Abstract: The present invention relates to novel lignin-derived compounds and compositions comprising the same and their use as redox flow battery electrolytes. The invention further provides a method for preparing said compounds and compositions as well as a redox flow battery comprising said compounds and compositions. Additionally, an assembly for carrying out the inventive method is provided.

Abstract: The instant invention provides photolysable compounds, and their use in reversible chemical induced dimerization and light-induced regulation of proteins.

Abstract: A method includes producing libraries of nanoparticles having highly controlled properties, which can be formed by mixing together two or more macromolecules in different ratios. One or more of the macromolecules may be a polymeric conjugate of a moiety to a biocompatible polymer. The nanoparticle may contain a drug. The moiety may include a polypeptide or a polynucleotide, such as an aptamer. The moiety may be a targeting moiety, an imaging moiety, a chelating moiety, a charged moiety, or a therapeutic moiety. Another aspect is directed to systems and methods of producing such polymeric conjugates. In some embodiments, a solution containing a polymer is contacted with a liquid, such as an immiscible liquid, to form nanoparticles containing the polymeric conjugate. Other methods use such libraries, use or administer such polymeric conjugates, or promote the use of such polymeric conjugates. Kits involving such polymeric conjugates are also described.

Abstract: The invention provides methods for attaching drugs, dyes or radiolabels to bis-MTX. This method can be used to prepare bis-MTX analogs that can be used to deliver agents, such as nanoparticles, drugs, dyes or radiolabels, to cells.

Abstract: Provided is a prodrug of 2-nitro-1-imidazolepropionic acid and a therapeutically active organic compound having on the molecule an amino group, a cyclic amino group or a hydroxyl group, particularly a prodrug in which the therapeutically active organic compound is selected from among antitumor agents. The prodrug cleaves specifically under hypoxic conditions in vivo to exhibit the inherent therapeutic activity.

Abstract: The present invention relates to diastereomers of 10-propargyl-10-deazaminopterin, compositions comprising optically pure diastereomers of 10-propargyl-10-deazaminopterin, in particular the two (R,S) diastereomers about the C10 position. Methods of preparation of these diastereomers, compositions containing them, and their use for the treatment of conditions related to inflammatory disorders and cancer are also disclosed.

Abstract: This invention relates to repeated administration of antigen-specific immunotherapeutics using protocols, or elements thereof, that do not induce immunosuppression. In some embodiments, the protocol has been previously shown not to induce immunosuppression in a subject.

Abstract: The present invention provides haloalkane substrates, and linkers for connecting such substrates to functional elements (e.g., tags, labels, surfaces, etc.). Substrates and linkers described herein find use, for example, in labeling, detection, and immobilization of proteins, cells, and molecules. In particular, the linkers provided herein find use within substrates for dehalogenase variants that form covalent bonds with their haloalkane substrates.

Abstract: Provided are modulators of TLRs of Formula II: pharmaceutically acceptable salts thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds.

Abstract: The present invention relates to dendrimer synthesis. Specifically, the present invention relates to dendrimer compositions (e.g., scaffolds) capable of copper-free click conjugation for use in the synthesis of functionalized dendrimers, and methods of use of the same.

Abstract: The present invention relates to diastereomers of 10-propargyl-10-deazaaminopterin, compositions comprising optically pure diastereomers of 10-propargyl-10-deazaaminopterin, in particular the two (R,S) diastereomers about the C10 position, specifically, diastereomers (2S)-2-[[4-[(1S)-1-[(2,4-diaminopteridin-6-yl)methyl]but-3-ynyl]benzoyl]amino]pentanedioic acid and/or (2S)-2-[[4-[(1R)-1-[(2,4-diaminopteridin-6-yl)methyl]but-3-ynyl]benzoyl]amino]pentanedioic acid. Methods of preparation of these diastereomers, compositions containing them, and their use for the treatment of conditions related to inflammatory disorders and cancer are also disclosed.

Abstract: It is discovered that sodium-channel blockers inhibit the secretion of glucagon from pancreatic alpha cells. The present disclosure, based on such discoveries, provides compositions and methods for the treatment of hyperglycemia and related diseases and conditions with Na-channel blockers.

