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: The present invention relates to compounds and compositions for treating diseases associated with cysteine protease activity. The compounds are reversible inhibitors of cysteine proteases S, K, F, L and B. Of particular interest are diseases associated with Cathepsin K.

Abstract: The present invention relates to novel boron comprising compounds, to pharmaceutical compositions comprising said compounds, to the therapeutic use of said compounds, and to a process for preparation of said compounds. The compounds are useful in boron neutron capture therapy (BNCT).

Abstract: This invention provides a process for efficient production of folic acid derivatives suitable for forming conjugates of anticancer drug with folic acid. It discloses a process comprising a step of reacting 2-amino-protected pteroylimidazole with ?-lower alkyl glutamate; and a step of reacting the resulting product with an amino compound having a reactive group which is readily reactable with a functional group of the drug.

Abstract: The present disclosure provides a method that efficiently produces (6R)-tetrahydrobiopterin in high yield and purity. The method includes the step of hydrolyzing diacetylbiopterin to biopterin under basic conditions in a biphasic mixture comprising an organic phase and an aqueous phase. After substantially complete hydrolysis of diacetylbiopterin, the aqueous phase containing biopterin can be separated from the organic phase containing most of the organic impurities, which avoids the time-consuming step of isolating biopterin as a solid. The aqueous solution containing biopterin is stereoselectively hydrogenated to (6R)-tetrahydrobiopterin under basic conditions and high hydrogen pressure in the presence of a metal catalyst (e.g., a platinum catalyst). To improve the purification of an acid addition salt of (6R)-tetrahydrobiopterin (e.g., (6R)-tetrahydrobiopterin dihydrochloride), any residual salts (e.g.

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: The present invention relates to the use of pteridines as inhibitors of HCV replication as well as their use in pharmaceutical compositions aimed to treat or combat HCV infections. In addition, the present invention relates to compounds per se and their use as medicines. The present invention also concerns processes for the preparation of such compounds, pharmaceutical compositions comprising them, and combinations of said compounds with other anti-HCV agents.

Abstract: Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of modulation of TGR5 activity in a human or animal subject are also provided for the treatment diseases mediated by TGR5.

Abstract: This invention relates to a group of trisubstituted and tetrasubstituted pteridine derivatives, their pharmaceutically acceptable salts, N-oxides, solvates, dihydro- and tetrahydro-derivatives and enantiomers, possessing unexpectedly desirable pharmaceutical properties, in particular which are highly active immunosuppressive agents, and as such are useful in the treatment in transplant rejection and/or in the treatment of certain inflammatory diseases. These compounds are also useful in preventing or treating cardiovascular disorders, allergic conditions, disorders of the central nervous system and cell proliferative disorders.

Abstract: The present invention relates to a specific salt of a dihydropteridione derivative, namely the trihydrochloride salt of the compound 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 its crystallisation in the form of an hydrate with water, to a process for the manufacture thereof, and to the use thereof in a pharmaceutical composition.

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 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: 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: The present invention is directed compounds for reversibly modification of biologically active molecules. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of reversible modification provides for physiologically responsive activity modulation.

Abstract: The present invention relates to a specific salt of a dihydropteridione derivative, namely the trihydrochloride salt of the compound 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 its crystallisation in the form of an hydrate with water, to a process for the manufacture thereof, and to the use thereof in a pharmaceutical composition.

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 provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders than involve abnormal activation of the Abl, Bcr-abl, Bmx, c-RAF, CSK, Fes, FGFR3, Flt3, GSK3?, IR, JNK1? 1, JNK2? 2, Lck, MKK4, MKK6, p70S6K, PDGFR?, Rsk1, SAPK2?, SAPK2?, Syk and Trk? kinases.

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: 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 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 tumours.

Abstract: Disclosed are new dihydropteridinones of general formula (I) whereby the groups L, R1, R2, R3, R4 and R5 have the meanings given in the claims and specification, the isomers thereof, processes for preparing these dihydropteridinones and their use as pharmaceutical compositions.

