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Inventi Impact - Med Chem

Patent Watch

  • Phenyl-substituted pyrimidine compounds useful as kinase inhibitors

    Compounds having the formula (I), ##STR00001## and pharmaceutically acceptable salts, and solvates thereof, are useful as kinase inhibitors, wherein: two of X.sub.1, X.sub.2, and X.sub.3 are N, and the remaining one of X.sub.1, X.sub.2, and X.sub.3 is --CR.sub.1; R.sub.1 is hydrogen or --CN; and N, G, Z, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are described in the specification. Also disclosed are pharmaceutical compositions containing compounds of formula (I), and methods of treating conditions associated with the activity of p38 kinase and/or conditions associated with the activity of LIM kinase.

  • Benzooxazoles as orexin antagonists

    The present invention is concerned with novel sulfonamides of formula I ##STR00001## wherein R.sup.1, R.sup.2, Ar, Hetaryl, m and n are as described in the description and claims. The compounds are orexin receptor antagonists, useful in the treatment of disorders, in which orexin pathways are involved.

  • Aromatic compounds and their use in medical applications

    Pharmaceutical compositions comprising at least one compound of the formulas (Ia) or (Ib) and a pharmaceutically acceptable carrier ##STR00001## wherein the symbols have the following meaning --X-- is e.g. ##STR00002## and Y being e.g. ##STR00003## or the pharmaceutically acceptable salts can be applied to modulate the in-vitro and in-vivo binding processes mediated by E-, P- or L-selectin binding.

  • Aromatic compounds and their use in medical applications

    Pharmaceutical compositions comprising at least one compound of the formulas (Ia) or (Ib) and a pharmaceutically acceptable carrier ##STR00001## wherein the symbols have the following meaning --X-- is e.g. ##STR00002## and Y being e.g. ##STR00003## or the pharmaceutically acceptable salts can be applied to modulate the in-vitro and in-vivo binding processes mediated by E-, P- or L-selectin binding.

  • Peptidomimetic inhibitors of PSMA, compounds comprising them, and methods of use

    Compounds of the formula, A--L--B, wherein A is glutamate or a glutamate analog; L is a phosphoramidate or a phosphoramidate analog; and B is serine or a serine analog are described which are potent inhibitors of prostate-specific membrane antigen (PMSA). Such compounds are useful in treatment of prostate cancer; and when chemically attached to a fluorescent dye, can efficiently and selectively label prostate cancer cells for fluorescent imaging.

  • Tricyclic inhibitors of 5-lipoxygenase

    Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of 5-lipoxygenase (5-LO). Also described herein are methods of using such 5-LO inhibitors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions, diseases, or disorders.

  • Anticancer compound, intermediate therefor, and processes for producing these

    The present invention provides a method for easily and inexpensively preparing a racemate or an optically-active 2-(1-hydroxyethyl)-5-hydroxynaphtho[2,3-b]furan-4,9-dione in high yields, 2-acetyl-2,3-dihydro-5-hydroxynaphtho[2,3-b]furan-4,9-dione which is useful as an intermediate for preparing NFD, and an anticancer agent comprising 2-(1-hydroxyethyl)-5-hydroxynaphtho[2,3-b]furan-4,9-dione as an active ingredient.Said 2-(1-hydroxyethyl)-5-hydroxynaphtho[2,3-b]furan-4,9-dione is obtained in 4 or 5 steps by using comparatively inexpensive 5 -hydroxynaphthalene-1,4-dione (also referred to as juglone) as a starting material.

  • 5-aryl isoxazolines for controlling invertebrate pests

    Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof wherein A.sup.1, A.sup.2 and A.sup.3 are independently selected from the group consisting of CR.sup.3 and N; B.sup.1 B.sup.2 and B.sup.3 are independently selected from the group consisting of CR.sup.2 and N; Q is a phenyl ring or a 5- or 6-membered saturated or unsaturated heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6 haloalkylthio, C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 haloalkylsufinyl, C.sub.1-C.sub.6 alkylsulfonyl, C.sub.1-C.sub.6 haloalkylsulfonyl, --CN, --NO.sub.2, --N(R.sup.4)R.sup.5, --C(W)N(R4)R.sup.5, --C(O)OR.sup.5 and R.sup.8; or --S(O).sub.2N(R.sup.21)R.sup.22; --S(O).sub.pR.sup.25 or --S(O)(.dbd.NR.sup.28)R.sup.29; R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.8, R.sup.21, R.sup.22, R.sup.25, R.sup.28, R.sup.29; p and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition of the invention. ##STR00001##

  • Substituted sulfonylaminoarylmethyl cyclopropanecarboxamide as VR1 receptor antagonists

    This invention provides a compound of the formula (I): ##STR00001## wherein A and B are independently CR.sup.12 or N; D and E are each independently CR.sup.9 or N; R.sup.1 represents (C.sub.1-C.sub.6)alkyl; R.sup.2 represents hydrogen, halogen, hydroxy, (C.sub.1-C.sub.6) alkyl, halo(C.sub.1-C.sub.6) alkyl, hydroxy(C.sub.1-C.sub.6) alkyl, (C.sub.1-C.sub.6)alkoxy or (C.sub.1-C.sub.6)alkoxy-(C.sub.1-C.sub.6)alkyl; R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.10 and R.sup.11 each independently represent hydrogen, halogen, (C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, hydroxy(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)alkoxy-(C.sub.1-C.sub.6)alkyl; or R.sup.3 and R.sup.4 are taken together with the carbon atom to which they are attached to form a 3- to 7-membered carbocyclic ring or heterocyclic ring in which one or two non-adjacent carbon atoms are optionally replaced by an oxygen atom, a sulfur atom or NH; R.sup.7 and R.sup.9 each independently represent hydrogen, halogen, (C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkyl, hydroxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, hydroxy(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkoxy-(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylthio, (C.sub.1-C.sub.6)alkylsulfinyl, (C.sub.1-C.sub.6)alkylsulfonyl, NH.sub.2, [(C.sub.1-C.sub.6)alkyl]NH--, [(C.sub.1-C.sub.6)alkyl].sub.2N--, H.sub.2N--(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkyl-NH--(C.sub.1-C.sub.6)alkoxy, [(C.sub.1-C.sub.6)alkyl].sub.2N(C.sub.1-C.sub.6)alkoxy; H.sub.2N--(C.sub.1-C.sub.6)alkoxy-(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-NH--(C.sub.1-C.sub.6)alkoxy-(C.sub.1-C.sub.6)alkyl- , [(C.sub.1-C.sub.6)alkyl].sub.2N(C.sub.1-C.sub.6)alkoxy-(C.sub.1-C.sub.6)- alkyl or 5- or 6- membered heterocyclic ring containing at least one nitrogen atom; R.sup.8 represents halogen, (C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkyl, hydroxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, hydroxy(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkoxy-(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-(C.sub.1-C.sub.6)alkoxy, halo(C.sub.1-C.sub.6)alkylsulfonyl, halo(C.sub.1-C.sub.6)alkylsulfinyl, halo(C.sub.1-C.sub.6)alkoxy, halo(C.sub.1-C.sub.6)alkylthio, [(C.sub.1-C.sub.6)alkyl]NH-- or [(C.sub.1-C.sub.6)alkyl].sub.2N--; or R.sup.7 and R.sup.8, when E is CR.sup.9, are taken together with the carbon atoms to which they are attached form a 5-8 membered carbocyclic or heterocyclic ring, in which one or two non-adjacent carbon atoms are optionally replaced by oxygen, sulfur, N or NH groups, wherein the carbocyclic ring or the heterocyclic ring is unsubstituted or substituted with one or more substituents each independently selected from the group consisting of hydroxy, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy and hydroxy(C.sub.1-C.sub.6)alkyl; and R.sup.12 represents hydrogen, halogen, (C.sub.1-C.sub.6)alkyl or hydroxy(C.sub.1-C.sub.6)alkyl; or a pharmaceutically acceptable salt or solvate thereof.

  • 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions

    Compounds of formula (I) (wherein variable groups are as defined within) pharmaceutically acceptable salts, solvates, solvates of such salts and prodrugs thereof and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia are described. Processes for their manufacture and pharmaceutical compositions containing them are also described. ##STR00001##

  • Pyrrole derivatives with angiotensin II antagonist activity

    Compounds which may be represented by the general formula (I) shown below and in which: R.sub.1 is a group independently selected from among: CHO, --COOH, --CH.sub.2OH R.sub.2 is hydrogen or a linear or branched C.sub.1-C.sub.6 alkyl group R.sub.3 is hydrogen or a halogen group selected from among Cl and Br R.sub.4 is a linear or branched C.sub.3-C.sub.5 alkyl group and the pharmaceutically acceptable salts thereof such as the sodium or potassium salt. The compounds exhibit potent and selective All antagonist activity and are useful for the treatment of any disorders in which elevated synthesis of All or overexpression of the AT.sub.1 receptor may play a primary pathological role, as in the case of arterial hypertension, congestive cardiac insufficiency, platelet aggregation and disorders associated therewith such as for example myocardial and cerebral infarction, renal ischaemia, venous and arterial thrombosis, peripheral vasculopathy, pulmonary hypertension, diabetes mellitus, diabetic neuropathy, glaucoma and diabetic retinopathy. ##STR00001##

  • Sulfonamide containing compounds for treatment of inflammatory disorders

    Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of an inflammatory condition, in particular asthma. The compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof: ##STR00001## wherein: X and Y are independently selected from --CH.sub.2-- or --CH.sub.2--CH.sub.2--; Z is selected from S(O).sub.m or Se(O).sub.m and m is 0, 1 or 2; R.sup.1 is optionally substituted heteroaryl or heterocyclic; R.sup.2 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6 straight alkyl, and C.sub.1-C.sub.6 branched alkyl, wherein all may be optionally substituted; and R.sup.3 and R.sup.4 are alkyl.

  • Conversion of 2-pyrazolines to pyrazoles using bromine

    This invention relates to a method for preparing a compound of Formula 1 wherein L, R.sup.1, R.sup.2 and X are as defined in the disclosure, comprising contacting a 2 pyrazoline of Formula 2 with bromine at a temperature of at least about 80.degree. C. (Formula 1) (Formula 2). This invention also discloses preparation of a compound of Formula 3 wherein X, Z, R.sup.5, R.sup.6, R.sup.7, R.sup.8a, R.sup.8b and n are as defined in the disclosure, using a compound of Formula 1a wherein R.sup.10 is as defined in the disclosure, prepared by the aforesaid method for preparing a compound of Formula 1. (Formula 3) (Formula 4). ##STR00001##

  • Crystalline forms of 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]Benzoic acid 471

    New crystalline forms of 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid; their use in the inhibition of 11.beta.HSD1, processes for making them and pharmaceutical compositions comprising them are also described.

  • Use of inhibitors of soluble epoxide hydrolase to synergize activity of COX and 5-LOX inhibitors

    The invention relates to methods, compositions, and uses of those compositions for making medicaments, for potentiating the beneficial effects of inhibitors of COX-1, COX-2, and 5-LOX, and reducing adverse effects, by also administering inhibitors of soluble epoxide hydrolase ("sEH"), with or without also administering one or more cis-epoxyeicosantrienoic acids. The invention further relates to the use of inhibitors of sEH as analgesics and to methods and compositions of epoxides of eicosapentaenoic acid and docosahexaenoic acid, optionally with an inhibitor of sEH, to reduce pain or inflammation or both.

