Pyrrolidine or thiazolidine carboxylic acid derivatives, pharmaceutical composition and methods for use in treating metabolic disorders as agonists of g-protein coupled receptor 43 (gpr43)

The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases.

Pyrrolysine analogs

Several different pyrrolysine analogs are disclosed in this application. Those analogs have distinct chemical and biophysical properties. Some analogs are useful in chemical ligation applications. Methods of making and using are also disclosed.

CYSTEINE DERIVATIVE

Cysteine compounds represented by the following formula 2. A cosmetic composition according to claim 1 , further comprising at least one ingredient selected from the group consisting of an oily component claim 1 , a surfactant claim 1 , an amino acid claim 1 , an amino acid derivative claim 1 , a lower alcohol claim 1 , a polyhydric alcohol claim 1 , a sugar alcohol claim 1 , an alkylene oxide adduct of a sugar alcohol claim 1 , a water-soluble polymer claim 1 , an antimicrobial agent claim 1 , a disinfectant claim 1 , an anti-inflammatory agent claim 1 , an analgesic claim 1 , an antifungal agent claim 1 , a stratum corneum peeling agent claim 1 , a skin colorant claim 1 , a hormone claim 1 , a UV absorber claim 1 , a hair-growth promoter claim 1 , a whitening agent claim 1 , an antiperspirant claim 1 , an astringent active ingredient claim 1 , a perspiration deodorant claim 1 , a vitamin claim 1 , a vasodilator claim 1 , a crude drug claim 1 , a pH adjuster claim 1 , a viscosity modifier claim 1 , a pearly pigment claim 1 , a natural perfume claim 1 , a synthetic perfume claim 1 , a dye claim 1 , an antioxidant claim 1 , a preservative claim 1 , am emulsifier claim 1 , a fat claim 1 , a wax claim 1 , a silicone compound claim 1 , a balm claim 1 , and a mixture thereof.3. A cosmetic composition according to claim 1 , wherein said at least one cysteine compound is one or more compounds selected from the group consisting of N-acetyl-2-methylthiazolidine-2 claim 1 ,4-dicarboxylic acid claim 1 , N-acetyl-2-methylthiazolidine-2 claim 1 ,4-dicarboxylic acid 2-ethyl ester claim 1 , and a salt thereof.4. A cosmetic composition according to claim 1 , wherein said at least one cysteine compound is one or more compounds selected from the group consisting of trans N-acetyl-2-methylthiazolidine-2 claim 1 ,4-dicarboxylic acid claim 1 , trans N-acetyl-2-methylthiazolidine-2 claim 1 ,4-dicarboxylic acid 2-ethyl ester claim 1 , and a salt thereof.6. A cosmetic composition according ...

O-CYCLOPROPYLCYCLOHEXYL-CARBOXANILIDES AND THEIR USE AS FUNGICIDES

The present invention relates to O-CYCLOPROPYLCYCLOHEXYL-CARBOXANILIDES derivatives of formula (I); their process of preparation, their use as fungicide, particularly in the form of fungicide compositions, and methods for the control of phytopathogenic fungi, notably of plants, using these compounds or compositions. 2. A compound of formula (I) as claimed in claim 1 , wherein{'sup': 1', '2, 'Rand Rare, independently, hydrogen or fluoro;'}{'sup': '3', 'sub': 2-6', '3-8, 'Ris Calkyl, optionally substituted Ccycloalkyl, phenyl, thienyl or furyl;'}A represents one of the radicals A1, A2, A3, A4, A5, A6, A9, A10, A11, A12 or A17;{'sup': '18', 'sub': 1', '2', '1', '2, 'Rrepresents hydrogen, cyano, fluorine, chlorine, bromine, iodine, methyl, ethyl, isopropyl, methoxy, ethoxy, methylthio, ethylthio, cyclopropyl, C-Chaloalkyl C-C-haloalkoxy having in each case 1 to 5 fluorine, chlorine and/or bromine atoms, trifluoromethylthio, difluoromethylthio, aminocarbonyl, aminocarbonylmethyl or aminocarbonylethyl;'}{'sup': '19', 'Rrepresents hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, methoxy, ethoxy, methylthio or ethylthio;'}{'sup': '20', 'sub': 1', '2, 'Rrepresents hydrogen, methyl, ethyl, n-propyl, isopropyl, C-C-haloalkyl having 1 to 5 fluorine, chlorine and/or bromine atoms, hydroxymethyl, hydroxyethyl, cyclopropyl, cyclopentyl, cyclohexyl or phenyl.'}{'sup': 21', '22, 'sub': 1', '2, 'Rand Rindependently of one another represent hydrogen, fluorine, chlorine, bromine, methyl, ethyl or C-C-haloalkyl having 1 to 5 fluorine, chlorine and/or bromine atoms;'}{'sup': '23', 'sub': 1', '2', '1', '2, 'Rrepresents fluorine, chlorine, bromine, cyano, methyl, ethyl, C-C-haloalkyl or C-C-haloalkoxy having in each case 1 to 5 fluorine, chlorine and/or bromine atoms;'}{'sup': 24', '25, 'sub': 1', '2, 'Rand Rindependently of one another represent hydrogen, fluorine, chlorine, bromine, methyl, ethyl or C-C-haloalkyl having 1 to 5 fluorine, chlorine and/or bromine atoms;'}{'sup ...

ENZYMATIC CONJUGATION OF POLYPEPTIDES

The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions 1. An antibody or antibody fragment comprising a functionalized acceptor glutamine residue , the functionalized acceptor glutamine residue having Formula IVa ,{'br': None, 'sub': n', 'z', 'q', 'q', 'r, '(Q)-NH—(C)—X-L-(V—(Y—(Z))))\u2003\u2003Formula IVa'}or a pharmaceutically acceptable salt or solvate thereof,wherein:Q is glutamine residue present in an antibody or antibody fragment;{'sub': 'n', '(C)is a substituted or unsubstituted alkyl or heteroalkyl chain, optionally wherein any carbon of the chain is substituted with an alkoxy, hydroxyl, alkylcarbonyloxy, alkyl-S—, thiol, alkyl-C(O)S—, amine, alkylamine, amide, or alkylamide;'}n is an integer selected from among the range of 2 to 20;X is NH, O, S, absent, or a bond;L is independently absent, a bond or a continuation of a bond, or a carbon comprising framework of 5 to 200 atoms substituted at one or more atoms;r is an integer selected from among 1, 2, 3 or 4;q is an integer selected from among 1, 2, 3 or 4;z is an integer selected from among 1, 2, 3 or 4; andV is independently absent, a bond or a continuation of a bond, a non-cleavable moiety or a conditionally-cleavable moiety;Y is independently absent, a bond or a continuation of a bond, or a spacer system which is comprised of 1 or more spacers; andZ is a moiety that improves pharmacokinetic properties, a therapeutic moiety or a diagnostic moiety, wherein Z is an organic compound that is electrically negatively charged, hydrophobic and/or that has a molecular weight of at least 400 g/mol.2. The antibody of claim 1 , wherein n is an integer selected from among the range of 10 to 20.3. The antibody of claim 1 , wherein (C)is a heteroalkyl chain that comprises a (CH—CH—O—)group claim 1 , wherein x is ...

APOPTOSIS PROMOTERS

Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member. 19-. (canceled)10. A compound , or a therapeutically acceptable salt thereof , wherein the compound is selected from the group consisting of:N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(5,6-dihydro-1(4H)-pyrimidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(2,4-dimenthyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-methyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)oxy)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;4-(((1R)-3-(bis(2-methoxyethyl)amino)-1 ...

CYCLIC AMIDE DERIVATIVE

[Problem] 4. The compound according to claim 3 , wherein X is an oxygen atom claim 3 , k is 0 claim 3 , and any one of q and s is 1 or more claim 3 ,a salt of the compound, or a solvate of the compound or the salt.6. The compound according to claim 5 , wherein E is Formula (c2) claim 5 , and any one of q and s is 1 or more claim 5 ,a salt of the compound, or a solvate of the compound or the salt.7. The compound according to any one of to claim 5 , wherein s is 1 claim 5 , a salt of the compound claim 5 , or a solvate of the compound or the salt.10. The compound according to claim 9 , wherein Ea is Formula (c1) claim 9 , and any one of q and s is 1 or more claim 9 ,a salt of the compound, or a solvate of the compound or the salt.11. A pharmaceutical composition characterized by comprising claim 9 , as an active ingredient claim 9 , at least one of the compound as claimed in any one of to claim 9 , a pharmaceutically acceptable salt of the compound claim 9 , and a pharmaceutically acceptable solvate of the compound or the salt.12. A prophylactic agent and/or a therapeutic agent against a GPR40-involving disease characterized by comprising claim 9 , as an active ingredient claim 9 , at least one of the compound as claimed in any one of to claim 9 , a pharmaceutically acceptable salt of the compound claim 9 , and a pharmaceutically acceptable solvate of the compound or the salt.13. An insulin secretagogues characterized by comprising claim 9 , as an active ingredient claim 9 , at least one of the compound as claimed in any one of to claim 9 , a pharmaceutically acceptable salt of the compound claim 9 , and a pharmaceutically acceptable solvate of the compound or the salt.14. A GPR40 activating agent comprising at least one of the compound as claimed in any one of to claim 9 , a pharmaceutically acceptable salt of the compound claim 9 , and a pharmaceutically acceptable solvate of the compound or the salt.15. A pharmaceutical composition characterized by comprising:{' ...

NOVEL SYNTHESIS FOR THIAZOLIDINEDIONE COMPOUNDS

The present invention provides novel methods for synthesizing PPARγ sparing compounds, e.g., thiazolidinediones, that are useful for preventing and/or treating metabolic disorders such as diabetes, obesity, hypertension, and inflammatory diseases.

METHOD OF INHIBITING TAU PHOSPHORYLATION

A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. - 1. A method of inhibiting phosphorylation of the tau protein that comprises the steps of administering to cells of the central nervous system in recognized need an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1 , inhibits at least about 60 percent of the FITC-labeled naloxone binding when present at a 10 μM concentration and using unlabeled naloxone as the control inhibitor at the same concentration , said administration being carried out in the absence of a mu opioid receptor- (MOR-) binding effective amount of a separate MOR agonist or antagonist.2. The method according to claim 1 , wherein said compound contains at least four of the six pharmacophores of .3. The method according to claim 1 , wherein said compound or a pharmaceutically acceptable salt thereof is present dissolved or dispersed in a pharmaceutically acceptable diluent as a pharmaceutical composition when administered.4. The method according to claim 1 , wherein said compound exhibits less than about 80 percent the MOR stimulation provided by DAMGO at the same concentration.13. The method according to claim 12 , wherein said anion claim 12 , X claim 12 , is selected from the group consisting of phosphate claim 12 , hydrogenphosphate claim 12 , dihydrogenphosphate claim 12 , sulfate claim 12 , bisulfate claim 12 , chloride claim 12 , bromide claim 12 , iodide claim 12 , acetate claim 12 , formate claim 12 , benzenesulfonate claim 12 , methanesulfonate claim 12 , and ...

Novel synthesis for thiazolidinedione compounds

The present invention provides novel methods for synthesizing PPARγ sparing compounds, e.g., thiazolidinediones, that are useful for preventing and/or treating metabolic disorders such as diabetes, obesity, hypertension, and inflammatory diseases.

Novel compound having skin-whitening, anti-oxidizing and ppar activities and medical use therefor

Provided are a novel compound having skin-whitening, anti-oxidizing and PPAR activities and a medical use thereof, and the compound has skin-whitening activities for the suppression of tyrosinase, and accordingly, is useful for use in skin-whitening pharmaceutical composition or cosmetic products; has anti-oxidant activities, and accordingly, is useful for the prevention and treatment of skin-aging; and has PPAR activities, and in particular, PPARα and PPARγ activities, and accordingly, is useful for use in pharmaceutical compositions or health foods which are effective for the prevention and treatment of obesity, metabolic disease, or cardiovascular disease.

NOVEL IMAGING COMPOSITION AND USES THEREOF

The invention discussed in this application relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. 2. The conjugate of claim 1 , wherein L is OR.3. The conjugate of claim 2 , wherein R is Cto Calkyl.4. The conjugate of claim 2 , wherein OR is selected from O-p-toluenesulfonate claim 2 , O-methanesulfonate claim 2 , O-trifluoromethanesulfonate claim 2 , O-benzenesulfonate claim 2 , and O-m-nitrobenzenesulfonate.5. The conjugate of claim 1 , wherein the target molecule is a polypeptide.6. The conjugate of claim 5 , wherein the polypeptide is an antibody.7. The conjugate of claim 6 , wherein the antibody is selected from trastuzumab claim 6 , rituximab and cetuximab.8. The conjugate of claim 1 , wherein the target molecule is a peptide.9. The conjugate of claim 8 , wherein the peptide is a targeting peptide.10. The conjugate of claim 9 , wherein the targeting peptide is selected from a cyclic RGD sequence claim 9 , bombesin and glu-N(CO)N-lys PSMA. This application is a Continuation of U.S. patent application Ser. No. 15/963,599, filed Apr. 26, 2018, which is a Continuation of U.S. patent application Ser. No. 15/518,333, filed Apr. 11, 2017, now U.S. Pat. No. 9,980,930, issued on May 29, 2018 and is a National Stage Application, filed under 35 U.S.C. 371, of International Application No. PCT/AU2015/050640, filed on Oct. 16, 2015, which claims priority to, and the benefit of, AU Application No. 2014904138, filed Oct. 16, 2014. The contents of each of these applications are incorporated by reference in their entirety.The present invention relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. The present invention also relates to compositions including the compounds, and to methods of imaging patients using the compounds.Zirconium-89 (Zr) is a positron-emitting ...

THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF

The invention provides compounds having the general Formula (I); 3. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris selected from the group consisting of F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , —CN claim 1 , —OH claim 1 , —NH claim 1 , Calkyl and Chaloalkyl.5. The compound or pharmaceutically acceptable salt of claim 1 , wherein ring “A” is a Cheterocycle and is selected from the group consisting of azetidine claim 1 , pyrrolidine claim 1 , piperidine claim 1 , morpholine claim 1 , homopiperazine claim 1 , piperazine and 8-azabicyclo[3.2.1]octane claim 1 , and is optionally substituted.16. The compound or pharmaceutically acceptable salt of claim 1 , wherein:{'sup': 'o', 'sub': '1-6', 'Ris hydrogen or Calkyl;'}{'sup': 1', '2, 'sub': '1-8', 'Rand Rare each independently selected from the group consisting of hydrogen and Calkyl;'}{'sup': '3', 'Ris selected from the group consisting of hydrogen and F;'}{'sup': 4', '1', '4, 'sub': '1-4', 'Ris selected from the group consisting of hydrogen or Calkyl; or Rand Rare combined to form a 3- to 7-membered heterocycle ring as described above;'}{'sup': '5', 'sub': 1-8', '3-8, 'Ris selected from the group consisting of F, Cl, Calkyl, and Ccycloalkyl;'}{'sub': '1-6', 'L is Calkylene;'}the subscript m represents the integer 0 or 1;{'sup': 1', '2', '1', '2, 'Xand Xare each independently selected from the group consisting of absent and —O—, and wherein if the subscript m is 0 then one of Xor Xis absent;'}the ring “A” in is selected from the group consisting of:{'sub': '2-11', 'claim-text': [{'sup': 'AA', 'sub': 1-8', '1-8', '1-8, 'Ris independently selected from the group consisting of Calkyl, Chaloalkyl, Cheteroalkyl, F, Cl, Br and I;'}, 'n is an integer from 0 to 5;', {'sup': A', 'RA', 'RA', 'A', 'RA', 'RA', 'RAi', 'RA, 'sub': 6-10', '1-2', '1-2', '6-10', '1-4', '1-4', '1-4', '2', '1-4, 'Ris selected from the group consisting of (Caryl)-(X)—, and (5- to 10-membered heteroaryl)-(X)—, wherein said ...

