherein the one or more organs or tissues or both includes prostate tissue claim 82 , kidney tissue claim 82 , brain tissue claim 82 , vascular tissue claim 82 , or tumor tissue.85. The method of claim 84 , wherein the disease claim 84 , disorder claim 84 , or condition is painful ...

HETERODIMERS OF GLUTAMIC ACID

Compounds of Formula (Ia) 167-. (canceled)68. A method for treating a PSMA-associated disease in a subject comprising administering a compound comprising glutamate-urea-lysine conjugated to a metal chelating moiety and a radionuclide.69. The method of claim 68 , wherein the PSMA-associated disease is a prostate cancer or colorectal cancer.70. The method of claim 68 , wherein the cancer is prostate cancer.72. The method of claim 68 , wherein the compound provides an analgesic effect.74. The process of wherein the PSMA-binding compound comprises a metal chelating moiety and a radionuclide.75. A kit comprising: (i) a compound comprising a glutamate-urea-lysine PSMA-binding moiety conjugated to a metal chelating moiety claim 73 , and (ii) a radionuclide.76. The kit of claim 75 , wherein the radionuclide is appropriate for the detection or treatment of prostate cancer.77. The kit of claim 76 , wherein the radionuclide is selected from technetium-99m claim 76 , rhenium-186 claim 76 , rhenium-188 claim 76 , or combinations thereof.78. A method of using the kit of for the production of a PSMA-binding compound claim 75 , wherein the PSMA-binding compound comprises a glutamate-urea-lysine PSMA-binding moiety conjugated to a radionuclide chelate complex.79. A process for producing a PSMA-binding compound comprising a glutamate-urea-lysine PSMA-binding moiety conjugated to a radionuclide chelate complex claim 75 , the process comprising chelating a radionuclide with a compound comprising a glutamate-urea-lysine PSMA-binding moiety conjugated to a metal chelating moiety.81. The PSMA-binding moiety of claim 80 , wherein the PSMA-binding moiety binds to a PSMA positive human prostate tumor in a mouse xenograft assay or in vitro cell binding assay at an ICof about 4 nM or less.82. The PSMA-binding moiety of claim 81 , wherein the PSMA-binding moiety binds to a PSMA positive human prostate tumor in a mouse xenograft assay or in vitro cell binding assay at an ICof about 2 nM or less. ...

PHARMACEUTICAL FORMULATIONS OF HDAC INHIBITORS

This invention pertains to pharmaceutical compositions comprising certain carbamic acid compounds (e.g., which inhibit HDAC (histone deacetylase) activity) (e.g., PXD-101, N hydroxyl-3-(3-phenylsulfamoyl-phenyl)-acrylamide)) and one or more additional ingredients selected from cyclodextrin, arginine, and meglumine. The present invention also pertains to the use of such compositions, for example, in the inhibition of HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc. 4. (canceled)5. A pharmaceutical composition according to claim 1 , wherein said cyclodextrin is selected from:α-cyclodextrin; β-cyclodextrin; γ-cyclodextrin; (C1-4alkyl)-α-cyclodextrin; (C1-4alkyl)-β-cyclodextrin; (C1-4alkyl)-γ-cyclodextrin; (hydroxy-C1-4alkyl)-α-cyclodextrin; (hydroxy-C1-4alkyl)-β-cyclodextrin; (hydroxy C1 4alkyl)-γ-cyclodextrin; (carboxy-C1-4alkyl)-α-cyclodextrin; (carboxy-C1-4alkyl)-β-cyclodextrin; (carboxy C1 4alkyl)-γ-cyclodextrin; saccharide ethers of α-cyclodextrin; saccharide ethers of β-cyclodextrin; saccharide ethers of γ-cyclodextrin; sulfobutyl ethers of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin.6. A pharmaceutical composition according to claim 1 , wherein said cyclodextrin is hydroxypropyl-β-cyclodextrin.7. A pharmaceutical composition according to claim 1 , wherein the molar ratio of cyclodextrin to said HDAC inhibitor is from 0.5 to 5.8. A pharmaceutical composition according to claim 1 , which is a liquid.9. A pharmaceutical composition according to claim 1 , which comprises said HDAC inhibitor at a concentration of 0.1-1000 mg/mL.10. A pharmaceutical composition according to claim 1 , which comprises said HDAC inhibitor at a concentration of 30-300 mg/mL.11. A pharmaceutical composition according to claim 1 , which comprises said HDAC inhibitor at a concentration of 0.3-3000 mM.12. A pharmaceutical composition according to claim 1 , which comprises said HDAC inhibitor at a concentration of 100-500 mM.13 ...

BENZENE DERIVATIVE

A compound represented by general formula (I) (in the formula, all symbols are as described in the description) or a salt thereof has a potent nerve-protecting and/or -repairing activity, and therefore can be used as a therapeutic agent for neuropathy (e.g., chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, periarteritis nodosa, allergic vasculitis, diabetic peripheral neuropathy, entrapment neuropathy, peripheral neuropathy associated with the administration of a chemotherapeutic drug, or peripheral neuropathy associated with Charcot-Marie-Tooth disease). 1. A method of promoting differentiation of a Schwann cell , comprising contacting a cell with 3-[2-[(E)-5-[3-(benzenesulfonamide)phenyl]pent-4-enoxy]phenyl]propanoic acid or a salt thereof.2. The method according to claim 1 , wherein the cell is contacted with 3-[2-[(E)-5-[3-(benzenesulfonamide)phenyl]pent-4-enoxy]phenyl]propanoic acid.3. The method according to claim 1 , wherein the cell is contact with a salt of 3-[2-[(E)-5-[3-(benzenesulfonamide)phenyl]pent-4-enoxy]phenyl]propanoic acid.4. A method for preventing or treating neuropathy claim 1 , comprising administering an effective amount of 3-[2-[(E)-5-[3-(benzenesulfonamide)phenyl]pent-4-enoxy]phenyl]propanoic acid or a salt thereof to a mammal.5. The method according to claim 4 , wherein 3-[2-[(E)-5-[3-(benzenesulfonamide)phenyl]pent-4-enoxy]phenyl]propanoic acid is administered.6. The method according to claim 4 , wherein a salt of 3-[2-[(E)-5-[3-(benzenesulfonamide)phenyl]pent-4-enoxy]phenyl]propanoic acid is administered.7. The method according to claim 4 , wherein the neuropathy is a peripheral neuropathy.8. The method according to claim 7 , wherein the peripheral neuropathy is chronic inflammatory demyelinating polyneuropathy claim 7 , Guillain-Barre syndrome claim 7 , periarteritis nodosa claim 7 , allergic vasculitis claim 7 , diabetic peripheral neuropathy claim 7 , entrapment neuropathy claim 7 , peripheral neuropathy ...

PROCESS FOR THE PREPARATION OF HIGH PURE ERIBULIN AND ITS MESYLATE SALT

The present invention relates to a process for the preparation of high pure Eribulin and Eribulin Mesylate. The present invention involves preparation of high pure Eribulin and its mesylate salt involving chiral acid addition salts of Eribulin. 2. A process for the preparation of high pure Eribulin comprising the steps of:a) reacting Eribulin free base with a protected chiral acid to form corresponding acid addition salt of Eribulin,b) purifying the acid addition salt of Eribulin by recrystallization to control the related impurities,c) treating the salt with a base to liberate high pure Eribulin,d) optionally converting the high pure Eribulin to Eribulin mesylate.3. The process as claimed in and , wherein chiral acid is amino acid.4. The amine acid according to claim 3 , wherein amino acid is selected from L-phenyl alanine claim 3 , L-Valine claim 3 , L-methionine claim 3 , L-isoleucine and L-Tyrosine.5. The process as claimed in and claim 3 , wherein solvent used to recrystallize acid addition salt of Eribulin is selected from acetonitrile claim 3 , dichloromethane claim 3 , n-pentane and hexane.6. The process as claimed in and claim 3 , wherein base used to liberate pure Eribulin from Eribulin chiral acid addition salt is selected from ammonia claim 3 , aqueous ammonia claim 3 , sodium hydroxide claim 3 , ammonium hydroxide claim 3 , sodium carbonate claim 3 , ammonium carbonate.7. A process for the preparation of Eribulin mesylate by treating pure Eribulin base with ammonium methanesulfonate.8. Eribulin base having the purity of more than 99%.9. Eribulin mesylate is having the purity of more than 99% claim 3 , preferably more than 99.5%. The present invention relates to the process for the preparation of high pure Eribulin and Eribulin Mesylate. The present invention involves less expensive reagents, solvents and the process conditions can be easily adopted for commercial scale.Eribulin, is a synthetic macrocyclic analogs of halichondrin B, and is represented by ...

Serine protease inhibitors

Potent low molecular weight, highly selective, competitive non-peptidic serine protease inhibitors and their use in treating serine protease-associated diseases are disclosed.

MAO-B INHIBITORS USEFUL FOR TREATING OBESITY

The invention provides novel compounds of formulae I and II: 113-. (canceled)1519-. (canceled)20. The method of claim 14 , wherein the disease is selected from obesity claim 14 , Type 2 diabetes claim 14 , hypertension claim 14 , dyslipidemia claim 14 , high blood pressure claim 14 , and insulin resistance.21. The method of claim 20 , wherein the compound is selected from Table A claim 20 , or a stereoisomer or pharmaceutically acceptable salt thereof.22. The method of claim 20 , wherein the compound is selected from Table I claim 20 , or a stereoisomer or pharmaceutically acceptable salt thereof.23. The method of claim 20 , wherein the compound is selected from Table IIa claim 20 , or a stereoisomer or pharmaceutically acceptable salt thereof.24. The method of claim 20 , wherein the compound is selected from Table IIb claim 20 , or a stereoisomer or pharmaceutically acceptable salt thereof.25. The method of claim 20 , wherein the compound is selected from Table IIIa claim 20 , or a stereoisomer or pharmaceutically acceptable salt thereof.26. The method of claim 20 , wherein the compound is selected from Table IIIb claim 20 , or a stereoisomer or pharmaceutically acceptable salt thereof.27. The method of claim 20 , wherein the compound is selected from Table IVa claim 20 , or a stereoisomer or pharmaceutically acceptable salt thereof.28. The method of claim 20 , wherein the compound is selected from Table IVb claim 20 , or a stereoisomer or pharmaceutically acceptable salt thereof.29. The method of claim 20 , wherein the compound is selected from Table IVc claim 20 , or a stereoisomer or pharmaceutically acceptable salt thereof.30. The method of claim 20 , wherein the compound is selected from Table IVd claim 20 , or a stereoisomer or pharmaceutically acceptable salt thereof.31. The method of claim 20 , wherein the compound is selected from Table V claim 20 , or a stereoisomer or pharmaceutically acceptable salt thereof.32. The method of claim 20 , wherein the ...

SULFAMOYL-ARYLAMIDES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B

Inhibitors of HBV replication of Formula (I) 2. The compound according to claim 1 , wherein the C-Calkyl group as defined in Rrepresents a branched C-Calkyl.4. A compound according to claim 3 , wherein Ris selected from the group consisting of C-Calkyl optionally substituted with —C≡CH claim 3 , —CN claim 3 , —OH claim 3 , C-Calkyloxy claim 3 , —C(═O)O—R claim 3 , —C(═O)N(R) claim 3 , —N(R) claim 3 , —NHC(═O)—Rand —NHC(═O)O—R.5. A compound according to or claim 3 , wherein at least one Ris —OH.6. A compound according to or claim 3 , wherein at least one Ris C-Calkyl substituted with OH.7. A compound according to any one of the previous claims for use in the prevention or treatment of an HBV infection in a mammal.8. A pharmaceutical composition comprising a compound according to any of to claim 3 , and a pharmaceutically acceptable carrier.9. A product containing (a) a compound of Formula (I) as defined in any one of to claim 3 , and (b) another HBV inhibitor claim 3 , as a combined preparation for simultaneous claim 3 , separate or sequential use in the treatment of HBV infections. The Hepatitis B virus (HBV) is an enveloped, partially double-stranded DNA (dsDNA) virus of the Hepadnavirus family (Hepadnaviridae). Its genome contains 4 overlapping reading frames: the precore/core gene; the polymerase gene; the L, M, and S genes, which encode for the 3 envelope proteins; and the X gene.Upon infection, the partially double-stranded DNA genome (the relaxed circular DNA; rcDNA) is converted to a covalently closed circular DNA (cccDNA) in the nucleus of the host cell and the viral mRNAs are transcribed. Once encapsidated, the pregenomic RNA (pgRNA), which also codes for core protein and Pol, serves as the template for reverse transcription, which regenerates the partially dsDNA genome (rcDNA) in the nucleocapsid.HBV has caused epidemics in parts of Asia and Africa, and it is endemic in China. HBV has infected approximately 2 billion people worldwide of which approximately ...

BENZYL SULFONAMIDE DERIVATIVES AS RORc MODULATORS

Compounds of the formula Ia or Ib: 2. The compound of claim 1 , wherein m is 0.3. The compound of claim 1 , wherein n is 0.4. The compound of claim 1 , wherein n is 1.5. The compound of claim 1 , wherein r is 0 or 1.6. The compound of claim 1 , wherein A is a bond.7. The compound of claim 1 , wherein A is —O—.8. The compound of claim 1 , wherein each of X claim 1 , X claim 1 , Xand Xis CR.9. The compound of claim 1 , wherein Ris hydrogen.10. The compound of claim 1 , wherein R claim 1 , R claim 1 , Rand Rare hydrogen.11. The compound of claim 1 , wherein Ris Calkyl.12. The compound of claim 1 , wherein Ris halo or trifluoromethyl.13. The compound of claim 1 , wherein Ris Calkylsulfonyl; Calkylsulfonylamino; aminosulfonyl; or aminocarbonyl.14. The compound of claim 1 , wherein Ris Calkylsulfonyl.15. The compound of claim 1 , wherein Ris aminosulfonyl.16. The compound of claim 1 , wherein Ris Calkylsulfonylamino.17. The compound of claim 1 , wherein Ris aminocarbonyl.18. The compound of claim 1 , wherein Ris Calkylsulfonylamino.19. The compound of claim 1 , wherein Ris hydrogen.22. A composition comprising:(a) a pharmaceutically acceptable carrier; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(b) a compound of .'}23. A method for treating arthritis claim 1 , said method comprising administering to a subject in need thereof an effective amount of a compound of . This application claims the benefit of priority of U.S. Provisional Patent Application Ser. No. 61/735,364 filed Dec. 10, 2012, the disclosure of which is incorporated herein by reference in their entirety.The invention pertains to compounds that modulate the function of retinoid-receptor related orphan receptor RORc (RORγ) and use of such compounds for treatment of autoimmune diseases.T helper 17 cells (Th17) are interleukin (IL)-17 secreting CD4+ T cells involved in pathogenesis of autoimmune diseases such as rheumatoid arthritis, irritable bowel disease, psoriasis, psoriatic arthritis and ...

Sulfonimide salts for battery applications

A class of sulfonimide salts for solid-state electrolytes can be synthesized based on successive S N Ar reactions of fluorinated phenyl sulfonimides: Fluorinated Aryl Sulfonimide Tags (FAST). The chemical and electrochemical oxidative stability of these FAST salts as well as other properties like solubility, Lewis basicity, and conductivity can be tuned by introducing different numbers and types of nucleophilic functional groups to the FAST salt scaffold.