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: Provided herein is dipterinyl calcium pentahydrate (DCP) and therapeutic methods based thereon. Also provided herein is the compound dipterinyl calcium pentahydrate (DCP) or an analog or polymorph thereof.

Abstract: The inventive method for the production of crystalline (6RS)-N(5)-formyl-5,6,7,8-tetrahydrofolic acid or amorphic (6S)-N(5)-formyl-5,6,7,8-tetrahydrofolic acid is characterized in that an aqueous solution of (6RS)- or (6S)-calcium folinate, which has a temperature of 40° C. to 50° C., and an aqueous solution of hydrochloric acid or acetic acid are added to stirred water having a temperature of 2° C. to 12° C., such that the temperature is kept at 2° C. to 12° C. in the mixture thus obtained when the two above-mentioned solutions are added and the pH value is kept at 2,5 to 3,5, the solid thus arising is isolated by means of filtration or centrifugation, the solid is initially washed with cold water and then with an aqueous organic solvent, and the washed solid, i.e. crystalline (6RS)-N(5)-formyl-5,6,7,8-tetrahydrofolic acid or amorphous (6S)-N(5)-formyl-5,6,7,8-tetrahydrofolic acid is dried at reduced pressure and obtained.

Abstract: Disclosed are new dihydropteridinones of general formula (I) wherein the groups R1 to R5, Ra to Rc, W, Q1 and Q2 have the meanings given in the claims and specification, the isomers thereof and the use thereof for preparing a pharmaceutical composition for the treatment of diseases characterised by excessive or abnormal cell proliferation.

Abstract: Disclosed are new dihydropteridinones of general formula (I) whereby the groups L, R1, R2, R3, R4 and R5 have the meanings given in the claims and specification, the isomers thereof, processes for preparing these dihydropteridinones and their use as pharmaceutical compositions.

Abstract: This invention relates to a group of trisubstituted and tetrasubstituted pteridine derivatives, having the formula: wherein X represents an oxygen atom or a group with the formula NZ and wherein: R1 C1-7 alkyl or arylalkyl; Z is a group independently defined as R1 or the group NZ together with R1 is an optionally substituted heterocyclic group containing at least one nitrogen atom; R2 is amino or acylamino; R4 is an atom or a group selected from the group consisting of hydrogen; C1-7 alkyl; and C1-7 alkoxy; and R3 is an atom or a group selected from the group consisting of aryl optionally substituted with one or more substituents selected from the group consisting of halogen, C1-7 alkyl, and C1-7 alkoxy, their pharmaceutically acceptable salts, and enantiomers, possessing unexpectedly desirable pharmaceutical properties, in particular which are highly active immunosuppressive agents, and being useful in the treatment in transplant rejection, certain inflammatory diseases, cardiovascular disorders, allergi

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: Quinazoline derivatives have the formula: or the pharmaceutically acceptable salts thereof; wherein each of Z5, Z6, Z7 and Z8 is N or CH and wherein one or two Z5, Z6, Z7 and Z8 are N and wherein two adjacent Z positions cannot be N; wherein m and n are each independently 0–3; wherein R1 is independently OH, SH, NH2, OR, SR, NHR, halo or R-halide; wherein two adjacent R1 groups may be joined to form an aliphatic hetero cycle ring of 5–6 members; wherein R2 is independently R, halo, R-halide, OR-halide, NH2, CONH2 or CONHR; wherein R is optionally substituted C1–C12 alkyl, C1–C12 alkenyl, C1–C12 alkynyl, or aryl C1–C12 alkyl, containing 0–4 heteroatoms in place of a carbon in the carbon backbone, where the optional substituents are ?O, ?N, or OH; and wherein R3 is H or CH3. Such compounds are useful in pharmaceutical compositions and methods of treating conditions characterized by enhanced TGF? activity.