CYSTEINE DERIVATIVE

Cysteine compounds represented by the following formula 111-. (canceled)13. A cysteine compound or salt thereof according to claim 12 , which is in the trans form.15. A cysteine compound or salt thereof according to claim 14 , which is in the trans form.1619-. (canceled)2224-. (canceled) This application is a divisional of U.S. patent application Ser. No. 13/686,384, filed on Nov. 27, 2012, which is a continuation of International Patent Application No. PCT/JP2011/062293, filed on May 27, 2011, and claims priority to Japanese Patent Application No. 2010-123169, filed on May 28, 2010, each of which are incorporated herein by reference in their entireties.1. Field of the InventionThe present invention relates to particular cysteine derivatives. Furthermore, the present invention relates to methods for producing particular cysteine derivatives, cosmetic agents which contain particular cysteine derivatives, and the like.2. Discussion of the BackgroundIn human pigment cells (melanocytes) in the skin, melanin is produced utilizing L-cysteine and L-tyrosine. When a greater amount of L-tyrosine, which is a starting material for eumelanin, is utilized for the synthesis of melanin, production of eumelanin is promoted and the skin becomes dark. On the other hand, when a greater amount of L-cysteine is utilized for the synthesis of melanin, production of eumelanin is suppressed, and the skin becomes closer to yellow. Therefore, it is considered that production of eumelanin is suppressed by supplying L-cysteine during melanin synthesis.Heretofore, many attempts have been made to utilize L-cysteine as cosmetics such as whitening agents utilizing L-cysteine and the like. However, L-cysteine is easily oxidized, and has problems such as poor stability and bad odor for formulating as a cosmetic agent or skin external preparation.To solve such problem, the development of a cysteine derivative with improved stability has been considered. JP-B-48-15938 discloses that L-2- ...

METHODS AND DOSE PACKS FOR MONITORING MEDICATION ADHERENCE

Provided herein are methods and dose packs for the monitoring of medication adherence. In one aspect, the dose pack comprises comprise a multiplicity of doses of an agent and a multiplicity of doses of a marker and be configured to isolate a pair of at least one of the multiplicity of doses of the agent and at least one of the multiplicity of doses of the marker for co-administration of the pair to the subject according to the dosing schedule. In another aspect, the method comprises obtaining a sample from the subject subsequent to the conclusion of a monitoring window and analyzing the sample for the presence or absence of a marker or a degradation product thereof. 153.-. (canceled)54. A method for monitoring adherence of a subject to a dosing schedule , the method comprising:providing a dose pack, the dose pack comprising a pair of a biomarkingly effective dose of a marker and a dose of an agent,obtaining a sample from the subject, andanalyzing the sample for the presence or absence of the marker or a degradation product of the marker,wherein the marker comprises a histamine receptor ligand compound, a metabolite thereof, or a degradation residue thereof andwherein the marker and the agent are different.55. The method of claim 54 , wherein the pair comprises a unitary formulation.56. The method of claim 55 ,wherein the unitary formulation comprises a solid dose form comprising a coating andwherein the coating comprises the marker.57. The method of claim 55 ,wherein the unitary formulation comprises a solid dose form comprising a capsule andwherein the marker is in a particulate form disposed in the capsule.58. The method of claim 55 ,wherein the unitary formulation comprises a solid dose form comprising a layered tablet having a first layer and a second layer, andwherein the first layer and the second layer of the solid dose form comprise the marker and the agent, respectively.59. The method of claim 54 , wherein the sample comprises a sample of urine claim 54 , ...

INHIBITORS OF SHORT-CHAIN DEHYDROGENASE ACTIVITY FOR TREATING FIBROSIS

A method of treating or preventing a fibrotic disease, disorder or condition includes administering to a subject in need of treatment a 15-PGDH inhibitor. 1: A method of treating or preventing a fibrotic disease , disorder or condition in a subject in need thereof , the method comprising administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor.2: The method of claim 1 , wherein the fibrotic disease claim 1 , disorder or condition is characterized claim 1 , in whole or in part claim 1 , by the excess production of fibrous material claim 1 , including excess production of fibrotic material within the extracellular matrix claim 1 , or the replacement of normal tissue elements by abnormal claim 1 , non-functional claim 1 , and/or excessive accumulation of matrix-associated components.3: The method of claim 1 , wherein the fibrotic disease claim 1 , disorder claim 1 , or condition is selected from the group consisting of systemic sclerosis claim 1 , multifocal fibrosclerosis claim 1 , nephrogenic systemic fibrosis claim 1 , scleroderma claim 1 , sclerodermatous graft-vs-host-disease claim 1 , kidney fibrosis claim 1 , glomerular sclerosis claim 1 , renal tubulointerstitial fibrosis claim 1 , progressive renal disease or diabetic nephropathy claim 1 , cardiac fibrosis claim 1 , pulmonary fibrosis claim 1 , glomerulosclerosis pulmonary fibrosis claim 1 , idiopathic pulmonary fibrosis claim 1 , silicosis claim 1 , asbestosis claim 1 , interstitial lung disease claim 1 , interstitial fibrotic lung disease claim 1 , chemotherapy/radiation induced pulmonary fibrosis claim 1 , oral fibrosis claim 1 , endomyocardial fibrosis claim 1 , deltoid fibrosis claim 1 , pancreatitis claim 1 , inflammatory bowel disease claim 1 , Crohn's disease claim 1 , nodular fascilitis claim 1 , eosinophilic fasciitis claim 1 , general fibrosis syndrome characterized by replacement of normal muscle tissue by fibrous tissue in varying degrees claim 1 , retroperitoneal ...

METAL-BINDING COMPOUNDS, HETEROLOGOUS PRODUCTION AND USES THEREOF

Provided are Ybt analogs and derivatives thereof and compositions comprising Ybt and Ybt analogs and derivatives thereof. Methods of making Ybt and Ybt analogs and methods of using Ybt and Ybt analogs are also provided. The methods use microbes modified to produce Ybt and Ybt analogs. The compounds and compositions can be used to remove metals from metal containing samples. 2. The compound of claim 1 , wherein Ris H.5. The method of claim 1 , further comprising isolating the one or more compounds of .6. A method of removing one or more metals from a metal-containing sample comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) contacting the metal-containing sample with one or more compounds of , wherein a complex between the one or more metals and the one or more compounds is formed;'}b) isolating the complex of a) from the sample.7. The method of claim 1 , further comprising reversing the isolated complex between the one or more metals and the one or more compounds of to provide one or more metal-free compounds of and uncomplexed one or more metals.8. The method of claim 1 , further comprising repeating a) on the metal-containing sample or a second metal-containing sample using the metal-free compounds of and isolating the complex between the one or more metals from the metal-containing sample and the metal-free compounds or the complex between the one or more metals of the second metal-containing sample and the metal-free compounds.9. The method of claim 1 , wherein the compounds of are attached to a polymeric bead claim 1 , polymeric resin claim 1 , non-polymeric resin claim 1 , activated carbon claim 1 , or inorganic material.10. The method of claim 9 , wherein the polymeric bead comprises a non-ionic crosslinked polymer or a hydrophobic resin.11. The method of claim 6 , wherein the metal-containing sample is selected from the group consisting of aqueous samples claim 6 , rust-containing surfaces claim 6 , soil claim 6 , electronic waste claim 6 , and ...

ANTIMICROBIIAL COMPOUNDS

The present invention relates to certain tetramic acid derivatives and, in particular, bicyclic tetramic acid derivatives that are suitable for use in the preparation and development of antimicrobial (e.g. antibacterial or antifungal) compositions. The present invention also relates to the use of such compounds as antimicrobial (e.g. antibacterial or antifungal agents) and, in particular, as topical antibacterial or antifungal agents. 2. (canceled)3. The compound as claimed in claim 1 , wherein n is 0 or 1 and Lis absent.4. (canceled)5. A compound as claimed in claim 1 , wherein Ris a straight chain claim 1 , branched or cyclic Cto Calkyl.6. The compound as claimed in claim 1 , where Ris an alkyl that is a bridged ring system.7. The compound as claimed in claim 1 , wherein Ris an alkyl group selected from adamantyl claim 1 , myrtanyl claim 1 , cyclohexyl and a Cto Cnon-cyclic aliphatic alkyl group.8. The compound as claimed in claim 1 , wherein Ris a phenyl group that is optionally substituted with at least one functional group selected from alkyl claim 1 , aryl claim 1 , halo claim 1 , trihaloalkyl claim 1 , alcohol claim 1 , thio-alcohol claim 1 , ester claim 1 , thioester claim 1 , ether claim 1 , thioether claim 1 , amide claim 1 , thioamide claim 1 , urea claim 1 , thiourea and heterocyclic group.9. The compound as claimed in claim 8 , wherein the phenyl group is substituted with a group selected from cyclohexyl claim 8 , Cto Calkyl claim 8 , halo claim 8 , halo(Cto C) alkyl claim 8 , OH claim 8 , SH claim 8 , heterocyclic and ORor SR claim 8 , where Ris a Cto Calkyl or phenyl group.10. The compound as claimed in claim 8 , wherein the phenyl group is substituted with a heterocyclic group selected from a piperidine and morpholine group claim 8 , or where the phenyl group is fused to an aromatic heterocyclic ring claim 8 , preferably a pyrrole ring.11. The compound as claimed in claim 1 , wherein Ris selected from H claim 1 , methyl claim 1 , C(O)R claim 1 , and ...

Enzymatic conjugation of polypeptides

The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions.

Anti-viral compounds

Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF

The invention provides compounds having the general Formula (I); 2. The method of claim 1 , wherein Ris F or Cl; and Ris selected from the group consisting of F claim 1 , Cl claim 1 , Calkyl claim 1 , Calkoxy claim 1 , and Ccycloalkyl.3. The method of claim 1 , wherein Ris F or Cl and Ris selected from the group consisting of F claim 1 , Cl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , and cyclopentyl.4. The method of claim 1 , wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is an optionally substituted Calkylene.5. The method of claim 1 , wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)CH)—CH— claim 1 , or —CHCHCHCH—.6. The method of claim 1 , wherein Xis —O—; the subscript m is 1 and -(L)- is —CH— claim 1 , —C(H)(CH)— claim 1 , or —CH—CH—.7. The method of claim 1 , wherein Xis absent; Xis —O— or —N(H)—; the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)(CH)—CH— claim 1 , or —CHCHCHCH—.8. The method of claim 1 , wherein Xand Xare absent; the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)(CH)—CH— claim 1 , or —CHCHCHCH—.9. The method of claim 1 , wherein Xand Xare absent: the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , and —CH—CH—.10. The method of claim 1 , wherein m is 0; Xis selected from —O— and —N(H)—; and Xis absent. This application is a divisional of U.S. application Ser. No. 16/150,070, filed 2 Oct. 2018 ...

Trans-2-decenoic acid derivative and drug containing same

The present invention relates to a novel trans-2-decenoic acid derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical agent containing the compound as an active ingredient. The trans-2-decenoic acid derivative or a pharmaceutically acceptable salt, which is the compound of the present invention, is specifically represented by the general formula (I): wherein X is a substituent such as a 1-pyrrolidyl, a 3-thiazolizyl, or a piperidino, and the compound is highly useful as a pharmaceutical agent, such as a prophylactic or therapeutic agent for a peripheral nerve disorder induced by administration of an anticancer agent, a prophylactic or therapeutic agent for neurodegenerative diseases or mental diseases such as dementia, Alzheimer's disease, Parkinson's disease, diabetic neuropathy, depression, glaucoma, or autistic disorder spectrum, a therapeutic or repairing agent for spinal cord injury, analgesics against various pain diseases, or the like.

Open bridge rack

An equipment rack includes a frame, a first pair of mounting rails and a second pair of mounting rails. Each pair of mounting rails includes a front mounting rail and a rear mounting rail and the front and rear mounting rails each include a first planar surface defining in part a first equipment-mounting interface when the front and rear mounting rails are coupled to the frame through a second planar surface of each of the front and rear mounting rails in a first configuration. The front and rear mounting rails each further include a third planar surface and a fourth planar surface defining in part a second equipment-mounting interface when the front and the rear mounting rails are coupled to the frame through the first planar surface in a second configuration. The first and second equipment-mounting interfaces can be defined by an equipment rack standard.

GUANIDINE COMPOUNDS AND USE THEREOF

The present invention relates to guanidine compounds for inhibiting mitochondrial oxidative phosphorylation (OXPHOS) and use thereof. More specifically, the present invention relates to a pharmaceutical composition for preventing or treating a OXPHOS-related disease, particularly cancer by inhibiting mitochondrial oxidative phosphorylation and reprogramming cellular metabolism. 2. The compound of claim 1 , wherein Rand Rare hydrogen in Chemical formula 1.4. The compound of claim 1 , wherein claim 1 , in Chemical formula 1 claim 1 , Rand Rare taken together with N to which they are attached for forming 5 to 6-membered saturated or unsaturated heterocycloalkyl group and is substituted with halogen claim 1 ,{'sup': 3', '4, 'Rand Rare independently H,'}n is 0, 1 or 2, and{'sup': 5', '6', '7', '8', '9', '10', '11', '12', '11', '12, 'sub': 1', '4', '1', '4', '1', '4', '1', '3', '1', '3', '6', '10, 'Ris aryl group represented by Chemical formula 2 where R, R, R, R, and Rare independently H, halogen, C-Calkyl, C-Calkoxy, halolalkyl, C-Chaloalkoxy, SRor ORwhere Rand Rare independently C-Calkyl, C-Chaloalkyl, or C-Caryl, or are linked with an adjacent substituent to form of 5 to 6 membered saturated ring.'}5. The compound of claim 1 , wherein claim 1 , in Chemical formula 1 claim 1 , Rand Rare taken together with N to which they are attached for forming 5 to 6-membered saturated or unsaturated heterocycloalkyl group and is substituted with halogen claim 1 ,{'sup': 3', '4, 'Rand Rare independently H,'}n is 0, and{'sup': 5', '6', '7', '8', '9', '10, 'sub': 1', '4, 'Ris aryl group represented by Chemical formula 2 where R, R, R, Rand Rare independently C-Chaloalkoxy.'}6. A compound selected from the group consisting of the following compounds claim 1 , pharmaceutically acceptable salts claim 1 , pharmaceutically acceptable solvates and prodrug derivatives:N—(N-phenylcarbamimidoyl)-4,4-difluoropiperidine-1-carboximidamideN—(N-(5,6,7,8-teterhydronaphthalene-2-yl)carbamimidoyl)-4,4 ...

METHOD OF INHIBITING TAU PHOSPHORYLATION

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

COMPOUNDS FOR TREATMENT OF CANCER

The present invention relates to a compound of formula XXII and a compound of formula 17ya, which are defined as anywhere in the specification, to a composition comprising the same, and to a method of using thereof in the treatment of various forms of cancer. 2. The method of claim 1 , wherein said cancer is selected from the group consisting of prostate cancer claim 1 , drug-resistant prostate cancer claim 1 , breast cancer claim 1 , ovarian cancer claim 1 , drug-resistant ovarian cancer claim 1 , skin cancer claim 1 , melanoma claim 1 , drug-resistant melanoma claim 1 , lung cancer claim 1 , colon cancer claim 1 , glioma claim 1 , leukemia claim 1 , lymphoma claim 1 , renal cancer claim 1 , CNS cancer claim 1 , uterine cancer claim 1 , drug-resistant uterine cancer claim 1 , and combinations thereof.3. The method of claim 2 , wherein said cancer is melanoma cancer.4. The method of claim 2 , wherein said cancer is metastatic melanoma.5. The method of claim 2 , wherein said cancer is prostate cancer.6. The method of claim 5 , wherein said prostate cancer is drug-resistant prostate cancer.7. The method of claim 2 , wherein said cancer is ovarian cancer.8. The method of claim 7 , wherein said ovarian cancer is drug-resistant ovarian cancer.9. The method of claim 2 , wherein said cancer is uterine cancer.10. The method of claim 9 , wherein said uterine cancer is drug-resistant uterine cancer.11. The method of claim 2 , wherein said cancer is lung cancer.12. The method of claim 2 , wherein said cancer is colon cancer.13. The method of claim 2 , wherein said administering is carried out in combination with another cancer therapy.15. The method of claim 14 , wherein said tumor is a melanoma cancer tumor.16. The method of claim 14 , wherein said tumor is a metastatic melanoma tumor.17. The method of claim 14 , wherein said tumor is a prostate cancer tumor.18. The method of claim 14 , wherein said tumor is an ovarian cancer tumor.19. The method of claim 14 , wherein said ...