SULFONAMIDE COMPOUNDS AND THEIR USE AS STAT5 INHIBITORS

The present disclosure relates to compounds having the Formula (Formula (I)) which are inhibitors of STAT5. 2. The compound according to claim 1 , wherein Ris —(C-C)-aryl claim 1 , —(CH)—(C-C)-aryl or —C(═O)—(C-C)-aryl.3. The compound according to claim 2 , wherein Ris phenyl claim 2 , naphthyl claim 2 , —CH— phenyl claim 2 , —CH-naphthyl claim 2 , —C(═O)-phenyl or —C(═O)-naphthyl.4. The compound according to claim 1 , the optional substituents on the aryl group of Rare selected from one to five of halo claim 1 , (C-C)-alkyl and (C-C)-alkoxy.5. (canceled)64. The compound according to claim 1 , the optional substituents on the aryl group of Rare selected from one to three substituents selected from fluoro claim 1 , methyl or t-butyl.7. (canceled)9. The compound according to claim 1 , wherein Ris —(C-C)-aryl or —(CH)—(C-C)-aryl.10. The compound according to claim 9 , wherein Ris phenyl or —CH-phenyl.11. The compound according to claim 9 , wherein the optional substituents on the aryl group of Rare selected from one to five of halo claim 9 , halo-substituted-(C-C)-alkyl claim 9 , -(cyclopropyl)-CF claim 9 , —NO claim 9 , CN claim 9 , —SOR′ and —COOR′ claim 9 , wherein R′ is H or (C-C)-alkyl.12. (canceled)13. The compound according to claim 11 , wherein the optional substituents on the aryl group of Rare one to three chloro groups.14. (canceled)15. The compound according to claim 1 , wherein Ris —(C-C)-aryl or —(CH)—(C-C)-aryl.16. (canceled)17. The compound according to claim 15 , wherein the optional substituents on the aryl group of Rare selected from one to five of halo claim 15 , OH claim 15 , (C-C)-alkyl claim 15 , and (C-C)-alkoxy.18. (canceled)19. The compound according to claim 17 , wherein the optional substituents on the aryl group of Rare selected from one to five of fluoro claim 17 , chloro claim 17 , bromo claim 17 , and (C-C)-alkyl.20. (canceled)21. (canceled)22. The compound according to claim 1 , wherein R is H claim 1 , OH claim 1 , fluoro claim 1 , ...

HALOGENATED PHENYLSULFONAMIDE HYDROXAMIC ACID COMPOUNDS, COMPOSITIONS AND USES THEREOF AS SELECTIVE HDAC6 INHIBITORS

The present application relates to fluorinated benzylsulfonamide hydroxamic acid compounds of Formula I and/or pharmaceutically acceptable salt, solvate and/or prodrug thereof: (I) for use as a inhibitor of HDAC6. The application also relates to methods of treating a disease, disorder or condition using the compounds and compositions of the application. 2. The compound of claim 1 , wherein Ris selected from H claim 1 , Calkyl claim 1 , Calkyleneheteroaryl claim 1 , Ccycloalkyl and Calkylenearyl claim 1 , the latter 4 groups optionally substituted with one or more groups independently selected from halo claim 1 , Calkyl claim 1 , N(Calkyl)(Calkyl) claim 1 , OCalkyl claim 1 , Ccycloalkyl claim 1 , Cheterocycloalkyl claim 1 , phenyl claim 1 , Cheteroayl claim 1 , in which groups Ccycloalkyl claim 1 , Cheterocycloalkyl claim 1 , phenyl claim 1 , and Cheteroayl are each unsubstituted or substituted with one or more Calkyl or halo.3. The compound of or claim 1 , wherein Ris selected from H claim 1 , Calkyl claim 1 , Ccycloalkyl claim 1 , Calkyleneheteroaryl claim 1 , and Calkylenearyl claim 1 , the latter 4 groups optionally substituted with one or more groups independently selected from halo claim 1 , Calkyl claim 1 , N(Calkyl)(Calkyl) claim 1 , and OCalkyl.4. The compound of any one of to claim 1 , wherein Ris selected from H claim 1 , methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , Ccycloalkyl claim 1 , benzyl claim 1 , pyridinylmethyl claim 1 , pyridazinylmethyl claim 1 , pyrimidinylemethyl and pyrazinylmethyl claim 1 , the latter 9 groups optionally substituted with one or more groups independently selected from F claim 1 , Calkyl claim 1 , N(CH) claim 1 , and OCH.5. The compound of claim 4 , wherein Ris pyridinylmethyl claim 4 , pyridazinylmethyl claim 4 , pyrimidinylemethyl or pyrazinylmethyl.6. The compound of claim 4 , wherein Ris Ccycloalkyl.7. The compound of claim 4 , wherein Ris benzyl.8. The compound of claim 4 , wherein Ris pyridinylmethyl.9. The ...

SMALL MOLECULE INHIBITORS OF STAT3 WITH ANTI-TUMOR ACTIVITY

The present invention concerns compounds, compositions containing these compounds, and methods of using these compounds and compositions as inhibitors of Stat3 signaling, Stat3 dimerization, Stat3-DNA binding, Stat5-DNA binding, and/or aberrant cell growth in vitro or in vivo, e.g., as anti-cancer agents for treatment of cancer, such as breast cancer. The compounds of the invention include, but are not limited to, NSC 74859 (S3I-201), NSC 42067, NSC 59263, NSC 75912, NSC 11421, NSC 91529, NSC 263435, and pharmaceutically acceptable salts and analogs of the foregoing. Other non-malignant diseases characterized by proliferation of cells that may be treated using the compounds of the invention, but are not limited to, cirrhosis of the liver; graft rejection; restenosis; and disorders characterized by a proliferation of T cells such as autoimmune diseases, e.g., type 1 diabetes, lupus and multiple sclerosis. The invention further includes an in-vitro screening test for the presence of malignant cells in a mammalian tissue; a method of identifying inhibitors of constitutive Stat3 activation, Stat3-DNA binding, Stat5-DNA binding, and/or Stat3 dimerization; and a method of identifying anti-cancer agents. 2. The method of claim 1 , wherein the proliferation disorder is cancer.3. The method of claim 1 , wherein the proliferation disorder is a non-malignant disease characterized by aberrant Stat3 activation of cells.4. The method of claim 1 , wherein the compound is administered locally at the site of the proliferation disorder.5. The method of claim 1 , wherein the subject is not suffering from the proliferation disorder claim 1 , and wherein the compound is administered to delay onset of the proliferation disorder.6. The method of claim 1 , wherein the subject is human or a non-human mammal.7. The method of claim 1 , further comprising identifying the subject as one suffering from the proliferation disorder.8. The method according to claim 1 , wherein for the compound of ...

Heterodimers of Glutamic Acid

Compounds of Formula (Ia) 167-. (canceled) This application claims priority to U.S. provisional application No. 60/857,490 filed Nov. 8, 2006 and U.S. provisional application No. 60/878,678 filed Jan. 5, 2007, the disclosures of which are incorporated herein by reference in their entireties.At least 1 million men suffer from prostate cancer and it's estimated that the disease will strike one in six U.S. men between the ages of 60 and 80. There are more than 300,000 new cases of prostate cancer diagnosed each year. Prostate cancer will affect one in six men in the United States, and the mortality from the disease is second only to lung cancer. An estimated $2 billion is currently spent worldwide on surgical, radiation, drug therapy and minimally invasive treatments, $1 billion of the spending in the U.S. There is presently no effective therapy for relapsing, metastatic, androgen-independent prostate cancer. New agents that will enable rapid visualization of prostate cancer and specific targeting to allow radiotherapy present are needed.N-acetylated alpha-linked acidic dipeptidase (NAALADase), also known as glutamate carboxypeptidase II (GCPII) is a neuropeptidase which cleaves N-acetylaspartyl-glutamate (NAAG) into N-acetylaspartate and glutamate in the nervous system, see below, depicting hydrolytic cleavage of NAAG by NAALDase through the tetrahedral intermediate. The enzyme is a type II protein of the co-catalytic class of metallopeptidases, containing two zinc atoms in the active site.Independent of its characterization in the nervous system, one form of NAALADase was shown to be expressed at high levels in human prostatic adenocarcinomas and was designated the prostate-specific membrane antigen (PSMA). The NAALADase/PSMA gene is known to produce multiple mRNA splice forms and based on previous immunohistochemical evidence, it has been assumed that the human brain and prostate expressed different isoforms of the enzyme.Human prostate-specific membrane antigen ( ...

CRYSTALLINE 5-(DIMETHYLAMINO)-N-(4-(MORPHOLINOMETHYL)PHENYL)NAPHTHALENE-1-SULFONAMIDE DI-HYDROCHLORIDE DI-HYDRATE

Crystalline 5-(dimethylamino)-N-(4-(morpholinomethyl)phenyl)naphthalene-1-sulfonamide dihydrochloride dihydrate, methods of preparing the crystalline salt, pharmaceutical compositions containing the crystalline salt, and methods of treatment using the crystalline salt are disclosed. 2. The compound of claim 1 , wherein the compound is characterized by an X-ray powder diffraction (XRPD) pattern comprising characteristic diffraction peaks at least at 13.1°±0.2° claim 1 , 14.6°±0.2° claim 1 , 15.0°±0.2° claim 1 , 18.1±0.2° claim 1 , 22.2±0.2° claim 1 , 22.6±0.2° claim 1 , and 24.4±0.2° expressed as 2θ angles and determined using Cu-Kα radiation.3. The compound of claim 1 , wherein the compound is characterized by an XRPD pattern comprising characteristic diffraction peaks at least at 13.1°±0.1° claim 1 , 14.6°±0.1° claim 1 , 15.0°±0.1° claim 1 , 18.1±0.1° claim 1 , 22.2±0.1° claim 1 , 22.6±0.1° claim 1 , and 24.4±0.1° expressed as 2θ angles and determined using Cu-Kα radiation.4. The compound of claim 1 , wherein the compound is characterized by an XRPD pattern as shown in .5. The compound of claim 1 , wherein the compound has a primary melting onset temperature from 158° C. to 164° C. claim 1 , and wherein the primary melting onset temperature is determined by differential scanning calorimetry.6. The compound of claim 1 , wherein the compound has a primary melting enthalpy from 60 J/g to 65 J/g claim 1 , and wherein the primary melting enthalpy is determined by differential scanning calorimetry.7. The compound of claim 1 , wherein the compound has a primary melting peak from 175 J/g to 182 J/g claim 1 , and wherein the primary melting peak is determined by differential scanning calorimetry.8. The compound of claim 1 , wherein the compound has a secondary melting onset temperature of 204.7° C. claim 1 , a secondary melting enthalpy of 20.7 J/g claim 1 , and a secondary melting peak at 211.2° C.9. The compound of claim 1 , wherein the compound exhibits a differential ...

N-substituted isopropyldimethyl azulene sulfonamide derivatives, and preparation method and use thereof

The present invention provides an N-substituted isopropyldimethyl azulene sulfonamide derivative as represented by formula (I), and preparation method and uses thereof, wherein R1 is an alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, amino, or a substituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and amino. The N-substituted isopropyldimethyl azulene sulfonamide derivative can be used in treating gastric ulcer.

INHIBITORS OF THE MITF MOLECULAR PATHWAY

Provided herein are compounds of the formula (IV) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful as MITF inhibitors, MITF pathway inhibitors and for the treatment of cancer. 3. The compound of claim 1 , wherein Ris hydrogen claim 1 , chlorine claim 1 , methyl claim 1 , methoxy claim 1 , phenyl claim 1 , piperazinyl claim 1 , methylpiperazinyl claim 1 , piperidinyl claim 1 , morpholinyl claim 1 , thiomorpholinyl claim 1 , phenyl-piperazinyl claim 1 , ethyl-piperazinyl claim 1 , —NHCHCH═CH claim 1 , —CHCH═CH claim 1 , —NH claim 1 , tert-butyl-piperazinyl claim 1 , pyrrolidinyl claim 1 , —NCHCHCHN(CHCH) claim 1 , —CHCHCHN(CHCH) claim 1 , or —CH(CH)phenyl.4. The compound of claim 1 , wherein Ris methyl claim 1 , hydrogen claim 1 , —CHCH═CH claim 1 , phenyl claim 1 , —CH-chlorophenyl claim 1 , chlorophenyl claim 1 , acetyl claim 1 , —C(O)-phenyl claim 1 , —C(O)— bromophenyl claim 1 , —S(O)-phenyl claim 1 , —S(O)-bromophenyl claim 1 , —S(O)-thiazolyl claim 1 , —S(O)-bromothiazolyl claim 1 , difluorophenyl claim 1 , methoxyphenyl or -phenyl-S(O)NH.5. The compound of claim 1 , wherein Ris hydrogen claim 1 , methyl or acetyl.11. The compound of claim 1 , wherein the compound is selected from the group consisting of compounds shown in Tables 5-10.12. The compound of claim 1 , wherein the compound is 4-((1 claim 1 ,4-dioxo-1 claim 1 ,4-dihydronaphthalen-2-yl)amino)benzenesulfonamide.13. A pharmaceutical composition claim 1 , comprising a therapeutically effective amount of a compound of and a pharmaceutically acceptable carrier.15. A method for treating cancer claim 1 , comprising administering a therapeutically effective amount of a compound of to a subject in need thereof.17. The method of claim 16 , wherein the cancer is a MITF-dependent cancer.18. The method of claim 15 , wherein the cancer is a MITF-dependent cancer. ...

PHENYL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF, AND THEIR THERAPEUTIC APPLICATIONS

Provided herein are compounds, for example, a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition. 6. The compound of any one of to , wherein X is —SO—.7. The compound of any one of to , wherein Y is —NR—.12. The compound of any one of to , wherein Ris hydrogen or Calkyl , optionally substituted with one or more substituents Q.13. The compound of any one of to , wherein Ris Calkyl , substituted with one or more substituents Q.14. The compound of any one of to , wherein Ris hydrogen , —CHR—O—C(O)R , —CHR—O—C(O)OR , or —CHR—O—C(O)NRR.15. The compound of claim 14 , wherein Ris —CHR—O—C(O)R.16. The compound of claim 14 , wherein Ris —CHR—O—C(O)OR.17. The compound of any one of to claim 14 , wherein Ris hydrogen or Calkyl claim 14 , optionally substituted with one or more substituents Q.18. The compound of any one of to claim 14 , wherein Ris Calkyl or Ccycloalkyl claim 14 , each optionally substituted with one or more substituents Q.19. The compound of any one of to claim 14 , wherein Ris hydrogen claim 14 , pivalyloxymethyl claim 14 , or 1-((cyclohexyloxy)carbonyloxy)ethyl.20. The compound of any one of to claim 14 , wherein Y is —NH—.21. The compound of any one of to claim 14 , wherein Y is —CRR—.22. The compound of any one of to and claim 14 , wherein Y is —CH—.23. The compound of any one of to claim 14 , wherein Y is —SO—.24. The compound of any one of to and claim 14 , wherein X is —NR—.25. The compound of claim 24 , wherein Ris hydrogen or Calkyl claim 24 , optionally substituted with one or more substituents Q.26. The compound of claim 24 , wherein Ris Calkyl claim 24 , ...

