Abstract: The present invention is directed towards new 18F-folate radiopharmaceuticals, 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 provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, X, R1, R2, R3, R4, R5 and R6, 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 present disclosure is generally related to methods of preventing oxidative stress injury induced by renal ischemia-reperfusion by a Folate-TEMPOL conjugate.

Abstract: The present invention relates to a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same; and a method for treating or preventing autoimmunity disease using the same.

Abstract: Particles, including nanoparticles and microparticles, and pharmaceutical formulations thereof, containing conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety via a linker have been designed which can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.

Abstract: The present invention relates to a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same; and a method for treating or preventing autoimmunity disease using the same.

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: A method of preparing a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof, wherein the variables of Structural Formula (I) are as described in the specification and claims. Additionally, the present invention relates to compounds of Structural Formula (I), which are useful as inhibitors of protein kinase.

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 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 relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

Abstract: The present disclosure relates to 1- or 2-(4-(aryloxy)-phenyl)ethylamino-, oxy- or sulfanyl)pteridines and 1- or 2-(4-(heteroaryloxy)-phenyl)ethylamino-, oxy- or sulfanyl)pteridines and their use as agrochemicals and animal health products.

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 present invention relates to a crystalline form a dihydropteridione derivative, namely a crystalline form of the free base N-[trans-4-[4-(cyclopropylmethyl)-1-piperazinyl]cyclohexyl]-4-[[(7R)-7-ethyl-5,6,7,8-tetrahydro-5-methyl-8-(1-methylethyl)-6-oxo-2-pteridinyl]amino]-3-methoxy-benzamide, to a process for the manufacture thereof, and to the use thereof in a pharmaceutical composition.

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 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: To provide a method for producing L-biopterin on a large industrial scale by using a reagent which is inexpensive and easy to handle, without requiring a use of any particular equipment or plants. A method for porducing a biopterin derivative represented by the formula (6): wherein R1 and R2, which are the same or different from each other, each represents a hydrogen atom, an alkyl group, or an aryl group, comprising: reacting a compound belonging to triacetoxy-5-deoxy-L-arabinose phenylhydrazones represented by the formula (4): wherein R1 and R2 are the same as defined above, with 6-hydroxy-2,4,5-triaminopyrimidine (5) under catalytic influence of a Lewis acid in an aqueous solvent.

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: Disclosed are 6-formyl-tetrahydropteridines of the formula (I) wherein the groups R1 to R6 have the meanings given in the claims and specification, the isomers thereof, methods of preparing these 6-formyl-tetrahydropteridines and their use as medicaments.

Abstract: Disclosed are compounds of Formulae (Ia), (Ib), (Ic), (Id) wherein: W is NH, S, SO, or SO2; R2 is (un)substituted aryl, (un)substituted heteroaryl, or (un)substituted carbocycle or heterocycle; Q is hydrogen or lower alkyl; R4 and R6 are the same or different and represent hydrogen, halogen, lower alkyl, lower alkoxy, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted arylalkyl or (un)substituted heteroarylalkyl; and R8 is hydrogen, lower alkyl or an (un)substituted carbocyclic group containing from 3–7 members, up to two of which members are optionally hetero atoms selected from oxygen and nitrogen; or R8 is (un)substituted aryl, (un)substituted heteroaryl, (un)substituted arylalkyl or (un)substituted heteroarylalkyl. These compounds are useful for treating cell proliferative disorders, such as cancer and restenosis. These compounds are potent inhibitors of cyclin-dependent kinases (cdks) and growth factor-mediated kinases.

Abstract: This invention features conjugates, compositions, methods of synthesis, and applications thereof, including folate derived conjugates of nucleosides, nucleotides, non-nucleosides, and nucleic acids including enzymatic nucleic acids and antisense nucleic acid molecules.

Abstract: Pteridine compounds of formula (I) processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in the treatment of inflammatory diseases such as psoriasis, rheumatoid arthritis, diseases in which angiogenesis is assocated with raised CXCR2 chemokine levels (diabetic retinopathy) and COPD. The compounds are ligands for chemokine receptors and medical indications mentioned in the description include: diseases of the respiratory tract (COPDD, asthma, bronchitis, rhinitis, fibroid lung, pneumonia, etc.), diseases of the bones and joints (arthritis, etc.), skin-diseases (psoriasis, etc), diseases of the gastrointestinal tract, diseases in other tissues and systemic disease (multipe sclerosis, atherosclerosis, AIDS, type 1 diabetes, leprosy, sepsis, etc.), allograft rejection, cancers, cystic fibrosis, stroke, burn wounds, skin ulcers, reproductive disease and more.

Abstract: The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula I: or pharmaceutically acceptable salt forms thereof, wherein rings D-E represent guanidine mimics, which are useful as inhibitors of factor Xa.

Abstract: Disclosed are novel piperazine derivatives, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction.

Abstract: The present invention relates to new dihydropteridinones of the formula (I) 1

Abstract: This invention is related to carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones represented by Formula I: 1

Abstract: This invention provides compounds of formula 1, having the structure which are useful as inhibitors of protein tyrosine kinase and are antiproliferative agents.

