Abstract: Disclosed are hydrates and polymorphs of 4-[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-benzamide, processes for preparing them and their use as pharmaceutical compositions.

Abstract: Crystalline solids A to E of biopterin are distinguished from each other by diffraction angle in an X-ray powder diffraction pattern measured using Cu—K? radiation. The crystalline solid A is characterized by strong peak at 4.6° and peaks at 13.6°, 18.1° and 27.5°; the crystalline solid B is characterized by strong peak at 4.85° and peaks at 2.4°, 13.2°, 18.1° and 27.3°; the crystalline solid C is characterized by strong peak at 5.35° and peaks at 10.8°, 21.9° and 27.3°; the crystalline solid D is characterized by strong peak at 5.1° and peaks at 2.6°, 9.2°, 13.4°, 15.4°, 18.3°, 21.8° and 27.3°; and the crystalline solid E is characterized by strong peaks at 4.5° and 5.8°, and peaks at 10.6°, 15.6°, 20.0°, 20.7°, 23.8° and 27.3°.

Abstract: The present invention provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, E1, E2, R1, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

Abstract: The invention relates to agents that contain folic acid, vitamin B6 and vitamin B12, and to the use thereof in hyperhomocysteinemia for controlling homocysteine levels. The agents are mainly suitable for the preventive and acute treatment of vascular diseases, of pregnant women and neurodegenerative diseases and are particularly advantageous in cases where the homocysteine levels to be controlled are found in an individual suffering from renal failure or being treated with immune suppressors. The invention particularly relates to pharmaceutical agents and food supplements comprising a corresponding active ingredient combination and to agents in the form of commercial packages containing corresponding combination preparations or monopreparations for the combined use.

Abstract: Compounds of formula (I) are PLK inhibitors, useful for the treatment of cell proliferative diseases: wherein R1 is hydrogen, or an optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl group; R2 is hydrogen, or an optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl group; R3 is hydrogen, —CN, hydroxyl, halogen, optionally substituted (C1C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl, —NR5R6 or C1-C4 alkoxy, wherein R5 and R6 are independently hydrogen or optionally substituted (C1-C6)alkyl; ring A is an optionally substituted mono- or bi-cyclic carbocyclic or heterocyclic ring or a ring system having up to 12 ring atoms; T is a radical of formula R-L1-Y1— wherein L1 and Y1 are as defined in the claims and R is an carbon-linked, alpha alpha disubstituted amino acid or amino acid ester residue.

Abstract: Provided herein are Heteroaryl Compounds having the following structure: wherein R1, R3, R4, L, X, Y, A and B are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.

Abstract: Dosage forms and methods of use are disclosed for a) adjuncts administered individually or simultaneously with HMg-CoA reductase inhibitors (statins) and/or selective phosphodiesterase 5 inhibitors or, b) the administration of a conjugate consisting of the adjuncts and an HMG-CoA reductase inhibitor and/or a selective phosphodiesterase 5 inhibitor. The invention is useful in the amelioration of side effects associated with HMG-CoA reductase inhibitors and will improve their effectiveness in diseases for which these are useful. The invention will also improve the effectiveness in the of selective phosphodiesterase 5 inhibitors in patients using these medications alone or in conjunction with statins, for the treatment of erectile dysfunction.

Abstract: The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same.

Abstract: This invention relates to the discovery of 3-and 5-substituted analogues of the selective platelet lowering agent anagrelide with reduced potential for cardiovascular side-effects which should lead to improved patient compliance and safety in the treatment of myeloproliferative diseases. More specifically, the present invention relates to certain imidazoquinazoline derivatives which have the general formula shown below wherein the substituents have the meanings defined in claim 1: and which have utility as platelet lowering agents in humans. The compounds of the present invention function by inhibiting megakaryocytopoeisis and hence the formation of blood platelets.

Abstract: Dihydropteridin-6-one derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.

Abstract: A cell population expressing folate receptors is selectively targeted with a folate mimetic. The folate mimetic is conjugated to a diagnostic or therapeutic agent to enable selective delivery of the agent to the targeted cell population.

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: Described herein are compositions and methods for diagnosing and/or monitoring pathogenic disease states using positron emission tomography, wherein the pathogenic cells uniquely express, preferentially express, or overexpress vitamin receptors. Also described herein are 18F conjugates of vitamins and vitamin receptor-binding analogs and derivatives.

