Abstract: The present invention is directed to a novel methods and compositions for the therapeutic intervention in hyperphenylalaninemia. More specifically, the specification describes methods and compositions for treating various types of phenylketonurias using compositions comprising BH4. Combination therapies of BH4 and other therapeutic regimens are contemplated.

Abstract: The present invention is directed towards new 18F-folate radiopharmaceuticals, wherein fluorine-18 is covalently linked to the glutamate portion of a folate or derivative thereof, a method of their preparation, as well as their use in diagnosis and monitoring of therapy of cancer and inflammatory and autoimmune diseases.

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: 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 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: Process for the preparation of tetrahydrobiopterin from neopterin and/or 6-substituted pterins with an improved yield and a high stereoselectivity. Also disclosed herein are novel individual intermediates prepared in the preparation of tetrahydrobiopterin, such as selectively protected neopterin useful for the preparation of tetrahydrobiopterin.

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 is directed towards new 18F-folate radiopharmaceuticals, wherein fluorine-18 is covalently linked through a triazole- or tetrazole linker to a folate or derivative thereof, a method of their preparation, as well as their use in diagnosis and monitoring of therapy of cancer and inflammatory and autoimmune diseases.

Abstract: The present invention is directed towards a new method of synthesis of 18F-folate radiopharmaceuticals, wherein fluorine-18 is attached to a pteroate (or folate) or derivative thereof, through direct radiolabeling with 18[F]fluoride, as well as 18F-folate radiopharmaceuticals obtained by such method of synthesis and their use in diagnosis and monitoring of cancer therapy and therapy of inflammatory and autoimmune diseases.

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 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 is directed to a novel methods and compositions for the therapeutic intervention in hyperphenylalaninemia. More specifically, the specification describes methods and compositions for treating various types of phenylketonurias using compositions comprising BH4. Combination therapies of BH4 and other therapeutic regimens are contemplated.

Abstract: The present invention is directed to a novel methods and compositions for the therapeutic intervention in hyperphenylalaninemia. More specifically, the specification describes methods and compositions for treating various types of phenylketonurias using compositions comprising BH4. Combination therapies of BH4 and other therapeutic regimens are contemplated.

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, folio acid salts, folio acid esters, folio 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: Method for selective targeting of one or more effector moiety such as diagnostic or a therapeutic agent to a cell or population of cells expressing a folate-receptor comprising simultaneous or sequential administration of an antifolate with a folate- or pteroate-conjugate comprising said one or more effector moiety.

Abstract: Process for the preparation of tetrahydrobiopterin from neopterin and/or 6-substituted pterins with an improved yield and a high stereoselectivity. Also disclosed herein are novel individual intermediates prepared in the preparation of tetrahydrobiopterin, such as selectively protected neopterin useful for the preparation of tetrahydrobiopterin.

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: A process for preparing and concentrating (6S,?S) or (6S,?R) tetrahydrofolic acid ester salts and (6S,?S) or (6S,?R) tetrahydrofolic acid, characterized by preparing or dissolving equimolar or concentrated mixtures of diastereomers of addition salts of tetrahydrofolic acid esters with aromatic sulphonic acids in organic solvents, followed by crystallizing them at least once, and then if applicable hydrolyzing the crystallizate to produce (6S,?S) or (6S,?R) tetrahydrofolic acid, crystallizing the latter as a free acid or isolating it in the form of a salt.

Abstract: The present invention relates to substituted isoindolone derivatives of the formula I, in which R1, R2, R3, R4, R5, R6 and R7 are as defined in the claims, which are useful pharmaceutically active compounds for the therapy and prophylaxis of illnesses, for example cardiovascular diseases such as hypertension, angina pectoris, cardiac insufficiency, thromboses or atherosclerosis. The compounds of the formula I are capable of modulating the body's production of cyclic guanosine monophosphate (cGMP) and are generally suitable for the therapy and prophylaxis of illnesses which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of the formula I, to their use for the therapy and prophylaxis of the abovementioned illnesses and for preparing pharmaceuticals for these, and also pharmaceutical preparations which comprise compounds of the formula I.