HDAC INHIBITORS

Compounds of formula (I) inhibit HDAC activity: 122-. (canceled)24. The compound or pharmaceutically acceptable salt thereof according to wherein the radical HONHC(═O)—W— is attached to the ring containing A claim 23 , B claim 23 , and D in a position meta- or para- to the radical RRCHNHYLX[CH]—.26. The compound or pharmaceutically acceptable salt thereof according to wherein the radical —YLX[CH]— is —CH—.27. The compound or pharmaceutically acceptable salt thereof according to wherein Ris methyl claim 23 , ethyl claim 23 , n- or iso-propyl claim 23 , n- claim 23 , sec- or tert-butyl claim 23 , cyclohexyl claim 23 , allyl claim 23 , phenyl claim 23 , benzyl claim 23 , 2- claim 23 , 3- or 4-pyridylmethyl claim 23 , N-methylpiperidin-4-yl claim 23 , tetrahydrofuran-3-yl or methoxyethyl.28. The compound or pharmaceutically acceptable salt thereof according to wherein Ris cyclopentyl.29. The compound or pharmaceutically acceptable salt thereof according to wherein Ris phenyl claim 23 , benzyl claim 23 , phenylethyl claim 23 , tert-butoxymethyl or iso-butyl.30. The compound or pharmaceutically acceptable salt thereof according to wherein Ris —CH(CH) claim 23 , cyclohexyl claim 23 , —CHO(t-Bu) claim 23 , —CHS(t-Bu) claim 23 , or phenyl.32. The compound or pharmaceutically acceptable salt thereof according to wherein Ris methyl claim 31 , ethyl claim 31 , n- or iso-propyl claim 31 , n- claim 31 , sec- or tert-butyl claim 31 , cyclohexyl claim 31 , allyl claim 31 , phenyl claim 31 , benzyl claim 31 , 2- claim 31 , 3- or 4-pyridylmethyl claim 31 , N-methylpiperidin-4-yl claim 31 , tetrahydrofuran-3-yl or methoxyethyl.33. The compound or pharmaceutically acceptable salt thereof according to wherein Ris cyclopentyl.34. The compound or pharmaceutically acceptable salt thereof according to wherein Ris phenyl claim 31 , benzyl claim 31 , phenylethyl claim 31 , tert-butoxymethyl or iso-butyl.35. The compound or pharmaceutically acceptable salt thereof according to wherein Ris —CH( ...

COMPOUND HAVING ENHANCING ACTIVITY FOR GLUCAGON-LIKE PEPTIDE-1 RECEPTOR ACTIONS

Compounds represented by formula (I): 2. The compound or salt according to claim 1 , wherein{'sub': '6-14', 'A is a Caryl group or a 5- or 6-membered monocyclic aromatic heterocyclic group, each of which is optionally further substituted,'}L is a bond or a methylene group,Q is an oxygen atom,{'sup': 4', '5, 'sub': '1-6', 'Rand Rare the same or different and are each independently a hydrogen atom or an optionally substituted Calkyl group, and'}n is 1 or 2.3. The compound or salt according to claim 1 , wherein{'sub': 1-6', '1-6', '1-6', '1-3', '1-6', '1-6', '1-6', '1-3', '1-6', '1-6', '1-6', '1-3, 'A is a phenyl group optionally further substituted by the same or different 1 to 5 substituents selected from the group consisting of a halogen atom, a hydroxy group, a carboxy group, a sulfanyl group, an optionally substituted Calkyl group, an optionally substituted Calkoxy group, an optionally substituted amino group, a Calkylthio group optionally substituted by a halogen atom, and a Calkylenedioxy group, or a pyridyl group optionally further substituted by the same or different 1 to 4 substituents selected from the group consisting of a halogen atom, a hydroxy group, a carboxy group, a sulfanyl group, an optionally substituted Calkyl group, an optionally substituted Calkoxy group, an optionally substituted amino group, a 4- to 7-membered monocyclic non-aromatic heterocyclic group, a Calkylthio group optionally substituted by a halogen atom, and a Calkylenedioxy group, B is a benzene ring optionally further substituted by the same or different 1 to 4 substituents selected from the group consisting of a halogen atom, a hydroxy group, a sulfanyl group, an optionally substituted Calkyl group, an optionally substituted Calkoxy group, an optionally substituted amino group, a Calkylthio group optionally substituted by a halogen atom, a Calkylenedioxy group, and a 4- to 7-membered monocyclic non-aromatic heterocyclic group,'}L is a bond or a methylene group,{'sup': '1', 'sub': 1 ...

Process

The present invention relates to a process for preparing (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione, and pharmaceutically acceptable salts thereof, especially the hydrochloride salt. The invention also relates to a process for making intermediates useful in the formation of said compound, and to the intermediates, per se. 23-. (canceled)5. A process according to claim 1 , wherein said deprotection step comprises treating a compound of formula K with thioglycolic acid in a suitable solvent claim 1 , in the presence of a base claim 1 , preferably LiOH or KOH.6. A process according to claim 1 , wherein the compound RY isolated from the deprotection step is purified.7. A process according to claim 6 , wherein purification is performed: via a two-step procedure comprising (i) formation of an HCl salt of a compound of formula RY and (ii) crystallisation of the HCl salt so formed from a suitable solvent claim 6 , preferably toluene; or via a re-slurry in 2-butanone.919-. (canceled)2223-. (canceled)25. A process according to claim 21 , wherein the reduction of compound D to the compound RY is carried out using a reducing agent comprising a NaBH—BF. complex.26. A process according to claim 25 , wherein the NaBH—BF. complex is NaBH—BF.THF.2834-. (canceled)36. A process according to claim 1 , wherein the process further comprises converting the compound RY to the HCl salt thereof.37. (canceled)39. (canceled)4142-. (canceled)4547-. (canceled)4950-. (canceled)5254-. (canceled) This application is a filing under 35 U.S.C. 371 of International Application No. PCT/PT2012/000024 filed Jun. 29, 2012, entitled “Process,” which claims priority to U.S. Provisional Patent Application No. 61/502,647 filed Jun. 29, 2011, which applications are incorporated by reference herein in their entirety.The present invention relates to a process for preparing ®-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione, and ...

NOVEL SULFONAMIDE DERIVATIVES HAVING SELECTIVE NOX INHIBITING ACTIVITY

A compound of formula (I) or a pharmaceutically acceptable salt thereof. The compound is useful in therapy, e.g. for the treatment of a condition or disorder associated with nicotinamide adenine dinucleotide phosphate oxidase 4 or 2 (Nox4 or Nox2) activity. A pharmaceutical composition comprising the compound. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from C1-C3 alkyl claim 1 , halogen claim 1 , hydroxy claim 1 , and hydroxy-C1-C3 alkyl.3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris selected from C1-C3 alkyl claim 2 , halogen claim 2 , and hydroxy.4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Ris hydroxy.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Ris independently selected from C1-C6 alkyl claim 1 , C3-C6 cyclolalkyl claim 1 , C3-C6 cycloalkyl-C1-C3 alkyl claim 1 , C1-C6 alkoxy claim 1 , C1-C6 alkoxy-C1-C3 alkyl claim 1 , hydroxy claim 1 , hydroxy-C1-C3 alkyl claim 1 , carboxy claim 1 , carboxy-C1-C3 alkyl claim 1 , and halogen; and when n is at least 2 claim 1 , two Rattached to adjacent atoms of the phenyl ring claim 1 , together with the phenyl ring atoms to which they are attached claim 1 , may form a 4- to 6-membered non-aromatic ring optionally containing one or more heteroatoms and optionally substituted with one or more moieties independently selected from C1-C3 alkyl and halogen.7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein k is 1.8. The compound of or claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein m is 1.9. The compound of claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein each Ris independently selected from C1-C3 alkyl claim 6 , hydroxy claim 6 , carboxy claim 6 , and halogen.10. The compound of claim 9 , or a pharmaceutically acceptable salt ...

ABA RECEPTOR AGONISTS THAT MODULATE TRANSPIRATION

The present invention provides agonist compounds that activate ABA receptors, agricultural formulations comprising the agonist compounds, and methods of use for the compounds and formulations. The agricultural formulations are useful for inducing ABA responses in plant vegetative tissues, reducing abiotic stress in plants, and inhibiting germination of plant seeds. The compounds are also useful for inducing expression of ABA-responsive genes in cells that express endogenous or heterologous ABA receptors. 2. The agricultural formulation of claim 1 , wherein Zis phenyl.3. The agricultural formulation of claim 1 , wherein at most one member selected from the group consisting of A claim 1 , A claim 1 , A claim 1 , and Ais N.5. The agricultural formulation of claim 1 , wherein no more than one ring substituent ortho- to Ris halo or haloalkyl.6. The agricultural formulation of claim 1 , wherein no more than one ring substituent is halo claim 1 , haloalkyl claim 1 , nitro claim 1 , or —SR.7. The agricultural formulation of claim 1 , wherein at least one ring substituent ortho- to Ris methyl.9. The agricultural formulation of claim 8 , wherein Ris hydrogen.10. The agricultural formulation of claim 8 , wherein Rand Rare hydrogen.11. The agricultural formulation of claim 8 , wherein Rand Rare each independently selected from the group consisting of halo claim 8 , nitro claim 8 , Calkyl claim 8 , cyclopropyl claim 8 , —OR claim 8 , and —N(R).12. The agricultural formulation of claim 11 , wherein Ris hydrogen or halo.13. The agricultural formulation of claim 11 , wherein Ris Calkyl.14. The agricultural formulation of claim 13 , wherein Ris methyl.15. The agricultural formulation of claim 1 , wherein each ring substituent ortho- to Ris selected independently from the group consisting of methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , chloro claim 1 , bromo claim 1 , trifluoromethyl claim 1 , methoxy claim 1 , and ethoxy.16. The agricultural formulation of claim 1 , wherein ...

PROCESSES AND INTERMEDIATES FOR PREPARING MCL1 INHIBITORS

The present disclosure provides methods for preparing MCL1 inhibitors or a salt thereof and related key intermediates. 16-. (canceled)2734-. (canceled) This application claims the benefit of U.S. provisional application Ser. No. 62/940,387 filed on Nov. 26, 2019. The entire contents of the application are incorporated herein by reference in its entirety.The present disclosure relates to methods and intermediates for the synthesis of certain compounds which inhibit MCL1, for use in the treatment of cancers.Apoptosis (programmed cell death) is a process for elimination of unwanted or potentially dangerous cells from an organism. Avoidance of apoptosis is critical for the development and sustained growth of tumors. Myeloid cell leukemia 1 protein (MCL1) is an antiapoptotic member of the Bcl-2 family of proteins. MCL1 is overexpressed in many cancers. Overexpression of MCL1 prevents cancer cells from undergoing apoptosis. Research has shown that MCL1 inhibitors can be used to treat cancers. Compounds that inhibit MCL1 have been disclosed, but there remains a need for synthetic methods for preparing such compounds on a manufacturing scale.PCT Application No. PCT/US2019/032053 (WO 2019/222112) discloses novel compounds useful as MCL1 inhibitors. This patent publication discloses that compounds according to Formula (A),and pharmaceutically acceptable salts thereof, are effective as inhibitors of MCL1, and are useful in the treatment of cancers.There is currently a need for synthetic methods and intermediates that can be used to prepare the compound of formula I and salts thereof. There is also a need for methods for preparing intermediate compounds that can be used to prepare the compound of formula I and salts thereof.The present disclosure provides methods for making compounds according to Formula (A), as shown above. In some embodiments, the present disclosure provides compounds according to Formula (I),wherein: is a single or double bond;In particular embodiments, the ...

SALICYCLIC ACID DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, COMPOSITION THEREOF AND METHOD OF USE THEREOF

The present invention relates to novel compounds, compositions containing same and methods for inhibiting STAT3 and/or STAT5 activity or for the treatment of a STAT3 or STAT5-dependent cancer using said compounds; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 2. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate or prodrug thereof claim 1 , wherein m=0 and Ris —CH.3. The compound of or claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate or prodrug thereof claim 1 , wherein Ris -(A)-(A) claim 1 , Aand Aboth having the definition as in .4. The compound of claim 3 , or a pharmaceutically acceptable salt claim 3 , solvate or prodrug thereof claim 3 , wherein Ais cyclohexyl and Ais benzyl.5. The compound of claim 3 , claim 3 , or claim 3 , or a pharmaceutically acceptable salt claim 3 , solvate or prodrug thereof claim 3 , wherein Ris pentafluorotoluene.6. A compound that is compound 22 claim 3 , 31 claim 3 , 32 or 33 from Table 1 claim 3 , or a pharmaceutically acceptable salt claim 3 , solvate or prodrug thereof.76. A pharmaceutical composition comprising a compound as defined in any one of to or a pharmaceutically acceptable salt claims 1 , solvate or prodrug thereof claims 1 , and an acceptable excipient.8. A method for inhibiting STAT3 and/or STAT5 activity claims 1 , comprising administering a therapeutically effective amount of a compound as defined in any one of to or a pharmaceutically acceptable salt claims 1 , solvate or prodrug thereof claims 1 , to a patient.9. A method for treating or preventing a cancer with cancer cells harbouring activated STAT3 or STAT5 claims 1 , comprising administering a therapeutically effective amount of a compound as defined in any one of to claims 1 , or a pharmaceutically acceptable salt claims 1 , solvate or prodrug thereof to a patient.10. The method of claim 9 , where said cancer is from solid or hematological tumors.11. The method of claim 10 , wherein said ...

HIGH AFFINITY BETA LACTAMASE INHIBITORS

Inhibitors of beta lactamases and their use in treating bacterial infections are disclosed.

Sulfonamide derivative and pharmaceutically acceptable acid addition salt thereof

The present invention aims to provide a novel low-molecular-weight compound exhibiting an orexin receptor agonist activity and expected to be useful as a prophylactic or therapeutic agent for narcolepsy and the like. The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the description, or a pharmaceutically acceptable acid addition salt thereof, which has an orexin receptor agonist activity, and an orexin receptor agonist containing the compound or a pharmaceutically acceptable acid addition salt thereof.

RECORDING MATERIAL AND RECORDING SHEET

A recording material and a recording sheet having excellent color-developing performance and storage stability and particularly having excellent heat-resistance of background. The recording material contains a color former (A), a compound represented by formula (I) (B), and a compound represented by formula (II) (C). 3. The recording material according to wherein the compound represented by the above formula (I) is at least one compound of 4 claim 1 ,4′-diaminodiphenyl sulfone and 3 claim 1 ,3′-diaminodiphenyl sulfone.4. The recording material according to wherein Ais SO—NH and X is O in a compound represented by the above formula (III) claim 2 , formula (IV) claim 2 , or formula (V).6. The recording material according to claim 5 , wherein the compound represented by the above formula (VI) is N-(2-(3-phenylureido)phenyl)benzenesulfonamide.7. The recording material according to claim 6 , wherein N-(2-(3-phenylureido)phenyl)benzenesulfonamide is in a crystalline form showing peaks at diffraction angles (2θ±0.10°) of 23.60° claim 6 , 20.80° claim 6 , 12.24° claim 6 , and 13.80° in powder X-ray diffractometry using Cu-Kα rays.8. The recording material according to claim 1 , wherein the color former is a fluoran dye.9. A recording sheet having a recording material layer formed from the recording material according to on a support The present invention relates to a recording material employing color development through a reaction between a color former and a color-developing agent, and a recording sheet using the recording material.The present application claims priority of Japanese Patent Application No. 2016-164088 filed on Aug. 24, 2016, the content of which is incorporated herein by reference.The recording material employing color development through a reaction between a color former and a color-developing agent, since record may be made by a relatively simple apparatus in a short time without applying a complicated treatment such as development and fixation, are ...