Abstract: Disclosed are new dihydropteridinones of general formula (I) wherein the groups L and R1-R5 have the meanings given in the claims and specification, the isomers thereof, intermediates and processes for preparing these dihydropteridinones and the use thereof as pharmaceutical compositions.

Abstract: The invention provides 4,6-di- and 2,4,6-tri-substituted pteridine derivatives with a specific substitution pattern which exhibit a significant and selective activity against certain types of viral infections, in particular selectively inhibit replication of Flaviridae such as the hepatitis C virus, and are useful for the prevention and treatment of such viral infections.

Abstract: Process for the preparation of tetrahydropterin and tetrahydropterin derivatives by hydrogenating pterin and pterin derivatives with hydrogen in the presence of a hydrogenating catalyst, in which the hydrogenation is carried out in a polar reaction medium and metal complexes that are soluble in the reaction medium are employed as the hydrogenation catalysts. The process is suited to the hydrogenation, particularly asymmetric hydrogenation, of folic acid, folic acid salts, folic acid esters, folic acid ester salts or dihydroforms thereof, with the proviso that in the event of using folic acid, carboxylic acid salts thereof or dihydroforms thereof the reaction medium is aqueous, and in the event of using folic acid esters, folic acid ester salts or dihydroforms thereof the reaction medium is an alcohol. The process opens up straightforward access to achiral and chiral pterin derivatives.

Abstract: Disclosed are compounds, compositions and methods for systemic and local delivery of biologically active molecules.

Abstract: Disclosed are new dihydropteridinones of the formula (I) wherein the groups L, R1, R2, R3, R4 and R5 have the meanings provided herein, the isomers thereof, processes for preparing these dihydropteridinones and their use as pharmaceutical compositions.

Abstract: Crystal forms of (6R)-L-erythro-tetrahydrobiopterin dihydrochloride, hydrates and solvates and processes for their preparation are provided. These crystal forms are either intermediates for the preparation of stable polymorphic form B or are suitable for solid formulations.

Abstract: The present invention relates to compounds that inhibit HSP90 function, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment in warm-blooded animals such as humans of diseases such as for treatment of solid tumors.

Abstract: It is thought that applications and use of tetrahydrobiopterin (BH4), which is used as a pharmaceutical, will expand due to its superior efficacy. However, in addition to BH4 being extremely expensive, since it is unstable with respect to oxidation, applications other than pharmaceuticals are considered to be difficult. Further, it is difficult for BH4 to permeate through a blood-brain barrier, so that BH4 concentrations in the brain tend not to increase under the present conditions. Biopterins are oxidized form of BH4, stable to oxidation, easy to handle, and can be produced inexpensively. The inventors found that administration of biopterin can be expected to demonstrate effects equal to or greater than those of administration of BH4.

Abstract: Disclosed are new dihydropteridinones of general formula (I) wherein the groups L and R1-R5 have the meanings given in the claims and specification, the isomers thereof, intermediates and processes for preparing these dihydropteridinones and the use thereof as pharmaceutical compositions.

Abstract: Compound of formula (I) are inhibitors of Polo-like kinases (PLKs), and are useful in treatment of cell proliferative diseases: wherein R1 and R2 are hydrogen, or an optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl group; R3 and R3? are independently selected from hydrogen, —CN, hydroxyl, halogen, optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl, —NR5R6 or C1-C4 alkoxy, wherein R5 and R6 are independently hydrogen or optionally substituted (C1-C6)alkyl; ring A is an optionally substituted mono- or bi-cyclic carbocyclic or heterocyclic ring or a ring system having up to 12 ring atoms; T is a radical of formula R-L1-Y1— wherein R is an alpha amino acid or alpha amino acid ester motif, linked to ring A by linker R-L1-Y1— as defined in the claims.

Abstract: Disclosed are compounds that are AGT inactivators that include a folate residue, e.g., a compound of formula (I), wherein X1, X2, R1, and R2 are as described herein. Also disclosed is a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable carrier. Also disclosed are methods of enhancing the chemotherapeutic treatment of tumor cells and inactivating AGT in a tumor cell. The methods comprise, inter alia, administering a compound or pharmaceutically acceptable salt of formula (I).