COMPOUNDS FOR TREATMENT OF CANCER

The present invention relates to a compound of formula XXII and a compound of formula 17ya, which are defined as anywhere in the specification, to a composition comprising the same, and to a method of using thereof in the treatment of various forms of cancer. 1. A compound selected from the following group:(2-(1-H-indol-1-yl)imidazol-4-yl)(3,4,5-trimethoxyphenyl)methanone;(2-(1-H-indol-2-yl)imidazol-4-yl)(3,4,5-trimethoxyphenyl)methanone;(2-(1-H-indol-4-yl)imidazol-4-yl)(3,4,5-trimethoxyphenyl)methanone;(2-(1-H-indol-5-yl)imidazol-4-yl)(3,4,5-trimethoxyphenyl)methanone;(2-(1-H-indol-6-yl)imidazol-4-yl)(3,4,5-trimethoxyphenyl)methanone; and(2-(1-H-indol-7-yl)imidazol-4-yl)(3,4,5-trimethoxyphenyl)methanone,or a pharmaceutically acceptable salt thereof, a hydrate thereof, or a combination thereof.2. A pharmaceutical composition comprising a compound according to and a pharmaceutically acceptable carrier.3. A compound according to for use as a medicament.4. Use of a compound of claim 1 , for the preparation of a medicament for treating prostate cancer claim 1 , breast cancer claim 1 , ovarian cancer claim 1 , skin cancer claim 1 , lung cancer claim 1 , colon cancer claim 1 , leukemia claim 1 , renal cancer or CNS cancer claim 1 , or a combination thereof.5. The use according to claim 4 , wherein the medicament is administered systemically.6. The use according to claim 4 , wherein the medicament is administered orally claim 4 , topically claim 4 , transdermally claim 4 , parenterally claim 4 , subcutaneously claim 4 , intravenously claim 4 , intramuscularly claim 4 , intraperitoneally claim 4 , by intranasal instillation claim 4 , by intracavitary or intravesical instillation claim 4 , intraocularly claim 4 , intraarterially claim 4 , intralesionally claim 4 , or by application to mucous membranes.7. The use according to claim 4 , wherein the medicament is administered directly to a site where cancer cells are present.8. The use according to claim 4 , wherein the ...

NOVEL IMAGING COMPOSITION AND USES THEREOF

The invention discussed in this application relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. 115-. (canceled)17. The conjugate of claim 16 , wherein L is OR.18. The conjugate of claim 17 , wherein R is Cto Calkyl.19. The conjugate of claim 17 , wherein OR is selected from O-p-toluenesulfonate claim 17 , O-methanesulfonate claim 17 , O-trifluoromethanesulfonate claim 17 , O-benzenesulfonate claim 17 , and O-m-nitrobenzenesulfonate.20. The conjugate of claim 16 , wherein the target molecule is a polypeptide.21. The conjugate of claim 20 , wherein the polypeptide is an antibody.22. The conjugate of claim 21 , wherein the antibody is selected from trastuzumab claim 21 , rituximab and cetuximab.23. The conjugate of claim 16 , wherein the target molecule is a peptide.24. The conjugate of claim 23 , wherein the peptide is a targeting peptide.25. The conjugate of claim 24 , wherein the targeting peptide is selected from a cyclic RGD sequence claim 24 , bombesin and glu-N(CO)N-lys PSMA. The present invention relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. The present invention also relates to compositions including the compounds, and to methods of imaging patients using the compounds.Zirconium-89 (Zr) is a positron-emitting radionuclide that is used in medical imaging applications. In particular, it is used in positron emission tomography (PET) for cancer detection and imaging. It has a longer half-life (t=79.3 hours) than other radionuclides used for medical imaging, such as F. For example, F has a tof 110 minutes, which means that its use requires close proximity to a cyclotron facility and rapid and high-yielding synthesis techniques for the preparation of the agents into which it is incorporated. Zr is not plagued by these same problems, which makes ...

Ethyl (2r)-2-acetamido-3-(4-methylbenzoylsulfanyl)propanoate and uses thereof

A novel substituted N-acetyl-L-cysteine (NAC) derivative and methods of using this compound for the treatment of diseases and/or conditions, including but not limited to diseases and/or conditions of, or involving, the Central Nervous System (CNS), including schizophrenia adrenoleukodystrophy, mitochondrial diseases (e.g. Leigh syndrome, Alpers' disease, and MELAS), Huntington's disease, trichotillomania, HIV-associated neurocognitive disorder, hypoxic-ischemic encephalopathy, drug craving, and drug addiction.

Novel onium salt compound, resist composition, and pattern forming process

Sulfonium and iodonium salts of a carboxylate having an aromatic ring to which a nitrogen-containing alkyl or cyclic structure is attached are novel. The onium salt functions as an acid diffusion controlling agent in a resist composition, enabling to form a pattern of good profile with high resolution, improved MEF, LWR and DOF.

HETEROCYCLIC CARBOXYLIC ACID AMIDE LIGAND AND APPLICATIONS THEREOF IN COPPER CATALYZED COUPLING REACTION OF ARYL HALOGENO SUBSTITUTE

Provided are a heterocyclic carboxylic acid amide ligand and applications thereof in a copper catalyzed coupling reaction. Specifically, provided are uses of a compound represented by formula (I), definitions of radical groups being described in the specifications. The compound represented by formula (I) can be used as the ligand in the copper catalyzed coupling reaction of the aryl halogeno substitute, and is used or catalyzing the coupling reaction for forming the aryl halogeno substitute having C—N, C—O, C—S and other bonds. 5: The method of claim 4 , wherein in the reaction claim 4 , the molar ratio of the ligand to the reactant aryl halide is 1-50:100 claim 4 , preferably 5-20:100; and/orthe molar ratio of the ligand to the copper catalyst is 1-5:1, preferably 1-2:1.7: The method of claim 4 , wherein the reaction temperature is 50-180° C. claim 4 , preferably 100-130° C.9: The method of wherein the copper catalyst is selected from the group consisting of CuI claim 4 , CuBr claim 4 , CuCl claim 4 , CuTc claim 4 , Cu(OAc) claim 4 , CuSO claim 4 , CuO claim 4 , CuBr claim 4 , CuCl claim 4 , CuO claim 4 , CuSCN claim 4 , CuCN claim 4 , Cu(acac) claim 4 , and combinations thereof; preferably CuI.10: The method of claim 4 , wherein the reaction is carried out in the presence of a base.11: The method of claim 8 , wherein claim 8 ,in the reaction (1), the ligand is preferably L-53 or L-103; and/orin the reaction (2), the ligand is preferably: L-13, L-15 or L-31; and/orin the reaction (3), the ligand is preferably: L-13, L-15 or L-35; and/orin the reaction (4), the ligand is preferably: L-92, and/or L-105; and/orin the reaction (5), the ligand is preferably L-13, L-112, L-114. The present invention relates to the field of organic synthesis. In particular, a copper-catalyzed coupling reaction of aryl halide catalyzed by a heterocyclic carboxylic acid amide ligand, especially a coupling reaction to form C—N, C—O, and C—S bonds is provided in the present invention. ...

METHOD OF INHIBITING TAU PHOSPHORYLATION

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

BUMETANIDE ANALGOS, COMPOSITIONS, AND METHODS OF USE

The present invention provides bumetanide analogs and compositions comprising such analogs. The present invention also provides pharmaceutical compositions containing these bumetanide analogs and methods for their use. These analogs are believed useful for the treatment and/or prophylaxis of conditions that involve the NaKCl co-transporter or GABAreceptor. 1107-. (canceled)109191-. (canceled)192. The compound of claim 108 , wherein R8 and R9 are the same.193. The compound of claim 108 , wherein each of R8 and R9 are alkyl.194. The compound of claim 193 , wherein each of R8 and R9 are ethyl.195. The compound of claim 108 , wherein each of R8 and R9 are alkaryl.196. The compound of claim 195 , wherein each of R8 and R9 are benzyl.197. The compound of claim 108 , wherein Rand Rtogether with the atom to which they are attached claim 108 , form a heterocycloalkyl group.200. A pharmaceutical composition comprising a compound of and one or more pharmaceutically acceptable carrier or excipient.201. A pharmaceutical composition comprising a compound of and one or more pharmaceutically acceptable carrier or excipient.202. A pharmaceutical composition comprising a compound of and one or more pharmaceutically acceptable carrier or excipient.203. A method of reducing seizure activity in subject in need thereof comprising administering an effective amount of a compound of .204. A method of reducing seizure activity in subject in need thereof comprising administering an effective amount of a compound of .205. A method of reducing seizure activity in subject in need thereof comprising administering an effective amount of a compound of .206. A method of treating idiopathic epilepsy claim 108 , treating symptomatic epilepsy claim 108 , treating cryptogenic epilepsy claim 108 , treating status epilepticus claim 108 , treating seizure disorders claim 108 , reducing the rate of seizure occurrence claim 108 , or reducing the severity of seizures in subject in need thereof comprising ...

PYRROLIDINE OR THIAZOLIDINE CARBOXYLIC ACID DERIVATIVES, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERS AS AGONISTS OF G-PROTEIN COUPLED RECEPTOR 43 (GPR43)

The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases. 132-. (canceled) The present invention relates to novel compounds including their pharmaceutically acceptable salts, solvates and prodrugs, which are agonists or partial agonists of G-protein coupled receptor 43 (GPR43) and are useful as therapeutic compounds, particularly in the treatment and/or prevention of Type 2 diabetes mellitus and conditions that are often associated with this disease including, lipid disorders such as dyslipidemia, hypertension, obesity, atherosclerosis and its sequelae.Under normal conditions, Free Fatty Acids (FFAs) are implicated in numerous physiological processes by serving as fuel in various metabolic pathways and/or acting as signaling molecules in different tissues such as the heart, liver, skeletal muscle, adipocytes and the pancreas (Newsholme et al., Biochem. J., 80 pp 655-662, 1961; Prentki et al., Endocrine Reviews, PubMed print ahead, 2008). Among FFAs, the short-chain fatty acids (SCFAs, carbon length C2-C6) are generated during anaerobic bacterial fermentation of fiber in the gut (Sellin et al., News. Physiol. Sci., 14, pp 58-64, 1999). Long-chain fatty acids (LCFAs, carbon length C14-C24) are products of dietary intake from adipose tissues and liver (McArthur et al., J. Lipid. Res., 40, pp 1371-1383, 1999).Obesity is an increasing, worldwide public health problem associated with devastating pathologies such as type 2 diabetes (T2D) and dyslipidemia (Wild et al., Diabetes Care 27, pp 1047-1053, 2004). Dyslipidemia is characterized by high levels of triglycerides and/or LDL (bad cholesterol) or low levels of HDL (good cholesterol). Dyslipidemia is a key independent risk factor for cardiovascular diseases. It has long been suggested that FFAs are implicated in the regulation and/or genesis of these diseases (Frazc et al., J. Clin. Endocrinol. Metab., 61, pp 807-811, 1985). It is well established ...

Urea derivatives and their use as fatty-acid binding protein (fabp) inhibitors

The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , R 3 , R 4 , W, A and B are as described herein, compositions including the compounds and methods of using the compounds.

Methods and compositions for gamma-glutamyl cycle modulation

The present disclosure provides pharmaceutical compositions comprising Gamma-glutamyl cycle inhibitors (GGCI) and certain pharmaceutically acceptable salts thereof, and methods of use.

THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF

The invention provides compounds having the general Formula (I); and pharmaceutically acceptable salts thereof; wherein the variables R, R, subscript n, subscript q, ring A, X, L, subscript m, X, R, R, R, R, R, D and E have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions. 317-. (canceled)2028-. (canceled)29. The compound of claim 1 , wherein in Formula (I) the ring “A” is (i) Cheterocycle and is selected from the group consisting of azetidine claim 1 , pyrrolidine claim 1 , piperidine claim 1 , morpholine claim 1 , homopiperazine claim 1 , piperazine and 8-azabicyclo[3.2.1]octane claim 1 , and is optionally substituted.3235-. (canceled)3739-. (canceled)43. (canceled)45. (canceled)49. A compound as described in claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '0', 'sub': '1-6', 'Ris hydrogen or Calkyl;'}{'sup': 1', '2, 'sub': '1-8', 'Rand Rare each independently selected from the group consisting of hydrogen and Calkyl;'}{'sup': 1', '2, 'or Rand Rare combined to form a 3- to 7-membered;'}{'sup': 1', '4', '1/4', '2, 'or Rand Rare combined to form a 3- to 7-membered heterocycle ring comprising 1 to 2 heteroatoms selected from N, O and S wherein said heterocycle ring is optionally substituted with 1 to 3 Rsubstituents selected from the group consisting of F and —OH; and Ris hydrogen;'}{'sup': '3', 'Ris selected from the group consisting of hydrogen and F;'}{'sup': 4', '1', '4, 'sub': '1-4', 'Ris selected from the group consisting of hydrogen or Calkyl; or Rand Rare combined to form a 3- to 7-membered heterocycle ring as described above;'}{'sup': '5', 'sub': 1-8', '3-8, 'Ris selected from the group consisting of F, Cl, Calkyl, and Ccycloalkyl;'}{'sub': '1-6', 'L is Calkylene;'}the subscript m represents the integer 0 or 1;{'sup': 1', '2', '1', '2, 'Xand Xare each independently selected from the group consisting of absent and —O—, and wherein if the subscript ...

ALPHA-AMINO ESTERS OF HYDROXYPROPYLTHIAZOLIDINE CARBOXAMIDE DERIVATIVE AND SALT FORM, CRYSTAL POLYMORPH THEREOF

The invention provides α-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1′-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorph s thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as pre-term labor at the early gestational stage by the administration of these substances to a patient in need of treatment. 126-. (canceled)28. The compound of claim 27 , wherein said compound binds human prostaglandin F2α receptor with an affinity of about 1 nM.29. The compound of claim 27 , wherein said compound is soluble in aqueous solution at a concentration of from about 300 μg/mL to about 500 μg/mL.30. The compound of claim 29 , wherein said compound is soluble in aqueous solution at a concentration of about 380 μg/mL.31. The compound of claim 27 , wherein said compound inhibits production of inositol trisphosphate in a uterine myocyte.32. The compound of claim 27 , wherein said compound induces a reduction in the amplitude of uterine contractions in a mammalian subject following administration of said compound to said mammalian subject.33. The compound of claim 32 , wherein said mammalian subject is a human.34. The compound of claim 27 , wherein said compound is in a crystalline state.35. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient.36. The pharmaceutical composition of claim 35 , wherein said pharmaceutical composition is formulated for oral administration to a human subject.37. The pharmaceutical composition of claim 36 , wherein said pharmaceutical composition is a tablet claim 36 , capsule claim 36 , gel cap claim 36 , powder claim 36 , liquid solution claim 36 , or liquid suspension.38. The pharmaceutical composition of claim 35 , wherein said pharmaceutical composition is formulated for intravenous administration to a human subject. ...

ENZYMATIC CONJUGATION OF ANTIBODIES

The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions. 1. A human or humanized antibody comprising one or more solvent-exposed glutamine residues in a variable region and at least one acceptor glutamine residue in its constant region or in a sequence fused to a variable or constant region , wherein said one or more solvent-exposed glutamine residues are present in a light chain variable domain (VL) CDR at a Kabat position selected from the group consisting of 27 , 55 , and a combination thereof ,{'sub': 'n', 'wherein said antibody is conjugated via said acceptor glutamine residue to one or more moieties-of-interest (Z) through a linker that comprises a NH—(C)— moiety,'}wherein{'sub': 'n', '(C)is a substituted or unsubstituted alkyl or heteroalkyl chain, optionally wherein any carbon of the chain is substituted with an alkoxy, hydroxyl, alkylcarbonyloxy, alkyl-S—, thiol, alkyl-C(O)S—, amine, alkylamine, amide, or alkylamide, and n is an integer selected from among the range of 2 to 20; and'}Z is a reactive moiety or a moiety that improves the pharmacokinetic properties, a therapeutic moiety or a diagnostic moiety.2. The antibody of claim 1 , wherein the antibody is a tetrameric antibody and said constant region is a heavy chain constant region.34-. (canceled)5. The antibody of claim 1 , wherein the antibody comprises:a heavy chain framework region 1 (FR-H1) comprising a glutamine residue at Kabat position 1, 3, 5, 6, 10, 11, 12, 13 and/or 16;a heavy chain framework region 2 (FR-H2) comprising a glutamine residue at Kabat position 38, 39, 43 and/or 45;a heavy chain framework region 3 (FR-H3) comprising a glutamine residue at Kabat position 66, 75, 77, 81 and/or 85;a heavy chain framework region 1 (CDR-H1) comprising a glutamine residue at Kabat position 26 and/ ...