  • Compounds effecting glucokinase

    The invention relates to the use of a compound of Formula (I) or a salt, solvate or prodrug thereof, wherein R.sup.1, R.sup.2, R.sup.3, n and m are as described in the specification, in the preparation of a medicament for the treatment or prevention of a disease condition mediated through glucokinase (GLK), such as type 2 diabetes. ##STR00001## The invention also relates to a novel group of compounds of Formula (I) and to methods for preparing compounds of Formula (I).

  • Pyridomorphinans, pyridazinomorphinans and use thereof

    Compounds represented by the formula: wherein R is C.sub.1-6 alkyl; C.sub.4-6 cycloalkylalkyl; or C.sub.3-6 alkenyl; R' is H or C.sub.1-6 alkyl; X is H or ##STR00001## OH; Y is alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl or aroyl; and Z is CH or N; provided that X is H, when Z is CH and R is C.sub.4 cycloalkylalkyl or C.sub.4 alkenyl; prodrugs thereof; and pharmaceutically acceptable salts thereof are provided. Compounds of the above formula are useful as analgesics for treating pain; as immunomodulators, to modulate the behavioral effects of drugs of abuse and to modulate the development of tolerance and dependence to .mu. agonists.

  • 4-aryl-pyridine-2-carboxyamide derivatives

    The present invention relates to novel pyridine-2-carboxyamide derivatives of formula (I) useful as metabotropic glutamate receptor antagonists: ##STR00001## wherein Y, Z, R.sup.1, R.sup.2 and R.sup.3 are as defined in the specification herein.

  • Triazole compounds useful as protein kinase inhibitors

    This invention describes novel triazole compounds of formula IX: ##STR00001## wherein Z.sup.1 is nitrogen or CR.sup.9 and Z.sup.2 is nitrogen or CH, provided that at least one of Z.sup.1 and Z.sup.2 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 --R.sup.1; Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; R.sup.x and R.sup.y are independently selected from T-R.sup.3, or R.sup.x and R.sup.y are taken together with their intervening atoms to form a fused ring; R.sup.1, R.sup.3, 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.

  • Imidazo[4, 5-B]pyridin-2-one and oxazolo[4, 5-B] pyridin-2-one compounds and analogs thereof as cancer therapeutic compounds

    The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5 b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.

  • Radiolabelled benzamide analogues, their synthesis and use in diagnostic imaging

    Fluoroalkoxybenzamide compounds which selectively bind Sigma-2 receptors are disclosed. These compounds, when labelled with .sup.18F, can be used as radiotracers for imaging of tumors by positron emission tomography (PET). In addition, these compounds, when labelled with .sup.123I, can be used as radiotracers for imaging of tumors by single photon emission computed tomography (SPECT). Methods for synthesis of these compounds are also disclosed.

  • Certain substituted amides, method of making, and method of use thereof

    At least one chemical entity chosen from compounds of Formula 2 ##STR00001## and pharmaceutically acceptable salts, solvates, chelates, non-covalent complexes, prodrugs, and mixtures thereof is described herein. Pharmaceutical compositions comprising at least one chemical entity of the invention, together with at least one pharmaceutically acceptable vehicle chosen from carriers adjuvants, and excipients, are described. Methods of treating patients suffering from certain diseases responsive to inhibition of Btk activity and/or B-cell activity are described. Methods for determining the presence of Btk in a sample are described.

  • Heterocyclic-substituted bis-1,8 naphthalimide compounds, antibody drug conjugates, and methods of use

    Bis 1,8 naphthalimide compounds including antibody drug conjugate (ADC) are described. Pharmaceutical compositions comprising an effective amount of a 1,8 bis-naphthalimide compound for treatment of hyperproliferative disorders and other disorders are described. Methods are described for killing or inhibiting the proliferation of tumor cells or cancer cells including administering to a patient an effective amount of a 1,8 bis-naphthalimide compound.

  • Synthesis and anti-proliferative effect of benzimidazole derivatives

    This invention provides for compounds, compositions, and methods that involve anti-proliferative and anti-neoplastic activity in cancer cells. In particular, a series of benzimidazole, purine, imidazopyridine, and imidazopyrizine compounds having selected substitution patterns are disclosed, and the activity of various subject compounds is demonstrated. For example, the invention provides compounds having the general formula: ##STR00001## their pharmaceutical compositions, and methods of treatment using the subject compounds and compositions.

  • Isoxazole compounds as histamine H.sub.3 modulators

    Certain isoxazole compounds are histamine H.sub.3 modulators useful in the treatment of histamine H.sub.3 receptor mediated diseases.

  • Bicyclic-substituted amines as histamine-3 receptor ligands

    Compounds of formula (I) ##STR00001## are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor ligands. Also disclosed are pharmaceutical compositions comprising the histamine-3 receptor ligands, methods for using such compounds and compositions, and a process for preparing compounds within the scope of formula (I).

  • Substituted thiazolo[5,4-d]pyrimidine urea derivatives

    There are presented compounds of the formula ##STR00001## or a pharmaceutically acceptable salt thereof, which are active adenosine A2B receptor antagonists and useful in the treatment of diabetes, diabetic retinopathy, asthma and diarrhea.

  • Cyclic n-hydroxy imides as inhibitors of flap endonuclease and uses thereof

    Acrylic n-hydroxy imides and their use in pharmaceutical compositions and in the inhibition of flap endonuclease are disclosed.

  • Pyrazine-2-carboxyamide derivatives

    The present invention is concerned with novel pyrazine 2-carboxyamide derivatives of formula (I) ##STR00001## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in the specification. These compounds are useful for the treatment of CNS disorders.

  • Fungicides

    The naphthyridine derivatives of formula (I) a and method of combating or controlling phytopathogenic fungi which comprises applying the compounds of formula (I) to a plant, to a seed of a plant and to the locus of the plant. ##STR00001##

  • Process for preparing telmisartan

    A process comprising cyclizing 3-amino-4-butyramido-5-methylbenzoic acid to form 2-n-propyl-4-methyl-benzimidazole-6-carboxylic acid. ##STR00001##

  • Glucopyranoside compound

    A compound of the formula: ##STR00001## wherein Ring A and Ring B are: (1) Ring A is an optionally substituted unsaturated monocyclic heterocyclic ring, and Ring B is an optionally substituted unsaturated monocyclic heterocyclic ring, an optionally substituted unsaturated fused heterobicyclic ring, or an optionally substituted benzene ring, (2) Ring A is an optionally substituted benzene ring, and Ring B is an optionally substituted unsaturated monocyclic heterocyclic ring or an optionally substituted unsaturated fused heterobicyclic ring, or (3) Ring A is an optionally substituted unsaturated fused heterobicyclic ring, and Ring B are independently an optionally substituted unsaturated monocyclic heterocyclic ring, an optionally substituted unsaturated fused heterobicyclic ring, or an optionally substituted benzene ring; X is a carbon atom or a nitrogen atom; Y is --(CH.sub.2).sub.n-- (n is 1 or 2); a pharmaceutically acceptable salt thereof, or a prodrug thereof.

  • Piperazine compounds useful as antagonists of C-C chemokines (Ccr2b and CcrS) for the treatment of inflammatory diseases

    A compound of formula (I) P--W--C(.dbd.X)-L-Q (I) wherein P is an optionally substituted aryl or heteroaryl group; W is an optionally substituted 6 or 7-membered aliphatic ring comprising ring atoms Y.sup.1 and Y.sup.2 independently selected from Oxygen and Nitrogen, X is selected from Oxygen, Nitrogen and Sulphur; L is an optional C.sub.1-4 linker; and Q is an optionally substituted 4-7 membered aliphatic ring: for use in the treatment of chemokine mediated diseases or disorders.

  • 3-.beta.-D-ribofuranosylthiazolo[4-5-d]pyrimidine nucleosides and uses thereof

    The invention is directed to 3-.beta.-D-ribofuranosylthiazolo[4,5-d]pyrimidine nucleosides and pharmaceutical compositions containing such compounds that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds.

  • Aryl substituted pyridines and the use thereof

    This invention relates aryl substituted pyridines of Formula I: ##STR00001## or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein Ar and R.sub.1-R.sub.4 are set in the specification. The invention is also directed to the use of compounds of Formula I for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), and for the treatment, prevention or amelioration of both acute or chronic pain, as antitinnitus agents, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy.

  • 3,9-diaza-spiro[5.5]undecane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors

    This invention relates to novel 3,9-diaza-spiro[5.5]undecane derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.

  • Carboxamide compound and use of the same

    A carboxamide compound represented by the formula (1): ##STR00001## [wherein Q represents a nitrogen-containing 6-membered aromatic heterocyclic group optionally fused with a benzene ring, one of ring constitutional atoms of the heterocyclic group is a nitrogen atom and the heterocyclic group may be substituted with a group selected from the group consisting of a C1-C3 alkyl and the like, R.sup.1 represents a C1-C3 alkyl group or the like, R.sup.2 represents a hydrogen atom or the like, and R.sup.3 represents a hydrogen atom or the like] and a plant disease controlling agent comprising this as an active ingredient.

  • Pyrimidine derivatives

    A compound of Formula (I): ##STR00001## or a pharmaceutically and/or veterinarily acceptable derivative thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.8 are as defined above.

  • Micronized composition of a 2,4-disubstituted phenol derivative

    A composition comprising a 2,4,-disubstituted phenol derivative in its micronized form and its use in the treatment of leukotriene-mediated diseases, gastrointestinal-inflammatory diseases or pulmonary fibrosis. More particularly, 2,4,6-triiodophenol can be used for the treatment of pulmonary fibrosis and arthritis.

  • SUBSTITUTED SULPHONAMIDO PHENOXYBENZAMIDES

    The present invention relates to substituted sulphonamido phenoxybenzamide compounds of general formula (I): ##STR00001## in which A, R1, R2, R3, R4, R5, R6, R7, R8 and n are as defined in the claims, to pharmaceutical compositions and combinations containing said compounds, to methods of preparing said compounds, and to the use of said compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.

  • METHODS AND SYSTEMS FOR SYNTHESIS OF A D-AMINOLUCIFERIN PRECURSOR AND RELATED COMPOUNDS

    Methods and systems to generate 6-amino-6-deoxy-D-luciferin precursor, 2-cyano-6-aminobenzothiazole and related compounds and derivatives

  • 5-Ring Heteroaromatic compounds and their use as binding partners for 5-ht5 receptors

    The invention relates to 5-ring heteroaromatic compounds of general formula (I), their use for the treatment and/or prevention of diseases, and medicaments containing same.

  • 8-CARBOXAMIDO-2,6-METHANO-3-BENZAZOCINES

    8-Substituted-2,6-methano-3-benzazocines of general structure I in which A is --CH.sub.2--OH, --CH.sub.2NH.sub.2, --NHSO.sub.2CH.sub.3, ##STR00001## and Y is O, S or NOH are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications. ##STR00002## 8-Carboxamides, thiocarboxamides, hydroxyamidines and formamides are preferred.

