Abstract: The present invention is directed to methods for screening for metallohydrolase inhibitors using metal binding moieties in combination with targeting moieties.

Abstract: The present invention relates to compounds of formula I wherein R1a to R1e and R2 to R5 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are glucocorticoid receptor antagonists useful for the treatment and/or prevention of diseases such as diabetes, dyslipidemia, obesity, hypertension, cardiovascular diseases, adrenal imbalance or depression.

Abstract: The invention provides a reagent for detecting amyloid deposited in a biological tissue which can detect amyloid in vitro and in vivo with high sensitivity using a compound which has affinity with amyloid and is suppressed in toxicity such as mutagencity. The reagent for detecting amyloid deposited in a biological tissue comprises a compound represented by the following formula (1) or a salt thereof: wherein A1, A2, A3 and A4 independently represent a carbon or nitrogen; R1 is a radioactive halogen substituent; R2 is a group selected from the group consisting of hydrogen, hydroxyl group, methoxy group, carboxyl group, amino group, N-methylamino group, N,N-dimethylamino group and cyano group; and m is an integer of 0 to 2, provided that at least one of A1, A2, A3 and A4 represents a carbon, and R1 binds to a carbon represented by A1, A2, A3 and A4.

Abstract: Dicationic compounds that are highly selective for binding G-quadruplex DNA are described. Several compounds exhibit groove binding toward G-quadruplex DNA and in vitro and in vivo activity versus Trypanosoma brucei rhodesiense. The compounds represent novel drugs for the treatment of cancer, malaria, leishmania, and trypanosomiasis.

Abstract: To provide a novel heterocyclic compound having a bipolar property. To improve element characteristics of a light-emitting element by application of the novel heterocyclic compound to the light-emitting element. A heterocyclic compound represented by a general formula (G1) and a light-emitting element formed using the heterocyclic compound represented by the general formula (G1) are provided. When the heterocyclic compound represented by the general formula (G1) is used for the light-emitting element, the characteristics of the light-emitting element can be improved.

Abstract: The invention relates to a compound which has affinity with amyloid, shows sufficiently rapid clearance from normal tissues and is suppressed in toxicity such as mutagenicity, and also relates to a low-toxic diagnostic agent for Alzheimer's disease containing the compound. The compound is represented by the following formula (1) or a salt thereof: wherein A1, A2, A3 and A4 independently represent a carbon or a nitrogen, and R3 is a group represented by the following formula: wherein R1 is a radioactive halogen substituent; m is an integer of 0 to 4; and n is an integer of 0 or 1, provided that at least one of A1, A2, A3 and A4 represents a carbon, and R3 binds to a carbon represented by A1, A2, A3 or A4.

Abstract: The invention provides a reagent for detecting amyloid in a biological tissue which can detect amyloid in vitro and in vivo with high sensitivity using a compound which has affinity with amyloid and is suppressed in toxicity such as mutagenicity. The reagent for detecting amyloid deposited in a biological tissue comprises the compound represented by the following formula (1) or a salt thereof: wherein A1, A2, A3 and A4 independently represent a carbon or a nitrogen, and R3 is a group represented by the following formula: wherein R1 is a radioactive halogen substituent; m is an integer of 0 to 4; and n is an integer of 0 or 1, provided that at least one of A1, A2, A3 and A4 represents a carbon, and R3 binds to a carbon represented by A1, A2, A3 or A4.

Abstract: The present invention provides new compounds of formula I, wherein Q, R1, R2, R4, R5, R6, Xi, R7, R8, M and G1n are defined as in formula I; invention compounds are modulators of follicle-stimulating hormone—(“FSH”) which are useful for male and female contraception as well as other disorders modulated by FSH receptor.

Abstract: A compound effective as a probe targeting amyloid for image diagnosis and a reagent comprising the compound for detecting amyloid deposited on a biological tissue are provided. Provided are a compound represented by the following formula (1): wherein R1 is a group selected from the group consisting of a halogen substituent, alkyl substituent with 1 to 4 carbon atoms, alkoxy substituent having alkyl chain with 1 to 4 carbon atoms and hydroxyl group, R2 is a group selected from the group consisting of a cyano substituent, alkyl substituent with 1 to 4 carbon atoms and halogen substituent, R3 is a group selected from the group consisting of a hydroxyl group, halogen substituent and substituent represented by the following formula: (wherein R4 is a hydrogen, halogen substituent or hydroxyl group, and m is an integer of 1 to 4), provided that at least one of R1, R2, R3 and R4 represents a radioactive halogen, and a reagent comprising the same.

Abstract: The present invention relates to novel 1,2,3-substituted indolizine derivative which are inhibitors of fibroblast growth factors, to methods or preparing such derivatives, to pharmaceutical compositions comprising such derivatives, and to methods of treatment comprising such derivatives.