HEAT-SENSITIVE RECORDING MATERIAL

A heat-sensitive recording material includes a heat-sensitive recording layer containing a basic dye and a developer and provided on a supporting body, in which the developer is at least one type of an N-substituted amino acid derivative represented by the following General Formula: 1. A heat-sensitive recording material comprising:a heat-sensitive recording layer containing a basic dye which is colorless or light-colored at room temperature and a developer capable of expressing a color through contact with the dye by heating and provided on a supporting body, {'br': None, 'sub': m', 'm, '(R—X)—Y—(Z)\u2003\u2003(1)'}, 'wherein the developer is at least one type of an N-substituted amino acid derivative represented by the following General Formula (1)in Formula (1), R represents an alkyl group having an aryl group having 6 to 10 carbon atoms, or an aryl group which may have a substituent of an alkyl group having 1 to 8 carbon atoms, an aralkyl group having 7 to 11 carbon atoms, an aryl group having 6 to 10 carbon atoms, or an alkoxy group having 1 to 8 carbon atoms,{'sub': 2', '2, 'X is a group bonded to an N-terminus of Y and represents —OCO—, —SONHCO—, —NHCO—, —NHCS—, or —SO—,'}{'sub': '2', 'Y represents an amino acid residue or a peptide residue and an OH group of a serine residue, a threonine residue, an aspartic acid residue, a glutamic acid residue, or a tyrosine residue in the Y group may be substituted with an OR group or an OR″ group, an SH group of a cysteine residue may be substituted with an SR group or an SR″ group, an NH group of a histidine residue may be substituted with an NR group or an NR′ group, an NHgroup of a lysine residue or an omithine residue may be substituted with an NHR group or an NHR′ group, R′ represents an amino protecting group, and R″ represents a carboxy protecting group,'}Z is a group bonded to a C-terminus of Y and represents an OH group or an OR″ group, anda plurality of R, R′, and R′ groups may be the same as or different from ...

COMPOUNDS AND METHODS FOR INDUCING CHONDROGENESIS

Described herein are compounds and compositions for the amelioration of arthritis or joint injuries by inducing mesenchymal stem cells into chondrocytes. 1119.-. (canceled)121. The method of claim 120 , wherein B is NHC(O)R.122. The method of claim 120 , wherein each Rand Ris independently optionally substituted alkyl.123. The method of claim 120 , wherein Rand Rtogether with the N to which they are attached make a ring.124. The method of claim 120 , wherein Ris optionally substituted phenyl.125. The method of claim 120 , wherein the phenyl of Ris monosubstituted or disubstituted.126. The method of claim 125 , wherein substitution on the phenyl of Ris independently selected from F claim 125 , Cl claim 125 , COH claim 125 , CN claim 125 , OCH claim 125 , C(O)CH claim 125 , CF claim 125 , CH claim 125 , CHOH claim 125 , CHCHOH claim 125 , and CHCHCHOH.129. The method of claim 128 , wherein X is O or NH and A is CH—CRR—C(O)R.130. The method of claim 128 , X is NRand A is C(O) or CH.131. The method of claim 128 , wherein Ris phenyl and the phenyl of Ris monosubstituted or disubstituted.132. The method of claim 131 , wherein substitution on the phenyl is independently selected from F claim 131 , Cl claim 131 , COH claim 131 , CN claim 131 , OCH claim 131 , C(O)CH claim 131 , CF claim 131 , CH claim 131 , CHOH claim 131 , CHCHOH claim 131 , and CHCHCHOH.133. The method of claim 128 , wherein n is 0 or 1.134. The method of claim 133 , wherein Ris independently selected from Cl claim 133 , F claim 133 , CHOH claim 133 , CHNH claim 133 , OCH claim 133 , OCF claim 133 , OCHF claim 133 , CN claim 133 , NO claim 133 , COH claim 133 , and COCH.137. A pharmaceutical composition comprising a compound of claim 136 , or a pharmaceutically acceptable salt claim 136 , solvate claim 136 , polymorph claim 136 , prodrug claim 136 , ester claim 136 , metabolite claim 136 , N-oxide claim 136 , stereoisomer claim 136 , or isomer thereof claim 136 , and a pharmaceutically acceptable ...

NOVEL COMPOUND HAVING ABILITY TO INHIBIT 11B-HSD1 ENZYME OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, METHOD FOR PRODUCING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT

The present invention relates to a novel compound or a pharmaceutically acceptable salt thereof inhibiting 11β-HSD1 enzyme activity, a preparation method of the same, and a pharmaceutical composition comprising the same as an active ingredient. Since the compound of the present invention selectively inhibits the activity of 11β-HSD1 (11β-Hydroxysteroid dehydrogenase type 1), the compound of the invention can be effectively used as a therapeutic agent for the treatment of diseases caused by the over-activation of 11β-HSD1 such as non-insulin dependent type II diabetes, insulin resistance, obesity, lipid disorder, metabolic syndrome, and other diseases or condition mediated by the excessive activity of glucocorticoid. 16-. (canceled)7. A compound or pharmaceutically acceptable salt thereof wherein the compound is selected from the group consisting of the following compounds:(3) E-4-[1-((2-fluoro-benzenesulfonylamino)methyl)cyclopropanecarboxamido]-adamantan-1-carboxylic acid amide;(71) E-4-[2-(2-fluoro-benzenesulfonylamino)-2-methylpropanamido]-adamantan-1-carboxylic acid amide;(84) E-4-[2-(2,6-difluoro-benzenesulfonylamino)-2-methylpropanamido]adamantan-1-carboxylic acid amide;(113) E-sodium[3-((5-carbamoyladamantan-2-yl)carbamoyl)phenyl]-2-fluoro-3-chloro-benzenesulfonylamide; and(119) E-4-[3-(3,5-dichloro-benzenesulfonylamino)-benzamido]-adamantan-1-carboxylic acid amide813-. (canceled)15. A pharmaceutical composition for the prevention or treatment of a disease claim 7 , comprising the compound or the pharmaceutically acceptable salt thereof according to as an active ingredient claim 7 , wherein the disease is non-insulin dependent type II diabetes claim 7 , insulin resistance claim 7 , obesity claim 7 , lipid disorder or metabolic syndrome.16. (canceled) 1. Field of the InventionThe present invention relates to a novel compound or a pharmaceutically acceptable salt thereof inhibiting 11β-HSD1 enzyme activity, a preparation method of the same, and a pharmaceutical ...

OXIME-BASED COMPOUND, PHARMACEUTICAL COMPOSITION CONTAINING THE SAME AND METHOD FOR PREPARING THE SAME

An oxime-based compound having the following formula (I) or a pharmaceutically acceptable salt thereof: 2. The oxime-based compound of claim 1 , wherein Y is a sulfonyl group.3. The oxime-based compound of claim 1 , wherein Ris selected from the group consisting of H and a C-Calkyl group.4. The oxime-based compound of claim 3 , wherein Ris selected from the group consisting of H claim 3 , methyl claim 3 , ethyl claim 3 , and n-propyl.5. The oxime-based compound of claim 1 , wherein Ris selected from the group consisting of OH claim 1 , a methoxyl group claim 1 , and —OROH.6. The oxime-based compound of claim 5 , wherein —OROH of Ris —OCHOH.7. The oxime-based compound of claim 1 , selected from the group consisting of:(E)-4-(N-(2-(1-(hydroxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate,(E)-4-(N-(2-(1-(hydroxyimino)propyl)phenyl)sulfamoyl)phenyl pivalate,(E)-4-(N-(2-(1-(hydroxyimino)butyl)phenyl)sulfamoyl)phenyl pivalate,(E)-4-(N-(2-((hydroxyimino)methyl)phenyl)sulfamoyl)phenyl pivalate,(E)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate,(Z)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate, and(E)-4-(N-(2-(1-(3-hydroxypropoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate.8. A pharmaceutical composition having inhibitory activity on neutrophil elastase claim 1 , comprising the oxime-based compound of or the pharmaceutically acceptable salt thereof.9. A pharmaceutical composition having inhibitory activity on proteinase 3 claim 1 , comprising the oxime-based compound of or the pharmaceutically acceptable salt thereof.10. A pharmaceutical composition for treatment of an inflammatory disorder claim 1 , comprising the oxime-based compound of or the pharmaceutically acceptable salt thereof.11. The pharmaceutical composition of claim 10 , wherein the inflammatory disorder is selected from the group consisting of: lung injury claim 10 , chronic obstructive pulmonary disease claim 10 , acute respiratory distress syndrome claim 10 , emphysema claim ...

STAT3 DIMERIZATION INHIBITORS

The subject matter disclosed herein relates to compositions and methods of making and using the compositions. In a further aspect, the subject matter disclosed herein relates to inhibitors of STAT3 dimerization. Methods of making these compositions as well as compositions comprising these compositions are also disclosed. Also disclosed are methods of treating or preventing certain cancers by administering to an individual in need thereof and effective amount of the compounds disclosed herein. Still further, disclosed herein are methods of inhibiting STAT3 by contacting a cell with a compound or composition as disclosed herein.

SULFONIMIDE SALTS FOR BATTERY APPLICATIONS

A class of sulfonimide salts for solid-state electrolytes can be synthesized based on successive SAr reactions of fluorinated phenyl sulfonimides: Fluorinated Aryl Sulfonimide Tags (FAST). The chemical and electrochemical oxidative stability of these FAST salts as well as other properties like solubility, Lewis basicity, and conductivity can be tuned by introducing different numbers and types of nucleophilic functional groups to the FAST salt scaffold. 2. The composition of claim 1 , wherein Ris —CF.3. The composition of claim 1 , wherein Ris a fluorinated phenyl.4. The composition of claim 3 , wherein the fluorinated phenyl has at least two fluorine groups.7. The composition of claim 1 , wherein Ris —CFor a fluorinated phenyl and Ris a fluorinated phenyl claim 1 , wherein at least one of Rand Ris substituted by a nucleophile.10. The composition of claim 9 , wherein each of X claim 9 , X claim 9 , and X claim 9 , independently claim 9 , is methoxy claim 9 , ethoxy claim 9 , propoxy claim 9 , butoxy claim 9 , pentoxy claim 9 , phenoxy claim 9 , piperidinyl claim 9 , or cycloocteneamino.12. The composition of claim 11 , wherein OR is methoxy claim 11 , ethoxy claim 11 , isopropoxy or neopentoxy.14. The energy storage device of claim 13 , wherein Ris —CF.15. The energy storage device of claim 13 , wherein Ris a fluorinated phenyl.16. The energy storage device of claim 15 , wherein the fluorinated phenyl has at least two fluorine groups.19. The energy storage device of claim 13 , wherein Ris —CFor a fluorinated phenyl and Ris a fluorinated phenyl claim 13 , wherein at least one of Rand Ris substituted by a nucleophile.22. The energy storage device of claim 21 , wherein each of X claim 21 , X claim 21 , and X claim 21 , independently claim 21 , is methoxy claim 21 , ethoxy claim 21 , propoxy claim 21 , butoxy claim 21 , pentoxy claim 21 , phenoxy claim 21 , piperidinyl claim 21 , or cycloocteneamino.24. The energy storage device of claim 23 , wherein OR is methoxy claim ...

MILD AND EFFICIENT PREPARATION METHOD FOR A-ACYLOXYENAMIDE COMPOUNDS AND USE THEREOF IN SYNTHESIS OF AMIDE AND POLYPEPTIDE

Disclosed are a mild and efficient preparation method for an α-acyloxyenamide compound and a use thereof in the synthesis of an amide and a polypeptide. The α-acyloxyenamide compound is obtained by an addition reaction of a ynamide and a carboxylic acid in dichloromethane under conditions where the temperature is 0° C. to 50° C.; the produced α-acyloxyenamide compound can react with an amine compound to produce an amide or a polypeptide; the two reactions can be carried out step by step, and can also be carried out in one pot. According to the invention, the reaction conditions are mild and no metal catalyst is required; when the carboxylic acid, which has chirality on an alpha site of carboxyl, forms an amide bond or a peptide bond, no racemization occurs; and the operation is simple and the application range is wide. 2. The mild and efficient preparation method for an α-acyloxyenamide compound according to claim 1 , wherein the carboxylic acid is selected from carboxylic acids such as an aliphatic acid claim 1 , an aromatic acid claim 1 , a heterocyclic acid claim 1 , an acetylenic acid claim 1 , an olefine acid claim 1 , an α-amino acid claim 1 , and a β-amino acid.3. The mild and efficient preparation method for an α-acyloxyenamide compound according to claim 1 , wherein the molar ratio of the ynamide to the carboxylic acid is 0.1-10.4. The mild and efficient preparation method for an α-acyloxyenamide compound according to claim 1 , wherein the dichloromethane solvent is replaced with a solvent such as chloroform or 1 claim 1 ,2-dichloroethane.5. The mild and efficient preparation method for an α-acyloxyenamide compound according to claim 1 , wherein the temperature is 25° C.7. The use of an α-acyloxyenamide compound in the synthesis of an amide and a polypeptide according to claim 6 , wherein the amine compound is a primary or secondary amine claim 6 , including an aliphatic amine and an aromatic amine.8. The use of an α-acyloxyenamide compound in the synthesis ...

HETERODIMERS OF GLUTAMIC ACID

Compounds of Formula (Ia) 167-. (canceled)69. The compound of claim 68 , wherein the compound inhibits PSMA in an vitro cell binding assay at an ICof about 10 nM or less.69. The compound of claim 68 , wherein the compound inhibits PSMA in an vitro cell binding assay at an ICof about 4 nM or less.70. The compound of claim 68 , wherein the compound inhibits PSMA in an vitro cell binding assay at an ICof about 2 nM or less.71. The compound of claim 68 , wherein the compound inhibits PSMA positive human prostate tumor in a mouse xenograft assay.72. The compound of claim 68 , wherein each Z is H.73. The compound of claim 68 , wherein the compound further comprises a radionuclide.74. The compound of claim 73 , wherein the PSMA-binding moiety is conjugated to the metal chelating moiety by a tether.75. The compound of claim 73 , wherein the radionuclide is a therapeutic radionuclide.76. The compound of claim 73 , wherein the radionuclide is an imaging radionuclide.77. The compound of claim 76 , wherein the radionuclide is selected from technetium-99m claim 76 , rhenium-186 claim 76 , rhenium-188 claim 76 , radio copper claim 76 , or combinations thereof.78. The compound of claim 68 , characterized in that uptake in a tumor of a mouse bearing a PSMA positive LNCaP xenograft is about 17±6% ID/g after 1 hour.80. A method for treating a PSMA-associated disease in a subject comprising administering a compound comprising a glutamate-urea-lysine moiety conjugated to a metal chelating moiety and a radionuclide.82. The method of claim 81 , wherein each Z is H.83. The method of claim 82 , wherein the radionuclide is selected from technetium-99m claim 82 , rhenium-186 claim 82 , rhenium-188 claim 82 , radio copper claim 82 , or combinations thereof.84. A process for producing a PSMA-binding compound comprising a glutamate-urea-lysine moiety conjugated to a radionuclide chelate complex claim 82 , the process comprising chelating a radionuclide with a compound comprising a glutamate- ...

PREPARATION OF SECONDARY AMINES WITH ELECTROPHILIC N-LINCHPIN REAGENTS

In one aspect, the present disclosure provides methods of preparing a secondary amine. In some embodiments, the secondary amine comprises two different groups or two identifical groups. Also provided herein are compositions for use in the preparation of the secondary amine. 3. The compound of claim 1 , wherein Rand Rare each amino or alkoxy claim 1 , cycloalkoxy claim 1 , alkylamino claim 1 , dialkylamino claim 1 , cycloalkylamino claim 1 , dicycloalkylamino claim 1 , or a substituted version of any of these groups.4. The compound of claim 1 , wherein Ris a leaving group selected from halo claim 1 , alkylsulfonyl claim 1 , substituted alkylsulfonyl claim 1 , arylsulfonyl claim 1 , substituted arylsulfonyl claim 1 , alkylsulfonyloxy claim 1 , substituted alkylsulfonyloxy claim 1 , arylsulfonyloxy claim 1 , or substituted arylsulfonyloxy.5. The compound of claim 1 , wherein Xand Xare C.1417.-. (canceled)18. A method of preparing a tertiary amine comprising reacting a compound of with a hard carbanion or an enolate.19. The method of claim 18 , wherein the hard carbanion is an organometallic reagent.20. The method of claim 19 , wherein the hard carbanion is a Gringard reagent or an organolithium compound.21. The method of claim 18 , wherein the method comprises reacting an enolate.23. The method of claim 18 , wherein the method comprises adding a mild acid.24. The method of further comprising converting the tertiary amine into a secondary amine comprising:(A) a mild base and air; or(B) a base and an oxidizing agent.2531.-. (canceled) This application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/507,577, filed on May 17, 2017, the entire contents of which are hereby incorporated by reference.This invention was made with government support under Grant No. GM114609 and CHE 1546097 awarded by the National Institute of Health and the National Science Foundation, respectively. The government has certain rights in the invention.The development of ...