Abstract: The present invention relates to novel N-sulfamoyl-piperidineamides of Formula I and their physiologically acceptable acid addition salts, to pharmaceutical compositions comprising them, processes for their preparation, and their use for the treatment of obesity and its concomitant and/or secondary diseases and related or other conditions.

Abstract: The present application discloses a compound, or enantiomers, stereoisomers, rotamers, tautomers, racemates or prodrug of said compound, or pharmaceutically acceptable salts, solvates or esters of said compound, or of said prodrug, said compound having the general structure shown in Formula 1: or a pharmaceutically acceptable salt, solvate or ester thereof, wherein the various moieties are defined herein. Also disclosed is a method of treating chemokine mediated diseases, such as, palliative therapy, curative therapy, prophylactic therapy of certain diseases and conditions such as inflammatory diseases (non-limiting example(s) include, psoriasis), autoimmune diseases (non-limiting example(s) include, rheumatoid arthritis, multiple sclerosis), graft rejection (non-limiting example(s) include, allograft rejection, xenograft rejection), infectious diseases (e.

Abstract: The present invention relates to new 2-benzylaminodihydropteridinones of general formula (I) wherein the groups R1 to R7, R10 and R11 have the meanings given in the claims and specification, the isomers thereof, methods of preparing these dihydropteridinones and their use as medicaments.

Abstract: Disclosed are processes for preparing dihydropteridinones of general formula (I) wherein the groups L and R1-R5 have the meanings given in the claims and in the specification.

Abstract: Compositions and methods for treating mitochondrial disorders are provided. The compositions include compounds having a mitochondrial targeting moiety, for example a lipophilic cation. Certain compounds are effective for increasing the ratio of phosphocreatine/creatine in a host, for example a mammal. Other compounds decrease the ratio of phophocreatine/creating in a host. An exemplary compound is defined by the following structure (Formula Ia): wherein R1 is H or phosphate and the double bond is between N1 and C1 or between N2 and C1; R2 is a mitochondrial targeting moiety; R3 an alkyl, alkylaryl, alkylheteroaryl spacer group, a cleavable linker, or absent; R4 is H or an alkyl, aryl, or heteroaryl group; and R5 is alkyl, aryl, or heteroaryl; or N1 C1, and N together form a heterocyclic ring containing at least 5 atoms, wherein N1, N3, and R1-R5 are as defined above, or N3 and R5 together form a heterocyclic ring containing at least four atoms; or a pharmaceutically acceptable salt or prodrug thereof.

Abstract: A process for the preparation of an aqueous solution of the calcium salt of (6S)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid, whereby (6S)-5,6,7,8-tetrahydrofolic acid having a content of the corresponding (6R)-diastereoisomer in the range from 4% by weight to 8% by weight is methylated in water comprises: treating the methylated reaction mixture with calcium chloride; crystallizing the calcium salt of (6RS)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid from the resulting aqueous solution; and obtaining an aqueous solution of the calcium salt of (6S)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid.

Abstract: The present invention is directed towards novel folate-conjugates of formula I wherein F is a folate or derivative thereof, Z1, Z2, Z3 are independently of each other C or N, S1 to S4 are independently of each other a single bond or a spacer, Ra, Ra?, and Rb are donor groups and/or another group F, Rc is optionally another group F and n is 1 or 2. The invention further contemplates the corresponding metal-chelate complexes as well as pharmaceutical compositions thereof, and their uses in diagnostic imaging and radiotherapy.

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: Disclosed are hydrates and polymorphs of 4-[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]Amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-benzamide: processes for preparing them and their use as pharmaceutical compositions with antiproliferative activity.

Abstract: Crystal forms of (6R)-L-erythro-tetrahydrobiopterin dihydrochloride, hydrates and solvates and processes for their preparation are provided. These crystal forms are either intermediates for the preparation of stable polymorphic form B or are suitable for solid formulations.

Abstract: Disclosed are new dihydropteridinones of the formula (I) wherein the groups L, R1, R2, R3, R4 and R5 have the meanings provided herein, the isomers thereof, processes for preparing these dihydropteridinones and their use as pharmaceutical compositions.

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 present invention discloses pteridinone derivatives for use as inhibitors of stearoyl-CoA desaturase having the structure of Formula I: The compounds are useful in treating and/or preventing various human diseases, mediated by stearoyl-CoA desaturase (SCD) enzymes, especially diseases related to abnormal lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome and the like.