Abstract: The present invention relates to pyrroloquinolinyl-pyrrolidine-2,5-dione compounds in combination with chemotherapeutic agents. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a pyrroloquinolinyl-pyrrole-2,5-dione compound or pyrroloquinolinyl-pyrrolidine-2,5-dione compound of the present invention and also administering a effective amount of a chemotherapeutic agent.

Abstract: Bicyclic piperazine compounds of Formula I are provided, including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Abstract: A new method for producing antifolate agents having glutamic acid part in their structure is developed by protecting carboxyl groups of glutamic acid or its N-subsituted derivatives as cyanomethyl ester to give compounds of formula (II) which are hydrolyzed under very mild conditions to afford antifolate agents in high yield with high analytical and optical purity.

Abstract: The present invention relates to diastereomers of 10-propargyl-10-deazaminopterin, compositions comprising optically pure diastereomers of 10-propargyl-10-deazaminopterin, in particular the two (R,S) diastereomers about the C10 position. Methods of preparation of these diastereomers, compositions containing them, and their use for the treatment of conditions related to inflammatory disorders and cancer are also disclosed.

Abstract: The present invention relates to inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme and their use in treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, central nervous system disorders, and diseases and conditions that are related to excessive glucocorticoids.

Abstract: There is disclosed a pharmaceutical composition comprising racemic aminopterin or pharmaceutically acceptable salts thereof. There is further disclosed a method to treat a disorder in a patient comprising administering a therapeutically effective amount of racemic aminopterin or pharmaceutically acceptable salts of racemic aminopterin. More particularly, there is disclosed a method for treating disorders modulated by at least dihydrofolate reductase activity, such as cancers and inflammatory disorders, wherein the method comprises administering to a patient in need thereof a therapeutically effective amount of racemic aminopterin or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates novel diaminopteridine derivatives, their compositions and method of treatment comprising the same for use as anti-infectives.

Abstract: Disclosed is a composition that includes a tetrahydrobiopterin in a controlled-release pharmaceutical preparation. Also disclosed is a method of treating a patient with phenylketonuria that includes administering, to the patient, a composition that contains tetrahydrobiopterin in a controlled-release pharmaceutical preparation. Also disclosed is a method of treating a patient with ADHD that includes administering a tetrahydropterin to the patient. Compositions for the treatment of ADHD are also described.

Abstract: A metal coordination complex of a biologically active moiety and a metal is disclosed. The complex confers to the biologically active moiety an improved performance which can include potency, stability, absorbability, targeted delivery, and combinations thereof.

Abstract: The present invention relates to dendrimer compositions configured for treating inflammatory disorders and autoimmune disorders, and related methods of synthesis. Specifically, the present invention relates to methods for treating rheumatoid arthritis with PAMAM dendrimers having functional ligands configured for treating rheumatoid arthritis (e.g., therapeutic agents, pro-drugs, targeting agents, trigger agents, imaging agents) (e.g., methotrexate).

Abstract: The present invention is a design and synthesis of a series of therapeutic conjugates which consists of tautomers of lipoic acid metabolites, with small molecule, vitamin, carbohydrates, peptides, chemotherapeutic agent wherein or not the conjugate possesses dual binding ability. The present invention can be used to therapeutics and diagnostics in vitro for cancer and other diseases associated with altered metabolic enzymes. The invention can also be used for the controlled release of more stable form of lipoic acid in its salt form with the minerals or vitamins.

Abstract: The present invention relates to diastereomers of 10-propargyl-10-deazaminopterin, compositions comprising optically pure diastereomers of 10-propargyl-10-deazaminopterin, in particular the two (R,S) diastereomers about the C10 position. Methods of preparation of these diastereomers, compositions containing them, and their use for the treatment of conditions related to inflammatory disorders and cancer are also disclosed.

Abstract: The present invention provides zebrafish based methods for the identification of compounds potentially useful in the treatment of motor neuron degenerative diseases (MNDDs), compounds identified by these methods and compositions, methods and medicaments for treating MNDDs.