Substituted 3-Haloallylamine Inhibitors of SSAO and uses thereof

The present invention is related to the preparation and pharmaceutical use of substituted 3-haloallylamine derivatives as SSAO/VAP-1 inhibitors having the structure of Formula I, as defined in the specification: 2. The compound of wherein Rand Rare each independently hydrogen or fluorine.4. The compound of wherein X is oxygen.7. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and at least one pharmaceutically acceptable excipient claim 1 , carrier or diluent.8. A method for inhibiting the amine oxidase activity of SSAO/VAP-1 in a subject in need thereof claim 1 , said method comprising the step of administering to said subject an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a composition comprising the foregoing claim 1 , and at least one pharmaceutically acceptable excipient claim 1 , carrier or diluent claim 1 , to effect a positive therapeutic response.9. A method for treating a disease associated with or modulated by SSAO/VAP-1 protein claim 1 , said method comprising the step of administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a composition comprising the foregoing claim 1 , and at least one pharmaceutically acceptable excipient claim 1 , carrier or diluent.10. The method of wherein the disease is inflammation.11. The method of wherein said inflammation is associated with liver disease.12. The method of wherein said inflammation is associated with respiratory disease.13. The method of wherein said inflammation is associated with cystic fibrosis.14. The method of wherein said inflammation is associated with asthma or chronic obstructive pulmonary disease.15. The method of wherein said inflammation is associated with ocular disease.16. The method of wherein the disease is a diabetes-induced disease selected from the ...

METHOD OF PRODUCING A SODIUM SALT OF (2,6-DICHLOROPHENYL)AMIDE CARBOPENTOXYSULFANILIC ACID

The invention relates to the field of organic chemistry and medicine, and more particularly to a method of producing synthetic biologically active derivatives of carbopentoxysulfanilic acid. The present method of producing a sodium salt of (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid is characterized in that the reaction mass formed during the production of (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid is agitated in a medium which is acidified with a solution of hydrochloric acid to pH 5-5.5, and the isolated precipitate may be washed with water acidified with a solution of hydrochloric acid to pH 5-5.5. This increases the yield of a sodium salt of (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid to 70% (compared to a prior art yield of 32%) and also increases the purity of the target sodium salt. 12.-. (canceled)4. The method of claim 3 , wherein the base is sodium hydroxide and the salt of (2 claim 3 ,6-dichlorophenyl)amide of carbopentoxysulfanilic acid is sodium salt.5. The method of claim 4 , wherein the overall yield of the sodium salt of (2 claim 4 ,6-dichlorophenyl)amide of carbopentoxysulfanilic acid is greater than 32%.6. The method of claim 5 , wherein the overall yield of the sodium salt of (2 claim 5 ,6-dichlorophenyl)amide of carbopentoxysulfanilic acid is about 56%.7. The method of claim 3 , wherein the solution of hydrochloric acid is an aqueous solution of hydrochloric acid.8. The method of claim 3 , wherein the carbopentoxysulfanilic acid chloride is added in portions at the temperature of about 85° C.9. The method of claim 3 , wherein the mixture of step (b) is stirred at about 80° C. for about 45 minutes prior to acidifying the mixture with a solution of hydrochloric acid to a pH of about 5 to about 5.5.10. The method of claim 9 , wherein after stirring at about 80° C. for about 45 minutes the mixture is cooled to room temperature prior to acidifying.11. The method of claim 3 , wherein hot water is added to the mixture of ...

STAT3 DIMERIZATION INHIBITORS

The subject matter disclosed herein relates to compositions and methods of making and using the compositions. In a further aspect, the subject matter disclosed herein relates to inhibitors of STAT3 dimerization. Methods of making these compositions as well as compositions comprising these compositions are also disclosed. Also disclosed are methods of treating or preventing certain cancers by administering to an individual in need thereof and effective amount of the compounds disclosed herein. Still further, disclosed herein are methods of inhibiting STAT3 by contacting a cell with a compound or composition as disclosed herein. 2. The compound of claim 1 , wherein Ris H claim 1 , C-Calkyl claim 1 , C(O)C-Calkyl claim 1 , COC-Calkyl claim 1 , benzyl claim 1 , 4-piperidyl claim 1 , 3-(4-pyridyl) claim 1 , or pyridinyl.5. The compound of claim 4 , wherein Ris cyclohexyl.6. The compound of claim 1 , wherein Ris OH claim 1 , Cl claim 1 , F claim 1 , Br claim 1 , I claim 1 , OCH claim 1 , C-Calkyl claim 1 , 4-piperidyl claim 1 , 3-(4-pyridyl) claim 1 , morpholinyl claim 1 , phenyl claim 1 , or pyridinyl.8. The compound of claim 7 , wherein X is O.9. The compound of claim 1 , wherein Ris OPh.10. The compound of claim 1 , wherein Ris H or OCH.11. The compound of claim 1 , wherein the compound has a formula shown in Table 3.14. The compound of claim 13 , wherein Ris H claim 13 , C-Calkyl claim 13 , C(O)C-Calkyl claim 13 , COC-Calkyl claim 13 , benzyl claim 13 , 4-piperidyl claim 13 , 3-(4-pyridyl) claim 13 , or pyridinyl.17. The compound of claim 16 , wherein Ris cyclohexyl.18. The compound of claim 13 , wherein Ris OH claim 13 , Cl claim 13 , F claim 13 , Br claim 13 , I claim 13 , OCH claim 13 , C-Calkyl claim 13 , 4-piperidyl claim 13 , 3-(4-pyridyl) claim 13 , morpholinyl claim 13 , phenyl claim 13 , or pyridinyl.20. The compound of claim 19 , wherein X is O.21. The compound of claim 13 , wherein Ris OPh.22. The compound of claim 13 , wherein Ris H or OCH.23. The compound ...

Plasminogen Activator Inhibitor-1 Inhibitors and Methods of Use Thereof to Modulate Lipid Metabolism

The invention relates to plasminogen activator-1 (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or condition associated with elevated PAI-1. The invention includes, but is not limited to, the use of such compounds to modulate lipid metabolism and treat conditions associated with elevated PAI-1, cholesterol, or lipid levels. 156-. (canceled)5960-. (canceled)6465-. (canceled)6768-. (canceled) This application is a divisional application of U.S. patent application Ser. No. 12/104,409 filed Apr. 16, 2008, which claims the benefit of U.S. Provisional Application No. 60/912,071 filed Apr. 16, 2007, the entire respective disclosures of which are incorporated herein by reference.This invention was made in part with government support under grant numbers HL055374 and HL054710 from the National Institute of Health. As such, the United States government has certain rights in the invention.The invention generally relates to methods and compositions for modulating lipid metabolism. More particularly, the invention is directed to methods of identifying inhibitors of plasminogen activator inhibitor-1 (PAI-1) and the uses of such inhibitors in regulating lipid metabolism. The invention also relates to uses of these inhibitors for the treatment of many conditions, diseases or disorders associated with PAI-1 activity. Such conditions or disorders include, but are not limited to, inflammation, cell migration and migration-driven proliferation of cells, and angiogenesis or thrombosis. Such inhibitors are also contemplated to be useful for modulation of endogenous fibrinolysis, and in conjunction with pharmacologic thrombolysis.Plasminogen activator inhibitor-1 (PAI-1) is a 50 kDa single-chain glycoprotein (Loskutoff et al., Proc. Natl. Acad. Sci. USA 80:2956-2960, 1983; Chmielewska et al., Thromb. Res. 31:427-436, 1983) that is the principal inhibitor of both urokinase type plasminogen activator (uPA) and tissue type PA (tPA) (Fay et al., N. Engl. J. Med. ...

SALICYLIC ACID DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, COMPOSITION THEREOF AND METHOD OF USE THEREOF

The present invention relates to novel compounds, compositions containing same and methods for inhibiting STAT3 and/or STAT5 activity or for the treatment of a STAT3 or STAT5-dependent cancer using said compounds;

Complexes and methods for their preparation

Disclosed are methods for the preparation of ligands for complexes, methods for preparing complexes and complexes having those ligands. Also provided is the use of a complex as a catalyst in a method of synthesis.

BENZENESULFONAMIDE COMPOUNDS FOR SOMATIC EMBRYOGENESIS IN PLANTS

Benzenesulfonamide compounds potentiate 2,4-D induced embryogenesis in plants. In particular, 4-chloro-N-methyl-N-(2-methylphenyl)benzenesulfonamide and analogs induce somatic embryogenesis in plants. Methods of inducing somatic embryogenesis comprise exposing selected plant tissues, e.g. seed embryos, to auxins, e.g. 2.4-D and the benzenesulfonamide compounds. Compounds can be prepared by reacting sulfonyl chloride, an amine and pyridine in CHCI. Crude product is suspended in ethyl acetate and washed in sodium and potassium hydrogen sulphates and brine, then dried and filtered. 3. A compound as claimed in or , wherein neither Rnor Ris H.4. A compound as claimed in any one of the preceding claims , (i) where Ris a Cto Chydrocarbyl , and where Ris —CHRRR , where R , Rand Rare independently selected from at least one of H , C-Chydrocarbyl and an ether functional group , or (ii) where N , Rand Rtogether form a heterocyclic ring.7. A method as claimed in claim 6 , wherein Rand/or Ris halogen selected from F claim 6 , Cl and Br.8. A method as claimed in or claim 6 , wherein Rand/or Ris methyl.9. A method as claimed in any of to claim 6 , wherein one or both of Rand Ris hydrogen.10. A method as claimed in any of to claim 6 , wherein Rand/or Ris an ether selected from —OCHand −OCH.11. A method as claimed in claim 9 , wherein Ris hydrogen claim 9 , and Ris a selected from halogen claim 9 , ether claim 9 , nitro and Cto Calkyl functional groups and is ortho claim 9 , meta or para claim 9 , preferably para to the sulfonyl group.12. A method as claimed in claim 6 , wherein where Rand Rtogether form a 6-membered aromatic ring that is fused to the phenyl group to which Rand Rare attached.13. A method as claimed in claim 6 , wherein Ris H or a Cto Chydrocarbyl claim 6 , and where Ris H or —CHRRR claim 6 , where R claim 6 , Rand Rare independently selected from at least one of H claim 6 , C-Chydrocarbyl and an ether functional group.14. A method as claimed in claim 13 , wherein ...

VITAMIN D RECEPTOR AGONISTS AND USES THEREOF

This invention features vitamin D receptor agonists, and their use in treating bone disorders, cardiovascular disease, hyperparathyroidism, immune disorders, proliferative disease, renal disease, and thrombosis. 6. The method of claim 1 , wherein Ris selected from H claim 1 , halide claim 1 , OCH claim 1 , and CH.7. The method of claim 1 , wherein Ris selected from H claim 1 , OH claim 1 , OCH claim 1 , and CHCH.8. The method of claim 1 , wherein Ris selected from H claim 1 , halide claim 1 , OH claim 1 , OCH claim 1 , CH claim 1 , and CHCH.9. The method of claim 1 , wherein Ris selected from H claim 1 , halide claim 1 , and OCH.10. The method of claim 1 , wherein Rselected from H and OCH.11. The method of claim 1 , wherein each of R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris H.12. The method of claim 1 , wherein Xis OR; and Ris selected from CHCH claim 1 , CHCHOCHCH claim 1 , CHCHSCHCH claim 1 , CHCHOPh claim 1 , and CHCHSPh.14. The method of claim 13 , wherein Ris selected from H claim 13 , halide claim 13 , CH claim 13 , and CHCH.15. The method of claim 13 , wherein Ris selected from H and CH.16. The method of claim 13 , wherein Ris selected from H claim 13 , halide claim 13 , and CH.17. The method of claim 13 , wherein each of R claim 13 , R claim 13 , R claim 13 , R claim 13 , and Ris claim 13 , independently claim 13 , selected from H claim 13 , OCH claim 13 , and CH.18. The method of claim 13 , wherein each of R claim 13 , R claim 13 , R claim 13 , R claim 13 , R claim 13 , and Ris H.19. The method of claim 13 , wherein Yis O.20. The method of claim 1 , wherein said vitamin D receptor-mediated condition is selected from bone disorders claim 1 , cardiovascular disease claim 1 , hyperparathyroidism claim 1 , immune disorders claim 1 , proliferative diseases claim 1 , renal disease and thrombosis.2155-. (canceled) This invention relates to the field of vitamin D receptor agonists. The agonists can be used as drugs to treat a variety of diseases, ...

Heterodimers of Glutamic Acid

Compounds of Formula (Ia) 167-. (canceled)69. The method of claim 68 , wherein the PSMA-binding compound comprises a radionuclide.70. The method of claim 69 , wherein the radionuclide is selected from the group consisting of technetium-99m claim 69 , rhenium-186 claim 69 , and rhenium-188.71. The method of claim 68 , wherein the PSMA-binding compound comprises a radiohalogen.72. The method of claim 71 , wherein the radiohalogen is selected from the group consisting of: I-123 claim 71 , I-125 claim 71 , I-131 claim 71 , I-124 claim 71 , Br-75 claim 71 , Br-77 claim 71 , and F-18.73. The method of claim 68 , wherein each Z is independently hydrogen.74. The method of claim 68 , wherein each Z is independently C-Calkyl.76. The method of claim 75 , wherein:{'sub': 6', '12, 'R is a C-Csubstituted or unsubstituted aryl;'}{'sub': '2', 'Y is C(O) or CH.'}77. The method of claim 75 , wherein R is a phenyl moiety substituted with a halogen.78. The method of claim 77 , wherein the halogen is a radiohalogen.79. The method of claim 77 , wherein the radiohalogen is selected from the group consisting of: I-123 claim 77 , I-125 claim 77 , I-131 claim 77 , I-124 claim 77 , Br-75 claim 77 , Br-77 claim 77 , and F-18.82. The method of claim 81 , wherein the halogen is a radiohalogen.83. The method of claim 81 , wherein Xis selected from the group consisting of: I claim 81 , Br claim 81 , Cl claim 81 , F claim 81 , I-123 claim 81 , I-125 claim 81 , I-131 claim 81 , I-124 claim 81 , Br-75 claim 81 , Br-77 claim 81 , F-18 claim 81 , and hydrogen.84. The method of claim 81 , wherein X is I-123 claim 81 , I-125 claim 81 , I-131 claim 81 , or I-124.86. The method of claim 85 , wherein the halogen is a radiohalogen.87. The method of claim 85 , wherein X is selected from the group consisting of: I claim 85 , Br claim 85 , Cl claim 85 , F claim 85 , I-123 claim 85 , I-125 claim 85 , I-131 claim 85 , I-124 claim 85 , Br-75 claim 85 , Br-77 claim 85 , F-18 claim 85 , and hydrogen.88. The method ...