Abstract: This invention relates to certain cyclic amine derivatives of Formula (I) 1

Abstract: The invention provides compounds of Formula (I): 1

Abstract: The present invention provides compounds of the formula: 1

Abstract: A compound of formula (I) (wherein R1 is a hydrogen atom, a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, R2 is a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, or R1 and R2 may combine to each other together with A to form a heterocyclic group which may be substituted; A is N or N+—R5.

Abstract: The present invention provides compounds having formula (I): 1

Abstract: This invention features conjugates, compositions, methods of synthesis, and applications thereof, including folate derived conjugates of nucleosides, nucleotides, non-nucleosides, and nucleic acids including enzymatic nucleic acids and antisense nucleic acid molecules.

Abstract: One aspect of the present invention relates to novel heterocyclic compounds. A second aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for various cellular receptors, including opiate receptors, other G-protein-coupled receptors, and ion channels. An additional aspect of the present invention relates to the use of the novel heterocyclic compounds as analgesics.

Abstract: There are provided novel compounds of formula (I), wherein R1, R2, X, Y, V, W and Z are as defined in the specification, and pharmaceutically acceptable salts thereof, and enantiomers and racemates thereof; together with processes for their preparation, compositions containing them and their use in therapy. The compounds are inhibitors of nitric oxide synthase and are thereby particularly useful in the treatment or prophylaxis of inflammatory disease and pain.

Abstract: The present invention relates to specific photochromic h-annellated benzo[f]chromene derivatives and their use in synthetic resins of all types, especially for ophthalmic applications. In particular, the present invention relates to photochromic compounds derived from benzo[f]chromenes, which in the open form have especially long-wave absorption maxima making it possible to obtain violet to blue tints when used in phototropic glasses.

Abstract: Described are compounds having the formula:

Abstract: This invention is directed to the novel composition of matter trimetrexate ascorbate, to compositions comprising trimetrexate ascorbate, and to compositions comprising trimetrexate and ascorbic acid. These compositions are useful in the treatment of diseases in mammals such as, but not limited to, cancer, bacterial and protozoal infections, malaria, psoriasis, and rheumatoid arthritis. The invention is further related to methods of stabilizing trimetrexate to degradation caused by heat, light, oxygen, or water.

Abstract: Highly purified 10-propargyl-10-deazaaminopterin (10-propargyl-10dAM) compositions tested in xenograft models for their efficacy against human tumors are shown to be far superior to methotrexate ("MTX") and are even superior to the newer clinical candidate edatrexate ("EDX"). Moreover, 10-propragyl-10dAM showed a surprising ability to cure tumors such that there was no evidence of tumor growth several weeks after the cessation of therapy. Thus, highly purified compositions containing 10-propargyl-10dAM can be used to treat human tumors, particularly human mammary tumors and human lung cancer.

Abstract: A quinazolinone derivative or a salt thereof expressed by the following Formula (I); ##STR1## wherein each of A and B is R.sup.1 or --(CH.sub.2).sub.n -NR.sup.2 R.sup.3 ; wherein R.sup.1 represents a hydrocarbon group of C.sub.10-30 ; wherein R.sup.2 and R.sup.3 individually represent a hydrogen atom, a lower alkyl group, a phenyl group, or a benzyl group, or together represent a heterocyclic ring having 3-7 members; and n represents an integer of 1-5; wherein when A is R.sup.1, B is --(CH.sub.2).sub.n -NR.sup.2 R.sup.3 and when A is --(CH.sub.2).sub.n -NR.sup.2 R.sup.3, B is R.sup.1 ; and wherein R.sup.4 is selected from the group consisting of a hydrogen atom, a halogen atom, a lower alkyl group, a lower acyl group, a nitro group, a cyano group, an amino group, a lower alkoxycarbonyl group, a lower alkylamino group, a lower alkoxy group, a lower acyloxy group, a carbamoyl group, a lower alkylcarbamoyl group, and a lower acylamino group.

Abstract: The present invention relates to the use of pteridine derivatives of the formula I ##STR1## in which X is O, NH or N--(C.sub.1-C.sub.5)-alkanoyl, R.sup.3 is the radical --OR.sup.4, --NR.sup.5 R.sup.6 or --S(O).sub.m R.sup.7, and R, R.sup.1, R.sup.2, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and m have the meanings given in claim 1, which are nitric oxide synthase inhibitors, for the treatment of diseases which are caused by an increased nitric oxide level.

Abstract: Inhibitor of the use of tetrahydrobiopterin as a cofactor for nitric oxide synthase, e.g., substituted 4-phenyl(hydropyridines) such as 1-methyl-4-(3',4'-dihydroxyphenyl)-1,2,3,6-tetrahydropyridine or, 4-(3',4'-dihydroxyphenyl)-1,2,3,6-tetrahydropyridine) or tetrahydropterin analog which does not replace tetrahydrobiopterin as a substrate for nitric oxide synthase such as (6R,S)-6,7-dimethyl-tetrahydropterin or (6R,S)-tetrahydrofolic acid or 2,4-diamino-, 2,6-diamino, or 4,6-diamino mono- or disubstituted pyrimidines or the corresponding pyrimidine-3-oxides such as 2,4-diamino-6-(diethylamino)pyrimidine, 2,4-diamino-6-piperidino-pyrimidine-3-oxide, 2,4-diamino-6-hydroxypyrimidine, 4,6-diamino-2-hydroxypyrimidine or 2,5-diamino-4,6-dihydroxypyrimidine is administered to inhibit nitric oxide synthesis from arginine in vascular cells in a subject in need of such inhibition (e.g., for prophylaxis or treatment of cytokine- or endotoxin-induced hypotension (e.g., septic shock).