Abstract: New process for the production of (6S)-5,6,7,8-tetrahydrofolic acid or derivatives thereof starting from the corresponding (6S, 6R) racemic mixture. The procedure comprises in the steps of adding an organic acid to a non-alkaline suspension of (6S,6R)-5,6,7,8-tetraydrofolic acid, up to a pH value in the range of 1 to 3; heating the suspension from 30° to 80° C.; cooling the suspension from 20° to 60° C., with selective crystallization of the (6S)-isomer. The procedure gives the (6S)-isomer in high yields and with a high degree of stereoselectivity. It follows that the synthetic access to a large number of pharmacologically active stereoisomers of folic acid is simpler and more-effective.

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: The present invention provides the compound having the formula: wherein each of R1 and R2 is, substituted or unsubstituted, aryl, cycloalkyl, cycloalkylamino, naphtha, pyridineamino, piperidino, t-butyl, aryloxy, arylalkyloxy, or pyridine group; wherein A is an amido moiety, —O—, —S—, —NH—, or —CH2—; and wherein n is an integer from 3 to 8. The present invention also provides a method of selectively inducing growth arrest, terminal differentiation and/or apoptosis of neoplastic cells and thereby inhibiting proliferation of such cells. Moreover, the present invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically acceptable amount of the compound above.

Abstract: This invention describes novel triazole compounds of formula IX: wherein Z1 is nitrogen or CR9 and Z2 is nitrogen or CH, provided that at least one of Z1 and Z2 is nitrogen; G is Ring C or Ring D; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from —R1; Ring D is a 5–7 membered monocyclic ring or 8–10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with their intervening atoms to form a fused ring; R1, R3, and T are as described in the specification. The compounds are useful as protein kinase inhibitors, especially as inhibitors of GSK-3 and Aurora, for treating diseases such as diabetes, cancer, and Alzheimer's disease.

Abstract: A reactive oxygen generating enzyme inhibitor with NO donor bioactivity, e.g., nitrated allopurinol, e.g., 1,5-bis(3-nitrooxypropyyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one is useful to treat heart failure, stable angina, ischemic disorder, ischemic reperfusion injury, atherosclerosis, sickle cell disease, diabetes, Alzheimer's disease, Parkinson's disease, ALS and asthma and to obtain proper contraction of heart, skeletal and smooth muscle. Where the disorder is heart failure, administration of the enzyme inhibitor mediates amelioration of acute coronary symptoms and/or myocardial infarction.

Abstract: The invention provides certain thiazolopyrimidine compounds of formula (I) or a pharmaceutically acceptable salt or solvate thereof: in which: A is a group of formula (a) or (b): processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy

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: The invention provides pteridine compounds of formula (I), processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy. Formula (I) in which A is a group of formula (a) or (b).

Abstract: The present invention relates to 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, processes for preparing these dihydropteridinones and the use thereof as pharmaceutical compositions.

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 the use of pteridine derivatives of the formula I in which X is O or NH and R4, for example, is hydrogen, phenyl or the radical R4a—CH2— and R4a, for example, is hydrogen, (C1-C4)-alkylmercapto, the radical —NR11R12 or the radical —OR13, and in which R1, R2, R3, R5, R6, R7, R11, R12 and R13 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: The present invention relates to the preparation of substantially pure diastereoisomers of derivatives of tetrahydrofolate and the use of such diastereoisomers. More particularly the present invention provides a process for the preparation of a desired substantially pure (6R or 6S) diastereoisomer of a derivative of tetrahydrofolic acid or salt or ester. The process comprises the steps of: attaching a chiral auxiliary group at either N-5 or N-10 of a mixture of 6R and 6S diastereoisomers of tetrahydrofolic acid, separating the new diastereoisomers, recovering the desired new diastereoisomer (6R or 6S) corresponding to the desired (6R or 6S) diastereoisomer, and converting the substantially pure new diastereoisomer recovered into the corresponding diastereoisomer.

Abstract: The present invention provides substituted 2-aminopyridines of formula I, wherein R1, A1, W, X, and Y are as defined in the specification, useful in treating cell proliferative disorders.