  • ANTITUMOR AGENT FOR THYROID CANCER

    The objective of the present invention is to provide a pharmaceutical composition and a therapeutic method that are specifically effective against at least one disease selected from multiple endocrine neoplasia, type IIA, multiple endocrine neoplasia, type IIB, familial medullary thyroid carcinoma, thyroid carcinoma, papillary thyroid carcinoma, sporadic medullary thyroid carcinoma, Hirschsprung disease, pheochromocytoma, parathyroid hyperplasia and mucosal neuromas of the gastrointestinal tract. 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinoli- necarboxamide and analogs thereof are specifically effective against at least one disease selected from multiple endocrine neoplasia, type IIA, multiple endocrine neoplasia, type IIB, familial medullary thyroid carcinoma, thyroid carcinoma, papillary thyroid carcinoma, sporadic medullary thyroid carcinoma, Hirschsprung disease, pheochromocytoma, parathyroid hyperplasia and mucosal neuromas of the gastrointestinal tract.

  • Azine Derivatives and Methods of Use Thereof

    The present invention relates to Azine Derivatives, pharmaceutical compositions comprising the Azine Derivatives and the use of these compounds for treating or preventing allergy, an allergy-induced airway response, congestion, a cardiovascular disease, an inflammatory disease, a gastrointestinal disorder, a neurological disorder, a metabolic disorder, obesity or an obesity-related disorder, diabetes, a diabetic complication, impaired glucose tolerance or impaired fasting glucose.

  • Novel Oxadiazole Compounds

    Novel oxadiazole compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions as agonists or antagonists of the S1P family of G protein-coupled receptors for treating diseases associated with modulation of S1P family receptor activity, in particular by affording a beneficial immunosuppressive effect are disclosed.

  • 3-Aminocarbonyl-substituted benzoylcyclohexanediones and their use as herbicides

    What is described are 3-aminocarbonyl-substituted benzoylcyclohexanediones of the formula (I) as herbicides. ##STR00001## In this formula (I), R.sup.1 to R.sup.5 are radicals such as hydrogen, organic radicals such as alkyl, and other radicals such as halogen. X is alkylene.

  • Methods for Forming Protected Organoboronic Acids

    Described are methods of forming protected boronic acids that provide in a manner that is straightforward, scalable, and cost-effective a wide variety of building blocks, such as building blocks containing complex and/or pharmaceutically important structures, and/or provide simple or complex protected organoboronic acid building blocks. A first method includes reacting an imino-di-carboxylic acid and an organoboronate salt. A second method includes reacting a N-substituted morpholine dione and an organoboronic acid.

  • CYCLIC GLYCYL-2-ALLYL PROLINE IMPROVES COGNITIVE PERFORMANCE IN IMPAIRED ANIMALS

    Embodiments of this invention provide methods for therapeutic use of cyclic G-2-Allyl Proline to treat cognitive disorders as well as manufacture of medicaments including tablets, capsules, injectable solutions that are useful for treatment of such conditions.

  • PYRIDO [2,3-D] PYRIMIDINES AND THEIR USE AS KINASE INHIBITORS

    The present invention provides derivatives of pyrido[2,3-d]pyrimidin-7-one. These compounds are kinase inhibitors, including compounds that show anti-proliferative activity, including against tumor cells, and are useful in the treatment of diseases including cancer.

  • Arylmethoxy Isoindoline Derivatives and Compositions Comprising and Methods of Using the Same

    Provided are 4'-arylmethoxy isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

  • METHIONINE ANALOGS AND METHODS OF USING SAME

    Provided are methionine analogs which may be useful for inhibiting protein synthesis, inhibiting microbial growth and/or treating infectious diseases. In some instances, the analogs exhibit bactericidal, antibacterial, anti-infective, antimicrobial, sporicidal, disinfectant, antifungal and/or antiviral properties. Also provided are methods of treatment and methods of preparation, as well as kits and unit dosages.

  • Bicyclic Kinase Inhibitors

    New compounds, compositions and methods of inhibition of Provirus Integration of Maloney Kinase (PIM kinase) activity associated with tumorigenesis in a human or animal subject are provided. In certain embodiments, the compounds and compositions are effective to inhibit the activity of at least one PIM kinase. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a serine/threonine kinase- or receptor tyrosine kinase-mediated disorder, such as cancer.

  • TETRAHYDRO- AND DIHYDROQUINAZOLINONES

    The present invention relates to the use of tetrahydro- and dihydroquinazolinones of formula (I) as protein kinase activators or inhibitors, a method for their manufacture, their use for the preparation of a medicament for the treatment of diseases, their use for the manufacture of a pharmaceutical composition and new tetrahydro- and dihydroquinazolinones. ##STR00001##

  • Heterocyclic Kinase Inhibitors

    New compounds, compositions and methods of inhibition of Provirus Integration of Maloney Kinase (PIM kinase) activity associated with tumorigenesis in a human or animal subject are provided. In certain embodiments, the compounds and compositions are effective to inhibit the activity of at least one PIM kinase. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a serine/threonine kinase- or receptor tyrosine kinase-mediated disorder, such as cancer.

  • INHIBITORS OF Akt ACTIVITY

    Invented are novel heterocyclic carboxamide compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

  • PEPTIDE ANALOGUES

    The present invention relates to compounds of Formula (I) ##STR00001## and their pharmaceutically acceptable salts, wherein the substituents are as described herein, and their use in medicine, in particular as opioid agonists.

  • Tri-Aryl/Heteroaromatic Cannabinoids and Use Thereof

    Cannabinoid derivatives according to formula (I) are disclosed ##STR00001## wherein, X, Y, R.sub.1, R.sub.2, and W can have the definitions provided herein. Without limitation, use of such compounds, their salts or pro-drug, or compositions containing the compounds, salts, or pro-drug, to modify the activity of CB1 and CB2 receptors and treat conditions mediated by these receptors.

  • 5' AND 2' BIS-SUBSTITUTED NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM

    The present invention provides modified nucleosides and oligomeric compounds prepared therefrom. More particularyl, the present invention provides modified nucleosides having at least one 5'-substituent and a 2'-O-substituent, oligomeric compounds comprising at least one of these modified nucleosides and methods of using the oligomeric compounds. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

  • DIHYDROFURO PYRIMIDINES AS AKT PROTEIN KINASE INHIBITORS

    The present invention provides compounds, including resolved enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof, comprising the Formula (I): Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer. ##STR00001##

  • CYCLIC COMPOUND HAVING HETERO ATOM

    Compounds exhibiting an osteogenesis-promoting action having the general formula (I) or a pharmacologically acceptable salt thereof: ##STR00001## wherein A is selected from among a 3- to 10-membered heterocyclyl group, B is selected from among an amino group, and X is selected from N and CH.

  • KINASE INHIBITORS

    The present invention provides a new group of protein kinase inhibitors, pyrido[4,3,-d]pyrimidin-5-one derivatives, and pharmaceutically acceptable salts thereof that are useful for intreating cell proliferative disease and disorder such as cancer, autoimmune diseases, infection, cardiovascular disease and neurodegenerative disease and disorder. The present invention provides methods for synthesizing and administering the protein kinase inhibitor compounds. The present invention also provides pharmaceutical formulations comprising at least one of the protein kinase inhibitor compounds together with a pharmaceutically acceptable carrier, diluent or excipient therefor. The invention also provides useful intermediates generated during the syntheses of the pyrido[4,3,-d]pyrimidin-5-one derivatives.

  • Hydroxamic Acid Derivatives

    The disclosure includes hydroxamic compounds of Formula I: (I) wherein P, Z, and m are defined herein. Also disclosed is a method for treating a neoplastic disease or an immune disease with these compounds. ##STR00001##

  • FORMULATIONS OF 5-FLUOROCYTOSINE AND USES THEREOF

    The disclosure provides an extended release formulation of 5-fluorocytosine. In another aspect, a method of treating a fungal disease is provided. The method comprises administering to a subject in need thereof a fungus-treating effective amount of a composition comprising 5-fluorocytosine. In yet another aspect, a method of treating a cancer is provided. The method comprises administering to a subject in need thereof a sufficient amount of an expression vector to induce expression of cytosine deaminase which is capable of converting 5-fluorocytosine to 5-fluorourcail in cells of the cancer and a cancer-treating effective amount of a composition comprising 5-fluorocytosine.

  • Azo Derivatives and Uses Thereof in Phototherapy

    The invention relates generally to optical agents, including Type 1 phototherapeutic agents, for biomedical applications, such as phototherapy. Provided are fused ring azo and diaza compounds comprising a plurality of fused rings including a first ring having an intra-ring azo or intra-ring diaza group capable of activation upon exposure to electromagnetic radiation in visible and/or infrared regions of the electromagnetic spectrum. Optical agents of the invention enable a versatile phototherapy platform for treatment of a range of pathological conditions, including the treatment of cancers, stenosis and inflammation. The invention further provides preparations and formulations comprising the fused ring azo and diaza compounds and methods of making and using the fused ring azo and diaza compounds as optical agents in in vivo or ex vivo biomedical procedures.

  • BICYCLIC HETEROCYCLE DERIVATIVES AND METHODS OF USE THEREOF

    The present invention relates to Bicyclic Heterocycle Derivatives, compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a GPCR in a patient.

  • PYRIMIDINE DERIVATIVES AS GPCR MODULATORS FOR USE IN THE TREATMENT OF OBESITY AND DIABETES

    The present invention relates to Pyriraidine Derivatives of formula (I), compositions comprising a Pyrimidine Derivative, and methods of using the Pyrimidine Derivatives for treating or preventing obesity, diabetes, a diabetic complication, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a G protein-coupled receptor (GPCR) in a patient. ##STR00001##

  • BICYCLIC COMPOUND

    The present invention provides to a compound having an ACC inhibitory action, which is useful as an agent for the prophylaxis or treatment of obesity, diabetes, hypertension, hyperlipidemia, cardiac failure, diabetic complications, metabolic syndrome, sarcopenia, cancer and the like, and has superior efficacy. The present invention relates to a compound represented by the formula (I): ##STR00001## wherein each symbol is as defined in the specification.

  • PYRIDONE AND PYRIDAZONE ANALOGUES AS GPR119 MODULATORS

    Novel compounds of structure Formula (I) or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein Z, R.sup.1, R.sup.2, R.sup.21, T.sup.1, T.sup.2, T.sup.3 and T.sup.4 are defined herein, are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds. ##STR00001##

  • NOVEL DIPHENYL PURINE DERIVATIVES USEFUL AS MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS

    This invention relates to novel (6-phenyl-5-amino/nitro-pyrimidin-4-yl)-phenyl-amines, which are found to be modulators of the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

  • SUBSTITUTED 3-HYDROXY-4-PYRIDONE DERIVATIVE

    This invention provides compounds having antiviral activities especially inhibiting activity for influenza virus, more preferably provides substituted 3-hydroxy-4-pyridone derivatives having cap-dependent endonuclease inhibitory activity.

  • METHOD OF PRODUCING PYRONE AND PYRIDONE DERIVATIVES

    The present invention provides a pyrone derivative and a pyridone derivative, which are novel intermediates for synthesizing an anti-influenza drug, a method of producing the same, and a method of using the same.