METHOD FOR PREPARING NOTA DERIVATIVE

A method for preparing a NOTA derivative is revealed. The method includes a plurality of steps. First take 4-toluenesulfonyl chloride and diethylenetriamine to carry out tosylation reaction and obtain a first product. Then the first substitution reaction takes place upon addition of the first product with sodium methoxide to get the second product. Next take 4-toluenesulfonyl chloride to react with ethylene glycol for preparing a third product by tosylation reaction therebewteen. Then a coupling reaction between the third product and the second product is carried out to produce a fourth product. The second substitution reaction occurs involving the fourth product in the presence of sulfuric acid. Lastly take the reaction product and hydrochloric acid to have bonding reaction and obtain a final product. The method solves the water-absorption problem of the cyclic organic compound TACN, a NOTA derivative. 1. A method for preparing a NOTA derivative comprising the steps of:taking 4-toluenesulfonyl chloride and diethylenetriamine to carry out tosylation reaction and obtain a first product, and then running the first substitution reaction by adding the first product with sodium methoxide to obtain a second product;taking 4-toluenesulfonyl chloride to react with ethylene glycol for preparing a third product by tosylation reaction therebetween, and then carrying out a coupling reaction between the third product and the second product to produce a fourth product, the solution of the coupling reaction is vacuum concentrated and vacuum dried overnight, the concentrated residual is dissolved in 75 ml ethanol and 75 ml dichloromethane and a solid product is obtained after filtration;running the second substitution reaction involving the fourth product in the presence of sulfuric acid to obtain a reaction product; andtaking the reaction product and hydrochloric acid to have bonding reaction and obtain a final product;wherein the final product is 1,4,7-Triazacyclononane ...

UV CURED BENZOPHENONE TERMINATED QUARTERNARY AMMONIUM ANTIMICROBIALS FOR SURFACES

The invention relates to benzophenone-terminated quaternary ammonium compounds of formula (I), processes for preparing benzophenone-terminated quaternary ammonium compounds of formula (I), environmentally friendly antimicrobial formulations of said quaternary ammonium compounds and their use as durable antimicrobial surface coatings for surfaces. 2. The compound of wherein Rand Rare methyl.3. The compound of wherein X is bromo or iodo.4. The compound of wherein Rand Rare independently methyl claim 1 , ethyl claim 1 , n-propyl or isopropyl and Ris hydrogen.6. The compound of wherein m is 13 claim 5 , 15 or 17 except when n is 1 claim 5 , X is bromo and Rand Rare methyl.9. The process of wherein R claim 8 , and Rare methyl.10. The process of wherein X is selected from the group consisting of bromo and iodo.11. The process of wherein Rand Rare independently methyl claim 8 , ethyl claim 8 , n-propyl or isopropyl and Ris hydrogen.13. The process of wherein m is 17.15. The process of wherein the alkali metal carbonate is potassium carbonate.17. The composition of wherein Rand Rare methyl.18. The composition of wherein X is bromo or iodo.19. The composition of wherein Rand Rare independently methyl claim 16 , ethyl claim 16 , n-propyl or isopropyl and Ris hydrogen.21. The composition of wherein m is 17.23. The composition of wherein the carrier is a mixture of water and an alcohol.24. The composition of wherein the alcohol is methanol.25. A process for coating a surface with an antimicrobial coating claim 23 , said process comprising the steps of:{'claim-ref': {'@idref': 'CLM-00015', 'claim 15'}, 'i) contacting the surface with a composition of ; and'}ii) irradiating the coated surface.26. The process of wherein the surface comprises a polymer or a fibre.27. The process of further comprising iii) a washing step wherein the washing step comprises the use of a water and isopropanol mixture.28. The process of wherein the irradiating step comprises irradiating the coated ...

2,2' -DIAMINO BIARYLS WITH TWO SECONDARY AMINES AND PRODUCTION THEREOF BY ELECTROCHEMICAL COUPLING

Novel 2,2′-diamino biaryls of formula (I), (II) and (III), wherein R1-R10, R1′-R10′, X1-X3 and X1-X3′ are defined in claim 1. The invention also relates to an electrochemical method for the production thereof. 2. Compound according to claim 1 ,{'sup': 1', '1, 'where Xand X′ are selected fromtert-butyloxycarbonyl, methyloxycarbonyl, benzyloxycarbonyl, phenyloxycarbonyl, acetyl, trifluoroacetyl, benzoyl.3. Compound according to claim 1 ,{'sup': 2', '2, 'where Xand X′ are selected fromtert-butyloxycarbonyl, methyloxycarbonyl, benzyloxycarbonyl, phenyloxycarbonyl, acetyl, trifluoroacetyl, benzoyl.4. Compound according to claim 1 ,{'sup': 3', '3, 'where Xand X′ are selected fromtert-butyloxycarbonyl, methyloxycarbonyl, benzyloxycarbonyl, phenyloxycarbonyl, acetyl, trifluoroacetyl, benzoyl.5. Compound according to claim 1 ,{'sup': 1', '2', '3', '4', '1', '2', '3', '4, 'where R, R, R, R, R′, R′, R′, R′ are selected from{'sub': 1', '12', '1', '12', '6', '20, '—H, —(C-C)-alkyl, —O—(CC)-alkyl, —O—(C-C)-aryl, —S-alkyl, —S-aryl, halogen.'}6. Compound according to claim 1 ,{'sup': 1', '2', '3', '4', '1', '2', '3', '4, 'where R, R, R, R, R′, R′, R′, R′ are selected from{'sub': 1', '12', '1', '12', '6', '20, '—H, —(C-C)-alkyl, —O—(C-C)-alkyl, —O—(C-C)-aryl.'}7. Compound according to claim 1 ,{'sup': 5', '6', '7', '8', '9', '10, 'where R′, R′, R′, R′, R′, R′ are selected from{'sub': 1', '12', '1', '12', '6', '20, '—H, —(CC)-alkyl, —O—(CC)-alkyl, —O—(C-C)-aryl, —S-alkyl, —S-aryl, halogen.'}8. Compound according to claim 1 ,{'sup': 5', '6', '7', '8', '9', '10, 'where R′, R′, R′, R′, R′, R′ are selected from{'sub': 1', '12', '1', '12', '6', '20, '—H, —(C-C)-alkyl, —O—(CC)-alkyl, —O—(C-C)-aryl.'}9. Compound according to claim 1 ,{'sup': 5', '6', '7', '8', '9', '10, 'where R, R, R, R, R, Rare selected from{'sub': 1', '12', '1', '12', '6', '20, '—H, —(C-C)-alkyl, —O—(C-C)-alkyl, —O—(C-C)-aryl, —S-alkyl, —S-aryl, halogen.'}10. Compound according to claim 1 ,{'sup': 5', '6', '7', '8', '9', ...

POLYAMINE SULFONAMIDES AND USES THEREOF

Cancer is a disease for which there remains a great unmet medical need, and therefore the discovery and development of new antineoplastic agents is critically important. The present invention relates in part to new therapeutic compounds with antineoplastic activity. Provided herein are polyamine sulfonamides such as compounds of Formula (I), or pharmaceutically acceptable salts thereof, which may be used in the treatment and/or prevention of diseases such as cancer. Also provided herein are pharmaceutical compositions and kits comprising the inventive compounds. Furthermore, the present invention provides methods of treating and/or preventing diseases (e.g., cancer) using compounds of Formula (I), or pharmaceutically acceptable salts thereof or pharmaceutical compositions thereof. Other methods provided include methods for inducing apoptosis of a cell, as well as methods for inhibiting alpha-enolase enzymatic activity in vivo and in vitro. 2. The compound of claim 1 , wherein Ris optionally substituted aryl.58-. (canceled)10. (canceled)12. (canceled)13. The compound of claim 1 , wherein Ris optionally substituted Calkyl.1419-. (canceled)20. The compound of claim 1 , wherein Ris optionally substituted Calkyl.2127-. (canceled)28. The compound of claim 3 , wherein n is 1.2932-. (canceled)33. The compound of claim 3 , wherein at least one instance of Ris halogen.34. (canceled)35. The compound of claim 3 , wherein at least one instance of Ris optionally substituted alkyl.3637-. (canceled)3944-. (canceled)48. (canceled)49. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and optionally a pharmaceutically acceptable excipient.5051-. (canceled)52. A method of treating a disease in a subject claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to a subject a therapeutically effective amount of , or a pharmaceutically acceptable salt thereof.'}5362-. (canceled)63 ...

PROCESS FOR PREPARING 4[[(BENZOYL)AMINO]SULPHONYL]BENZOYL CHLORIDES AND PREPARATION OF ACYLSULPHAMOYLBENZAMIDES

Process for preparing 4-[[(benzoyl)amino]sulphonyl]benzoyl chlorides of the formula (II) This application is a division of U.S. application Ser. No. 15/024,352, filed Mar. 23, 2016, which is a §371 National Stage Application of PCT/EP2011/071388, filed Oct. 7, 2014, which claims priority to European 13188179.9 filed Oct. 10, 2013, the contents of each are incorporated herein in their entireties.The invention relates to an improved process for preparing 4-[[(benzoyl)amino]-sulphonyl]benzoyl chlorides.More particularly, the invention relates to an improved process for preparing 4-[[(2-methoxybenzoyl)amino]sulphonyl]benzoyl chloride and to the use thereof for preparing N-[4-(cyclopropylcarbamoyl)phenylsulphonyl]-2-methoxybenzamide.N-[4-(Cyclopropylcarbamoyl)phenylsulphonyl]-2-methoxybenzamide (N-[4-(cyclo-propylcarbamoyl)phenylsulphonyl]-o-anisamide) is also referred to as cyprosulfamide.Cyprosulfamide is used as a safener in conjunction with a herbicide, or with a plurality of different herbicides. A safener serves to improve the selectivity of the herbicides used with respect to the crop plants of the particular crop being treated. The term “selectivity” refers to the crop plant compatibility of a herbicide.Document WO 99/16744 discloses acylsulphamoylbenzamide derivatives and the preparation and use thereof as safeners. However, the preparation processes disclosed in WO 99/16744 relate to the laboratory scale and are found to be not particularly suitable for the industrial preparation of the compounds.A two-stage process which has likewise been developed for use on the industrial scale for preparation of acylsulphamoylbenzamides is known from document WO 2005/000797 A1. Solvents proposed for the performance of the process known from WO 2005/000797 A1, as well as nonpolar silicone oils, are nonpolar and polar organic solvents.Organic solvents mentioned explicitly are aliphatic and aromatic hydrocarbons, namely alkanes, for example heptane, octane or alkylated ...

Enantioselective Syntheses of Heteroyohimbine Natural Product Intermediates

Enantioselective syntheses of cis- and trans-bicyclic dihydropyran compounds, and other intermediates, en route to heteroyohimbine alkaloids. 111-. (canceled)13. The method of wherein said dehydration is achieved with sodium iodide.14. The method of wherein said reprotection is achieved with magnesium metal and benzyl carbamate.15. The method of wherein said hydroboration is achieved with 9-borabicyclo[3.3.1]nonane 9-BBN.16. The method of wherein said acylation is achieved with sodium hydride and acyl chloride.17. The method of wherein said acid catalyst is p-toluenesulfonic acid.18. The method of further comprising removing said benzyl carbamate protecting group by hydrogenating said cis-bicyclic dihydropyran compound over palladium-carbon.1920-. (canceled)22. The compound of claim 21 , wherein Ris selected from tosylate (Ts) and benzyl carbamate (Cbz) protecting groups.23. The compound of claim 21 , wherein Ris methyl.24. The compound of claim 21 , wherein Ris methyl. This application is a divisional of U.S. patent application Ser. No. 15/145,586 filed May 3, 2016, which claims priority to and the benefit of U.S. Provisional Patent Application 62/156,591 filed May 4, 2015, the entirety of which is incorporated herein by reference.Alstonine (1) and serpentine (2) are pentacyclic alkaloids proposed to contain a zwitterionic indolo[2,3-a]quino-lizidine, referred to as an anhydronium base (). This structural motif is rare among natural products and is especially unusual in total synthesis, with the only examples being strychnoxanthine (3) and melinonine-E (4). Alstonine has recently been identified as the major component of a plant-based treatment used in Nigeria by traditional healers to treat psychotic disorders. However, the scarcity and lack of purity from natural sources, as well as the uncertainty regarding its exact mechanism of action, illustrates the need for an asymmetric synthesis to enable further study. The related trans diastereomer, serpentine, exhibits ...

Methods and Pharmaceutical Compositions for the Treatment of X-Linked Charcot-Marie-Tooth

The present invention relates to methods and pharmaceutical compositions for the treatment of X-linked Charcot-Marie-Tooth. In particular, the present invention relates to a method for the treatment of CMTX in a subject in need thereof comprising administering the subject with a therapeutically effective amount of an inhibitor of CamKII activity or expression.

(Z)-3,4,5-TRIMETHOXYSTYRYLBENZENESULFONAMIDES AS POTENTIAL ANTICANCER AGENTS

(Z)-3,4,5-Trimethoxystyrylbenzenesulfonamides as potential anticancer agents [Formula should be inserted here] The present invention relates to a compound of general formula A. The invention provides the synthesis of (Z)-3,4,5-trimethoxystyrylbenzenesulfonamides useful as potential antitumor agents against human cancer cell lines and a process for the preparation thereof. 3. The compound as claimed in claim 1 , wherein the representative compounds of (Z)-trimethoxystyryl)phenyl) benzene sulfonamide comprising:(Z)-4-methoxy-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9a)(Z)-3,4-dimethoxy-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9b)(Z)-4-chloro-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9c)(Z)-3-chloro-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide(9d)(Z)-3,4-dichloro-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide(9e)(Z)-4-fluoro-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9f)(Z)-4-tert-butyl-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9g)(Z)-4-nitro-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9h)(Z)-4-amino-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9i)(Z)-3-(trifluoromethyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9J)(Z)-3-(trifluoromethoxy)-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9k)(Z)-4-(trifluoromethyl)-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9l)(Z)-4-(trifluoromethoxy)-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9m)(Z)-3-nitro-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9n)(Z)-3-amino-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide(9o)(Z)-3-fluoro-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9p)(Z)-3-tert-butyl-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide (9q)(Z)-3-fluoro-4-methoxy-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide(9r)(Z)-3-hydroxy-4-methoxy-N-(2-(3,4,5-trimethoxystyryl)phenyl)benzenesulfonamide(9s)(Z)-4-methoxy-3-nitro-N-(2-(3,4,5- ...

TETRACYCLINE COMPOUNDS

The present invention is directed to a compound represented by Structural Formula (I): 2. The compound of claim 1 , wherein:{'sub': 1', '4', '2', '1-4', '1', '6', 'm', '1', '4', 'm', 'm', '1', '4, 'sup': 2', '3', '2', '2', '4', '2', '3', '2', '3', 'F', '5a', '5b', '2', '3', 'F', 'F', 'F', 'F', '2', '3', 'F', '2', '4', 'F, 'Y is selected from hydrogen, —(C-C)alkylene-N(R)(R), —CH═N—OR, —C(O)—N(R)(R), —NO, —COOH, —OH, —N═CH—N(R)(R), —N(R)(R), —N(R)—C(O)—[C(R)(R)]—N(R)(R), —N(R)—C(O)—(C-C)alkyl, —N(R)—C(O)-heterocyclyl, —N(R)—C(O)-carbocyclyl, —N(R)—S(O)—(C-C)alkylene-N(R)(R), —N(R)—S(O)—N(R)(R), and —N(R)—S(O)—(C-C) alkylene-carbocyclyl, wherein{'sup': '2', 'sub': 1', '3, 'each Ris independently selected from hydrogen, and (C-C)alkyl;'}{'sup': '3', 'sub': 1', '6', '1', '6', '0', '6', '0', '6', 'm-', '1', '6', 'm', 'm, 'each Ris independently selected from hydrogen, (C-C)alkyl, —O—(C-C)alkyl, —(C-C) alkylene-carbocyclyl, —(C-C)alkylene-heterocyclyl, —S(O)—(C-C)alkyl, —S(O)-carbocyclyl, and —S(O)-heterocyclyl; and'}{'sup': '4', 'sub': 1', '6', '1', '6', '0', '6', '0', '6, 'each Ris independently selected from hydrogen, (C-C)alkyl, —O—(C-C)alkyl, —(C-C) alkylene-carbocyclyl, and —(C-C)alkylene-heterocyclyl; or'}{'sup': 2', '3, 'Rand R, taken together with the nitrogen atom to which they are bound form a heterocyclyl, wherein the heterocylyl optionally comprises 1 to 4 additional heteroatoms independently selected from N, S and O;'}{'sup': 5a', '5b, 'sub': 1', '6, 'each Rand each Ris independently selected from hydrogen, (C-C)alkyl, carbocyclyl, heterocyclyl, or a naturally occurring amino acid side chain moiety, or'}{'sup': 5a', '5b', '5a', '5b, 'Rand Rtaken together with the carbon atom to which they are bound form a 3-7 membered saturated carbocyclyl or a 4-7 membered saturated heterocyclyl, wherein the saturated heterocyclyl formed by Rand Roptionally comprises one to two additional heteroatoms independently selected from N, S and O,'}{'sup': 'F', 'sub': 1', '3, 'Ris ...