Abstract: Lymphoma is treated using therapeutic combinations of PDX and gemcitabine by administering to a patient suffering from lymphoma a therapeutically effective amount of PDX in combination with a therapeutically effective amount of gemcitabine. The two agents can be administered together or in either order, although administration of PDX followed by gemcitabine is preferred. As in the case of MTX and Ara-C, synergism is observed, but the extent of the synergism is greater. Further, test results indicate that mechanism of action for combinations of PDX and Gem is different than for MTX and Ara-C, with more emphasis on induction of apoptosis.

Abstract: The invention relates to compounds of the formula I, or pharmaceutically acceptable salts thereof: wherein: Z=O or S; n=1-3; R3=—CO2R8, —C(O)SR8, —C(O)NHR8, —C(S)OR8, —C(S)SR8, —C(S)NHR8, —C(NH)SR8 or —C(NH)NHR8, wherein R8 is —H or alkyl; R4=—H, —CH2R5 or —CH2CH2R5, wherein R5 independently has one of the meanings of R3; B=—NR2—, —CH2NR2—, —CH2CH2NR2—, —CH2CHR7— or —CH2O—, wherein R2 is H or a C1-3 alkyl, alkenyl or alkynyl group, and R7 is H or a C1-3 alkyl or alkoxy group; wherein R1=—NH2 or —OH, and C and D are each, independently, a 5- or 6-membered, substituted or unsubstituted, aromatic or non-aromatic ring which may also contain one or more heteroatoms, and C is connected to group B in any available position.

Abstract: The processes for the preparation of alkyl derivatives of N-[4-(2,4-diaminopteridin-6-ylmethylamino)benzoyl]-N-piperidin-2-carboxylic acid and N-[4-(2,4-diaminopteridin-6-ylmethylamino)benzoyl]-N-piperidin-4-carboxylic acid and of N-[4-(2,4-diaminopteridin-6-ylmethylamino)benzoyl]-N-pyrrolidin-2-carboxylic acid and N-[4-(2,4-diaminopteridin-6-ylmethylamino)benzoyl]-N-pyrrolidin-4-carboxylic acid. Their specific properties of inhibition versus Pteridine reductase of parasitic species. The processes for the preparation of alkyl derivatives of 1[4-(quinoxalin-2-ylamino)benzoyl]piperidin-mono and di-carboxylic acid and alkyl derivatives of 1-[4-(quinoxalin-2-ylamino)benzoyl]pyrrolidin-mono and di-carboxylic acid. The specific properties of inhibition versus Pteridine reductase of parasitic species.

Abstract: The present invention relates generally to branched macromolecules bearing functional moieties. In particular, the invention relates to dendrimers, derived from lysine or lysine analogues, bearing a plurality of functional moieties. The invention further relates to the use of such macromolecules, particularly in therapeutic applications, and compositions comprising them.

Abstract: New metabolism blocked antifolates and their salts are provided along with new indications (coronary heart disease, cardiovascular diseases, stroke and termination of tubal or ectopic pregnancy) and methods (sublingual dosage forms, filmstrips or patches) for their use and delivery. Sublingual dosage forms or trans-dermal patches of metabolically blocked entities of this invention offer superior alternatives to traditional oral dosage forms to achieve greater and predictable therapeutic efficacy, lower toxicity and to overcome drug resistance by virtue of elimination of oxidative deactivation and production of toxic metabolites. Metabolism blocked antifolates bearing a fluorinated benzene ring, a thiophene ring, a pyrrole ring, a furan ring or a 8-deazapteridine ring that are provided in this invention are not previously described.

Abstract: The invention relates to compounds of formula 1 wherein R1-R2 is a guanine derivative; X is oxygen or sulfur; R3 is a heteroaromatic, unsaturated heterocyclyl or an alkynyl group with the double or triple bond connected to CH2; R4 is a linker; and L is a label, a plurality of same or different labels, a bond connecting R4 to R1 forming a cyclic substrate, or a further group —R3—CH2—X—R1-R2. The invention relates also to methods of manufacture of such novel AGT substrates, to intermediates useful in the synthesis of such AGT substrates, and to a method of transferring a label from such AGT substrates to O6-alkylguanine-DNA alkyltransferase (AGT) fusion proteins comprising proteins of interest.