ALPHA-AMINO ESTERS OF HYDROXYPROPYLTHIAZOLIDINE CARBOXAMIDE DERIVATIVE AND SALT FORM, CRYSTAL POLYMORPH THEREOF

The invention provides α-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1′-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorph s thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as pre-term labor at the early gestational stage by the administration of these substances to a patient in need of treatment. 2. The compound of claim 1 , wherein said compound binds human prostaglandin F2α receptor with an affinity of about 1 nM.3. The compound of claim 1 , wherein said compound is soluble in aqueous solution at a concentration of about 380 μg/mL.4. The compound of claim 1 , wherein said compound is in a crystalline state.5. The compound of claim 4 , wherein said compound exhibits characteristic X-ray powder diffraction peaks at about 7.0° 2θ claim 4 , about 8.1° 2θ claim 4 , about 10.0° 2θ claim 4 , about 12.0° 2θ claim 4 , about 13.1° 2θ claim 4 , about 14.1° 2θ claim 4 , about 16.4° 2θ claim 4 , about 18.4° 2θ claim 4 , about 20.1° 2θ claim 4 , about 21.0° 2θ claim 4 , about 23.5° 2θ claim 4 , and about 29.5° 2θ.6. The compound of claim 5 , wherein said compound is characterized by an X-ray powder diffraction spectrum substantially as depicted in .7. The compound of claim 4 , wherein said compound exhibits H nuclear magnetic resonance (NMR) peaks centered at about 1.1 ppm claim 4 , about 3.3 ppm claim 4 , about 4.9 ppm claim 4 , about 5.4 ppm claim 4 , about 7.1 ppm claim 4 , about 7.7 ppm claim 4 , about 7.9 ppm claim 4 , and about 8.0 ppm.8. The compound of claim 7 , wherein said compound is characterized by a H NMR spectrum substantially as depicted in .9. The compound of claim 4 , wherein said compound exhibits an endotherm at from about 145° C. to about 147° C. as measured by differential scanning calorimetry.10. The compound of claim 9 , wherein said compound is characterized ...

Arthropod repellent chemicals

Compositions and methods for repelling arthropods. The compositions include a carrier and an arthropod repelling compound, which can be a compound discovered by a novel and complex cheminformatic process to demonstrate repellency behavior across a broad spectrum of arthropods. The compound can be a thiane compound, a pyrrolidone compound, a cyclohexadiene compound, a cyclohexenone compound, a cyclohexene compound, a furanone compound, a pyran compound, a tetrahydropyran compound, a thiazolidine compound, a thiazoline compound, a dihydrothiophene compound, a dithiolane compound, a dithiane compound, an epoxide compound, an oxathiane compound, a cyclopentene compound, a cyclohexane compound, a quinoline compound, an oxazoline compound, a tetrahydropyridine compound, and an imidazolidinone compound, or a combination thereof.

ALPHA-AMINO ESTERS OF HYDROXYPROPYLTHIAZOLIDINE CARBOXAMIDE DERIVATIVE AND SALT FORM, CRYSTAL POLYMORPH THEREOF

The invention provides α-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1′-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorphs thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as pre-term labor at the early gestational stage by the administration of these substances to a patient in need of treatment. 126-. (canceled)28. The kit of claim 27 , wherein said human subject is characterized by a gestational age of from about 24 to about 34 weeks29. The kit of claim 27 , wherein said compound is formulated for oral administration to said human subject.30. The kit of claim 27 , wherein said compound is formulated for intravenous administration to said human subject.31. The kit of claim 27 , wherein said compound is present within a pharmaceutical composition that further comprises one or more pharmaceutically acceptable excipients.32. The kit of claim 31 , wherein said pharmaceutical composition is a tablet claim 31 , capsule claim 31 , gel cap claim 31 , powder claim 31 , liquid solution claim 31 , or liquid suspension.33. The kit of claim 27 , wherein said compound is in a crystalline state.34. The kit of claim 33 , wherein said compound exhibits characteristic X-ray powder diffraction peaks at about 7.0° 2θ claim 33 , about 8.1° 2θ claim 33 , about 10.0° 2θ claim 33 , about 12.0° 2θ claim 33 , about 13.1° 2θ claim 33 , about 14.1° 2θ claim 33 , about 16.4° 2θ claim 33 , about 18.4° 2θ claim 33 , about 20.1° 2θ claim 33 , about 21.0° 2θ claim 33 , about 23.5° 2θ claim 33 , and about 29.5° 2θ.35. The kit of claim 34 , wherein said compound is characterized by an X-ray powder diffraction spectrum substantially as depicted in .36. The kit of claim 33 , wherein said compound exhibits H nuclear magnetic resonance (NMR) peaks centered at about 1.1 ppm claim 33 , about 3.3 ppm claim 33 , ...

SUBSTITUTED N-ACETYL-L-CYSTEINE DERIVATIVES AND RELATED COMPOUNDS

Novel substituted N-acetyl-L-cysteine (NAC) derivatives and related compounds and methods of using these compounds for the treatment of diseases and/or conditions, including but not limited to diseases and/or conditions of, or involving, the Central Nervous System (CNS), including schizophrenia adrenoleukodystrophy, mitochondrial diseases (e.g. Leigh syndrome, Alpers′ disease, and MELAS), Huntington's disease, trichotillomania, HIV-associated neurocognitive disorder, hypoxic-ischemic encephalopathy, drug craving, and drug addiction. 3. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.4. A pharmaceutical composition comprising a therapeutically effective amount of the compound of and a pharmaceutically acceptable carrier.5. A method of treating a central nervous system (CNS) disorder or condition selected from the group consisting of trichotillomania claim 1 , schizophrenia claim 1 , drug addiction claim 1 , inherited mitochondrial disease claim 1 , adrenoleukodystrophy claim 1 , Huntington's disease claim 1 , HIV-associated neurocognitive disorder claim 1 , and hypoxic-ischemic encephalopathy comprising administering a therapeutically effective amount of the compound of to a subject in need thereof.6. The method of claim 5 , wherein the CNS disorder or condition is trichotillomania.7. The method of claim 5 , wherein the CNS disorder or condition is schizophrenia.8. The method of claim 5 , wherein the CNS disorder or condition is drug addiction.9. The method of claim 5 , wherein the CNS disorder or condition is an inherited mitochondrial disease.10. The method of claim 9 , wherein the inherited mitochondrial disease is (a) Leigh syndrome claim 9 , (b) Alpers' disease claim 9 , or (c) mitochondrial encephalomyopathy claim 9 , lactic acidosis claim 9 , and stroke-like episodes (MELAS).11. The method of claim 5 , wherein the CNS disorder or condition is adrenoleukodystrophy claim 5 , Huntington's disease claim 5 , HIV- ...

INHIBITION OF GLUTAMINASE C

The present invention relates to a method of reducing the production of glutamate from glutamine by glutaminase C in a cell or tissue. The method involves inhibiting glutaminase C activity in the cell or tissue under conditions effective to reduce production of glutamate from glutamine. Compounds for carrying out this method are also disclosed. 110-. (canceled)11. A method of treating a subject with a condition mediated by production of glutamate from glutamine by glutaminase C , said method comprising:selecting a subject with a condition mediated by production of glutamate from glutamine by glutaminase C andadministering to said selected subject an inhibitor of glutaminase C activity under conditions effective to treat the condition mediated by production of glutamate from glutamine.12. The method of claim 11 , wherein the inhibitor inhibits phosphorylation of glutaminase C.13. The method of claim 11 , wherein the inhibitor inhibits expression-independent glutaminase C activity and/or glutaminase C activity independent of exogenous phosphate addition.1518-. (canceled)20. The method of claim 14 , wherein the condition is selected from the group consisting of breast cancer claim 14 , lung cancer claim 14 , brain cancer claim 14 , pancreatic cancer claim 14 , and colon cancer.21. The method of claim 14 , wherein said administering is performed parenterally claim 14 , orally claim 14 , subcutaneously claim 14 , intravenously claim 14 , intramuscularly claim 14 , extraperitoneally claim 14 , by intranasal instillation claim 14 , or by application to mucous membranes.2230-. (canceled) This application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/163,304, filed Mar. 25, 2009, which is hereby incorporated by reference in its entirety.This invention was made with government support under grant numbers RO1 GM40654, RO1 GM47458, and RO1 GM61762 awarded by National Institutes of Health. The U.S. Government has certain rights in this invention.The ...

METHODS AND COMPOSITIONS FOR GAMMA-GLUTAMYL CYCLE MODULATION

The present disclosure provides pharmaceutical compositions comprising Gamma-glutamyl cycle inhibitors (GGCI) and certain pharmaceutically acceptable salts thereof, and methods of use. 3. The compound of claim 2 , wherein R1 is —OCH.7. A pharmaceutical composition comprising a compound claim 2 , salt claim 2 , crystal or polymorph in any one of - claim 2 , and a pharmaceutically acceptable excipient.8. A composition for selectively treating tumor cells claim 2 , comprising an effective amount of a 5-oxoproline analog claim 2 , whereby the analog is metabolized and is effective in inhibiting the synthesis of glutamic acid in the gamma-glutamyl cycle.9. The composition according to claim 8 , wherein the composition inhibits glutathione-S-transferase.10. The composition according to claim 8 , wherein the composition that inhibits glutathione-S-transferase comprises 2-imino-3-para methoxy Benzyl-4 sulfanyl-5 dimethyl 1-carboxylic acid.11. The composition according to claim 10 , wherein the composition comprising the salt and polymorphs of the 2-imino-3-para methoxy Benzyl-4 sulfanyl-5 dimethyl 1-carboxylic acid.12. A composition comprising a substantially pure GGCI crystal having alternating layers of GGCI molecules and besylate molecules (besylate salt).13. (canceled)14. (canceled)15. A method of treating cancer comprising administering to a subject claim 10 , in need thereof claim 10 , a therapeutically effective amount of a pharmaceutical composition comprising a gamma-glutamyl cycle inhibitor (GGCI) claim 10 , whereby biosynthesis by the gamma-glutamyl cycle is inhibited.16. The method of claim 15 , wherein the GGCI is a 5-oxoproline analog.17. The method of claim 15 , whereby the reaction step catalyzed by 5-oxo-prolinase in the GGC cycle is inhibited.18. The method of claim 16 , wherein the 5-oxoproline analog is 2-Imino-3-para methoxy Benzyl-4 sulfanyl-5 dimethyl 1-carboxylic acid.19. The method of claim 16 , whereby the level of glutathione is reduced in cancer ...

NOVEL IMAGING COMPOSITION AND USES THEREOF

The invention discussed in this application relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. 1. A radionuclide complex of a compound of formula (I):or a pharmaceutically acceptable salt thereof, wherein L is a leaving group. This application is a Continuation of U.S. patent application Ser. No. 16/511,577, filed Jul. 15, 2019, which is a Continuation of U.S. patent application Ser. No. 15/963,599, filed Apr. 26, 2018, now U.S. Pat. No. 10,398,660 issued on Sep. 3, 2019, which is a Continuation of U.S. patent application Ser. No. 15/518,333, filed Apr. 11, 2017, now U.S. Pat. No. 9,980,930, issued on May 29, 2018 and is a National Stage Application, filed under 35 U.S.C. 371, of International Application No. PCT/AU2015/050640, filed on Oct. 16, 2015, which claims priority to, and the benefit of, AU Application No. 2014904138, filed Oct. 16, 2014. The contents of each of these applications are incorporated by reference in their entirety.The present invention relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. The present invention also relates to compositions including the compounds, and to methods of imaging patients using the compounds.Zirconium-89 (Zr) is a positron-emitting radionuclide that is used in medical imaging applications. In particular, it is used in positron emission tomography (PET) for cancer detection and imaging. It has a longer half-life (t=79.3 hours) than other radionuclides used for medical imaging, such as F. For example, F has a tof 110 minutes, which means that its use requires close proximity to a cyclotron facility and rapid and high-yielding synthesis techniques for the preparation of the agents into which it is incorporated. Zr is not plagued by these same problems, which makes Zr particularly attractive for use in ...

ALPHA-AMINO ESTERS OF HYDROXYPROPYLTHIAZOLIDINE CARBOXAMIDE DERIVATIVE AND SALT FORM, CRYSTAL POLYMORPH THEREOF

The invention provides α-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1′-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorph s thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as pre-term labor at the early gestational stage by the administration of these substances to a patient in need of treatment. 126-. (canceled)28. The method of claim 27 , wherein the human subject is characterized by a gestational age of from about 24 to about 34 weeks.29. The method of claim 27 , wherein the compound is orally administered to the human subject.30. The method of claim 27 , wherein the compound is intravenously administered to the human subject.31. The method of claim 27 , wherein the compound is present within a pharmaceutical composition that further comprises one or more pharmaceutically acceptable excipients.32. The method of claim 31 , wherein the pharmaceutical composition is a tablet claim 31 , capsule claim 31 , gel cap claim 31 , powder claim 31 , liquid solution claim 31 , or liquid suspension.33. The method of claim 27 , wherein the compound is in a crystalline state.34. The method of claim 33 , wherein the compound exhibits characteristic X-ray powder diffraction peaks at about 7.0° 2θ claim 33 , about 8.1° 2θ claim 33 , about 10.0° 2θ claim 33 , about 12.0° 2θ claim 33 , about 13.1° 2θ claim 33 , about 14.1° 2θ claim 33 , about 16.4° 2θ claim 33 , about 18.4° 2θ claim 33 , about 20.1° 2θ claim 33 , about 21.0° 2θ claim 33 , about 23.5° 2θ claim 33 , and about 29.5° 2θ.35. The method of claim 34 , wherein the compound is characterized by an X-ray powder diffraction spectrum substantially as depicted in .36. The method of claim 33 , wherein the compound exhibits H nuclear magnetic resonance (NMR) peaks centered at about 1.1 ppm claim 33 , about 3.3 ppm claim 33 , about 4.9 ppm ...

ANTHROPOD REPELLENT CHEMICALS

Compositions and methods for repelling arthropods. The compositions include a carrier and an arthropod repelling compound, which can be a compound discovered by a novel and complex cheminformatic process to demonstrate repellency behavior across a broad spectrum of arthropods. The compound can be a thiane compound, a pyrrolidone compound, a cyclohexadiene compound, a cyclohexenone compound, a cyclohexene compound, a furanone compound, a pyran compound, a tetrahydropyran compound, a thiazolidine compound, a thiazoline compound, a dihydrothiophene compound, a dithiolane compound, a dithiane compound, an epoxide compound, an oxathiane compound, a cyclopentene compound, a cyclohexane compound, a quinoline compound, an oxazoline compound, a tetrahydropyridine compound, and an imidazolidinone compound, or a combination thereof. 2. The composition of claim 1 , wherein the compounds are selected from the group consisting of 4-methylcyclohexene claim 1 , ethyl cyclopentenolone claim 1 , 3 claim 1 ,4-Dihydro-2H-pyran claim 1 , and lemon hexadiene.3. The composition of claim 1 , wherein the alkyl is a C-Calkyl claim 1 , the alkenyl is a C-Calkenyl claim 1 , the alkoxy is a C-Calkoxy claim 1 , the aldehyde group is a C-Caldehyde group claim 1 , the ester group a C-Cester group claim 1 , or any combination thereof.5. The composition claim 1 , wherein the arthropod repellant compounds are selected from the group consisting of 1 claim 1 ,2-epoxyhexane claim 1 , 1-methyl-1 claim 1 ,4-cyclohexadiene claim 1 , 1-ethyl-2-pyrrolidone claim 1 , 2-isobutyl-4-methyl-1 claim 1 ,3-dioxolane claim 1 , 2-methyl tetrahydrofuran claim 1 , 3 claim 1 ,4-Dihydro-2H-pyran claim 1 , 4-hydroxy-2 claim 1 ,5-dimethyl-3(2H)-furanone claim 1 , 4-methyl cyclohexene claim 1 , dihydropyran claim 1 , ethyl cyclopentenolone claim 1 , isopropyl quinoline claim 1 , methyl 2-(4-tert-butylphenyl)acetate and nerol oxide.6. The composition claim 1 , comprising two or more of the arthropod repellant compounds ...

THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF

The invention provides compounds having the general Formula (I); 7. The method of claim 1 , wherein:{'sup': 'o', 'sub': '1-6', 'Ris hydrogen of Calkyl;'}{'sup': '1/4', 'each Rsubstituent is selected from the group consisting of F and —OH;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3', 'Ris selected from the group consisting of hydrogen and F;'}{'sup': '5', 'sub': 1-8', '3-8, 'Ris selected from the group consisting of F, Cl, Calkyl, and Ccycloalkyl;'}{'sub': '1-6', 'L is Calkylene;'}the subscript m represents the integer 0 or 1;{'sup': 1', '2', '1', '2, 'Xand Xare each independently selected from the group consisting of absent and —O—, and wherein if the subscript m is 0 then one of Xor Xis absent;'}{'sub': '3-12', 'claim-text': [{'sup': 'A', 'sub': 1-8', '1-8, 'Ris selected from the group consisting of Calkyl, Chaloalkyl, F, and —CN; and'}, 'q is the integer 0 to 6., 'the ring “A” is a Cmembered carbocycle; wherein'}11. The method of claim 1 , wherein said pain is selected from the group consisting of acute pain claim 1 , chronic pain claim 1 , neuropathic pain claim 1 , inflammatory pain claim 1 , visceral pain claim 1 , cancer pain claim 1 , chemotherapy pain claim 1 , trauma pain claim 1 , surgical pain claim 1 , post-surgical pain claim 1 , labor pain claim 1 , persistent pain claim 1 , peripherally mediated pain claim 1 , centrally mediated pain claim 1 , chronic headache claim 1 , migraine headache claim 1 , sinus headache claim 1 , tension headache claim 1 , phantom limb pain claim 1 , dental pain or a combination thereof.12. The method of claim 1 , wherein said pain is selected from the group consisting of pain associated with: HIV claim 1 , HIV treatment induced neuropathy claim 1 , trigeminal neuralgia claim 1 , post-herpetic neuralgia claim 1 , eudynia claim 1 , heat sensitivity claim 1 , tosarcoidosis claim 1 , irritable bowel syndrome claim 1 , Crohns disease claim 1 , multiple sclerosis (MS) claim 1 , amyotrophic lateral sclerosis (ALS) claim 1 , diabetic ...

MOLECULES THAT INDUCE DISEASE RESISTANCE AND IMPROVE GROWTH IN PLANTS

Described herein are methods and compositions for enhancing pathogen immunity in plants and improving plant growth. 2. The agricultural composition of claim 1 , wherein Ris hydrogen or hydroxyl.3. The agricultural composition of claim 1 , wherein Ris hydrogen or bromo.4. The agricultural composition of claim 1 , wherein Ris hydrogen.5. The agricultural composition of claim 1 , wherein Ris a carboxyl-substituted thiazolidine.6. The agricultural composition of claim 1 , wherein Ris hydrogen or bromo.7. The agricultural composition of claim 1 , wherein Ris hydrogen or methoxy.9. The agricultural composition of claim 1 , further comprising at least one of an herbicide claim 1 , an herbicide safener claim 1 , a surfactant claim 1 , a fungicide claim 1 , a pesticide claim 1 , a nematicide claim 1 , a plant activator claim 1 , a synergist claim 1 , a plant growth regulator claim 1 , an insect repellant claim 1 , an acaricide claim 1 , a molluscicide claim 1 , or a fertilizer.12. The method of claim 10 , wherein the compound is applied in solution at a concentration of 10-100 uM.1316-. (canceled)17. The method of claim 10 , wherein the pathogen is present on or in the plant at the time of the contacting step.18. The method of claim 10 , further comprising comparing the amount of pathogen present on the plant before and after the contacting step.19. (canceled)20. The method of claim 10 , wherein the compound is applied in combination with at least one of an herbicide claim 10 , an herbicide safener claim 10 , a surfactant claim 10 , a fungicide claim 10 , a pesticide claim 10 , a nematicide claim 10 , a plant activator claim 10 , a synergist claim 10 , a plant growth regulator claim 10 , an insect repellant claim 10 , an acaricide claim 10 , a molluscicide claim 10 , or a fertilizer.23. The method of claim 21 , wherein the compound is applied in solution at a concentration of 0.5-50 uM.2427-. (canceled)28. The method of any one of claim 21 , wherein a pathogen is present on ...

SUBSTITUTED PYRROLIDINES AS G-PROTEIN COUPLED RECEPTOR 43 AGONISTS

The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases. 132-. (canceled)35. Method according to claim 34 , wherein the compound is an agonist or partial agonist of GPR43 receptor activity. The present invention relates to novel compounds including their pharmaceutically acceptable salts, solvates and prodrugs, which are agonists or partial agonists of G-protein coupled receptor 43 (GPR43) and are useful as therapeutic compounds, particularly in the treatment and/or prevention of Type 2 diabetes mellitus and conditions that are often associated with this disease including, lipid disorders such as dyslipidemia, hypertension, obesity, atherosclerosis and its sequelae.Under normal conditions, Free Fatty Acids (FFAs) are implicated in numerous physiological processes by serving as fuel in various metabolic pathways and/or acting as signaling molecules in different tissues such as the heart, liver, skeletal muscle, adipocytes and the pancreas (Newsholme et al., Biochem. J., 80 pp 655-662, 1961; Prentki et al., Endocrine Reviews, PubMed print ahead, 2008). Among FFAs, the short-chain fatty acids (SCFAs, carbon length C2-C6) are generated during anaerobic bacterial fermentation of fiber in the gut (Sellin et al., News. Physiol. Sci., 14, pp 58-64, 1999). Long-chain fatty acids (LCFAs, carbon length C14-C24) are products of dietary intake from adipose tissues and liver (McArthur et al., J. Lipid. Res., 40, pp 1371-1383, 1999).Obesity is an increasing, worldwide public health problem associated with devastating pathologies such as type 2 diabetes (T2D) and dyslipidemia (Wild et al., Diabetes Care 27, pp 1047-1053, 2004). Dyslipidemia is characterized by high levels of triglycerides and/or LDL (bad cholesterol) or low levels of HDL (good cholesterol). Dyslipidemia is a key independent risk factor for cardiovascular diseases. It has long been suggested that FFAs are implicated in the regulation and/or ...

SUBSTITUTED PYRROLIDINES AS G-PROTEIN COUPLED RECEPTOR 43 AGONISTS

The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases. 132-. (canceled) The present invention relates to novel compounds including their pharmaceutically acceptable salts, solvates and prodrugs, which are agonists or partial agonists of G-protein coupled receptor 43 (GPR43) and are useful as therapeutic compounds, particularly in the treatment and/or prevention of Type 2 diabetes mellitus and conditions that are often associated with this disease including, lipid disorders such as dyslipidemia, hypertension, obesity, atherosclerosis and its sequelae.Under normal conditions, Free Fatty Acids (FFAs) are implicated in numerous physiological processes by serving as fuel in various metabolic pathways and/or acting as signaling molecules in different tissues such as the heart, liver, skeletal muscle, adipocytes and the pancreas (Newsholme et al., Biochem. J., 80 pp 655-662, 1961; Prentki et al., Endocrine Reviews, PubMed print ahead, 2008). Among FFAs, the short-chain fatty acids (SCFAs, carbon length C2-C6) are generated during anaerobic bacterial fermentation of fiber in the gut (Sellin et al., News. Physiol. Sci., 14, pp 58-64, 1999). Long-chain fatty acids (LCFAs, carbon length C14-C24) are products of dietary intake from adipose tissues and liver (McArthur et al., J. Lipid. Res., 40, pp 1371-1383, 1999).Obesity is an increasing, worldwide public health problem associated with devastating pathologies such as type 2 diabetes (T2D) and dyslipidemia (Wild et al., Diabetes Care 27, pp 1047-1053, 2004). Dyslipidemia is characterized by high levels of triglycerides and/or LDL (bad cholesterol) or low levels of HDL (good cholesterol). Dyslipidemia is a key independent risk factor for cardiovascular diseases. It has long been suggested that FFAs are implicated in the regulation and/or genesis of these diseases (Fraze et al., J. Clin. Endocrinol. Metab., 61, pp 807-811, 1985). It is well established ...

CEPHALOSPORIN DERIVATIVES AND METHODS OF USE

This invention provides cephalosporin derivatives for killing or inhibiting the spread of microorganisms such as non-replicating and in the treatment of infectious disease. 2. The compound of claim 1 , wherein said compound is not Compound 4a claim 1 , 5a claim 1 , 5d claim 1 , 5i claim 1 , 5k claim 1 , 11c claim 1 , 12b claim 1 , 12c claim 1 , 13 claim 1 , 14 claim 1 , 40 or 80.3. A pharmaceutical composition comprising one or more compounds of in admixture with a pharmaceutically acceptable carrier.4. The pharmaceutical composition of claim 3 , further comprising one or more antitubercular agents.5. A method for killing or inhibiting the spread of a microorganism comprising contacting a bacterial agent with the compound of claim 1 , thereby killing or inhibiting the spread of the bacterial agent.6. The method of claim 5 , wherein the bacterial agent is a mycobacterial agent.7Mycobacterium tuberculosis.. The method of claim 6 , wherein the mycobacterial agent is8M. tuberculosisM. tuberculosis.. The method of claim 7 , wherein the is non-replicating9. A method for preventing claim 3 , mitigating or treating an infectious disease comprising administering to a subject in need thereof the pharmaceutical composition of so that the subject's infectious disease is prevented claim 3 , mitigated or treated.10. The method of claim 9 , wherein the infectious disease is tuberculosis claim 9 , leprosy claim 9 , Crohn's Disease claim 9 , lyme disease claim 9 , cat-scratch disease or Rocky Mountain Spotted fever. This application claim benefit of priority from U.S. Provisional Application Ser. No. 61/796,128, filed Nov. 2, 2012, the content of which is incorporated herein by reference in its entirety.The β-lactam ring (Hoten & Onusko (2000) 62:611-620) is part of the structure of several antibiotic families, principally the penicillin derivatives, cephalosporins and related compounds, which are therefore also called β-lactam antibiotics (Gilchrist (1997) Harlow: Longman). As a ...

SUBSTITUTED PYRROLIDINES AS G-PROTEIN COUPLED RECEPTOR 43 AGONISTS

The present invention is directed to novel compounds of formula (I) and their use in treating and or preventing metabolic diseases. 132-. (canceled) The present invention relates to novel compounds including their pharmaceutically acceptable salts, solvates and prodrugs, which are agonists or partial agonists of G-protein coupled receptor 43 (GPR43) and are useful as therapeutic compounds, particularly in the treatment and/or prevention of Type 2 diabetes mellitus and conditions that are often associated with this disease including, lipid disorders such as dyslipidemia, hypertension, obesity, atherosclerosis and its sequelae.Under normal conditions, Free Fatty Acids (FFAs) are implicated in numerous physiological processes by serving as fuel in various metabolic pathways and/or acting as signaling molecules in different tissues such as the heart, liver, skeletal muscle, adipocytes and the pancreas (Newsholme et al., Biochem. J., 80 pp 655-662, 1961; Prentki et al., Endocrine Reviews, PubMed print ahead, 2008). Among FFAs, the short-chain fatty acids (SCFAs, carbon length C2-C6) are generated during anaerobic bacterial fermentation of fiber in the gut (Sellin et al., News. Physiol. Sci., 14, pp 58-64, 1999). Long-chain fatty acids (LCFAs, carbon length C14-C24) are products of dietary intake from adipose tissues and liver (McArthur et al., J. Lipid. Res., 40, pp 1371-1383, 1999).Obesity is an increasing, worldwide public health problem associated with devastating pathologies such as type 2 diabetes (T2D) and dyslipidemia (Wild et al., Diabetes Care 27, pp 1047-1053, 2004). Dyslipidemia is characterized by high levels of triglycerides and/or LDL (bad cholesterol) or low levels of HDL (good cholesterol). Dyslipidemia is a key independent risk factor for cardiovascular diseases. It has long been suggested that FFAs are implicated in the regulation and/or genesis of these diseases (Fraze et al., J. Clin. Endocrinol. Metab., 61, pp 807-811, 1985). It is well established ...

ANTI-ALPHAVBETA1 INTEGRIN COMPOUNDS AND METHODS

Provided herein, inter alia, are methods and compositions for inhibiting αvβ1 integrin and for treating fibrosis. 2. The compound of claim 1 , wherein Lis a bond.3. The compound of or claim 1 , wherein Lis unsubstituted methylene.4. The compound of claim 1 , wherein Lis substituted or unsubstituted C-Calkylene claim 1 , substituted claim 1 , unsubstituted 2 to 6 membered heteroalkylene claim 1 , or substituted or unsubstituted alkylarylene.5. The compound of claim 1 , wherein{'sup': 3', '6, 'sub': 1', '3, 'Lis R-substituted C-Calkylene;'}{'sup': 6', '6A, 'Ris —NHC(O)R;'}{'sup': 6A', '6C', '6C', '3C', '6C, 'Ris —C(NCN)R, —C(NH)R, R-substituted or unsubstituted alkyl, or R-substituted or unsubstituted heteroalkyl;'}{'sup': 6C', '6D', '6D', '6D', '6E', '6E', '6D', '6E', '6D', '6D', '6D', '6D', '6E', '6D', '6E', '6D', '6E', '6D', '6D', '6F', '6F', '6F', '6F', '6F', '6F, 'sub': 3', '3', '3', '3', '3', '2', 'n6, 'Rhydrogen, halogen, oxo, —N, —CF, —CCl, —CBr, —CI, —CN, —COR, —OR, —NRR, —COOR, —CONRR, —NHC(O)R, —NO, —SR, —SOR, —NHNRR, ONRR, —NHC(O)NHNRR, —C(NCN)R, —C(NH)R, R-substituted or unsubstituted alkyl, R-substituted or unsubstituted heteroalkyl, R-substituted or unsubstituted cycloalkyl, R-substituted or unsubstituted heterocycloalkyl, R-substituted or unsubstituted aryl, or R-substituted or unsubstituted heteroaryl;'}n6 is 2, 3, or 4; and{'sup': 6D', '6E', '6F, 'sub': 3', '3', '3', '3', '3', '2', '2', '2', '2', '2', '2', '3', '3', '4', '2', '2', '2', '2', '2, 'R, Rand Rare independently hydrogen, halogen, oxo, —N, —CF, —CCl, —CBr, —CI, —CN, —CHO, —OH, —NH, —COOH, —CONH, —NO, —SH, —SO, —SOCl, —SOCH—SOH, —SOH, —SONH, —NHNH, —ONH, —NHC(O)NHNH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a detectable moiety.'}6. (canceled)7. (canceled)8. The compound of claim 1 , wherein ...

NOVEL IMAGING COMPOSITION AND USES THEREOF

The invention discussed in this application relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. 2. The radionuclide complex of claim 1 , wherein L is OR.3. The radionuclide complex of claim 2 , wherein R is selected from Cto Calkyl claim 2 , Cto Cheteroalkyl claim 2 , Cto Calkene claim 2 , C2 to Cm alkyne and aryl claim 2 , each of which is optionally substituted.4. The radionuclide complex of claim 3 , wherein R is Cto Calkyl claim 3 , preferably Cto Calkyl claim 3 , more preferably methyl or ethyl claim 3 , even more preferably ethyl.5. The radionuclide complex of claim 1 , wherein the leaving group is selected from OCHCH claim 1 , O-p-toluenesulfonate claim 1 , O-methanesulfonate claim 1 , O-trifluoromethanesulfonate claim 1 , O-benzenesulfonate claim 1 , O-m-nitrobenzenesulfonate claim 1 , cyanate claim 1 , azide and halogen.6. The radionuclide complex of claim 1 , wherein the radionuclide is selected from radioisotopes of zirconium claim 1 , gallium claim 1 , lutetium claim 1 , holmium claim 1 , scandium claim 1 , titanium claim 1 , indium and niobium.7. The radionuclide complex of wherein the radionuclide is a radioisotope of zirconium claim 6 , gallium or indium.8. The radionuclide complex of claim 7 , wherein the radionuclide is a radioisotope of zirconium.9. The radionuclide complex of further conjugated to a target molecule to form a radionuclide-labelled conjugate.10. The radionuclide-labelled conjugate of claim 9 , wherein the target molecule is a polypeptide.11. The radionuclide-labelled complex of wherein the complex or conjugate has improved affinity when compared to with DFO-Ph-NCS or a conjugate of DFO-Ph-NCS and the target molecule.12. A method of imaging a patient claim 1 , the method including:{'claim-ref': {'@idref': 'CLM-00009', 'claim 9'}, 'administering to a patient the radionuclide-labelled conjugate of ; and'}imaging said patient.13. ...