  • INDOLES, DERIVATIVES AND ANALOGS THEREOF AND USES THEREFOR

    Indole derivatives and analogous compounds and pharmaceutical compositions comprising the same are provided. Also provided are methods of using these compounds to inhibit tubulin polymerization in a cell associated with a proliferative disease or to treat cancer, metastatic cancer, resistant cancer or multidrug resistant cancer, including inter-alia: prostate cancer, breast cancer, melanoma, colon cancer and bladder cancer.

  • HETEROCYCLIC ANTAGONISTS OF PROSTAGLANDIN D2 RECEPTORS

    Described herein are heteroaryl compounds that are antagonists of PGD.sub.2 receptors. Also described are pharmaceutical compositions and medicaments that include the heteroaryl compounds described. Also described herein are methods of using such antagonists of PGD.sub.2 receptors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other PGD2-dependent or PGD2-mediated conditions or diseases.

  • DERIVATIVES OF N-(ARYLAMINO)SULFONAMIDES AS INHIBITORS OF MEK

    This invention concerns N-(2-arylamino)aryl sulfonamides, which are inhibitors of MEK and are useful in treatment of cancer and other hyperproliferative diseases.

  • BICYCLIC COMPOUNDS AS INHIBITORS OF DIACYGLYCEROL ACYLTRANSFERASE

    The present invention relates to novel heterocyclic compounds as diacylglycerol acyltransferase ("DGAT") inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the invention is shown below (I).

  • SUBSTITUTED HETEROCYCLIC COMPOUNDS

    Disclosed are compounds of Formula (I) ##STR00001## or pharmaceutically acceptable salts thereof, wherein Q is ##STR00002## R.sup.1 is cycloalkyl, heteroaryl, or heterocyclyl, each optionally substituted with one to five substituents independently selected from C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.4 haloalkyl, --OR.sup.4, and/or halogen; and R.sup.2, R.sup.3, R.sup.4, and n are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as vascular disease and autoimmune diseases.

  • SULFONYL SEMICARBAZIDES, SEMICARBAZIDES AND UREAS, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS FOR TREATING HEMORRHAGIC FEVER VIRUSES, INCLUDING INFECTIONS ASSOCIATED WITH ARENAVIRUSES

    Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain novel semicarbazides, sulfonyl carbazides, ureas and related compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by hemorrhagic fever viruses is disclosed, i.e., including but not limited to Arenaviridae (Junin, Machupo, Guanavito, Sabia and Lassa), Filoviridae (ebola and Marburg viruses), Flaviviridae (yellow fever, omsk hemorrhagic fever and Kyasanur Forest disease viruses), and Bunyaviridae (Rift Valley fever).

  • TETRAHYDROPYRAN NUCLEIC ACID ANALOGS

    The present disclosure describes tetrahydropyran nucleoside analogs, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, novel tetrahydropyran nucleoside analogs are provided having at least one chiral substituent that are expected to be useful for enhancing one or more properties of oligomeric compounds such as nuclease resistance and/or binding affinity. In certain embodiments, the oligomeric compounds are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

  • BICYCLIC PIPERIDINE AND PIPERAZINE DERIVATIVES AS GPCR MODULATORS FOR THE TREATMENT OF OBESITY, DIABETES AND OTHER METABOLIC DISORDERS

    The present invention relates to Bicyclic Piperidine and piperazine Derivatives, compositions comprising a Bicyclic Piperidine and piperazine Derivative, and methods of using the Bicyclic Piperidine and piperazine Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a GPCR in a patient.

  • (4-HALOALKYL-3-THIOBENZOYL)CYCLOHEXANEDIONES AND USE THEREOF AS HERBICIDES

    A description is given of (4-haloalkyl-3-thiobenzoyl)cyclohexanediones of the formula (I) and of their use as herbicides. ##STR00001## In this formula (I), X, Y, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are radicals such as hydrogen and organic radicals such as alkyl. A and Z are oxygen or alkylene.

  • HETEROBIFUNCTIONAL POLYMERS AND METHODS FOR LAYER-BY-LAYER CONSTRUCTION OF MULTILAYER FILMS

    In one aspect, the present invention is directed to methods for modification of functionalized substrates. In another aspect, the invention relates to systems and methods for fabricating multilayer polymer compositions. In certain embodiments, the multilayer polymer compositions described herein can comprise heterobifunctional polymers and heterotrifunctional molecules.

  • 1'-SUBSTITUTED-CARBA-NUCLEOSIDE PRODRUGS FOR ANTIVIRAL TREATMENT

    Provided are prodrugs of pyrrolo[1,2-f][1,2,4]triazin-7-yl nucleoside phosphates wherein the 1' position of the nucleoside sugar is substituted with CN. The compounds, compositions, and methods provided are useful for the treatment Hepatitis C infections.

  • 5-5-MEMBERED FUSED HETEROCYCLIC COMPOUND AND USE THEREOF AS HCV POLYMERASE INHIBITOR

    The present invention relates to a fused ring compound represented by the following formula [I] ##STR00001## wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and a therapeutic agent for hepatitis C containing this compound. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.

  • Macrolides with Anti-Inflammatory Activity

    The present invention relates to novel semi-synthetic macrolides having anti-inflammatory activity. More particularly, the invention relates to 14- and 15-membered macrolides substituted at the 4'' position, to their pharmaceutically acceptable derivatives, to processes and intermediates for their preparation, to pharmaceutical compositions containing them and to their activity and use in the treatment of inflammatory diseases and conditions in humans and animals, especially those diseases associated with excessive secretion of TNF-.alpha., IL-1, IL-8, IL-2 or IL-5; and/or inhibitor of excessive lymphocyte proliferation; and/or excessive granulocyte degranulation.

  • ANTI-INFLAMMATORY MODALITIES

    Anti-inflammatory modalities are described with reference to select isoflavonoid compounds, compositions containing same and the use of said compounds and/or compositions in treatment, particularly for the treatment of inflammatory diseases and related conditions.

  • PALLADIUM-CATALYZED ORTHO-FLUORINATION

    A new method of ortho-fluorination where an aryl C--H bond is directly replaced by an aryl C-F bond in a palladium-catalyzed reaction is provided. The method includes the ortho-fluorination of a triflamide protected benzylamine, a palladium catalyst, such as Pd(OTf).sub.2, a fluorinating reagent such as N-fluoro-2,4,6-trimethylpyridinium triflate, and a ligand to promote the reaction such as N-methylpyrrolidinone (NMP).

  • THIOPHENE ANALOGUES FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTIONS

    Compounds represented by formula I: ##STR00001## or pharmaceutically acceptable salts and solvates thereof, wherein R.sub.1, X, Y, and Z are as defined herein, are useful for treating flaviviridae viral infections.

  • PYRAZINO[2,3-b]PYRAZINE mTOR KINASE INHIBITOR FOR ONCOLOGY INDICATIONS AND DISEASES ASSOCIATED WITH THE mTOR/PI3K/AKT PATHWAY

    Provided herein are Heteroaryl Compounds having the following structure: ##STR00001## wherein R.sup.1-R.sup.4 are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, neurodegenerative diseases, diabetes, obesity, neurological disorders, age-related diseases, or cardiovascular conditions, comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.

  • FUSED IMIDAZOLE DERIVATIVE HAVING TTK INHIBITORY ACTION

    Provided are a compound represented by general formula (1) and having a TTK inhibitory action and a medicine containing the compound. In formula (1), (X, Y, V, W) is (--N.dbd., .dbd.CR.sup.1--, .dbd.N--, --CR.sup.7.dbd.), (--CR.sup.2.dbd., .dbd.N--, .dbd.N--, --CR.sup.7.dbd.), etc.; A is an (un)substituted aromatic hydrocarbon ring, etc.; L is a single bond, --C(.dbd.O)--NR.sup.A--, etc.; Z is a group represented by the formula --NR.sup.3R.sup.4 or a group represented by the formula --OR.sup.5; R.sup.1 to R.sup.3, R.sup.6, and R.sup.7 each is a hydrogen atom, etc.; R.sup.4 and R.sup.5 each is an (un)substituted alkyl, etc.; and R.sup.8 is an (un)substituted cycloalkyl, etc.

  • METHODS OF USING OLIGOMERIC COMPOUNDS COMPRISING 2'-SUBSTITUTED NUCLEOSIDES

    The present disclosure provides oligomeric compounds comprising at least one 2'-fluoroethoxy modified nucleoside of formula I and methods of using these oligomeric compounds. The methods provided herein include contacting a cell or administering to an animal at least one of the oligomeric compounds. In certain embodiments, the oligomeric compounds hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

  • HETEROCYCLIC COMPOUND AND USE THEREOF

    The present invention provides a heterocycle derivative having a superior amyloid .beta. production inhibitory activity and/or a superior .gamma.-secretase modulation activity, and use thereof. A compound represented by the formula (I): ##STR00001## wherein each symbol is as defined in the present specification, or a salt thereof.

  • THIENO [2, 3-B] PYRIDINE DERIVATIVES AS VIRAL REPLICATION INHIBITORS

    The present invention relates to a series of compounds having antiviral activity, more specifically HIV (Human Immunodeficiency Virus) replication inhibiting properties. The invention also relates to methods for the preparation of such compounds, as well as to novel intermediates useful in one or more steps of such syntheses. The invention also relates to pharmaceutical compositions comprising an effective amount of such compounds as active ingredients. This invention further relates to the use of such compounds as medicines or in the manufacture of a medicament useful for the treatment of animals suffering from viral infections, in particular HIV infection. This invention further relates to methods for the treatment of viral infections in animals by the administration of a therapeutic amount of such compounds, optionally combined with one or more other drugs having anti-viral activity.

  • CGRP Receptor Antagonist

    The disclosure generally relates to the compound of formula I, (R)-N-(3-(7-methyl-1H-indazol-5-yl)-1-(4-(1-methylpiperidin-4-yl)piperazi- n-1-yl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-c- arboxamide, including pharmaceutically acceptable salts, which is a CGRP-receptor antagonist. The disclosure also relates to pharmaceutical compositions and methods for using the compound in the treatment of CGRP related disorders including migraine headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and cancer. ##STR00001##

  • PIPERIDINE AND PIPERAZINE DERIVATIVES AS AUTOTAXIN INHIBITORS

    The present invention relates to piperidine and pyrazine derivatives according to formulae (Ia), (Ib) and (II) as autotaxin inhibitors and the use of such compounds for the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propagated by increased lysophosphatic acid levels and/or the activation of autotaxin, in particular of different cancers.

  • DIALKYLAMINO ALKYL ESTERS OF PIVAGABINE AS MEDICAMENTS FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISORDERS

    The present embodiments are related to the compound of Formula 1 or Formula 2 below and pharmaceutical formulations thereof as well as treatments for a wide variety of Central Nervous System disorders with the pharmaceutical formulations. Some embodiments include the use of a variety of the instant compounds which surprisingly and advantageously exhibit improved pharmacokinetic and therapeutic profiles in comparison to pivagabine. ##STR00001##

  • CARBAZOLE AND CARBOLINE KINASE INHIBITORS

    The present invention provides compounds of Formula (I) ##STR00001## and pharmaceutically acceptable salts thereof The Formula (I) compounds inhibit tyrosine kinase activity of Jak2, thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.

