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 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 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: 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: 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: This invention relates to stable pharmaceutical compositions of 5,10-methylene-(6R)-, -(65)- or -(6R,S)-tetrahydrofolate by adjusting to a basic pH and the simultaneous use of citrate. Stabilisation is effected even in the absence of a reducing agent. The present invention is particularly suitable for producing lyophilisation solutions and lyophilisates or dry powders and dry mixtures, since the stable MTHF solutions can be used in high concentrations for filling corresponding vessels such as phials, ampoules, etc. The lyophilisates have a surprisingly long shelf life and are surprisingly stable. They can be reconstituted without problems by adding water or aqueous solutions, and the final clear injection solutions again exhibit excellent stability properties. Moreover, the present invention even makes it possible to prepare difficultly soluble calcium or acidic salts of MTHF in high concentrations and as physiologically compatible isotonic solutions.

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: An improved method of synthesis of a 9-substituted hypoxanthine derivative comprises the steps of: (1) reacting aminocyanacetamide with triethyl orthoformate to form an imidoester derivative of aminocyanacetamide; (2) forming a compound having a reactive amino group on a hydrocarbyl moiety, the hydrocarbyl moiety being linked through an amide group to a physiologically active moiety or an esterified derivative of a physiologically active moiety including therein an esterified benzoyl group; (3) reacting the imidoester with the compound having the reactive amino group on the hydrocarbyl moiety to form a derivative of aminoimidazole-4-carboxamide substituted at the 1-position with a hydrocarbyl moiety linked through an amide group to a physiologically active moiety including therein an optionally esterified benzoyl group; (4) forming the six-membered heterocyclic ring of the purine moiety of the hypoxanthine by reacting the derivative of 5-aminoimidazole-4-carboxamide formed in step (3) with triethyl orthoforma

Abstract: The invention relates to the use of at least folic acid or a folate and tetrahydrobiopterin (BH4) or derivatives thereof for treating or preventing cardiovascular or neurological disorders by modulation of the activity of nitric oxide synthase (NOS).

Abstract: Pure and extremely stable crystalline (6R)-tetrahydrofolic acids, absolutely inert even when exposed to air and elevated temperature without stabilizers being added, are prepared by a crystallization process at a pH of ≧2.

Abstract: This invention relates to stable crystalline salts of 5-methyl-(6R,S)-, -(6S)- and -(6R)-tetrahydrofolic acid, to methods of producing these salts and to the use thereof use as a constituent for the production of drugs or as a food additive, and to preparations containing these salts.

Abstract: Pure and extremely stable crystalline (6S)- and (6R)-tetrahydrofolic acids, absolutely inert even when exposed to air and elevated temperature without stabilizers being added, are prepared by a crystallization process at a pH of ≧3.5 for the preparation of crystalline (6S)-tetrahydrofolic acid and at a pH of ≧2 for the preparation of crystalline (6R)-tetrahydrofolic acid.

Abstract: This invention relates to the use of tetrahydrofolates in natural stereoisomeric form for the production of a pharmaceutical preparation suitable for influencing the homocysteine level, particularly for assisting the remethylation of homocysteine. Clinical areas of application include all anomalies of the homocysteine level, particularly the prevention and treatment of cardiovascular diseases and the prevention of neural tube deficiencies.

Abstract: This invention relates to stable crystalline salts of (6R,S)-, (6S)- and (6R)-tetrahydrofolic acid, to methods of preparing these salts and to their use as an ingredient for the production of drugs and pharmaceutical preparations.

Abstract: The invention relates to a process for preparing (6S)-folinic acid and its salts by recrystallization of alkaline-earth salts of (6R,S)-folinic acid and, where necessary, liberation of the acid from the alkaline-earth folinates and/or, where necessary, conversion into the alkali salts by at least one recrystallization in the presence of a base.The invention also relates to calcium-, magnesium-, potassium- and sodium-(6S)-folinates and to (6S)-folinic acid prepared in accordance with the invention.