SUBSTITUTED N-ACETYL-L-CYSTEINE DERIVATIVES AND RELATED COMPOUNDS

Novel substituted N-acetyl-L-cysteine (NAC) derivatives and related compounds and methods of using these compounds for the treatment of diseases and/or conditions, including but not limited to diseases and/or conditions of, or involving, the Central Nervous System (CNS), including schizophrenia adrenoleukodystrophy, mitochondrial diseases (e.g. Leigh syndrome, Alpers' disease, and MELAS), Huntington's disease, trichotillomania, HIV-associated neurocognitive disorder, hypoxic-ischemic encephalopathy, drug craving, and drug addiction. 2. The method of claim 1 , wherein the compound of formula I is administered orally.3. The method of claim 1 , wherein the compound of formula I is administered rectally claim 1 , parenterally claim 1 , intracisternally claim 1 , intravaginally claim 1 , transdermally claim 1 , transmucosally claim 1 , sublingually claim 1 , pulmonarily claim 1 , intraperitoneally claim 1 , topically claim 1 , intranasally claim 1 , or bucally.4. The method of claim 1 , wherein the compound of formula I is administered in a solid form.5. The method of claim 1 , wherein the compound of formula I is administered in a capsule.6. The method of claim 1 , wherein the compound of formula I is administered in a soft gelatin capsule.7. The method of claim 1 , wherein the compound of formula I is administered in a hard gelatin capsule.8. The method of claim 1 , wherein the compound of formula I is administered as a tablet.9. The method of claim 1 , wherein the compound of formula I is administered with an enteric coating.10. The method of claim 1 , wherein the compound of formula I is administered in a solid form with an enteric coating.11. The method of claim 1 , wherein the compound of formula I is administered as an enteric formulation.12. The method of claim 1 , wherein the compound of formula I is administered in a composition that releases the compound in a delayed manner.13. The method of claim 1 , wherein the compound of formula I is administered in a ...

Novel compound having skin-whitening, anti-oxidizing and ppar activities and medical use thereof

Provided are a novel compound having skin-whitening, anti-oxidizing and PPAR activities and a medical use thereof, and the compound has skin-whitening activities for the suppression of tyrosinase, and accordingly, is useful for use in skin-whitening pharmaceutical composition or cosmetic products; has anti-oxidant activities, and accordingly, is useful for the prevention and treatment of skin-aging; and has PPAR activities, and in particular, PPARα and PPARγ activities, and accordingly, is useful for use in pharmaceutical compositions or health foods which are effective for the prevention and treatment of obesity, metabolic disease, or cardiovascular disease.

COMPOSITIONS AND METHODS OF TREATMENT FOR NEUROLOGICAL DISORDERS COMPRISING A DEMENTIA

This invention, in at least some embodiments, relates to an inventive molecule, compositions comprising same, and methods of use thereof for treatment of a neurological disorder. 128-. (canceled)3022. The molecule of claim :{'sub': 1', '2, 'wherein for Family A, Ris nitrogen substituted benzyl or H, and Ris H.'}3122. The molecule of claim :wherein for Family A, the molecule is selected from the group consisting of A1-A3 of Appendix I (molecules having catalog numbers F228-0422, F228-0350 or F228-0534);wherein for Family I, the molecule is selected from the group consisting of I1-I5 and I7 of Appendix I (molecules having catalog numbers T636-1937, T636-1114, T636-2387, T636-0134, T636-1210 and T636-2425).3222. A pharmaceutical composition comprising the molecule of claim .3322. A method for treating a mammal in need of treatment thereof , comprising administering to the mammal an inventive molecule of claim , or a pharmaceutical composition comprising the same , for treatment of a neurological disease , wherein said neurological disease includes Alzheimer's disease , a subtype thereof or a related disease.3426. The method of claim , wherein said molecule is selected from the group consisting of:an inventive molecule selected from the group consisting of a molecule given in Appendix I, wherein said molecule is selected from the group consisting of catalogID numbers: T0502-5560; T0508-5190, T202-1455, T202-0973, K851-0113, T5630309, T5672380, T5967389, T5884038, T5231424, T0517-8250, T0511-9200 and T5627721;a molecule as shown in Table 1 herein; anda molecule given in Appendix II, wherein said molecule is selected from the group consisting of catalogID numbers: T6010789, T5993799, T5813085, T6947848, 10517-4117, T5729557, T5705522, Z606-8352, L115-0403, T5712071, T5790476, T5788339, G433-0293, T5719257, T5798761, T5821723, T5787526, T5827594, K405-2595, T5274959, M950-1515, T5450239, G508-0015, T5707230, T5710343, 887-0183, T5453923, 10505-4087, T5673322, T5800607, ...

SUBSTITUTED PYRROLIDINES AS G-PROTEIN COUPLED RECEPTOR 43 AGONISTS

The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases. 132-. (canceled)52. The method according to claim 33 , wherein the compound is selected from the group consisting of:1 (2S,5R)-5-(2-chlorophenyl)-1-(2′-methoxy-[1, T-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid2 (2S,5R)-5-(2-chlorophenyl)-1-(2′-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid3 (2S,5R)-1-(3-((4-chlorobenzyl)oxy)-5-methoxybenzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid4 (2S,5R)-5-(2-chlorophenyl)-1-(2′-fluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid5 (2S,5R)-5-(2-chlorophenyl)-1-(4′-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid6 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-5-phenethoxybenzoyl)pyrrolidine-2-carboxylic acid8 (2S,5R)-1-([1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid9 (2S,5R)-5-(2-chlorophenyl)-1-(3-(3,3-diphenylpropoxy)-5-methoxybenzoyl)pyrrolidine-2-carboxylic acid10 (2S,5R)-5-(2-chlorophenyl)-1-(3′-fluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid11 (2S,5R)-5-(2-chlorophenyl)-1-(3′-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid12 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-5-((4-(methylsulfonyl)benzyl)oxy)benzoyl)pyrrolidine-2-carboxylic acid13 (2S,5R)-5-(2-chlorophenyl)-1-(3′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid14 (2S,5R)-5-(2-chlorophenyl)-1-(3,5-dimethoxybenzoyl)pyrrolidine-2-carboxylic acid15 (2S,5R)-5-(2-chlorophenyl)-1-(4-(phenoxymethyl)benzoyl)pyrrolidine-2-carboxylic acid16 (2S,5R)-5-(2-chlorophenyl)-1-(4-((2-fluorobenzyl)oxy)benzoyl)pyrrolidine-2-carboxylic acid17 (2S,5R)-1-(3-chloro-5-methoxybenzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid18 (2S,5R)-5-(2-chlorophenyl)-1-(4′-fluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid19 (2S,5R)-5-(2-chlorophenyl)-1-(4-phenethoxybenzoyl)pyrrolidine-2-carboxylic acid21 (2S,5R)-5-(2-chlorophenyl)-1 ...

ANTI-ALPHAVBETA1 INTEGRIN COMPOUNDS AND METHODS

Provided herein, inter alia, are methods and compositions for inhibiting αvβ1 integrin and for treating fibrosis. 2. The compound of claim 1 , wherein Lis a bond.3. The compound of or claim 1 , wherein Lis unsubstituted methylene.4. The compound of claim 1 , wherein Lis substituted or unsubstituted C-Calkylene claim 1 , substituted claim 1 , unsubstituted 2 to 6 membered heteroalkylene claim 1 , or substituted or unsubstituted alkylarylene.5. The compound of claim 1 , wherein{'sup': 3', '6, 'sub': 1', '3, 'Lis R-substituted C-Calkylene;'}{'sup': 6', '6A, 'Ris —NHC(O)R;'}{'sup': 6A', '6C', '6C', '3C', '6C, 'Ris —C(NCN)R, —C(NH)R, R-substituted or unsubstituted alkyl, or R-substituted or unsubstituted heteroalkyl;'}{'sup': 6C', '6D', '6D', '6D', '6E', '6E', '6D', '6E', '6D', '6D', '6D', '6D', '6E', '6D', '6E', '6D', '6E', '6D', '6D', '6F', '6F', '6F', '6F', '6F', '6F, 'sub': 3', '3', '3', '3', '3', '2', 'n6, 'Rhydrogen, halogen, oxo, —N, —CF, —CCl, —CBr, —CI, —CN, —COR, —OR, —NRR, —COOR, —CONRR, —NHC(O)R, —NO, —SR, —SOR, —NHNRR, ONRR, —NHC(O)NHNRR, —C(NCN)R, —C(NH)R, R-substituted or unsubstituted alkyl, R-substituted or unsubstituted heteroalkyl, R-substituted or unsubstituted cycloalkyl, R-substituted or unsubstituted heterocycloalkyl, R-substituted or unsubstituted aryl, or R-substituted or unsubstituted heteroaryl;'}n6 is 2, 3, or 4; and{'sup': 6D', '6E', '6F, 'sub': 3', '3', '3', '3', '3', '2', '2', '2', '2', '2', '2', '3', '3', '4', '2', '2', '2', '2', '2, 'R, Rand Rare independently hydrogen, halogen, oxo, —N, —CF, —CCl, —CBr, —CI, —CN, —CHO, —OH, —NH, —COOH, —CONH, —NO, —SH, —SO, —SOCl, —SOCH—SOH, —SOH, —SONH, —NHNH, —ONH, —NHC(O)NHNH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a detectable moiety.'}6. (canceled)7. (canceled)8. The compound of claim 1 , wherein ...

ANTHROPOD REPELLENT CHEMICALS

Compositions and methods for repelling arthropods. The compositions include a carrier and an arthropod repelling compound, which can be a compound discovered by a novel and complex cheminformatic process to demonstrate repellency behavior across a broad spectrum of arthropods. The compound can be a thiane compound, a pyrrolidone compound, a cyclohexadiene compound, a cyclohexenone compound, a cyclohexene compound, a furanone compound, a pyran compound, a tetrahydropyran compound, a thiazolidine compound, a thiazoline compound, a dihydrothiophene compound, a dithiolane compound, a dithiane compound, an epoxide compound, an oxathiane compound, a cyclopentene compound, a cyclohexane compound, a quinoline compound, an oxazoline compound, a tetrahydropyridine compound, and an imidazolidinone compound, or a combination thereof. 2. The composition of claim 1 , wherein the compounds are selected from the group consisting of 4-methylcyclohexene claim 1 , ethylcyclopentenol one claim 1 , 3 claim 1 ,4-Dihydro-2H-pyran claim 1 , and lemon hexadiene.3. The composition of claim 1 , wherein the alkyl is a C-Calkyl claim 1 , the alkenyl is a C-Calkenyl claim 1 , the alkoxy is a C-Calkoxy claim 1 , the aldehyde group is a C-Caldehyde group claim 1 , the ester group a C-Cester group claim 1 , or any combination thereof5. The composition claim 1 , wherein the arthropod repellant compounds are selected from the group consisting of 1 claim 1 ,2-epoxyhexane claim 1 , 1-methyl-1 claim 1 ,4-cyclohexadiene claim 1 , 1-ethyl-2-pyrrolidone claim 1 , 2-isobutyl-4-methyl-1 claim 1 ,3-dioxolane claim 1 , 2-methyl tetrahydrofuran claim 1 , 3 claim 1 ,4-Dihydro-2H-pyran claim 1 , 4-hydroxy-2 claim 1 ,5-dimethyl-3(2H)-furanone claim 1 , 4-methyl cyclohexene claim 1 , dihydropyran claim 1 , ethyl cyclopentenolone claim 1 , isopropyl quinoline claim 1 , methyl 2-(4-tert-butylphenyl)acetate and nerol oxide.6. The composition claim 1 , comprising two or more of the arthropod repellant compounds ...

METHODS AND COMPOSITIONS FOR GAMMA-GLUTAMYL CYCLE MODULATION

The present disclosure provides pharmaceutical compositions comprising Gamma-glutamyl cycle inhibitors (GGCI) and certain pharmaceutically acceptable salts thereof, and methods of use. 114.-. (canceled)16. The method of claim 15 , wherein the GGCI is a 5-oxoproline analog.17. The method of claim 15 , whereby the reaction step catalyzed by 5-oxo-prolinase in the GGC cycle is inhibited.18. The method of claim 16 , wherein the 5-oxoproline analog is 2-Imino-3-para methoxy Benzyl-4 sulfanyl-5 dimethyl 1-carboxylic acid.19. The method of claim 16 , whereby the level of glutathione is reduced in cancer cells.20. The method according to claim 15 , wherein the compound inhibits glutathione-S-transferase.21. The method of claim 15 , wherein the effective dose of GGCI ranges from about 10 mg/kg to about 6 g/kg.22. The method of claim 15 , wherein the effective dose of GGCI is given in one or more doses of about 3.5 g/kg to about 4.0 g/kg for each dose.23. The method of claim 15 , wherein the one or more effective doses of GGCI are administered subcutaneously claim 15 , intravenously claim 15 , or intramuscularly.24. The method of claim 15 , wherein the one or more effective doses of GGCI are administered orally.25. The method of claim 15 , wherein the cancer is a solid tumor.26. The method of claim 25 , wherein the solid tumor comprises sarcomas claim 25 , carcinomas claim 25 , or lymphomas.27. The method of claim 26 , wherein the cancer is selected from the group consisting of: lung claim 26 , breast claim 26 , prostate claim 26 , pancreatic claim 26 , ovarian claim 26 , bladder claim 26 , head and neck claim 26 , thyroid claim 26 , brain claim 26 , skin and kidney.2834. The method of claim claim 26 , wherein each dose of GGCI is between about 1 ng/kg and less than about 10 mg/kg claim 26 , and said dose is administered by a delivery route selected from the group consisting of intradermal claim 26 , intramuscular claim 26 , intraperitoneal claim 26 , intravenous claim 26 , ...

Aldimine mit aktivem wasserstoff aufweisenden reaktivgruppen sowie deren verwendung

Die vorliegende Erfindung betrifft Aldimine der Formel (I), deren Folgeprodukte sowie deren Verwendungen. Die Aldimine und Aldimin-haltigen Verbindungen zeichnen sich dadurch aus, dass sie geruchsfrei sind und bei der Hydrolyse geruchsfreie Aldehyde abspalten. Sie dienen deshalb als Quelle für Aldehyde und Amine.

Anti-viral compounds

Compounds effective in inhibiting replication of Hepatitis C virus ("HCV") are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

Novel herbicides

Bicyclic dione compounds, and derivatives thereof, which are suitable for use as herbicides. formula (I)

Compouds and uses thereof in modulating amyloid beta

Novel compounds, compositions, and kits are provided. Methods of modulating Aβ levels, and methods of treating a disease associated with aberrant Aβ levels are also provided.

헤테로사이클 유도체 및 그의 용도

하기 화학식 1의 헤테로사이클 유도체, 이의 약학적으로 허용가능한 염 또는 입체이성체는 STAT3 단백질의 활성화 억제 효과가 우수하므로, 이를 함유하는 약학적 조성물은 STAT3 단백질의 활성화와 관련된 질환을 치료 또는 예방하는데 유용하다: [화학식 1] 상기 식에서, X 1 , X 2 , X 3 , X 4 , Y, Z, Rx, A, B, Rc, R N , L B , R A , R B , p 및 q는 명세서 본문에서 정의한 바와 같다.

Heterocyclic derivatives and uses thereof

ORAL GSNOR INHIBITOR AND PHARMACEUTICAL USE THEREOF

Disclosed are a thiazolone derivative of N6022 and a pharmaceutical use thereof. The characteristic structure of the thiazolone derivative of N6022 is: 2. A use of the thiazolone derivative of N6022 of or a pharmaceutically acceptable salt thereof in preparing medicines for improvement and treatment on diseases related to asthma claim 1 , cystic fibrosis claim 1 , diabetic vascular complications claim 1 , aortic aneurysm/dissection. The present invention relates to a thiazolone derivative of an s-nitrosoglutathione reductase (GSNOR) N6022 and a pharmaceutical use thereof, and in particular to a use thereof for preparing medicines for improvement and treatment on diseases related to asthma, cystic fibrosis, diabetic vascular complications and aortic aneurysm/dissection.N6022 is a specific and reversible s-nitrosoglutathione reductase (GSNOR) inhibitor;and studies have shown that N6022 can effectively mitigate asthma and allergic airway inflammation. The phase I and phase II clinical trials of N6022 for treating chronic asthma and cystic fibrosis have finished.Diabetes has become a leading health problem causing morbidity and mortality worldwide. 70% of the deaths of the diabetic patients are attributed to cardiovascular complications; and the diabetic vascular complications, including atherosclerosis, peripheral arterial diseases, retinopathy and nephropathy, are also major factors affect the quality of life. Vascular endothelial cells are located on the inner membrane of the vascular wall and serve as a barrier between blood and tissues. Under various physiological and pathological conditions, the endothelial cells can also play a role as “first response” effector cells for adjusting vascular functions. Diabetes induces endothelial cell dysfunction which is mainly manifested by an increase in vascular endothelial permeability, an impairment of angiogenesis ability. This impairment constitutes a main inducement and a pathophysiological basis of various vascular ...