METHODS AND COMPOSITIONS FOR TREATMENT OF MUSCLE WASTING, MUSCLE WEAKNESS, AND/OR CACHEXIA

Embodiments of the invention include methods of treating, preventing, and/or reduce the risk or severity of a condition selected from the group consisting of muscle wasting, muscle weakness, cachexia, and a combination thereof in an individual in need thereof. In some embodiments, particular small molecules are employed for treatment, prevention, and/or reduction in the risk of muscle wasting. In at least particular cases, the small molecules are inhibitors of STAT3. 1. A method of treating a condition selected from the group consisting of muscle wasting , muscle weakness , cachexia , and a combination thereof in an individual that has muscle wasting or cachexia or that is at risk of having muscle wasting or cachexia , comprising the step of providing to the individual an effective amount of one or more compositions selected from the group consisting of N-(1′ ,2-dihydroxy-1 ,2′-binaphthalen-4′-yl)-4-methoxybenzenesulfonamide , N-(1′ ,2-dihydroxy-1 ,2′-binaphthalen-4′-yl)-4-methoxybenzenesulfonamide , N-(3 ,1′-Dihydroxy-[1 ,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide , N-(4 ,1′-Dihydroxy-[1 ,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide , N-(5 ,1′-Dihydroxy-[1 ,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide , N-(6 ,1′-Dihydroxy-[1 ,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide , N-(7 ,1′-Dihydroxy-[1 ,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide , N-(8 ,1′-Dihydroxy-[1 ,2′]binaphthalenyl-4′-yl)-4-methoxy-benzenesulfonamide , 4-Bromo-N-(1 ,6′-dihydroxy-[2 ,2′]binaphthalenyl-4-yl)-benzenesulfonamide , 4-Bromo-N-[4-hydroxy-3-(1H-[1 ,2 ,4]triazol-3-ylsulfanyl)-naphthalen-1-yl]-benzenesulfonamide , Table 6-11 , , , and a functional derivative thereof.2. The method of claim 1 , wherein muscle wasting claim 1 , muscle weakness claim 1 , or both is part of cachexia.3. The method of claim 1 , wherein the condition selected from the group consisting of muscle wasting claim 1 , muscle weakness claim 1 , cachexia claim 1 , and a ...

PREPARATION OF SULFONAMIDE-CONTAINING ANTIMICROBIALS AND SUBSTRATE TREATING COMPOSITIONS OF SULFONAMIDE-CONTAINING ANTIMICROBIALS

A quaternary ammonium sulfonamide compound of formula (I): wherein R=(II), C-Clinear or branched alkyl, Rand Rare the same or different and selected from Cto Clinear or branched alkyl, Rand Rare the same or different and selected from Cto Clinear or branched alkyl, CF, ORwhere Ris Cto Clinear or branched alkyl or polyethylene oxide, l is 1, 2, 3, 4, 5, 6, 7 or 8, m is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17, n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18, wherein the aryl groups of R may be substituted or unsubstituted, X=halogen, and Y=(III) wherein R, R, R, Rand Rare the same or different and selected from Cto Clinear or branched alkyl and the benzophenone is selected from the group consisting of substituted benzophenone and unsubstituted benzophenone, process for preparing the compound and antimicrobial surface coating compositions of the compound. 2. The compound of wherein the X is Br.3. The compound of wherein the X is Cl.4. The compound of wherein l is 1 claim 1 , m is 2 and n is 0.5. The compound of wherein Rand Rare the same and methyl.8. The compound of wherein the benzophenone is selected from the group consisting of substituted benzophenone and unsubstituted benzophenone.10. The compound of any one of to wherein the aryl group of R is selected from the group consisting of substituted aryl and unsubstituted aryl.1222-. (canceled)2438-. (canceled)4041-. (canceled)4348-. (canceled)5057-. (canceled)5963-. (canceled)64. A method of reducing growth of at least one microbe on a substrate treated with an antimicrobial composition of .65. A method of reducing growth of at least one microbe on a substrate treated with an antimicrobial composition comprising 3-(4-benzoylphenoxy)-N claim 23 ,N-dimethyl-N-(3-(2 claim 23 ,4 claim 23 ,6-trimethylphenylsulfonamido)propyl)propan-1-aminium bromide.66. A method of reducing growth of at least one microbe on a substrate treated with an antimicrobial composition comprising 3-(4- ...

HEAT-SENSITIVE RECORDING MATERIAL

A heat-sensitive recording material including a substrate, a heat-sensitive recording layer which includes N-(4-methylphenylsulfonyl)-/V-(3-(4-methylphenylsulfonyloxy)pheny-purea and/or N42-(3-phenylureido)phenyl]benzol sulfonamide, and an intermediate layer which is arranged between the substrate and the heat-sensitive recording layer and which includes calcined aluminum silicate, and a method for producing a heat-sensitive recording material and to the use of calcined aluminum silicate in an intermediate layer of a heat-sensitive recording material. 128.-. (canceled)30. The heat-sensitive recording material as claimed in claim 29 , wherein the compound of the formula (I) is in a crystalline form in which an IR spectrum has an absorption band at 3401±20 cm.31. The heat-sensitive recording material as claimed in claim 29 , wherein the calcined aluminum silicate in the interlayer is platelet-shaped.32. The heat-sensitive recording material as claimed in claim 31 , wherein the platelet-shaped claim 31 , calcined aluminum silicate has an aspect ratio of at least one of:3 to 100,5 to 95, and10 to 90.33. The heat-sensitive recording material as claimed in claim 29 , whereina compound of the formula (II) is present as a color developer andthe heat-sensitive recording layer or the heat-sensitive recording material comprises no compound of the formula (I).34. The heat-sensitive recording material as claimed in claim 29 , whereina compound of the formula (I) is present as color developer andthe heat-sensitive recording layer or the heat-sensitive recording material comprises no compound of the formula (II).35. The heat-sensitive recording material as claimed in claim 29 , wherein the heat-sensitive recording layer comprises a sensitizer.36. The heat-sensitive recording material as claimed in claim 29 , wherein the heat-sensitive recording layer comprises a sensitizer and the sensitizer is selected from the group consisting of 1 claim 29 ,2-bis(3-methylphenoxy)ethane claim 29 ...

Degradation accelerator for polymers and polymer article comprising it

Disclosed are a method for improving the degradation of natural and/or synthetic polymers or a polymer article made from such polymer(s) by light and/or heat and/or humidity, comprising the incorporation of a compound of formula (I) into said natural and/or synthetic polymers: Formula (I); wherein m is 1 or 2, n is 1 to 100, X is selected from certain benzophenone-derived moieties and R, R1; R2 are each selected from list of certain residues; novel compounds of said formula (I) and polymeric articles of improved degradability in the presence of light and/or heat and/or humidity being made of a composition comprising: A) a natural and/or a synthetic polymer and B) a degradation accelerator being a compound of said formula (I).

INHIBITORS OF OPLOPHORUS LUCIFERASE-DERIVED BIOLUMINESCENT COMPLEXES

Compounds that may selectively inhibit luciferase-derived bioluminescent complexes, e.g., NanoBiT® bioluminescent complex, are disclosed as well as compositions and kits comprising the compounds, and methods of using the compounds.

Process for preparitn n,n-di-n-propyl-4-hydroxy-3-methanesulfonamidophenethylamine

Aminophosphine metal complex for asymmetric reactions

Human T2R bitterness receptors and uses thereof

본 발명은, T2R 미각 수용체 패밀리 중 특정 인간 미각 수용체가 예를 들어 커피에 존재하는 특정 쓴맛 화합물에 반응한다는 발견에 관한 것이다. 또한, 본 발명은, 쓴맛 차단제로서 기능을 하는 특정 화합물 및 조성물, 및 예를 들어 커피와 커피맛 식품, 음료 및 의약에서 쓴맛 차단제 또는 풍미 조절제로서의 이의 용도의 발견에 관한 것이다. 또한, 본 발명은 수많은 상이한 인간 T2R에 길항작용을 하는 화합물, 및 분석에서 및 인간 및 동물이 섭취하는 조성물 중 쓴맛 차단제로서의 이의 용도의 발견에 관한 것이다. The present invention relates to the discovery that certain human taste receptors in the T2R taste receptor family respond to certain bitter compounds, for example, present in coffee. The present invention also relates to the discovery of certain compounds and compositions which function as bitter taste blockers and their use as bitter taste blockers or flavor control agents, for example in coffee and coffee flavored foods, drinks and medicines. The invention also relates to compounds which antagonize a number of different human T2Rs and their use in the analysis and in the compositions ingested by humans and animals as bitter taste blockers.

히스톤 디아세틸라제의 억제제

본 발명은 히스톤 디아세틸라제의 억제에 관한 것으로, 히스톤 디아세틸라제 효소 활성을 억제하는 화합물 및 방법을 제공하는 것이고, 세포 증식 질병 및 질환을 치료하기 위한 조성물 및 방법을 제공하는 것이다.

N-сульфониламиноацетонитрилы, обладающие пестицидными свойствами

ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (51) ÌÏÊ 7 (11) 2005 101 203 (13) A C 07 C 311/13 ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÇÀßÂÊÀ ÍÀ ÈÇÎÁÐÅÒÅÍÈÅ (21), (22) Çà âêà: 2005101203/04, 18.06.2003 (71) Çà âèòåëü(è): ÍÎÂÀÐÒÈÑ Àà (CH) (30) Ïðèîðèòåò: 19.06.2002 GB 0214117.4 (43) Äàòà ïóáëèêàöèè çà âêè: 27.10.2005 Áþë. ¹ 30 (86) Çà âêà PCT: EP 03/06483 (18.06.2003) (87) Ïóáëèêàöè PCT: WO 2004/000798 (31.12.2003) Àäðåñ äë ïåðåïèñêè: 101000, Ìîñêâà, Ì.Çëàòîóñòèíñêèé ïåð., 10, êâ.15, "ÅÂÐÎÌÀÐÊÏÀÒ", È.À.Âåñåëèöêîé (54) N-ÑÓËÜÔÎÍÈËÀÌÈÍÎÀÖÅÒÎÍÈÒÐÈËÛ, ÎÁËÀÄÀÞÙÈÅ ÏÅÑÒÈÖÈÄÍÛÌÈ ÑÂÎÉÑÒÂÀÌÈ R U 1. Ñîåäèíåíèå ôîðìóëû â êîòîðîé R1 îáîçíà÷àåò àðèë èëè ãåòåðîàðèë, êàæäûé èç êîòîðûõ âë åòñ íåçàìåùåííûì èëè îäíî- ëèáî ìíîãîçàìåùåí çàìåñòèòåëåì R7, ïðè ýòîì çàìåñòèòåëè, åñëè èõ êîëè÷åñòâî ïðåâûøàåò 1, â êàæäîì ñëó÷àå ìîãóò áûòü èäåíòè÷íûìè èëè ðàçëè÷íûìè; R2 îáîçíà÷àåò C1-Ñ6àëêèë, ãàëî-Ñ1-Ñ6àëêèë, Ñ3-Ñ8öèêëîàëêèë, ãàëî- Ñ3-Ñ8öèêëîàëêèë, NHR8, àðèë èëè ãåòåðîàðèë, êàæäûé èç êîòîðûõ âë åòñ íåçàìåùåííûì èëè îäíî- ëèáî ìíîãîçàìåùåí çàìåñòèòåëåì R7, ïðè ýòîì çàìåñòèòåëè, åñëè èõ êîëè÷åñòâî ïðåâûøàåò 1, â êàæäîì ñëó÷àå ìîãóò áûòü èäåíòè÷íûìè èëè ðàçëè÷íûìè, èëè îáîçíà÷àåò ïèððîëèäèíèë, ïèïåðèäèíèë, èìèäàçîëèäèíèë, ïèïåðàçèíèë, ïèðàçîëèäèíèë, ìîðôîëèíèë, èíäîëèíèë èëè èçîèíäîëèíèë, êàæäûé èç êîòîðûõ ïðèñîåäèíåí ÷åðåç àòîì N; R3 îáîçíà÷àåò âîäîðîä, C1-Ñ6àëêèë, ãàëî-Ñ 1-Ñ6àëêèë, C1-Ñ6àëêîêñè-C1-Ñ6àëêèë, áåíçèë, C1-Ñ6àëêèëãåòåðîàðèë, C1-Ñ6àëêîêñèêàðáîíèë èëè C1-Ñ6àëêèëêàðáîíèë; R4, R5 è R6 íåçàâèñèìî äðóã îò äðóãà îáîçíà÷àþò âîäîðîä, ãàëîãåí, C1-Ñ6àëêèë, ãàëî-C 1-Ñ6àëêèë, C1-Ñ6àëêîêñèãðóïïó, ãàëî-C1-Ñ6àëêîêñèãðóïïó, C1-Ñ6àëêèëòèîãðóïïó, ãàëî-C1-Ñ6àëêèëòèîãðóïïó, Ñ2-Ñ6àëêåíèë, Ñ2-Ñ6àëêèíèë, íåçàìåùåííûé ëèáî çàìåùåííûé Ñ3-Ñ8öèêëîàëêèë, çàìåñòèòåëè êîòîðîãî, êîãäà îí âë åòñ çàìåùåííûì, âûáðàíû èç ãðóïïû, âêëþ÷àþùåé ãàëîãåí è C1-Ñ6àëêèë, èëè íåçàìåùåííûé ëèáî çàìåùåííûé ôåíèë, Ñòðàíèöà: 1 RU A 2 0 0 5 1 0 1 2 0 3 A Ôîðìóëà èçîáðåòåíè 2 0 0 5 1 0 1 2 0 3 (74) ...