  • Phosphonate Compounds

    The present invention relates to phosphonate compounds, compositions containing them, processes for obtaining them, and their use for treating a variety of medical disorders, e.g., osteoporosis and other disorders of bone metabolism, cancer, viral infections, and the like.

  • Aryl- and Heteroarylcarbonyl derivatives of substituted nortropanes, medicaments containing such compounds and their use

    The present invention relates to compounds defined by formula (I) wherein the groups R.sup.1 and R.sup.2 are defined as in claim 1, possessing valuablepharmacological activity. Particularly the compounds are inhibitors of 11 .beta.-hydroxysteroid dehydrogenase (HSD) 1 and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme, such as metabolic diseases, in particular diabetes type 2, obesity, and dyslipidemia. ##STR00001##

  • Process for Enantioselective Synthesis of Single Enantiomers of Modafinil by Asymmetric Oxidation

    The invention relates to a method for preparing a sulphoxide compound of formula (I) either as a single enantiomer or in an enantiomerically enriched form, comprising the steps of: a) contacting a pro-chiral sulphide of formula (II) with a metal chiral complex, a base and an oxidizing agent in an organic solvent; and optionally b) isolating the obtained sulphoxide of formula (I). ##STR00001## wherein n, Y, R.sub.1, R.sub.1a, R.sub.2 and R.sub.2a are as defined in claim 1.

  • SYNTHESIS AND ANTI-PROLIFERATIVE EFFECT OF BENZIMIDAZOLE DERIVATIVES

    This invention provides for compounds, compositions, and methods that involve anti-proliferative and anti-neoplastic activity in cancer cells. In particular, a series of benzimidazole, purine, imidazopyridine, and imidazopyrizine compounds having selected substitution patterns are disclosed, and the activity of various subject compounds is demonstrated. In particular, the disclosure provides for substituted imidazo[4,5-c]pyridine compounds having the general formula ##STR00001## their salts, pharmaceutical compositions, and methods of treatment using the subject compounds and compositions.

  • NEW ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS

    The invention provides certain compounds and salts of Formula I and Formula II: ##STR00001## which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables A.sub.1, R.sub.2, R.sub.3, R.sub.5, R.sub.6, R.sub.7, A.sub.8 and R.sub.9 are defined herein. Certain compounds of Formula I and Formula II disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of a compound of Formula I or Formula II and one or more other active agents. The invention also provides methods for treating microbial infections in animals.

  • PEPTIDIC ANTIGEN THAT INDUCES ANTIBODY RECOGNIZING THREE-DIMENSIONAL STRUCTURE OF HIV AND METHOD FOR SYNTHESIZING SAME

    An object of the present invention is to provide an HIV antibody-inducing peptide antigen that can be used without problems for HIV, which is highly prone to mutation, and is effective in developing an antibody or a vaccine having excellent specificity and binding activity even for the three-dimensional structure of a neutralization target, i.e. the mechanism by which HIV invades a target cell; a method for synthesizing the same; a vaccine comprising the peptide antigen, or an HIV three-dimensional structure-recognizing antibody induced by the peptide antigen; and a preventive and/or therapeutic agent for HIV infection comprising the peptide antigen, the vaccine, or the HIV three-dimensional structure-recognizing antibody as an active ingredient. The synthesis method comprises using a trimer of N36 peptide derivative which is synthesized by ligating a derivative of a helical region N36 peptide in N-terminal of an HIV particle transmembrane protein gp41 to a C3-symmetric template compound having three equivalent linker structures.

  • TRICYCLIC PYRIDINE DERIVATIVES, MEDICAMENTS CONTAINING SUCH COMPOUNDS, THEIR USE AND PROCESS FOR THEIR PREPARATION

    The present invention relates to compounds defined by formula I ##STR00001## wherein the variables R.sup.1-R.sup.8 are defined as in the description, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of cholesterol ester transfer protein (CETP) and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme.

  • Aminopyridine- and Aminopyrimidinecarboxamides as CXCR2 Modulators

    There is disclosed aminopyridine-and aminopyrimidinecarboxamide compounds useful as pharmaceutical agents, synthesis processes, and pharmaceutical compositions which include aminopyridine- and aminopyrimidinecarboxamides compounds. More specifically, there is disclosed a genus of CXCR2 inhibitor compounds that are useful for treating a variety of inflammatory and neoplastic disorders.

  • Compounds, Compositions, and Methods for the Treatment of Beta-Amyloid Diseases and Synucleinopathies

    Dihydroxyaryl compounds and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.

  • HEPARAN SULFATE SYNTHESIS

    The invention provides an efficient modular chemical synthesis for heparan sulfate oligosaccharides based on orthogonal protection strategies. Modular disaccharide building blocks, themselves the product of a novel combinatorial synthesis, are combined in numerous ways to produce a range of oligosaccharides.

  • Compositions of (-)-E-10-OH-NT and Methods for Their Synthesis and Use

    This present disclosure provides compositions comprising E-10-OH-NT metabolites of AT and NT, methods for their synthesis and methods for their use.

  • SYNTHESIS OF DENDRIMER CONJUGATES

    The present invention relates to novel methods of synthesis of therapeutic and diagnostic dendrimers. In particular, the present invention is directed to novel dendrimer conjugates, novel methods of synthesizing the same, compositions comprising the conjugates, as well as systems and methods utilizing the conjugates (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer, inflammatory disease) diagnosis and/or therapy, pain therapy, etc.)). Accordingly, dendrimer conjugates of the present invention may further comprise at least two different components for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and/or monitoring response to therapy. Furthermore, the novel synthesis methods of certain embodiments of the present invention provide significant advantages with regard to total reaction time and simplicity.

  • PROTECTED MONOMERS AND METHODS OF DEPROTECTION FOR RNA SYNTHESIS

    A nucleoside monomer that is protected by a thionocarbamate protecting group and contains one or more .sup.2H, .sup.13C, or .sup.15N isotopes in the ribose and/or base part is provided, as well as a method for making a polynucleotide that uses the same. Also provided is a polynucleotide synthesis method that employs a diamine to deprotect a protected polynucleotide.

  • NOVEL MEDITOPES AND RELATED MEDITOPE-MONOCLONAL ANTIBODY DELIVERY SYSTEMS, SYNTHESIS AND THERAPEUTIC USES THEREOF

    Meditope variants and methods for their use are provided herein. A meditope variant as described herein comprises a peptide having a sequence CQFDLSTRRLKC (SEQ ID NO:1) or CQYNLSSRALKC (SEQ ID NO:2) that has one or more modifications at of least one amino acid residue of the sequence. Multivalent meditope variant tethering entities are also provided. Such entities may include two or more meditopes coupled via a long linker, multivalent scaffold, biotin-streptavidin, or IgG Fc domain. Further, methods of treating, imaging or diagnosing a disease or condition are provided. Such methods may include administering a therapeutically effective amount of a pharmaceutical composition to a subject, the pharmaceutical compound comprising an antibody-meditope complex; a multivalent tethering agent in combination with a monoclonal antibody or functional fragment thereof; or a combination thereof.

  • MACROLIDE SYNTHESIS PROCESS AND SOLID-STATE FORMS

    Described are methods for making macrolides, and, in particular, a method for making optionally substituted 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide and derivatives thereof, as well as uses of macrolides to make medicaments, methods of treatment using macrolides, and methods for making intermediates that, inter alia, may be used to make macrolides. Also described are solvated and non-solvated crystalline forms of 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide, as well as methods for making such crystalline forms, medicaments comprising (or derived from) such crystalline forms, methods for making medicaments comprising (or derived from) such crystalline forms, methods of treatment using such crystalline forms, and kits comprising such crystalline forms.

  • CONTAINERLESS SYNTHESIS OF AMORPHOUS AND NANOPHASE ORGANIC MATERIALS

    The invention provides a method for producing a mixture of amorphous compounds, the method comprising supplying a solution containing the compounds; and allowing at least a portion of the solvent of the solution to evaporate while preventing the solute of the solution from contacting a nucleation point. Also provided is a method for transforming solids to amorphous material, the method comprising heating the solids in an environment to form a melt, wherein the environment contains no nucleation points; and cooling the melt in the environment.

  • SYNTHESIS OF HOMOPOLYMERS AND BLOCK COPOLYMERS

    The present invention relates to the field of polymer chemistry and more particularly to homopolymers and block copolymers and methods of preparing the same.

  • PROCESS FOR THE SYNTHESIS OF 2-AMINOTHIAZOLE COMPOUNDS AS KINASE INHIBITORS

    The present invention relates to an industrial process of preparing pharmaceutical compounds having the formula I: ##STR00001## which are useful as certain tyrosine kinase inhibitors and more particularly as c-kit and bcr-abl inhibitors. The groups R1 and R2, identical or different, represent each a hydrogen, halogen atom, an alkyl, an alkoxy, a trifluoromethyl, an amino, an alkylamino, a dialkylamino, a solubilising group; m is 0-5 and n is 0-4; the group R3 represents an aryl or an heteroaryl group as described in claims herein.

  • LovD MUTANTS EXHIBITING IMPROVED PROPERTIES TOWARDS SIMVASTATIN SYNTHESIS

    The invention disclosed herein relates to methods and materials for producing simvastatin and related compounds such as huvastatin. In particular, the disclosure teaches that variants of the LovD acyltransferase polypeptide can be engineered to exhibit properties that facilitate their use in the production of simvastatin and/or huvastatin. The materials and processes disclosed herein are designed so that fermentation facilities currently producing lovastatin can be converted to producing simvastatin and related compounds with minimal modifications.

  • PROTECTED MONOMERS AND METHODS OF DEPROTECTION FOR RNA SYNTHESIS

    A nucleoside monomer that is protected by a thionocarbamate protecting group and contains one or more .sup.2H, .sup.13C, or .sup.15N isotopes in the ribose and/or base part is provided, as well as a method for making a polynucleotide that uses the same. Also provided is a polynucleotide synthesis method that employs a diamine to deprotect a protected polynucleotide.

  • Compositions of (-)-E-10-OH-NT and Methods for Their Synthesis and Use

    This present disclosure provides compositions comprising E-10-OH-NT metabolites of AT and NT, methods for their synthesis and methods for their use.

  • SYNTHESIS OF DENDRIMER CONJUGATES

    The present invention relates to novel methods of synthesis of therapeutic and diagnostic dendrimers. In particular, the present invention is directed to novel dendrimer conjugates, novel methods of synthesizing the same, compositions comprising the conjugates, as well as systems and methods utilizing the conjugates (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer, inflammatory disease) diagnosis and/or therapy, pain therapy, etc.)). Accordingly, dendrimer conjugates of the present invention may further comprise at least two different components for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and/or monitoring response to therapy. Furthermore, the novel synthesis methods of certain embodiments of the present invention provide significant advantages with regard to total reaction time and simplicity.