Abstract: The present invention pertains to compounds effective at modulating (inhibiting or enhancing) RNA interference in a cell or organism. Featured compounds are set forth and exemplified herein. Therapeutic methods and pharmaceutical compositions featuring the compounds are also provided. The invention further pertains to knock-out or knock-down cells and organisms including the compounds, and methods of analysis of gene expression profiles and proteomes.

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

Abstract: A compound of the formula: [wherein R1 is a hydrocarbon group which may be substituted; R2 is a cyclic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; R3 is halogen atoms, a carbamoyl group which may be substituted, a sulfamoyl group which may be substituted, an acyl group derived from sulfonic acid, a C1-4 alkyl group which may be substituted, a C1-4 alkoxy group which may be substituted, an amino group which may be substituted, a nitro group or a cyano group; R4 is hydrogen atoms or a hydroxy group; n is 0 or 1; and p is 0 or 1 to 4]; or a salt thereof, has potent CCR5 antagonistic activity and can be advantageously used as a medicament for inhibition of HIV infection to human peripheral blood mononuclear cells, especially for the treatment or prevention of AIDS.

Abstract: This invention concerns a bicyclic compound of Formula (I), wherein: G is N, CH or C(CN); ring X is a 5- or 6-membered fused heteroaryl ring which contains 1, 2, or 3 heteroatoms selected from oxygen, sulphur and nitrogen; m is 0-2; R1 is a group such as hydroxy, halo, trifluoromethyl, cyano, mercapto, nitro, amino, carboxy and carbamoyl; each of R2 and R3 is hydrogen, halo, C1-6alkyl, C2-6alkenyl or C2-6 alkynyl; R4 is a group such as hydrogen, hydroxy, C1-6alkyl, C1-6alkoxy, amino and N-C1-6alkylamino; R5 is a group such as hydrogen, halo, trifluoromethyl, cyano, nitro, amino and hydroxy, and q is 0-4; or a pharmaceutically acceptable salt or an in vivo cleavable ester thereof; processes for its preparation, a pharmaceutical composition containing it and its use in the treatment of diseases or medical conditions mediated by cytokines.

Abstract: The present invention relates to compounds of formula (I), in which B, D, E, G, X, Y, Z, R1, R2 and s have the meanings indicated in the claims, their physiologically tolerable salts and their prodrugs. The compounds of formula (I) are valuable pharmacologically active compounds. They are vitronectin receptor antagonist and inhibitors of cell adhesion and are suitable for the therapy and prophylaxis of illnesses which are based on the interaction between vitronectin receptors and their ligands in cell-cell or cell-matrix interaction processes or which can be prevented, alleviated or cured by influencing such interactions. For example, they can be applied for inhibiting bone resorption by osteoclasts and thus for treating and preventing osteoporosis, or for inhibiting undesired angiogenesis or prolifertion of cells of the vascular smooth musculature.

Abstract: Pteridine compounds of formula (I) in which R1, R2, R3 and R4 are as specified in the claims, 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: Squaric acid derivatives of formula (1) are described: wherein Het is an optionally substituted bicyclic fused ring heteroaromatic group; L2 is a covalent bond or an atom or group —O—, —S—, —C(O)—, —C(S)—, —S(O)—, —S(O)2, —N(R8)— or —C(R8)(R8a)—; Ar2 is an optionally substituted aromatic or heteroaromatic group; Alk is a chain  in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof; R1 is a hydrogen atom or a C1-6alkyl group; L1 is a covalent bond or a linker atom or group; Alk1 is an optionally substituted aliphatic chain; n is zero or the integer 1; R2 is a hydrogen atom or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic, polycycloalphatic, heteropolycycloaliphatic, aromatic or heteroaromatic group other than a 2,6-naphthyridin-1-yl, isoquinolin-1-yl, 2,7-naphthyridin-1-yl or quinazolin-4-yl group; and the salt

Abstract: The invention relates to conjugates comprising a D-enantiomer of a folic acid antagonist and a carrier. Furthermore, the invention relates to the production of such conjugates as well as their use.