Sulphonylated diphenylethylene diamines, synthesis method thereof and use in transfer hydrogenation catalysis

FIELD: chemistry. SUBSTANCE: invention relates to a diamine of formula , in which A is hydrogen; B is a C1-C6 alkyl group, a phenyl-C1-C6 alkyl group; or a group selected from phenyl, naphthyl, optionally substituted with a substitute selected from C1-C6 alkyl, C1-C6 alkoxy, or a halogen; X 1 , X 2 , Y 1 , Y 2 denote hydrogen; Z is a C1-C6 alkyl group or a C1-C6 alkoxy group. The invention also relates to a method of producing a diamine of formula (I). The invention also relates to an asymmetric hydrogenation catalyst obtained from reaction a diamine of formula (I) and a compound of formula [MX 2 (arene)] 2 , where M is selected from Ru, Rh, Ir, Co, Ni, Fe, Pd, Pt and X is a halogen. The catalyst is used for transfer hydrogenation and the transfer hydrogenation reaction is carried out with a cyclic ketone. EFFECT: obtaining sulphonylated diphenylethylene diamines used in transfer hydrogenation catalysis. 12 cl, 4 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 446 154 (13) C2 (51) МПК C07C B01J B01J C07B C07C 311/16 (2006.01) 31/22 (2006.01) 31/18 (2006.01) 41/02 (2006.01) 303/38 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2007122501/04, 01.11.2005 (24) Дата начала отсчета срока действия патента: 01.11.2005 (73) Патентообладатель(и): БИАЛ-ПОРТЕЛА ЭНД КА, С.А. (PT) (43) Дата публикации заявки: 27.12.2008 Бюл. № 36 (56) Список документов, цитированных в отчете о поиске: CORVEY E.J. et al. Convenient routes to symmetrical benzyls and chiral 1,2-diaryl-1,2diamines, useful controllers and probes for enantioselective synthesis // TETRAHEDRON: Asymmetry, 1995, vol.6, no.1, pp.3-6. XIAOGUANG LI et al. Asymmetric transfer hydrogenation of ketones with a polymer-supported chiral diamine // TETRAHEDRON LETTERS, 2004, (см. прод.) C 2 C 2 2 4 4 6 1 5 4 (45) Опубликовано: 27.03.2012 Бюл. № 9 R U 2 4 4 6 1 5 4 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 18.06.2007 (86) Заявка PCT: GB 2005/050190 (01. ...

Optically active transition metal-diamine complex and method for producing optically active alcohols using the same

【課題】本発明は、分液等により容易に反応生成物と分離することができ、リサイクルが可能な水溶性の遷移金属−ジアミン錯体、及びその配位子を構成する光学活性ジアミン化合物、並びにこれらからなる不斉合成用の触媒を提供する。【解決手段】本発明は、一般式（２）【化２８】［式中、Ｒ１、Ｒ２は、水素原子、炭化水素基、−ＳＯ２Ｒ１３（Ｒ１３は炭化水素基、置換アミノ基等）等を示し、Ｒ３〜Ｒ１２は、水素原子、炭化水素基、アルコキシ基、置換アミノ基等を示し、Ｍは遷移金属、Ｘはハロゲン原子、Ｌは配位子を夫々示し、＊は不斉炭素を示す。但し、Ｒ３〜Ｒ７、及びＲ８〜Ｒ１２の内の少なくとも１つは置換アミノ基である。］で表される水溶性の光学活性遷移金属−ジアミン錯体、及びこれを含んでなる不斉合成触媒、並びにこれを用いるケトン類の不斉還元による光学活性アルコール類の製造法に関する。【選択図】 なし The present invention relates to a water-soluble transition metal-diamine complex that can be easily separated from a reaction product by liquid separation or the like and can be recycled, an optically active diamine compound constituting the ligand, and A catalyst for asymmetric synthesis comprising these is provided. The present invention relates to a compound represented by the general formula (2): wherein R 1 and R 2 are a hydrogen atom, a hydrocarbon group, —SO 2 R 13 (R 13 is a hydrocarbon group, a substituted amino group, etc.), etc. , R3 to R12 represent a hydrogen atom, a hydrocarbon group, an alkoxy group, a substituted amino group, etc., M represents a transition metal, X represents a halogen atom, L represents a ligand, and * represents an asymmetric carbon. However, at least one of R3 to R7 and R8 to R12 is a substituted amino group. ] The water-soluble optically active transition metal-diamine complex represented by the above, an asymmetric synthesis catalyst comprising the same, and a method for producing optically active alcohols by asymmetric reduction of ketones using the same. [Selection figure] None

一种对位环丙烷基取代的苯磺酰苯胺及其制备方法

本发明公开了一种对位环丙烷基取代的苯磺酰苯胺及其制备方法，步骤如下：将对溴苯磺酸与苯胺溶解于吡啶中，然后加入缩合剂EDC‑HCl，在50‑80℃的条件下反应2~3h，得到对溴苯磺酰苯胺；将对溴苯磺酰苯胺溶于二氧六环溶液中，然后加入环丙基硼酸，碳酸钠和水溶液，Pd（dppf）Cl 2 ，混合体系在氮气氛围下，110℃反应8~10h，后处理制得对环丙烷基苯磺酰苯胺，该制备方法条件相对温和，产物易处理纯化，适合批量制备。

O-cyclopropylbenzene sulfonanilide and preparation method thereof

本发明公开了一种邻环丙基苯磺酰苯胺及其制备方法，将2‑溴苯磺酸与苯胺溶解于吡啶中，然后加入缩合剂EDC‑HCl，在60‑80℃的条件下反应2~4h，得到2‑溴‑N‑苯基苯磺酰胺；将2‑溴‑N‑苯基苯磺酰胺溶于二氧六环溶液中，然后加入环丙基硼酸，碳酸钠和水溶液，Pd（dppf）Cl 2 ，混合体系在氮气氛围下，110℃反应8~10h，后处理制得邻环丙基苯磺酰苯胺，本发明所公开的合成路线简短，只有两步反应，反应易于操作；所用的制备方法可操作性强，收率高，是一种适合大批量制备的优异方法。由于此类化合物是有价值的药物中间体，因此本发明公开的内容具有重要的研究和实用价值。

Аминопиридинил-, аминогуанидинил- и алкоксигуанидинилзамещенные фенилацетамиды и их применение в качестве ингибиторов протеаз

2003113205 А ко РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) (51) МПК” ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (11) КО 13) ма 205 А ха & ` ; < > М х \ к Ка АХ СО7С 279/00, А 61 К 31/155 2 2 и р 2 и ‚7 (12 ИЗВЕЩЕНИЯ К ЗАЯВКЕ НА ИЗОБРЕТЕНИЕ (21), (22) Заявка: 2003113205/04, 05.10.2001 (30) Конвенционный приоритет: 06.10.2000 Ц$ 60/238,132 (43) Дата публикации заявки: 10.11.2004 (85) Дата перевода заявки РСТ на национальную фазу: 06.05.2003 (86) Заявка РСТ: ($ 01/31249 (05.10.2001) (87) Публикация РСТ: М/О 02/28825 (11.04.2002) Адрес для переписки: 127055, Москва, а/я 11, пат.пов. Н.К.Попеленскому (71) Заявитель(и): 3-Дименшенл Фамэсьютикэлс, Инк. (Ц$) (72) Автор(ы): ЛУ Тианбао (1$), МАРКОУТЭН Томас П. (ЦЗ), ПЭН Уэнкси (1$), ТОМКЗУК Брюс Э. (1$) (74) Патентный поверенный: Попеленский Николай Константинович (54) АИИНОПИРИДИНИЛ-, АМИНОГУАНИДИНИЛ- И АЛКОКСИГУАНИДИНИЛЗАМЕЩЕННЫЕ ФЕНИЛАЦЕТАМИДЫ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ИНГИБИТОРОВ ПРОТЕАЗ ГАЭА - Признание заявки на изобретение отозванной в связи с непредставлением в установленном порядке документа, подтверждающего уплату патентной пошлины за регистрацию изобретения и выдачу патента Дата, с которой заявка признана отозванной: Извещение опубликовано: 10.09.2008 23.07.2008 БИ: 25/2008 Страница: 1 па <0$$511$00сС У

IL-8 receptor antagonists

This invention relates to novel compounds and a novel use of phenyl ureas in the treatment of disease scates mediated by the chemokine, Interleukin-8 (IL-8). In particular, this invention relates to the novel compounds of Formula (Ia) and their use in treating chemokine mediated diseases wherein the chemokine binds to an IL-8 a or b receptor. Compounds of Formula (Ia) are represented by the structure: ##STR1## wherein interalia, X is oxygen or sulfur; Rb is NR 6 R 7 , alkcyl, aryl, arylC 1-4 alkyl, aryl C 2-4 alkenyl, heteroaryl, heteroarylC 1-4 alkyl, heteroarylC 2-4 alkenyl, heterocyclic or heterocyclic C 1-4 alkyl, or a heterocyclic C 2-4 alkenyl moiety, camphor, all of which may be optionally substituted; R 1 is independently selected from hydrogen; halogen; nitro; cyano; C 1-10 alkyl; halosubstituted C 1-10 alkyl; C 2-10 alkoxy; halosubstituted C 1-10 alkoxy; azide; (CR 8 R 8 )q S(O) t R 4 ; hydroxy; hydroxy substituted C 1-4 alkyl; aryl; aryl C 1-4 alkyl; aryl C 2-10 alkenyl; aryloxy; aryl C 1-4 alkyloxy; heteroaryl; heteroarylalkyl; heteroaryl C 2-10 alkenyl; heteroaryl C 1-4 alkyloxy; heterocyclic; heterocyclic C 1-4 alkyl; heterocyclicC 1-4 alkyloxy; heterocyclic C 2-10 alkenyl; q is 0 or an integer having a value of 1 to 10; n is an integer having a value of 1 to 3; m is an integer having a value of 1 to 3; Y is hydrogen; halogen; nitro; cyano; halosubstituted C 1-10 alkyl; C 1-10 alkyl; C 2-10 alkenyl C 1-10 alkoxy; halosubstituted C 1-10 alkoxy; azide; (CR 8 R 8 )qS(O) t R 4 , (CR 8 R 8 )qOR 4 ; hydorxy; hydroxy substituted C 1-4 alkyl; aryl; aryl C 1-4 alkyl; aryloxy; arylC 1-4 alkyloxy; aryl C 2-10 alkenyl; heteroaryl; heteroarylalkyl; heteroaryl C 1-4 alkyloxy; heteroaryl C 2-10 alkenyl; heterocyclic, heterocyclic C 1-4 alkyl; heterocyclicC 2-10 alkenyl; or a pharmaceutically acceptable salt thereof.

NEW CATALYTIC SYSTEMS FOR (CO) POLYMERIZATION OF LACTONS WITH CYCLING DISCLOSURE

Настоящее изобретение относится к применению системы, образованной основанием и сульфонамидом, в качестве катализатора (со)полимеризации лактонов с раскрытием цикла. Изобретение относится также к новым сульфонамидам и способу (со)полимеризации лактонов с раскрытием цикла, при этом сульфонамиды в сочетании с основанием применяют в качестве каталитической системы. The present invention relates to the use of a system formed by a base and a sulfonamide as a catalyst for the (co) polymerization of lactones with ring opening. The invention also relates to new sulfonamides and a process for the (co) polymerization of lactones with ring opening, wherein sulfonamides in combination with a base are used as a catalytic system.

Compounds inhibiting (blocking) bitter taste, methods for use and production thereof

FIELD: chemistry.SUBSTANCE: invention relates to a compound of general formula(I) or pharmaceutically acceptable salts thereof, where Alk is an C-Calkyl group; G is C=O and Q is CRRor NR, where Rand R, being identical or different, independently denote H, C-Calkyl, optionally substituted with a substitute selected from a group comprising carboxy, phenoxy, benzyloxy, C-Calkoxy or hydroxy; C-CcycloalkylC-Calkyl; phenylC-Calkyl, optionally substituted with a halogen; phenylamidoC-Calkyl; phenylC-CalkylamidoC-Calkyl, optionally substituted with a C-Calkoxy group; or Rand R, together with a carbon atom with which they are bonded form a C=O or C-Calkenyl group, optionally substituted with a phenyl; Mis CR, where Ris H; Mis CR, where Ris H; Ris H, C-Calkyl, substituted with a phenoxy group; C-CcycloalkylC-Calkyl; arylC-Calkyl, optionally substituted with 1 or 2 substitutes selected from a group comprising C-Calkyl, C-Calkoxy, C-Calkoxycarbonyl, carboxyl, N-methylamido, hydroxy, C-CalkoxyC-Calkoxy, C-Calkylthio, C-Calkylsulphanyl, cyano, halogen, perfluoroC-Calkyl, nitro, formyl, hydroxyC-Calkyl and amino, wherein the aryl moiety is a phenyl or naphthyl; and heteroarylC-Calkyl, where the heteroaryl moiety is pyridinyl, optionally substituted with 1 or 2 groups selected from C-Calkoxy or hydroxyC-Calkyl, pyrazolyl or isoxazolyl, substitute with 1 or 2 C-Calkyl groups; Rand Ris C-Calkyl. The invention also relates to specific compounds, a method of reducing or weakening bitter taste, a composition of a food/non-food product or beverage or drug for reducing or lightening bitter taste and a method of producing a compound of formula (I).EFFECT: obtaining novel compounds which are useful as bitter taste inhibitors or taste modulators.37 cl, 6 dwg, 12 tbl, 186 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07D 413/06 C07D 413/14 C07D 407/14 C07D 409/14 C07D 417/14 C07C 311/16 ФЕДЕРАЛЬНАЯ СЛУЖБА C07C 311/12 ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ C07C 311/15 C07C 335/12 C07D 213/36 (12) ...

Phenylalanine derivatives, optically active substances, salts or coordination compounds thereof, and their use as fungicides

The present invention provides a phenylalanine derivative represented by general formula (I), [wherein R1 is H or an alkyl group, R2 is H, an alkyl group, an alkoxycarbonyl group, a phenylalkyl group or the like, R?1 and R2¿ being able to be taken together to represent an alkylene group which may contain O or N between adjacent carbon atoms of the carbon chain, or a phthaloyl group, R?3 is OR4, N(R5)-R6¿ or NHCH(R7)(CH2)nCOOR?8 (R4, R5, R6, R7 and R8¿ are as defined in the specification], a salt thereof, their optically active substances or coordination compounds, and a novel fungicide for fruit gardening containing any of them as an active ingredient.

Plant growth regulators

FIELD: chemistry. SUBSTANCE: invention relates to chemical agents for increasing crop yield of winter wheat and sunflower. Substances used to stimulate plant growth of winter wheat and sunflower, increase their productivity, are N-substituted naphthalene-2-sulphonyl amides of formula 1-2, where R = CH 3 ; C 2 H 5 . EFFECT: high yield of winter wheat and sunflower. 1 cl, 2 tbl, 4 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 611 418 C2 (51) МПК C07C 311/15 (2006.01) A01N 41/04 (2006.01) A01P 21/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ФОРМУЛА (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ 2015126515, 02.07.2015 (24) Дата начала отсчета срока действия патента: 02.07.2015 Дата регистрации: Приоритет(ы): (22) Дата подачи заявки: 02.07.2015 (43) Дата публикации заявки: 12.01.2017 Бюл. № 2 Адрес для переписки: 350039, г. Краснодар, п/о 39, ВНИИБЗР (56) Список документов, цитированных в отчете о поиске: RU 2430915 C2, 10.10.2011. FR 2 6 1 1 4 1 8 R U C 2 C 2 2283885 A1, 02.04.1976. Nikam, Sham S.; Kornberg, Brian E.; Ault-Justus, Stephanie E.; Rafferty, Michael F. " Novel quenchers for solution phase parallel synthesis." Tetrahedron Letters, 39(10), 1121-1124 (English) 1998. DOI: 10.1016/S0040-4039(97)10781-X. 2 6 1 1 4 1 8 (45) Опубликовано: 22.02.2017 Бюл. № 6 (73) Патентообладатель(и): Федеральное государственное бюджетное научное учреждение "Всероссийский научно-исследовательский институт биологической защиты растений" Краснодар-39 (RU) R U 22.02.2017 (72) Автор(ы): Дядюченко Людмила Всеволодовна (RU), Назаренко Дарья Юрьевна (RU), Морозовский Валентин Васильевич (RU), Надыкта Владимир Дмитриевич (RU), Ткач Лидия Никифоровна (RU) (54) Регуляторы роста растений (57) Формула изобретения Регуляторы роста озимой пшеницы и подсолнечника, представляющие собой Nзамещенные нафталин-2-сульфониламиды формулы 1-2 где 1 R = C2H5; 2 R = CH3. Стр.: 1