Abstract: The invention relates to a method for diagnosing a kidney disease state. The method comprises the steps of administering to a patient a composition comprising a conjugate or complex of the general formula V-L-D where the group V comprises a vitamin receptor binding ligand that binds to kidney proximal tubule cells and the group D comprises a diagnostic marker, and diagnosing the kidney disease state. The invention also relates to a method for treating a kidney disease state. The method comprises the steps of administering to a patient suffering from the disease state an effective amount of a composition comprising a conjugate or complex of the general formula V-L-D where the group V comprises a vitamin receptor binding ligand that binds to kidney proximal tubule cells and the group D comprises an antigen, a cytotoxin, or a cell growth inhibitor, and eliminating the disease state.

Abstract: New compounds of Formula (1) are provided which by virtue of their pharmaceutical activity as PI3-kinase modulators may be used in the therapeutic field for the treatment of inflammatory or allergic diseases. Examples of these include inflammatory and allergic respiratory complaints, inflammatory diseases of the gastro-intestinal tract and motor apparatus, inflammatory and allergic skin diseases, inflammatory eye diseases, diseases of the nasal mucosa, inflammatory or allergic conditions involving autoimmune reactions or inflammations of the kidney.

Abstract: Crystal forms of (6R)-L-erythro-tetrahydrobiopterin dihydrochloride, hydrates and solvates and processes for their preparation are provided. These crystal forms are either intermediates for the preparation of stable polymorphic form B or are suitable for solid formulations.

Abstract: Novel substituted 1,5,7-trisubstituted-3,4-dihydro-pyrimido[4,5-d]pyrimidin-2-(1H)-one compounds and compositions, and their use in therapy as CSBP/RK/p38 kinase inhibitors.

Abstract: Novel substituted 1,5,7-trisubstituted-3,4-dihydro-pyrimido[4,5-d]pyrimidin-2-(1H)-one compounds and compositions, and their use in therapy as CSBP/RK/p38 kinase inhibitors.

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 is directed towards new 18F-folate radio-pharmaceuticals, wherein the fluorine-18 is covalently linked to the aminobenzoyl moiety, which connects the condensed pyrimidine heterocycle to the amino acid portion within folate structures, as well as their precursors and their non-radioactive references, a method of their preparation, as well as their use in diagnosis of a cell or population of cells expressing a folate-receptor and monitoring of cancer and inflammatory and autoimmune diseases and therapy thereof.

Abstract: The present invention discloses pteridinone derivatives for use as inhibitors of stearoyl-CoA desaturase having the structure of Formula I: The compounds are useful in treating and/or preventing various human diseases, mediated by stearoyl-CoA desaturase (SCD) enzymes, especially diseases related to abnormal lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome and the like.

Abstract: Disclosed herein are analogs of tetrahydrobiopterin, compositions containing the same, and methods of treating an individual suffering from a condition responsive to tetrahydrobiopterin by administration of the analog. These analogs are contemplated for use wherever tetrahydrobiopterin is currently used to treat conditions responsive to tetrahydrobiopterin therapies.

Abstract: Compounds of formula (I) are inhibitors of Polo-like kinases (PLKs), and are useful, inter alia, in the treatment of proliferative diseases: wherein R1 is hydrogen, or a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl group; R2 is hydrogen, or an optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl group; R3 and R3? are independently selected from hydrogen, —CN, hydroxyl, halogen, optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl, —NR6R7 or C1-C4 alkoxy, wherein R6 and R7 are independently hydrogen or optionally substituted (C1-C6)alkyl; ring A is an optionally substituted mono- or bi-cyclic carbocyclic or heterocyclic ring or ring system having up to 12 ring atoms; T is a radical of formula (II) R4R5CH—NH—Y-L1-X1—??(II) Wherein R4 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular esterase enzymes to a carboxylic acid group; R5 is the side chain of a natura

Abstract: Compounds of formula (I), or optionally the pharmacologically acceptable acid addition salts thereof, and their use in the inhibition of PLK activity are described.

Abstract: Disclosed are new dihydropteridinones of the formula (I) wherein the groups L, R1, R2, R3, R4 and R5 have the meanings provided herein, the isomers thereof, processes for preparing these dihydropteridinones and their use as pharmaceutical compositions.

Abstract: Disclosed are hydrates and polymorphs of 4-[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-benzamide, processes for preparing them and their use as pharmaceutical compositions.