  • NOVEL MEDITOPES AND RELATED MEDITOPE-MONOCLONAL ANTIBODY DELIVERY SYSTEMS, SYNTHESIS AND THERAPEUTIC USES THEREOF

    Meditope variants and methods for their use are provided herein. A meditope variant as described herein comprises a peptide having a sequence CQFDLSTRRLKC (SEQ ID NO:1) or CQYNLSSRALKC (SEQ ID NO:2) that has one or more modifications at of least one amino acid residue of the sequence. Multivalent meditope variant tethering entities are also provided. Such entities may include two or more meditopes coupled via a long linker, multivalent scaffold, biotin-streptavidin, or IgG Fc domain. Further, methods of treating, imaging or diagnosing a disease or condition are provided. Such methods may include administering a therapeutically effective amount of a pharmaceutical composition to a subject, the pharmaceutical compound comprising an antibody-meditope complex; a multivalent tethering agent in combination with a monoclonal antibody or functional fragment thereof; or a combination thereof.

  • NOVEL PROCESS FOR THE SYNTHESIS OF PEMETREXED DISODIUM SALT

    The present invention relates to a novel process for the preparation of pemetrexed diethyl ester 2 ##STR00001## by purifying the mixture obtainable by reacting compounds 1 and 1a in the presence of a chemical agent capable of promoting the formation of a peptide bond in an aprotic organic solvent ##STR00002## characterized in that the mixture is subjected to the following steps: a) washing with a basic aqueous solution; b) concentration of the organic phase; c) addition of a polar organic solvent and/or a mixture of polar organic solvents; d) precipitation of the pemetrexed diethyl ester 2.

  • Oxabicycloheptanes and Oxabicycloheptenes, Their Preparation and Use

    This invention provides compounds having the structure ##STR00001## which may be used for the treatment of tumors.

  • ANTI-CANCER COMPOUNDS, SYNTHESIS THEREOF, AND METHODS OF USING SAME

    Embodiments relate to the field of chemistry and biochemistry, and, more specifically, to anti-cancer compounds, synthesis thereof, and methods of using same. Disclosed herein are various heterocyclic compounds and methods of using the novel anti-cancer compounds to inhibit the growth of a cancer cell, for instance a leukemia, non-small cell lung, central nervous system (CNS), skin, ovarian, renal, prostate, breast, or colon cancer cell. Other embodiments include methods of treating cancer in a subject, such as using the disclosed heterocyclic anti-cancer agents.

  • Synthesis And Use Of Glycoside Pro-Drug Analogs

    The present invention relates to methods and compositions for the synthesis, production, and use of pro-drug analogs. This invention relates to a method for the production of a broad group of glycosylated drugs, including but not limited to propofol, acetaminophen, and camptothecin carbohydrate derivatives.

  • PROTECTED MONOMER AND METHOD OF FINAL DEPROTECTION FOR RNA SYNTHESIS

    A method of deprotecting a solid support bound polynucleotide includes the step of contacting the polynucleotide with a composition comprising a diamine under conditions sufficient to deprotect the 2'-protected ribonucleotide residue. The solid support bound polynucleotide has at least one 2'-protected ribonucleotide residue, which has the following structure: ##STR00001## wherein B.sup.P is a protected or unprotected heterocycle; R.sup.12 is a protecting group selected from a hydrocarbyl, a substituted hydrocarbyl, an aryl, and a substituted aryl; X is O or S; and PG is a thionocarbamate protecting group.

  • Protein Synthesis Required for Long-Term Memory is Induced by PKC Activation on Days Preceding Associative Learning

    The present invention provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to stimulate the synthesis of proteins sufficient to consolidate long-term memory. The present invention also provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to downregulate PKC.

  • Photoproducts of Tryptophan, Their Synthesis and Uses Thereof

    We have found that exposure of an aqueous tryptophan solution to window sunlight results in the production of multiple tryptophan photoproducts that have the capability of activating the aryl hydrocarbon receptor and increasing the production of AhR target genes and proteins in hepatocytes. We have isolated three of those photoproducts not previously identified as AhR activators, their chemical identification and synthesis and the demonstration that all three have biologic activities as novel AhR activators. Further, one of the three is a completely novel, not previously described, chemical compound.

  • Novel Compounds and Synthesis of Tellurium-Derivatized Oligonucleotides for Structural and Functional Studies

    Disclosed are compounds of formula (I), a derivative, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. Also disclosed are methods of preparing compound of formula (I), a derivative, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. Further disclosed are methods of conducting drug discovery and research comprises applying the compound of formula (I), a derivative, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in an investigation.

  • HYDROLASES, NUCLEIC ACIDS ENCODING THEM AND METHODS FOR BIOCATALYTIC SYNTHESIS OF STRUCTURED LIPIDS

    Provided are hydrolases, including lipases, saturases, palmitases and/or stearatases, and polynucleotides encoding them, and methods of making and using these polynucleotides and polypeptides. Further provided are polypeptides, e.g., enzymes, having a hydrolase activity, e.g., lipases, saturases, palmitases and/or stearatases and methods for preparing low saturate or low trans fat oils, such as low saturate or low trans fat animal or vegetable oils, e.g., soy or canola oils.

  • STEREOSELECTIVE SYNTHESIS OF VITAMIN D ANALOGUES

    The present invention relates to intermediates useful for the synthesis of calcipotriol or calcipotriol monohydrate, to methods of producing said intermediates, and to methods of stereoselectively reducing said intermediates.

  • STEREOSELECTIVE SYNTHESIS OF VITAMIN D ANALOGUES

    The present invention relates to intermediates useful for the synthesis of calcipotriol or calcipotriol monohydrate, to methods of producing said intermediates, and to methods of stereoselectively reducing said intermediates.

  • Heterocyclic Modulators of Lipid Synthesis

    Compounds that are fatty acid synthesis modulators are provided. The compounds may be used to treat disorders characterized by disregulation of the fatty acid synthase function by modulating the function and/or the fatty acid synthase pathway. Methods are provided for treating such disorders including viral infections, such as hepatitis C infection, cancer and metabolic disorders.

  • Synthesis And Use Of Glycoside Derivatives of Propofol

    The present invention relates to methods and compositions for the synthesis, production, and use of pro-drug propofol analogs. This invention relates to a method for the production of a broad group of glycosylated propofol carbohydrate derivatives.

  • THERMOSTABLE BIOCATALYST COMBINATION FOR NUCLEOSIDE SYNTHESIS

    The present invention relates to a recombinant expression vector comprising: a) the sequence encoding a purine nucleoside phosphorylase (PNPase, E. C. 2.4.2.1), b) the sequence encoding a uridine phosphorylase (UPase, E. C. 2.4.2.3), c) or both; each of the sequences operably linked to one or more control sequences that direct the production of said phosphorylases in a suitable expression host; said sequences originating from the Archaea Thermoprotei class, characterized in that the PNPase is from Sulfolobus solfataricus (SEQ ID NO. 7) and the UPase is from Aeropyrum pernix (SEQ ID NO. 8). In addition, the present invention relates to A transglycosylation method between a sugar-donating nucleoside and an acceptor base in the presence of phosphate ions, characterised in that said method comprises the use of a uridine phosphorylase (UPase) of Aeropyrum pernix (NC_000854.2), a purine nucleoside phosphorylase (PN-Pase) of Sulfolobus solfataricus (NC_002754.1), or a combination thereof.

  • DIAZONIUM-FREE METHOD TO MAKE AN INDAZOLE INTERMEDIATE IN THE SYNTHESIS OF BICYCLIC 5-(TRIFLUORMETHOXY)-1H-3-INDAZOLECARBOXYLIC ACID AMIDES

    The present invention provides novel methods for preparing 5-(trifluoromethoxy)-1H-3-indazolecarboxylic acid (3), which is a useful precursor for the preparation of bicyclic-5-trifluoromethoxy-1H-indazole-3-carboxylic acid amides of Formula (1). Compounds of Formula (1) are active as agonists and partial agonists of the nicotinic .alpha.-7 receptor and are being studied for their use in the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain, such as for the treatment of Alzheimer's disease and schizophrenia, as well as other psychiatric and neurological disorders. The present methods are useful for preparing compound (3) on scale up levels.

  • Enzymatic Production or Chemical Synthesis and Uses for 5,7-Dienes and UVB Conversion Products Thereof

    Provided herein are steroidal compounds that are androsta-5,7-dienes or pregna-5,7-dienes and ultraviolet B (UVB) conversion products thereof and cholecalciferol derivatives hydroxylated at one or more of C1, C17, C20, C23, C24, C25, and C26 which includes pharmaceutical, cosmeceutical or nutraceutical compositions of the steroidal compounds as shown in Tables 1A, 2A and 3. Also provided is a method for producing hydroxylated metabolites of cholecalciferol via CYP11A1, CYP24, CYP27A1, or CYP27B1 enzyme systems where the hydroxylase has an activity to hydroxylate position C1 or C20 or other position of the sidechain of a secosteroid or its 5,7-dieneal precursor and the hydroxylated metabolites so produced. Methods are provided for inhibiting proliferation of either a normally or abnormally proliferating cell, for modifying immune activity, or for treating a condition associated with the proliferating or quiescent cell or immune cells by contacting the cell with or administering any of the compounds described herein.

  • COMPOSITIONS, SYNTHESIS, AND METHODS OF USING INDANONE BASED CHOLINESTERASE INHIBITORS

    The present invention provides novel indanone derivatives which can be advantageously used for treating and/or preventing of a medical condition for which inhibition of a cholinesterase is desired.

  • Regulating the Amino Acid Pool Used for the Acute-Phase Protein Synthesis

    The present invention is directed at a combination of (i) serine, (ii) cysteine, (iii) arginine and (iv) at least one branched amino acid, for use in the therapeutic or prophylactic treatment of inflammation or infection, wherein the combination is to be administered enterally and at a combination of (i) serine, (ii) cysteine, (iii) arginine and (iv) at least one branched amino acid, for use in the therapeutic or prophylactic treatment of an imbalance in the metabolic use of amino acid resources from the body or from nutrition in a subject having an inflammation or an infection, wherein the combination is to be administered enterally.

  • Synthesis, Recharging and Processing of Hydrogen Storage Materials Using Supercritical Fluids

    Processes for synthesizing, recharging, reprocessing and chemical doping of hydrogen storage materials utilizing supercritical fluids. The processes include dissolution or suspension of the material in a supercritical fluid mixed with hydrogen.

  • Method of Synthesizing Acetonide-Protected Catechol-Containing Compounds and Intermediates Produced Therein

    The inventors disclose here a novel, facile approach to the synthesis of acetonide-protected catechol-containing compounds having at least one amine group. In specific embodiments, the invention provides novel methods of synthesizing 3,4-dihydroxyphenylalanine (H-DOPA(acetonide)-OH (6)), Fmoc-protected H-DOPA(acetonide)-OH (Fmoc-DOPA(acetonide)-OH (7)), Fmoc-protected dopamine (Fmoc-dopamine(acetonide) (10)), TFA-protected dopamine (TFA-dopamine(acetonide) (13)) and acetonide-protected 4-(2-aminoethyl)benzene-1,2-diol (acetonide-protected dopamine (14)).

  • Pyrimidinyl Aryl Urea Derivatives being FGF Inhibitors

    The invention relates to heteroaryl aryl ureas of the formula IA, ##STR00001## wherein the radicals and symbols have the meanings as defined herein, the use of such compounds in the treatment of protein kinase dependent diseases; to pharmaceutical preparations comprising said heteroaryl aryl ureas, to processes for the manufacture of such novel compounds and to methods of treatment comprising the use of such heteroaryl aryl ureas.