Abstract: The invention relates to novel pteridines of formula (1), suitable for the treatment of airway or gastrointestinal complaints or diseases, inflammatory diseases of the joints, the skin or eyes, diseases of the peripheral or central nervous systems or cancerous diseases and pharmaceutical compositions comprising said compounds.

Abstract: There is disclosed a pharmaceutical composition comprising racemic aminopterin or pharmaceutically acceptable salts thereof. There is further disclosed a method to treat a disorder in a patient comprising administering a therapeutically effective amount of racemic aminopterin or pharmaceutically acceptable salts of racemic aminopterin. More particularly, there is disclosed a method for treating disorders modulated by at least dihydrofolate reductase activity, such as cancers and inflammatory disorders, wherein the method comprises administering to a patient in need thereof a therapeutically effective amount of racemic aminopterin or a pharmaceutically acceptable salt thereof.

Abstract: The invention relates to compounds of the formula I, or pharmaceutically acceptable salts thereof: wherein: Z=O or S; n=1?3; R3?—CO2R8, —C(O)SR8, —C(O)NHR8, —C(S)OR8, —C(S)SR8, —C(S)NHR8, —C(NH)SR8 or —C(NH)NHR8, wherein R8 is —H or alkyl; R4?.H, —CH2R5 or —CH2CH2R5, wherein R5 independently has one of the meanings of R3; B?—NR2—, —CH2NR2—, —CH2CH2NR2, —CH2CHR7— or —CH2O—, wherein R2 is H or a C1-3 alkyl, alkenyl or alkynyl group, and R7 is H or a C13 alkyl or alkoxy group; A= wherein R1?—NH2 or —OH, and C and D are each, independently, a 5- or 6-membered, substituted or unsubstituted, aromatic or non-aromatic ring which may also contain one or more heteroatoms, and C is connected to group B in any available position.

Abstract: The invention relates to new pteridine compounds of formula 1 wherein R1, R2 , R3 and R4 have the meanings given herein, which are useful for the treatment of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin or eyes, diseases of the peripheral or central nervous system, or cancers. The invention further relates to pharmaceutical compositions which contain these compounds.

Abstract: Compositions and methods and are provided for treating disorders associated with compromised vasculostasis. Invention methods and compositions are useful for treating a variety of disorders including for example, stroke, myocardial infarction, cancer, ischemia/reperfusion injury, autoimmune diseases such as rheumatoid arthritis, eye diseases such as uveitis, retinopathies or macular degeneration, macular edema or other vitreoretinal diseases, inflammatory diseases such as autoimmune diseases, vascular leakage syndrome, edema, or diseases involving leukocyte activation, transplant rejection, respiratory diseases such as asthma, adult or acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease, and the like.

Abstract: The invention relates to new pteridines which are suitable for treating respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin or eyes, diseases of the peripheral or central nervous system and cancers. This invention also relates to pharmaceutical compositions containing these compounds.

Abstract: The present invention relates to pharmaceutical compositions and their uses in therapy. In particular, the invention relates to compositions comprising methotrexate, preferably wherein the compositions are for administration via the inhaled or intranasal route.

Abstract: Concentrated methotrexate solutions are described which are suitable for the use of an active substance in the production of a parenterally administered medicament for the treatment of inflammatory autoimmune diseases. The methotrexate is added to a pharmaceutically acceptable solvent at a concentration of more than 25 mg/ml. The invention also relates to a ready-made syringe and a carpule containing such a pharmaceutical solution formulation, as well as a pen injector comprising such a carpule and/or a ready-made syringe.

Abstract: Described are new pteridine compounds of the formula 1, where the variables are as described herein. The compounds are useful for the treatment of: respiratory or gastrointestinal complaints or diseases; inflammatory diseases of the joints, skin or eyes; diseases of the peripheral or central nervous system; and cancers. Also described are pharmaceutical compositions which contain these compounds.