Abstract: Novel quinazolinone derivatives with good binding affinity for the CCK-A and CCK-B receptors, pharmaceutical compositions containing them, methods of using them and a novel process for their preparation are taught. The compounds are useful agents to suppress appetite, reduce gastric acid secretion, and the like.

Abstract: Compounds of general formula I and their salts and solvates are antifungal agents and as such are useful in the treatment of various fungal infections. Pharmaceutical compositions including these compounds and processes for their preparation are also provided.

Abstract: This invention is directed to bicyclic pyrimidine derivatives which are useful as anti-coagulants. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat disease-states characterized by thrombotic activity.

Abstract: 3,4,N-triaryl-4,5-dihydro-1H-pyrazole-1-carboxamide compounds having an aryl moiety in the 4-position that is an optionally substituted pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or quinolinyl moiety and aryl moieties in the 3-position and the N-position that are optionally substituted phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or quinolinyl moieties, such as N-(4-chlorophenyl)-4,5-dihydro-3-(4-fluorophenyl)-4-(5-trifluoromethyl-2-p yridinyl)-1H-pyrazole-1-carboxamide, were prepared and found to possess insecticidal utility. 1,2-Diarylethanone compounds were converted to 1,2-diaryl-2-propen-1-one compounds by treatment with bis(dimethylamino)methane, the 1,2-diaryl-2-propen-1-one compounds were converted to 3,4-diaryl-4,5-dihydro-1H-pyrazole compounds by treatment with hydrazine, and the 3,4-diaryl-4,5-dihydro-1H-pyrazole compounds were converted to the insecticidal subject compounds by treatment with an aryl isocyanate.

Abstract: The present invention provides compounds of the formula ##STR1## chelated with a paramagnetic metal ion wherein Z1 and Z2 each represent the atoms necessary to complete a monocyclic or polycyclic carbocyclic or heterocyclic ring system, said Z1 and Z2 independently optionally substituted with R.sup.6 and R.sup.7, respectively;R.sup.l, R.sup.2, R.sup.3 and R.sup.4 are independently carboxyalkyl (C.sub.1 -C.sub.2), --(CH.sub.2).sub.n --C(.dbd.O)--NH--R.sup.8, or --(CH.sub.2).sub.n --C(.dbd.O)--O--R.sup.8R.sup.5 is carboxyalkyl (C.sub.1 -C.sub.2);R.sup.6 and R.sup.7 are independently hydrogen, benzyl, or benzyloxy, said benzyl or benzyloxy optionally substituted with one, two or three substituents selected from the group consisting of amino, isocyanato (--N.dbd.C.dbd.O), isothiocyanato (--N.dbd.C.dbd.S), --NH--C(.dbd.O)--X or --NH--C(.dbd.S)--X;R.sup.8 is alkyl (C.sub.1 -C.sub.20), --(CH.sub.2).sub.m --Ar, or polyhydroxyalkyl (C.sub.1 -C.sub.

Abstract: Process for the preparation of the optically active [6(S)(-)]N.sup.5 alkaline earth metal salts of methyltetrahydrofolic acid and formyltetrahydrofolic acid wherein an aqueous solution of folic acid is hydrogenated with a high stoichiometric excess of sodium borohydride followed by treating the reaction product with formic aldehyde and optionally further with sodium borohydride when the methyl derivative is desired. Reaction with a salt of the alkaline earth metal precipitates the desired optically active alkaline earth metal salt.

Abstract: This invention relates to certain conjugates of folates and antifolates with difluoroglutamic acid which are useful in the treatment of patients suffering from certain neoplastic diseases including leukemia, melanomas, carcinomas, sarcomas and mixed neoplasias.

Abstract: Intermediates and a process for the synthesis of 6-monosubstituted tetrahydropteridine C6-stereoisomers, including (6S)-tetrahydrofolic acid. The intermediates are shown in their two enantiomeric forms as follows: ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and represent hydrogen, methyl, hydroxy, amino, alkyl or dialkylamino, alkoxy, benzyloxy, or benzylthio; R.sub.3 represents an alkene, alkyne, cycloalkyl, benzyl, alkyl (substituted with hydroxy, acetoxy, benzyloxy, alkoxy, alkylthio, amino, carboxy, oxo, or phosphate), a protected aldehyde, or ##STR2## wherein n=1 or 2, R.sub.4 is hydrogen, formyl, methyl, or propargyl, and ZZ represents an amino acid or amino acid polymer. Also, a process for tetrahydropteridine N5-formylation for the preparation of, for example, N5-formyl-(6S)-tetrahydrofolic acid.