  • HETEROCYCLIC COMPOUNDS AND USES THEREOF

    Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

  • SUBSTITUTED DIAMINOCARBOXAMIDE AND DIAMINOCARBONITRILE PYRIMIDINES, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH

    Provided herein are Diaminopyrimidine Compounds having the following structures: ##STR00001## wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are as defined herein, compositions comprising an effective amount of a Diaminopyrimidine Compound, and methods for treating or preventing liver fibrotic disorders or a condition treatable or preventable by inhibition of a JNK pathway.

  • Isoxazolines as Therapeutic Agents

    The present invention provides compound of Formula (I) ##STR00001## biologically active metabolites, pro-drugs, isomers, stereoisomers, solvates, hydrates and pharmaceutically acceptable salts thereof wherein the variables are defined herein. The compounds of the invention are useful for treating immunological conditions.

  • N-PHENYL-(PIPERAZINYL OR HOMOPIPERAZINYL)-BENZENESULFONAMIDE OR BENZENESULFONYL-PHENYL-(PIPERAZINE OR HOMOPIPERAZINE) COMPOUNDS SUITABLE FOR TREATING DISORDERS THAT RESPOND TO MODULATION OF THE SEROTONIN 5-HT6 RECEPTOR

    The present invention relates to N-phenyl-(piperazinyl or homopiperazinyl)-benzenesulfonamide or benzenesulfonyl-phenyl-(piperazine or homopiperazine) compounds, pharmaceutical compositions containing them, and their use in therapy. The compounds possess valuable therapeutic properties and are particularly suitable for treating diseases that respond to modulation of the serotonin 5-HT.sub.6 receptor.

  • Fused substituted aminopyrrolidine derivative

    A quinolone synthetic antibacterial agent having excellent properties as a medicine is provided, which has strong antibacterial activity not only to Gram-negative bacteria but also to Gram-positive cocci that have low sensitivity to quinolone antibacterial agents, and which exhibits high safety and excellent pharmacokinetics. A compound represented by the formula (I) or a salt thereof, or a hydrate thereof. Specifically, a quinolone derivative of the formula (I) wherein substituents R6 and R7 taken together with the carbon atoms to which they are bonded form a cyclic structure which may contain an oxygen atom as a ring constituent atom, the cyclic structure forming a 5-4, 5-5, or 5-6 fused bicyclic pyrrolidinyl substituent, the substituent being bonded to a quinolone mother skeleton Q containing a pyridobenzoxazine structure. ##STR00001##

  • ALBUMIN FUSION PROTEINS

    The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

  • Isoxazolines as Therapeutic Agents

    The present invention provides compound of Formula (I) ##STR00001## biologically active metabolites, pro-drugs, isomers, stereoisomers, solvates, hydrates and pharmaceutically acceptable salts thereof wherein the variables are defined herein. The compounds of the invention are useful for treating immunological conditions.

  • PROCESS FOR SYNTHESIS OF SILANE DIPEPTIDE ANALOGS

    The invention provides a method of preparing silane dipeptide analogs, comprising the steps of treating a solution of a substituted 1,2-oxasilolane with lithium metal to form a solution of the dilithium salt of a substituted 3-hydroxypropylsilanol, and reacting the solution of the dilithium salt of the substituted 3-hydroxypropylsilanol with a substituted enamine.

  • BIOCATALYSTS AND METHODS FOR THE SYNTHESIS OF (S)-3-(1-AMINOETHYL)-PHENOL

    The present disclosure provides engineered transaminase polypeptides having improved properties as compared to naturally occurring transaminases including the ability of converting the substrate, 3'-hydroxyacetophenone to (S)-3-(1-aminoethyl)-phenol in enantiomeric excess and high percentage conversion. Also provided are polynucleotides encoding the engineered transaminases, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases to synthesize (S)-3-(1-aminoethyl)-phenol and related compounds useful in the production of active pharmaceutical ingredients.

  • Synthesis of Chirally Purified Substituted Benzothiazole Diamines

    Methods for preparing chirally purified substituted 4,5,6,7-tetrahydro-benzothiazole diamines such as, for example, (6R)2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole and purifying a dominant enantiomer of substituted 4,5,6,7-tetrahydro-benzothiazole diamines from entantiomerically enriched mixtures of substituted 4,5,6,7-tetrahydro-benzothiazole diamines are provided herein.

  • PROCESS FOR PREPARING MODIFIED V-Ti-P CATALYSTS FOR SYNTHESIS OF 2,3-UNSATURATED CARBOXYLIC ACIDS

    The invention relates to a catalyst composition comprising a mixed oxide of vanadium, titanium, and phosphorus modified with alkali metal. The titanium component is derived from a water-soluble, redox-active organo-titanium compound. The catalyst composition is highly effective at facilitating the vapor-phase condensation of formaldehyde with acetic acid to generate acrylic acid, particularly using an industrially relevant aqueous liquid feed.

  • PROCESS FOR PREPARING MODIFIED V-Ti-P CATALYSTS FOR SYNTHESIS OF 2,3-UNSATURATED CARBOXYLIC ACIDS

    The invention relates to a catalyst composition comprising a mixed oxide of vanadium, titanium, and phosphorus modified with alkali metal. The titanium component is derived from a water-soluble, redox-active organo-titanium compound. The catalyst composition is highly effective at facilitating the vapor-phase condensation of formaldehyde with acetic acid to generate acrylic acid, particularly using an industrially relevant aqueous liquid feed.

  • PROCESS FOR PREPARING MODIFIED V-Ti-P CATALYSTS FOR SYNTHESIS OF 2,3-UNSATURATED CARBOXYLIC ACIDS

    The invention relates to a catalyst composition comprising a mixed oxide of vanadium, titanium, and phosphorus modified with alkali metal. The titanium component is derived from a water-soluble, redox-active organo-titanium compound. The catalyst composition is highly effective at facilitating the vapor-phase condensation of formaldehyde with acetic acid to generate acrylic acid, particularly using an industrially relevant aqueous liquid feed.

  • PROCESS FOR STEREOSELECTIVE SYNTHESIS OF 5-FLUORO-1-(2R,5S)-[2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-5-YL]CYTOSINE

    The present invention provides an improved process for stereoselective preparation of 5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine and pharmaceutically acceptable salts thereof.

  • PROCESS FOR STEREOSELECTIVE SYNTHESIS OF 5-FLUORO-1-(2R,5S)-[2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-5-YL]CYTOSINE

    The present invention provides an improved process for stereoselective preparation of 5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine and pharmaceutically acceptable salts thereof.

  • GENES AND PROTEINS FOR AROMATIC POLYKETIDE SYNTHESIS

    Nucleic acid molecules encoding polypeptides having polyketide synthase activity have been identified and characterized. Expression or over-expression of the nucleic acids alters levels of cannabinoid compounds in organisms. The polypeptides may be used in vivo or in vitro to produce cannabinoid compounds.

  • Fascile synthesis of biocompatible polymer capsule nanoparticles for drug encapsulation

    The present invention relates to a method for preparing a capsule nanoparticle used in encapsulating hydrophobic medicines, comprising the following steps: (A) providing a biocompatible polymer and an organic solution containing a hydrophobic medicine; (B) stirring the organic solution at 3-10.degree. C., and titrating with an alcohol solution, so as to make the biocompatible polymer encapsulate hydrophobic medicine to form a capsule nanoparticle; (C) ultrasonic vibrating the capsule nanoparticle at 3-10.degree. C.; (D) filtering the capsule nanoparticle to an average size controllable in the range of 60-450 nm; and (E) lyophilizing the encapsulated particles.

  • RNA SYNTHESIS-PHOSPHORAMIDITES FOR SYNTHETIC RNA IN THE REVERSE DIRECTION, AND APPLICATION IN CONVENIENT INTRODUCTION OF LIGANDS, CHROMOPHORES AND MODIFICATIONS OF SYNTHETIC RNA AT THE 3'-END

    The present invention relates to novel phosphoramidites, A-n-bz, C-n-bz, C-n-ac, G-n-ac and U are produced with an HPLC purity of greater than 98% and .sup.31P NMR purity greater than 99%. A novel process of reverse 5'.fwdarw.3' directed synthesis of RNA oligomers has been developed and disclosed. Using that method demonstrated high quality RNA synthesis with coupling efficiency approaching 99%.

  • MEMBRANE ENHANCED POLYMER SYNTHESIS

    This invention relates to the synthesis of polymers. More specifically, the present invention relates to the synthesis of heterobifunctional polymers and polymers with narrow and mono-disperse molecular weight distributions, and especially to the application of membranes to the synthesis of these polymers.

  • SIALIC ACID (A-(2-6))-D-AMINOPYRANOSE DERIVATIVES, SYNTHESIS METHODS AND USES THEREOF

    N-acyl modified sialic acid (.alpha.-(2.fwdarw.6))-D-aminopyranose derivatives, their synthesis methods and uses are disclosed. Sialic acid (.alpha.-(2.fwdarw.6))-D-aminopyranose derivatives represented by formula 1 are synthesized by using D-aminogalactose (glucose) and sialic acid as raw materials, which are coupled with carrier proteins or polypeptides to obtain glycoprotein (glycopeptide) conjugates. Acetyl is replaced by derivative acyl in the structures of said compounds, therefore the compounds show good activity in antitumor vaccines.

  • CHIRAL SPIRO-PYRIDYLAMIDOPHOSPHINE LIGAND COMPOUND, SYNTHESIS METHOD THEREFOR AND APPLICATION THEREOF

    The present invention relates to a chiral spiro-pyridylamidophosphine ligand compound, synthesis method therefor and application thereof. The chiral spiro-pyridylamidophosphine compound is a compound having a structure of Formula (I), a racemate or optical isomer thereof, or a catalytically acceptable salt thereof, and is mainly characterized by having a chiral spiro-dihydro-indene skeleton in its structure. The chiral spiro-pyridylamidophosphine compound may be synthesized with optical active 7-diaryl/alkylphosphino-7'-amino-1,1'-spiro-dihydro-indene or substituted 7-diaryl/alkylphosphino-7'-amino-1,1'-spiro-dihydro-indene having a spiro-skeleton as chiral starting material. The chiral spiro-pyridylamidophosphine compound may be used as a chiral ligand in asymmetric hydrogenation of a carbonyl compound catalyzed by iridium, in which the reaction activity is very high, the amount of the catalyst may be 0.0001 mol %, and the enantioselectivity of the reaction is up to 99.9% ee. ##STR00001##

  • USE OF AZIDES IN SYNTHESIS

    Described herein are inventive methods for synthesis of tetrazoles. In some embodiments, the method involves the use of a flow reactor. The methods provided herein are capable at being carried out in short reaction times, with high yields, with minimal side reactions, and/or with minimal chance of explosions caused by the presence of azides.