Abstract: Tri-substituted pteridines and tetra-substituted pteridines exhibit a significant and selective activity against certain types of viral infections, in particular they selectively inhibit the replication of the hepatitis C virus, and are useful for the prevention and treatment of such infections.

Abstract: This invention is in the field of chemical restructuring of antimetabolite agents known to have poor oral bioavailability and to cause tissue toxicity as a side effect, by producing their orotate derivatives. More particularly, it concerns orotate derivatives of the methotrexate and trimetrexate, that are found to improve the oral bioavailability and clearance compared with their respective forms—methotrexate and trimetrexate, currently in use.

Abstract: The present invention relates in a first aspect to a B-cell depleting anti-CD20 antibody or a CD20-binding antibody fragment thereof for the treatment of chronic fatigue syndrome and myalgic encephalomyelitis. In particular, the present invention relates to the use of anti-CD20 monoclonal antibodies or fragments thereof which are preferably humanized for the treatment of chronic fatigue syndrome/myalgic encephalomyelitis in a subject afflicted with said disease.

Abstract: The present invention provides a method for synthesizing 1-(acyloxy)-alkyl derivatives from 1-acyl-alkyl derivatives, which typically proceeds stereospecifically, in high yield, does not require the use of activated intermediates and/or toxic compounds and is readily amendable to scale-up. The current invention also provides 1-acyl-alkyl derivatives of known drug components and methods for synthesizing these 1-acyl-alkyl derivatives.

Abstract: The present invention relates to the area of NO synthase inhibition and, more particularly, relates to novel 4-amino-7,8-dihydropteridines, pharmaceutical compositions containing said compounds, and the use of said compounds in the treatment of a disorder characterized by a disturbed nitric oxide level.

Abstract: An object of the present invention is to provide a hyaluronic acid-methotrexate conjugate useful as a therapeutic drug for joint disorders. There is provided a hyaluronic acid-methotrexate conjugate useful for the treatment of joint disorders, wherein methotrexate is conjugated with a hydroxy group of hyaluronic acid through a linker containing a peptide chain consisting of 1 to 8 amino acids, and the linker is conjugated with the hyaluronic acid through a carbamate group.

Abstract: Pyrrolopyrimidine derivatives of the formula I in which R3, R4, R5, R6 and X are as defined in claim 1, act as phosphodiesterase VII inhibitors and can be employed for the treatment of osteoporosis, tumours, cachexia, atherosclerosis, rheumatoid arthritis, multiple sclerosis, diabetes mellitus, inflammatory processes, allergies, asthma, autoimmune diseases, myocardial diseases and AIDS.

Abstract: The invention relates to compounds of the formula I, or pharmaceutically acceptable salts thereof: wherein: Z=O or S; n=1-3; R3=—CO2R8, —C(O)SR8, —C(O)NHR8, —C(S)OR8, —C(S)SR8, —C(S)NHR8, —C(NH)SR8 or —C(NH)NHR8, wherein R8 is —H or alkyl; R4=—H, —CH2R5 or —CH2CH2R5, wherein R5 independently has one of the meanings of R3; B=—NR2—, —CH2NR2—, —CH2CH2NR2—, —CH2CHR7— or —CH2O—, wherein R2 is H or a C13 alkyl, alkenyl or alkynyl group, and R7 is H or a C1-3 alkyl or alkoxy group; wherein R1=—NH2 or —OH, and C and D are each, independently, a 5- or 6-membered, substituted or unsubstituted, aromatic or non-aromatic ring which may also contain one or more heteroatoms, and C is connected to group B in any available position.

Abstract: Oxetane-containing nucleosides, particularly non-reducing psiconucleoside oxetanes are described herein. Therapeutic application of these oxetane compounds toward the treatment of nucleoside analog related disorders such as disorders involving cellular proliferation and infection are also described.

Abstract: The present invention relates to the area of NO synthase inhibition and, more particularly, relates to novel 4-amino-7,8-dihydropteridines, pharmaceutical compositions containing said compounds, and the use of said compounds in the treatment of a disorder characterized by a disturbed nitric oxide level.