3,5-dihydroxypentanoic acid derivatives useful as antihypercholesterolemic agents and method for preparing same

3,5-Dihydroxypentanoic acid derivatives are provided which are 6-hydroxy-8-(2,2-dimethyl-1-oxybutoxy-2-methyl)-substituted-thiazolidine derivatives and have the structure ##STR1## wherein Z is ##STR2## R 6 is an alkali metal, lower alkyl or H; R 1 and R 2 are the same or different and are H, lower alkyl or aryl; X is S, O, ##STR3## or a single bond; R 7 is lower alkyl; R 3 is lower alkyl or aryl; R 4 and R 5 are the same or different and are H or lower alkyl; and --- represents a single bond or a double bond, and are HMG CoA reductase inhibitors and thus are useful as antihypercholesterolemic agents and in treating atherosclerosis, and also as antifungal agents. In addition, novel intermediates for use in preparing the above mevinic acid derivatives are also provided.

聚烯烃油催化剂及其应用

本发明涉及新型聚烯烃油催化剂及其应用，公开了一类新型聚烯烃催化剂及其制备。具体地，本发明公开了一类催化体系，该催化体系包含一类新型：铁、钴、镍、钯、铂配合物。在该催化体系的作用下，只需要温和的条件即可以由简单烯烃，例如乙烯，高效地获得油状高支化烷烃混合物。该烷烃混合物可以用于加工助剂和高性能润滑油的基础油。本发明还提供了催化剂的制法以及油状烯烃聚合物的制备方法，还包括功能化聚烯烃油的制备方法。

Antiviral compounds

FIELD: medicine, pharmaceutics. SUBSTANCE: invention refers to new compounds of formula I, such as below, or its pharmaceutically acceptable salts. What is described is a method for preparing them. , wherein: A independently from B means phenyl, , or , and B independently from A means phenyl, , or , and the values Z, Y, D, L 1 , L 2 , L 3 , Z 1 , Z 2 are presented in the patent claim. EFFECT: compounds are effective for hepatitis C virus (HCV) replication inhibition. 17 cl, 3 tbl, 8 dwg, 177 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07D 207/16 C07D 209/52 C07D 205/02 C07D 401/12 C07D 403/04 C07D 403/12 ФЕДЕРАЛЬНАЯ СЛУЖБА C07D 413/12 ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ C07D 417/12 A61P 29/00 (12) ОПИСАНИЕ (21)(22) Заявка: (13) 2 541 571 C2 (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) ИЗОБРЕТЕНИЯ К ПАТЕНТУ 2011146145/04, 14.04.2010 (24) Дата начала отсчета срока действия патента: 14.04.2010 15.04.2009 US 61/169,449; 02.07.2009 US 61/222,591 (45) Опубликовано: 20.02.2015 Бюл. № 5 (56) Список документов, цитированных в отчете о поиске: WO 2008070447 A2, 12.06.2008. US 20090047247 A1, 19.02.2009. EA 7722 B1, 29.12.2006 (73) Патентообладатель(и): ЭББВИ ИНК. (US) (86) Заявка PCT: C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 15.11.2011 US 2010/031102 (14.04.2010) (87) Публикация заявки PCT: 2 5 4 1 5 7 1 WO 2010/120935 (21.10.2010) R U 2 5 4 1 5 7 1 (43) Дата публикации заявки: 20.05.2013 Бюл. № 14 R U Приоритет(ы): (30) Конвенционный приоритет: (72) Автор(ы): ДЕГОЙ Дэвид А. (US), ХАТЧИНС Чарльз В. (US), КАТИ Уоррен М. (US), ДОННЕР Памела Л. (US), НЕЛЬСОН Лисса Т. (US), ДЖИНКЕРСОН Тамми К. (US), КЕДДИ Райан Дж. (US), МОТТЕР Кристофер Э. (US), МАТУЛЕНКО Марк А. (US), КРЮГЕР Аллан К. (US), ПАТЕЛ Сачин В. (US), РАНДОЛФ Джон Т. (US), СОЛТВЕДЕЛ Тодд Н. (US) Адрес для переписки: 129090, Москва, ул. Большая Спасская, 25, стр. 3, ООО "Юридическая фирма "Городисский и Партнеры" (54) ПРОТИВОВИРУСНЫЕ СОЕДИНЕНИЯ ...

杂环衍生物及其用途

所提供的是一种由式(I)表示的杂环衍生物或其药学上可接受的盐或立体异构体，其对STAT3蛋白的活化具有抑制作用，并且可用于预防或治疗与STAT3蛋白激活相关的疾病。

Inhibitors of histone deacetylase

Disclosed are compounds which inhibit histone deacetylase (HDAC) enzymatic activity. Also disclosed are pharmaceutical compositions comprising such compounds as well as methods to treat conditions, particularly proliferative conditions, mediated at least in part by HDAC.

Novel tricyclic compound

본 발명은 화학식 1 로 표현되는 화합물, 및 이를 함유하는 약학적 조성물을 제공한다: The present invention provides a compound represented by Formula 1, and a pharmaceutical composition containing the same: [식 중, A 고리. B 고리 및 C 고리는 각각 독립적으로 임의치환된 방향족 탄소고리, 또는 벤젠 고리와 융합될 수 있는 임의치환된 5- 또는 6-원의 헤테로고리이고, [Wherein, A ring. The B ring and the C ring are each independently an optionally substituted aromatic carbon ring or an optionally substituted 5- or 6-membered heterocycle which may be fused with a benzene ring, W 1 , W 2 및/또는 W 3 은 A 고리, B 고리 및/또는 C 고리가 임의치환된 5-원의 헤테로고리일 때 결합을 나타내고, W 1 , W 2 and / or W 3 represent a bond when the A ring, B ring and / or C ring is an optionally substituted 5-membered heterocycle, X는 -O- 또는 -NR 1 - (식 중 R 1 은 수소, 저급 알킬 등이다) 등이고, X is -O- or -NR 1- (wherein R 1 is hydrogen, lower alkyl, etc.), and Y는 수소, 저급 알킬, 저급 알케닐 등이고, Y is hydrogen, lower alkyl, lower alkenyl, and the like, V 1 및 V 2 중 하나는 결합이고, 다른 하나는 결합, -O- 등이다]. One of V 1 and V 2 is a bond and the other is a bond, —O— and the like].

4-aminopyperidine derivatives

FIELD: chemistry. SUBSTANCE: invention relates to novel compounds of formula (I) , where R 1 is selected from group, including: phenyl, unsubstituted or mono-, di- or tri-substituted independently with lower alkyl, lower alkoxy group, halogen or lower halogenalkyl; naphtyl; tetrahydronaphtyl; C 3 - 7 cycloalkyl; -(CHR 3 ) m -phenyl, where m stands for 1, 2, or 3; and phenyl is unsubstituted or mono-, di- or tri-substituted with lower alkoxy group, and where R 3 is independently selected from hydrogen and lower alkyl; -(CH 2 ) n -heteroaryl, where n stands for 1, 2 or 3; term "heteroaryl" relates to aromatic 5- or 6- member ring or bicyclic 9-member aromatic groups, which can include 1, 2 or 3 atoms, selected from nitrogen and/or sulphur; -(CH 2 ) n -heteroaryl, where n stands for 1, 2 or 3; term "heteroaryl" relates to aromatic 5- or 6- member ring or bicyclic 9-member aromatic groups, which can include 1, 2 or 3 atoms, selected from nitrogen and/or sulphur, and heteroaryl is mono-, di- or tri-substituted independently with lower alkoxy group; and R 2 is selected from group including: n-butyl; phenyl, unsubstituted or mono-, di- or tri-substituted independently with lower alkyl, halogen or lower alkoxy group; heteroaryl, where term "heteroaryl" relates to aromatic 5-member ring, which can include 1, 2 or 3 atoms, selected from nitrogen and/or sulphur; unsubstituted or mono-, di- or tri-substituted independently with lower alkoxy group; -C(O)-NR 4 R 5 ; where R 4 and R 5 stand for lower alkyl or together with nitrogen atom, to which they are bound, form 5-member heterocycle, which can additionally contain heteroatom, selected from N or S, and to their pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition. EFFECT: obtaining novel biologically active compounds, able to inhibit DPP-IV. 13 cl, 43 ex (19) РОССИЙСКАЯ ФЕДЕРАЦИЯ RU (11) 2 396 257 (13) C2 (51) МПК C07D C07D C07D C07D C07D C07D ФЕДЕРАЛЬНАЯ СЛУЖБА A61K ...

Method of preparing n-substituted thiobutyramides or their salts

The invention provides compounds of the formula <IMAGE> in which R is a hydrogen atom, a lower alkyl, lower alkenyl or aryl-lower alkyl group or the acyl radical of a lower alkyl-carboxylic acid or an aryl- carboxylic acid each having up to 10 carbon atoms; R1 is a hydroxy, lower alkoxy, di- (lower alkyl)-amino-lower alkoxy, amino, monosubstituted amino, disubstituted amino or dihydroxy-lower alkyl group; A and B together are a lower alkylene group of the formula (CH2)m-CH2-, a group of the formula <IMAGE> a group of the formula (CH2)ml- CH = CH or a disubstituted lower alkylene group of the formula <IMAGE> Z is sulphur or a sulphinyl or sulphonyl group; R' is a hydrogen atom or a lower alkyl group; R'' is a lower alkyl group; n is zero or 1; m is 1 or 2; m1 is zero, 1 or 2; and m2 is 1 or 2; and their diastereoisomers, optically active isomers and salts with inorganlc and organic bases. The invention also provides a process for preparing such compounds, and pharmaceutical compositions containing them. The compounds may be used in the treatment of hypertension.

Cell adhesion inhibitors

본 발명은 세포 유착과 세포 유착에 의해 매개되는 병리학적 증상을 억제 및 예방하는 데 유용한 신규 화합물에 관한 것이다. 또한, 본 발명은 이러한 화합물을 포함하는 약제 조성물과 이를 세포 유착 및 세포 유착에 의해 매개되는 병리학적 증상을 억제 및 예방하는 데 사용하는 방법에 관한 것이다. 본 발명의 화합물과 약제 조성물은 치료제 또는 예방제로서 사용할 수 있다. 이들은 다수의 염증성 질환과 자가 면역 질환을 치료하는 데 특히 적합하다. The present invention relates to novel compounds useful for inhibiting and preventing cell adhesion and pathological symptoms mediated by cell adhesion. The invention also relates to pharmaceutical compositions comprising such compounds and methods of using the same to inhibit and prevent cell adhesion and pathological symptoms mediated by cell adhesion. The compounds of the present invention and pharmaceutical compositions can be used as therapeutic or prophylactic agents. They are particularly suitable for treating many inflammatory diseases and autoimmune diseases.

Aldimines containing reactive groups containing active hydrogen, as well as use thereof

FIELD: chemistry. SUBSTANCE: invention relates to aldimines used to produce a polymer precursor, obtained via reaction of at least one sterically hindered aliphatic aldehyde A of formula with an aliphatic amine B, where all values of substitutes are given in the claim, via a condensation reaction with splitting of water, a product containing an aldimine-containing compound, and use thereof as a protected cross-linking agent for the polymer precursor and as a source of amines [H 2 N] m -R 4 -[XH] y (B). EFFECT: obtaining polymer precursors containing isocyanate groups, which are characterised by high stability during storage. 15 cl, 51 ex, 4 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 432 353 (13) C2 (51) МПК C07C C07C C07C C07D C07C C07C ФЕДЕРАЛЬНАЯ СЛУЖБА C07D ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, C08G 251/08 275/06 275/18 265/06 275/28 275/24 277/04 18/38 (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2008117163/04, 29.09.2006 (24) Дата начала отсчета срока действия патента: 29.09.2006 (73) Патентообладатель(и): ЗИКА ТЕКНОЛОДЖИ АГ (CH) R U Приоритет(ы): (30) Конвенционный приоритет: 30.09.2005 EP 05109110.6 (72) Автор(ы): БУРКХАРДТ Урс (CH) (43) Дата публикации заявки: 10.11.2009 Бюл. № 31 2 4 3 2 3 5 3 (45) Опубликовано: 27.10.2011 Бюл. № 30 (56) Список документов, цитированных в отчете о поиске: RU 2005105296 А, 20.07.2005. ЕР 1544204 А, 22.06.2005. ЕР 1384709 А1, 28.01.2004. US 4469831 А, 04.09.1984. 2 4 3 2 3 5 3 R U (86) Заявка PCT: EP 2006/066924 (29.09.2006) C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 30.04.2008 (87) Публикация заявки РСТ: WO 2007/036571 (05.04.2007) Адрес для переписки: 129090, Москва, ул. Б.Спасская, 25, стр.3, ООО "Юридическая фирма Городисский и Партнеры", пат.пов. Е.Е.Назиной (54) АЛЬДИМИНЫ, СОДЕРЖАЩИЕ РЕАКЦИОННОСПОСОБНЫЕ ГРУППЫ, ВКЛЮЧАЮЩИЕ АКТИВНЫЙ ВОДОРОД, А ТАКЖЕ ИХ ПРИМЕНЕНИЕ (57) Реферат: Настоящее ...

Тиазолидин-4-карбонитрилы и их аналоги, применение указанных соединений в качестве ингибиторов дипептидилпептидаз

ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (51) ÌÏÊ 7 (11) 2004 132 719 (13) A C 07 D 277/06, 207/16, 403/06, 401/12, 417/14, A 61 K 31/496, 31/426, 31/4439, 31/454, 31/4545, A 61 P 3/10 ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÇÀßÂÊÀ ÍÀ ÈÇÎÁÐÅÒÅÍÈÅ (21), (22) Çà âêà: 2004132719/04, 03.04.2003 (71) Çà âèòåëü(è): ÒÎÐÐÅÍÒ ÔÀÐÌÀÑÜÞÒÈÊÀËÇ ËÒÄ. (IN) (30) Ïðèîðèòåò: 08.04.2002 US 60/370,224 (72) Àâòîð(û): ÑÀÍÊÀÐÀÍÀÐÀßÍÀÍ Àëàíãóäè (IN) (85) Äàòà ïåðåâîäà çà âêè PCT íà íàöèîíàëüíóþ ôàçó: 09.11.2004 (74) Ïàòåíòíûé ïîâåðåííûé: Íàçèíà Åëåíà Åâãåíüåâíà (86) Çà âêà PCT: IB 03/01330 (03.04.2003) Àäðåñ äë ïåðåïèñêè: 129010, Ìîñêâà, óë. Á.Ñïàññêà , 25, ñòð.3, ÎÎÎ "Þðèäè÷åñêà ôèðìà Ãîðîäèññêèé è Ïàðòíåðû", ïàò.ïîâ. Å.Å.Íàçèíîé (54) ÒÈÀÇÎËÈÄÈÍ-4-ÊÀÐÁÎÍÈÒÐÈËÛ È ÈÕ ÀÍÀËÎÃÈ, ÏÐÈÌÅÍÅÍÈÅ ÓÊÀÇÀÍÍÛÕ R U Ôîðìóëà èçîáðåòåíè 1. Ñîåäèíåíèå, ïðåäñòàâëåííîå îáùåé ôîðìóëîé (I), åãî ïðîèçâîäíûå, àíàëîãè, òàóòîìåðíûå ôîðìû, ñòåðåîèçîìåðû, ïîëèìîðôû, ôàðìàöåâòè÷åñêè ïðèåìëåìûå ñîëè, ôàðìàöåâòè÷åñêè ïðèåìëåìûå ñîëüâàòû, A 2 0 0 4 1 3 2 7 1 9 A ÑÎÅÄÈÍÅÍÈÉ Â ÊÀ×ÅÑÒÂÅ ÈÍÃÈÁÈÒÎÐΠÄÈÏÅÏÒÈÄÈËÏÅÏÒÈÄÀÇ ãäå Õ îçíà÷àåò Î, S, SO, SO2, NR7 èëè CHR1; n ðàâíî íóëþ èëè 1; k ðàâíî 1; Z îçíà÷àåò Î, S è NR7; R1, â äâóõ ïîëîæåíè õ, íåçàâèñèìî âûáðàíû èç âîäîðîäà, ëèáî çàìåùåííîé èëè Ñòðàíèöà: 1 RU 2 0 0 4 1 3 2 7 1 9 (87) Ïóáëèêàöè PCT: WO 03/084940 (16.10.2003) R U (43) Äàòà ïóáëèêàöèè çà âêè: 27.08.2005 Áþë. ¹ 24 A 2 0 0 4 1 3 2 7 1 9 A R U 2 0 0 4 1 3 2 7 1 9 Ñòðàíèöà: 2 R U íåçàìåùåííîé ãðóïïû, âûáðàííîé èç ãðóïïû, âêëþ÷àþùåé ëèíåéíûé èëè ðàçâåòâëåííûé (C 1-C12)àëêèë, (C2-C12) àëêåíèë, (Ñ3-Ñ7) öèêëîàëêèë, (Ñ5-Ñ7) öèêëîàëêåíèë, áèöèêëîàëêèë, áèöèêëîàëêåíèë, ãåòåðîöèêëîàëêèë, àðèë, àðèëîêñè, àðàëêèë, àðàëêîêñè, ãåòåðîàðèë, ãåòåðîàðàëêèë, ãåòåðîàðèëîêñè, ãåòåðîàðàëêîêñè, ãäå îäèí èëè íåñêîëüêî ãåòåðîàòîìîâ íåçàâèñèìî âûáðàíû èç Î, N èëè S; R2, R3, R4 è R7 íåçàâèñèìî âûáðàíû èç ãðóïïû, âêëþ÷àþùåé âîäîðîä, ïåðãàëîãåíàëêèë, -(CO)NR8R9, -(CO)R8, -(CO)OR8, -SO2R8, -SOR8, çàìåùåííûå èëè ...