  • SYNTHESIS OF CYCLOHEXANE DERIVATIVES USEFUL AS SENSATES IN CONSUMER PRODUCTS

    The present invention provides synthetic routes for preparing various isomers of cyclohexane-based coolants, such as menthyl esters and menthanecarboxamide derivatives, in particular those substituted at the amide nitrogen, for example with an aromatic ring or aryl moiety. Such structures have high cooling potency and long lasting sensory effect, which make them useful in a wide variety of consumer products. One synthetic route involves a copper catalyzed coupling of a primary menthanecarboxamide with an aryl halide, such reaction working best in the presence of potassium phosphate and water. Using this synthetic route, specific isomers can be prepared including the menthanecarboxamide isomer having the same configuration as l-menthol and new isomers such as a neoisomer having opposite stereochemistry at the carboxamide (C-1) position. The neoisomer unexpectedly has potent and long lasting cooling effect. Preparation schemes for neoisomers of other menthyl derivatives which are useful as coolants, including esters, ethers, carboxy esters and other N-substituted carboxamides are also provided.

  • METHOD OF SYNTHESIS OF SUBSTISTUTED HEXITOLS SUCH AS DIANHYDROGALACTITOL

    The present invention provides an efficient method of synthesizing and purifying dianhydrohexitols such as dianhydrogalactitol. In general, as applied to dianhydrogalactitol, the method comprises: (1) reacting dulcitol with a concentrated solution of hydrobromic acid at a temperature of about 80.degree. C. to produce dibromogalactitol; (2) reacting the dibromogalactitol with potassium carbonate in t-butanol to produce dianhydrogalactitol; and (3) purifying the dianhydrogalactitol using a slurry of ethyl ether to produce purified dianhydrogalactitol.

  • SYNTHESIS OF BICYCLIC COMPOUNDS AND METHOD FOR THEIR USE AS THERAPEUTIC AGENTS

    Disclosed embodiments concern the synthesis and use of therapeutic compounds that for treating emerging flu strains and minimizing resistance to such strains. Methods for making the disclosed compounds concern using a base-mediated addition/cyclization sequence followed by functional group manipulation to develop functionalized compounds that can target neuraminidase, which makes them ideal candidates for treating influenza. Pharmaceutical compositions comprising the therapeutic compounds and biologically-acceptable materials are also described. Methods of inhibiting neuraminidase in subjects that are suspected of containing neuraminidase are also described. The use of metabolites of the disclosed compounds can also be used in diagnostic assays for therapeutic dosing of the disclosed compounds.

  • Synthesis of Drug Conjugates Via Reaction With Epoxide-Containing Linkers

    The present invention relates to drug derivatives and linkers. The invention specifically relates to compounds and methods of phosphonates and linkers, that are useful as carriers for imaging agents and useful in the treatment of various bone diseases.

  • LINKER AND SUPPORT FOR SOLID PHASE SYNTHESIS OF NUCLEIC ACID

    The invention provides a universal linker capable of synthesizing nucleic acid having a hydroxy group at the 3' terminal, a universal support carrying the linker, and a synthesis method of nucleic acid using the universal support. The linker contains a compound represented by the formula ##STR00001## wherein each symbol is as defined in the specification

  • SHORT SYNTHESIS OF TOLTERODINE, INTERMEDIATES AND METABOLITES

    A process is described for the preparation of intermediates which can be used for preparation of agents for urinary incontinence therapy, specifically to 2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxymethyl)phenol and its prodrugs.

  • SYNTHESIS OF ANTIVIRAL COMPOUND

    The present disclosure provides processes for the preparation of a compound of formula I: ##STR00001## which is useful as an antiviral agent. The disclosure also provides compounds that are synthetic intermediates to compounds of formula I.

  • METHODS AND COMPOSITIONS FOR SYNTHESIS OF NUCLEIC ACID MOLECULES USING MULTIPLERECOGNITION SITES

    The present invention provides compositions and methods for recombinational cloning. The compositions include vectors having multiple recombination .sites and/or multiple topoisomerase recognition sites. The methods permit the simultaneous cloning of two or more different nucleic acid molecules. In some embodiments the molecules are fused together while in other embodiments the molecules are inserted into distinct sites in a vector. The invention also generally provides for linking or joining through recombination a .number of molecules and/or compounds (e.g., chemical compounds, drugs, proteins or peptides, lipids, nucleic acids, carbohydrates, etc.) which may be the same or different. The invention also provides host cells comprising nucleic acid molecules of the invention or prepared according to the methods of the invention, and also provides kits comprising the compositions, host cells and nucleic acid molecules of the invention, which may be used to synthesize nucleic acid molecules according to the methods of the invention.

  • SYNTHESIS OF R-N-METHYLNALTREXONE

    This invention relates to stereoselective synthesis of R-MNTX and intermediates thereof, pharmaceutical preparations comprising R-MNTX or intermediates thereof and methods for their use.

  • PROSTHETIC GROUPS ATTACHED TO STANNYL POLYMER IN THE SYNTHESIS OF RADIOPHARMACEUTICALS

    The present invention relates to compositions and methods for preparing radiopharmaceutical compounds in high chemical-purity and isotopic-purity. The present invention provides polymer-bound precursors to radiopharmaceutical compounds that can be converted to radiopharmaceutical compounds in one step. In a preferred embodiment, a radiopharmaceutical precursor is bound to a polymeric support via a prosthetic group comprising an alkenyl-tin bond. The radiopharmaceutical precursor is converted to a radiopharmaceutical compound in one step involving cleavage of the alkenyl-tin bond and incorporation of a radioisotope to form the radiopharmaceutical compound. Importantly, the polymeric support containing the toxic tin by-product can be easily removed from the radiopharmaceutical compound by filtration. The present invention can be used to install a large number of different radioisotopes. In a preferred embodiment, the radioisotope is .sup.211At, .sup.123I, or .sup.131I.

  • METHODS OF SYNTHESIS AND/OR PURIFICATION OF DIAMINOPHENOTHIAZINIUM COMPOUNDS

    Described are methods of synthesis and/or purification of certain 3,7-diamino-phenothiazin-5-ium compounds (referred to herein as "diaminophenothiazinium compounds") including Methylthioninium Chloride (MTC) (also known as Methylene Blue), the resulting (high purity) compounds, compositions comprising such compounds (e.g., tablets, capsules), and the use of such high purity compounds. The compounds are useful in inactivating pathogens, and methods of medical treatment, prophylaxis, and diagnosis of diseases including a tauopathy, related neurological and infectious diseases.

  • COMPOSITION, SYNTHESIS, AND USE OF NEW SUBSTITUTED PYRAN AND PTERIN COMPOUNDS

    The present invention relates to substituted pterin compounds, their synthesis and use. In particular, the present invention relates to a new precursor compound and its analogs for synthesizing a new substituted pterin compound and its analogs. These new compounds are particularly suitable for treating molybdenum cofactor deficiency.

  • Fluoro-homoneplanocin A and nucleoside derivatives, method for the synthesis thereof, and the pharmaceutical compositions comprising the same as an active component for treatment of cancer

    The present invention relates to a fluoro-homoneplanocin A, its nucleoside derivative, and synthetic methods. The novel fluoro-homoneplanocin A and its nucleoside derivative in the present invention have an effect on cancer prevention or treatment, and therefore can be used as anticancer drugs.

  • BORONIC ESTER AND ACID COMPOUNDS, SYNTHESIS AND USES

    Disclosed herein is a method for reducing the rate of degradation of proteins in an animal, comprising contacting cells of the animal with certain boronic ester and acid compounds. Also disclosed herein are novel boronic ester and acid compounds, their synthesis and uses.

  • PROCESS FOR SYNTHESIS OF PHENOXY DIAMINOPYRIMIDINE DERIVATIVES

    A method for preparing a compound of formula k ##STR00001## or a salt or solvate thereof, wherein R.sup.1 is as defined herein, the method comprising treating a compound of formula j ##STR00002## or a salt or solvate thereof, with ammonia, to form the compound of formula k.

  • COMPOSITIONS, SYNTHESIS, AND METHODS OF USING PHENYLCYCLOALKYLMETHYLAMINE DERIVATIVES

    The present invention provides novel phenylcycloalkylmethylamine derivatives, and methods of preparing phenylcycloalkylmethylamine derivatives. The present invention also provides methods of using phenylcycloalkylmethylamine derivatives and compositions of phenylcycloalkylmethylamine derivatives. The pharmaceutical compositions of the compounds of the present invention can be used for treating and/or preventing obesity and obesity related co-morbid indications and depression and depression related co-morbid indications.

  • PROCESS FOR THE PREPARATION OF KEY INTERMEDIATES FOR THE SYNTHESIS OF STATINS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

    The invention relates to commercially viable process for the synthesis of key intermediates for the preparation of statins, in particular Rosuvastatin and Pitavastatin or respective pharmaceutically acceptable salts thereof. A new simple and short synthetic route for key intermediates is presented which benefits from the use of cheap and readily available starting materials, by which the conventionally most frequently used DIBAL-H as reducing agent can be avoided.

  • Phosphonate Ester Derivatives and Methods of Synthesis Thereof

    The disclosure describes methods of synthesis of phosphonate ester derivatives. Preferred methods according to the disclosure allow for large-scale preparation of phosphonate ester compounds having high purity. In some embodiments, preferred methods according to the disclosure also allow for the preparation of phosphonate ester derivatives without the use of chromatographic purification methods and in better yield than previously used methods for preparing such compounds. Also disclosed are morphic forms of phosphonate ester derivatives.

  • BITOPIC MUSCARINIC AGONISTS AND ANTAGONISTS AND METHODS OF SYNTHESIS AND USE THEREOF

    Compositions for treating a condition associated with activity of a muscarinic receptor (e.g., one or more of M.sub.1, M.sub.2, M.sub.3, M.sub.4, M.sub.5) and for anesthetizing a subject include a bitopic muscarinic antagonist or agonist. A bitopic muscarinic antagonist named JB-D4 was discovered. This bitopic ligand and its structural analogs, as well as bitopic muscarinic agonists, may be used as neuromuscular blocking agents (e.g., for use in compositions for anesthetizing a subject) and for the treatment of central nervous system disorders (e.g., Parkinson's disease, Schizophrenia, etc.), Overactive Bladder Syndrome, Chronic Obstructive Pulmonary Disease, asthma, and many other diseases associated with the activation or inhibition of M.sub.1-M.sub.5 acetylcholine receptors.

  • SYNTHESIS OF INTERMEDIATE FOR TREPROSTINIL PRODUCTION

    The compound according to Formula I is an intermediate in the synthesis of prostacylin analogs. The present invention provides an efficient method for synthesizing a Formula I compound. ##STR00001##

  • APPLICATION OF MULTIDIMENSIONAL MATRIX FOR DRUG MOLECULAS DESIGN AND THE METHODOLOGIES FOR DRUG MOLECULAR DESIGN

    The present invention relates to the application of multidimensional matrix for drug design and the methodology for drug design, which for the first time introduces the concept of matrix optimization in mathematics to the design of drugs and the relevant molecules. The present invention uses multidimensional matrix to analyze the permutation and combination of factors that affect the chemical structures and properties of drugs, and classifies and compares the huge amounts of factors need to be considered in the drug discovery according to certain features, thus utilizes fewer number of variables to represent the huge number of variable factors to specifically obtain chemical structures for effective drugs and improves the physicochemical properties of the compounds. By structural comparison of the results with the experimental data of known drugs or compounds in all stages of drug discovery, the present invention further optimizes the molecular chemical structure of drugs and significantly increases the specificity and efficiency of drug design, and significantly increases the efficiency of synthesis.