Process for preparing thizolidine derivatives

Title compds. ≮I; R = OH, lower alkoxy, NH2, OM(M = alkli or alkali earth metal); R1 = aralkyl, phenyl, furyl, thienyl, pyridyl, naphtyl; n = 1, 2≉, useful as blood lowering agent, were prepd. by cyclization of thiazolydine carbothionic acid (II) to give III followed by hydrolysing III. Thus, Et3N was added to 2-(2-hydroxyphenyl)-4-thiazolydine carboxylic acid and the mixt. was refluxed with thionylchloride. After removing solvent, the resultant reacted with potassium bisulfide to give 2-(2-hydroxyphenyl)-4-thiazolydinecarbothionic acid.

티아졸리딘 유도체 및 이의 약학적 용도

본 발명은 하기 화학식 I의 티아졸리딘 유도체 및 이의 약학적 허용염은 강력한 DPP-IV 억제 활성을 나타내기 때문에 당뇨병의 예방, 치료제 또는 비만의 예방, 치료제 등으로서 제공할 수 있다. 화학식 I 상기 화학식에서, X는 하기 화학식 I-a 또는 화학식 I-b로부터 선택되는 치환체이고, Y는 메틸렌, 황 원자 등을 나타내고, Z는 수소 원자 또는 시아노를 나타낸다. 화학식 I-a 화학식 I-b 여기서 m은 1 또는 2의 정수를 나타내고, n은 1∼5까지의 정수를 나타내며, X'는 수소 원자 등을 나타내고, Y'는 아릴 치환 아미노기, 복소환 등을 나타내고, A는 탄소 원자 또는 질소 원자를 나타내고, Q는 아릴 등을 나타낸다.

2-thiazolidine derivatives having beta;-amino group, pharmaceutical acceptable salts and preparation process thereof

2-Thiazolidine derivatives having beta-amino group are provided to inhibit activity of DPP-IV(dipeptidyl peptidase-IV) associated with activity regulation of various hormones, so that the compounds are useful for treating diseases mediated by DPP-IV including type 2 diabetes mellitus. The 2-thiazolidine derivatives having beta-amino group represented by the formula(1) are prepared by reacting an amino acid represented by the formula(2) with 2-thiazolidine compounds represented by the formula(3) to prepare compounds represented by the formula(4), and deprotecting the compounds represented by the formula(4), wherein BOC is a protecting group; A is -NR^e(CH2)nR2 or -OR^b; R^a is hydrogen, C1-6 alkyl, C1-6 alkoxy, -OCF3, halogen, -CN or -CF3; R^b is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, isopropyl, t-butyl, -CH2CH2OH, -CH2CH2NH2, -CH2CH2N(CH2CH2)2O, -CH2CH2N(CH2CH3)2 or -CH2CH2NHCOCH3; R^c is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, benzyl, isopropyl or t-butyl; R^d and R^e are each independently hydrogen, C1-6 alkyl or C3-6 cycloalkyl; Y is carbon, oxygen, sulfur or nitrogen; Z is hydrogen, C1-6 alkyl, C3-6 cycloalkyl or -CO2R^b; and n is an integer of 0, 1 or 2.

Penicillamine production method

New polyolefin catalyst and use thereof

The method of obtaining-penicillamine

Способ получени -тиопропионами-дОВ или иХ КиСлОТНО-АддиТиВНыХСОлЕй

HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2017 123 170 A (51) МПК C07D 333/52 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2017123170, 30.11.2015 (71) Заявитель(и): Си ЭНД Си РИСЕРЧ ЛЭБОРЕТРИЗ (KR) Приоритет(ы): (30) Конвенционный приоритет: 02.12.2014 KR 10-2014-0170860 01 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 03.07.2017 KR 2015/012920 (30.11.2015) (87) Публикация заявки PCT: A WO 2016/089060 (09.06.2016) Адрес для переписки: 129090, Москва, ул. Б. Спасская, 25, стр. 3, ООО "Юридическая фирма Городисский и Партнеры" R U (57) Формула изобретения 1. Соединение, выбранное из группы, включающей гетероциклическое производное, представленное формулой (I), и его фармацевтически приемлемая соль и его стереоизомер: где один из X1, X2, X3 и X4 является -C(-Rx)=, и каждый другой независимо является -C (-Rx')= или -N=; один из Y и Z является -S- или -NH-, и другой является -CH= или -N=; Rx является ; Xs является =O или =NH; Ls является -C(-Rs')(-Rs'')- или -N(-Rs')-; Стр.: 1 A 2 0 1 7 1 2 3 1 7 0 (54) ГЕТЕРОЦИКЛИЧЕСКИЕ ПРОИЗВОДНЫЕ И ИХ ПРИМЕНЕНИЕ 2 0 1 7 1 2 3 1 7 0 (86) Заявка PCT: R U (43) Дата публикации заявки: 09.01.2019 Бюл. № (72) Автор(ы): ПАРК Чан Хее (KR), ЛИ Санг Хви (KR), ИМ Дзунхван (KR), ЛИ Соон Ок (KR), КИМ Дзонгмин (KR), КО Кванг Сеок (KR), КИМ Бьюнгхо (KR), КОНГ Миндзунг (KR), КИМ Ми Сун (KR), МООН Хиунг Дзо (KR) A 2 0 1 7 1 2 3 1 7 0 A R U 2 0 1 7 1 2 3 1 7 0 Стр.: 2 R U Rs является C1-6алкилом, галоC1-6алкилом, C1-6алкокси-C1-6алкилом, C1-6алкилкарбонил-C1-6алкилом, C2-7алкенилом, амино, аминоC1-6алкилом или 5-10членным гетероциклилом, или Rs соединен с Rs' с образованием цепи; Rs' и Rs'' каждый независимо является водородом, галогеном, C1-6алкилом, карбамоил-C1-6алкилом, C1-6алкиламино-C1-6алкилом или диC1-6алкиламино-C1-6алкилом, или Rs' и Rs'' соединены вместе с образованием цепи, или Rs' соединен с Rs с образованием цепи; Rx' каждый независимо является водородом, ...

Heterocyclic derivatives and use thereof

Изобретение относится к новым соединениям, представленным формулой (I), и их фармацевтически приемлемым солям, а также к фармацевтическим композициям на их основе, применению и способу лечения. Технический результат: получены новые соединения, обладающие ингибирующим действием на активацию белка ПСАТ3, которые могут применяться для профилактики или лечения заболеваний, связанных с активацией белка ПСАТ3. 4 н. и 9 з.п. ф-лы, 13 табл., 123 пр. РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 734 390 C2 (51) МПК C07D 333/52 (2006.01) C07D 495/04 (2006.01) A61K 31/381 (2006.01) A61P 35/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07D 333/52 (2020.08); C07D 495/04 (2020.08); A61K 31/381 (2020.08); A61P 35/00 (2020.08) (21)(22) Заявка: 2017123170, 30.11.2015 (24) Дата начала отсчета срока действия патента: Дата регистрации: 15.10.2020 02.12.2014 KR 10-2014-0170860 (43) Дата публикации заявки: 09.01.2019 Бюл. № 1 (73) Патентообладатель(и): Си ЭНД Си РИСЕРЧ ЛЭБОРЕТРИЗ (KR) (45) Опубликовано: 15.10.2020 Бюл. № 29 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 03.07.2017 KR 2015/012920 (30.11.2015) (87) Публикация заявки PCT: R U 2 7 3 4 3 9 0 WO 2016/089060 (09.06.2016) Адрес для переписки: 129090, Москва, ул. Б. Спасская, 25, стр. 3, ООО "Юридическая фирма Городисский и Партнеры" (54) ГЕТЕРОЦИКЛИЧЕСКИЕ ПРОИЗВОДНЫЕ И ИХ ПРИМЕНЕНИЕ (57) Реферат: Изобретение относится к новым соединениям, применяться для профилактики или лечения представленным формулой (I), и их заболеваний, связанных с активацией белка фармацевтически приемлемым солям, а также к ПСАТ3. 4 н. и 9 з.п. ф-лы, 13 табл., 123 пр. фармацевтическим композициям на их основе, применению и способу лечения. Технический результат: получены новые соединения, обладающие ингибирующим действием на активацию белка ПСАТ3, которые могут Стр.: 1 C 2 C 2 (86) Заявка PCT: (56) Список документов, цитированных в отчете о поиске: WO2008124000A2, 16.10.2008. ...

3,5-di-tert-butyl-4-hydroxyphenyl-substituted heterocyclic compound

Amine derivatives for the treatment of apoptosis

The present invention is related to substituted amine derivatives I notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such piperazine derivatives of carbazole. Said substituted amine derivatives are efficient modulators, in particular inhibitors, of the Bax function and/or activation. The present invention is furthermore related to novel substituted amine derivatives as well as methods of their preparation. A 1 and A 2 are selected independently from each other from the group consisting of -C(O)- and -SO 2 -. R a , R b , R 0 , R 1 and R 2 are as the application.

Apoptosis promoters

Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member.

COMPOUNDS FOR THE TREATMENT OF CANCER

Method for modification of organic molecules

The present invention is directed to a method of alkylating a thiol group (R-S-H) or seleno group (R-Se-H) in a target molecule wherein the method comprises: reacting a target molecule comprising at least one thiol group with a compound of formula (I) or (II): wherein R is an acetyl group or any other acyl group or is a group comprising any one of: or wherein R in formula (II) can also be an alkyl group; and wherein R' is selected from a group consisting of a hydrogen, a methyl group and an ethyl group.

Method of producing deoivatives of pleuromutiline or their hydrochlorides

Изобретение относитс  к полициклическим соединени м, в частности к получению производных плевромутилина ф-лы @ где R 1-C 1-C 6-аминоалкил, или их гидрохлоридов, которые про вл ют антимикробную активность. Цель - получение более активных соединений. Получение ведут реакцией соответствующего замещенного амина со сложным эфиром соединени  ф-лы HOOCR 2, где R 2-C 1-C 6-алкиламин, аминогруппа которого содержит защитные группы (такую как C(O)OC(CH 3/ 3) при комнатной температуре, после удалени  защитных групп целевой продукт выдел ют в виде основани  или его гидрохлорида. 2 табл. The invention relates to polycyclic compounds, in particular to the preparation of pleuromutilin derivatives @ where R 1 -C 1 -C 6-aminoalkyl, or their hydrochlorides, which show antimicrobial activity. The goal is to get more active compounds. The preparation is carried out by the reaction of the corresponding substituted amine with an ester of the compound f-ly HOOCR 2, where R 2 -C 1-C 6 -alkylamine, the amino group of which contains protecting groups (such as C (O) OC (CH 3/3) at room temperature , after removing the protective groups, the target product is isolated in the form of a base or its hydrochloride.

Process for preparing intermediates

本发明涉及制备中间体的方法，所述中间体可用于制备某些为肽脱甲酰基酶抑制剂的抗菌的N－甲酰基羟胺化合物。该方法利用αβ－内酰胺中间体。还要求保护某些光学纯的中间体。

Inhibitors of proteases decomposing after proline

FIELD: chemistry, pharmaceutics. SUBSTANCE: invention relates to compounds of formula 1 and their pharmaceutically acceptable salts as inhibitors of post-proline aminopepdidases, as well as to pharmaceutical composition based on them and application for manufacturing such composition, and to method of inhibition with their application. Compounds can be applied for treatment of diseases mediated by activity of post-proline aminopeptidases, such as type II diabetes and disturbed tolerance to glucose. In general formula 1 , either G 1 represents -CH 2 -X 2 -(CH 2 ) a -G 3 , and G 2 represents H, or G 2 represents -CH 2 -(CH 2 ) a -G 3 , and G 1 represents H; G 3 is selected from group according to general formula 2 , group according to general formula 3 and group according to general formula 4 ; a is 0, 1 or 2; b is 1 or 2; X 1 is selected from CH 2 , S, CF 2 , CHF and O; X 2 is selected from CH 2 ; X 3 , X 4 and X 5 are selected from N; X 6 is selected from NH; X 7 is selected from NH; R 1 is selected from H and CN; R 2 represents H; R 3 is selected from H, Cl, OH, NH 2 , NH-C 1 -C 10 alkyl and N(C 1 -C 10 alkyl) 2 ; R 4 , R 5 , R 6 , R 7 and R 8 are independently selected from H, Br, Cl, F, OH, NO 2 ; R 9 represents H; R 10 , R 11 , R 12 , R 13 and R 14 are independently selected from H, Cl and CF 3 ; R 15 and R 16 are independently selected from H, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, C 3 -C 10 cycloalkyl, C 3 -C 10 cycloalkenyl, quinoline, naphtyl and -CH 2 -L-R 17 ; R 17 is selected from C 1 -C 10 alkyl, phenyl, naphtyl, quinolinyl and indolyl; L is selected from covalent bond, CH=CH and -C 6 H 4 -; on condition that when R 15 and R 16 both represent H, and b is 1, then X 1 does not represent S or CH 2 . EFFECT: obtaining compounds that can be applied for treatment of diseases mediated by activity of post-proline aminopeptidases, such as type II diabetes and disturbed tolerance to glucose. 58 cl, 10 tbl, 1705 ex ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (11) 2 345 065 (13) C2 ( ...

Novel onium salt compound, resist composition, and pattern forming process

[해결수단] 일반식(1)로 표시되는 오늄염 화합물. (R 11 , R 22 , R 33 , R 44 , R 55 및 R 01 은 수소 원자 또는 1가 탄화수소기를 나타내고, j는 0 또는 1이다. Z + 는 일반식(a)로 표시되는 술포늄 양이온 또는 일반식(b)로 표시되는 요오도늄 양이온을 나타낸다.) (R 100 , R 200 및 R 300 은 1가 탄화수소기를 나타낸다. R 400 및 R 500 은 1가 탄화수소기를 나타낸다.) [효과] 본 발명의 레지스트 조성물에 포함되는 오늄염 화합물은, 산확산제어제로서 양호하게 기능하고, 결과적으로 MEF 및 LWR이 작으며, 초점 심도가 우수하여 고해상인 패턴 프로파일을 구축할 수 있다.

Novel alpha-amino acid compound, its preparation process and medicinal composition contaiing same

作为药物的式(I)的化合物、其可能存在的互变异构体、旋光异构体及其与药学上可接受的酸形成的加成盐：其中： 代表一个任选取代的5-元含氮杂环，Ak代表一个亚烷基链，X代表一条单键或一个亚苯基，R 1 和R 2 可以相同或不同，各自代表氢原子或烷基，R 3 代表烷基、硝基或氰基，Y代表NR 4 或CHNO 2 ，R 4 代表氢原子或烷基，其中不包括这样的化合物：其中 代表一个未取代的5-元含氮杂环，同时Ak代表基团-(CH 2 ) 3 -，同时X代表一条单键，同时Y代表NH，并且R 3 代表硝基。