Abstract: Compounds of formula (I), combinations and uses thereof for disease therapy, or a pharmaceutically acceptable salt or solvate thereof, including all tautomers, stereoisomers and polymorphs thereof wherein: R1 represents C2-8alkyl; C2-8alkenyl; —(C1-6alkyl)-aryl; —(C1-6alkyl)-heteroaryl; —(C1-6alkyl)-carbocyclyl; —(C1-6alkyl)-heterocyclyl; -aryl; -heteroaryl; -carbocyclyl or -heterocyclyl; wherein said aryl or heteroaryl groups may be optionally substituted by one or more substituents selected from, C1-4alkyl, C1-4-fluoroalkyl, C1-4alkoxy, C1-4-fluoroalkoxy, hydroxy, —SO2(C1-4alkyl), —SO2N(C1-4alkyl)(C1-4alkyl), —SOC1-4alkyl, —SOC3-6cycloalkyl —C(O)O(C1-4alkyl), benzyloxy and phenyl; and wherein said carbocyclyl and heterocyclyl groups may be optionally substituted by one or more substituents selected from —C1-4 alkyl, —C1-4 alkoxy, hydroxyl, halogen and oxo; R2 represents H; C1-4alkyl or halogen; R3 represents H; C1-4alkyl or halogen; and R4 represents H; C1-4alkyl or halogen.

Abstract: Compounds, compositions and methods are provided which are useful in the treatment of diseases through the modulation of potassium ion flux through voltage-dependent potassium channels. More particularly, the invention provides heterocycles, compositions and methods that are useful in the treatment of central or peripheral nervous system disorders (e.g., migraine, ataxia, Parkinson's disease, bipolar disorders, trigeminal neuralgia, spasticity, mood disorders, brain tumors, psychotic disorders, myokymia, seizures, epilepsy, seizure, retinal degeneration, hearing and vision loss, Alzheimer's disease, age-related memory loss, learning deficiencies, anxiety, neuronal degeneration and motor neuron diseases, maintaining bladder control or treating urinary incontinence) and as neuroprotective agents (e.g., to prevent stroke and the like) by modulating potassium channels associated with the onset or recurrence of the indicated conditions.

Abstract: The present invention encompasses compounds of general formula (1) wherein the groups R2 to R4, L, Q and n are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use for preparing a pharmaceutical composition with the above-mentioned properties.

Abstract: Provided herein are compounds of the formula where A1, A2, A3, A4, L, Q, R1, R2, R3, R4, Rx, Ry, Rz, X, Y1, Y2, Y4 and Z are as described herein, and compositions thereof that are useful in the treatment of inflammatory and immune conditions and diseases. In particular, the invention provides aryl nitrile compounds which modulate the expression and/or function of a chemokine receptor.

Abstract: The invention relates to novel pyrazolo[1,5-a]pyridine-3-carboxylic acid compounds of the formula in which all of the variables are as defined in the specification, in free form or in salt form, to their preparation, to their use as medicaments and to medicaments comprising them.

Abstract: Pyrazolo[1,5-a]pyridines are described, including methods for their preparation, and their use as agents or drugs for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

Abstract: The present invention provides compounds of formula (I): including salts, solvates, and pharmaceutically acceptable derivatives thereof, pharmaceutical formulations containing them, processes for their preparation, and methods of treatment using them.

Abstract: The present invention is directed to novel compounds of formula (I) wherein the variables are as defined herein. The compounds of formula (I) are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases and proliferative disorders and conditions, for example, cancers.

Abstract: The present invention relates to new compounds, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals.

Abstract: The present invention relates to compounds of Formula (I), pharmaceutical compositions thereof, and use thereof as corticotropin releasing factor 1 (CRF1) receptor antagonists in the treatment of psychiatric and neuroendocrine disorders, neurological diseases, and metabolic syndrome.

Abstract: Disclosed is a commercially advantageous method for producing a pyrazole fused ring derivative (such as a 7-phenylpyrazolo[1,5-a]pyridine derivative).

Abstract: Tricyclic compounds containing a cyclopropanecarboxylic acid fused to a bicyclic ring, including pharmaceutically acceptable salts, are agonists of G-protein coupled receptor 40 (GPR40) and are useful as therapeutic compounds, particularly in the treatment of Type 2 diabetes, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

Abstract: The invention provides a reagent which can detect amyloid in vitro and in vivo with high sensitivity using a compound which has affinity with amyloid. The reagent for detecting amyloid deposited in a biological tissue comprises the compound represented by the following formula (1) or a salt thereof: wherein A1, A2, A3 and A4 independently represent a carbon or nitrogen, R2 is a group selected from the group consisting of a hydrogen, hydroxyl group, carboxyl group, sulfuric acid group, amino group, nitro group, cyano group, non-radioactive halogen substituent, alkyl substituent with 1 to 4 carbon atoms and alkoxy substituent with 1 to 4 carbon atoms, and R2 is a radioactive halogen substituent, provided that at least one of A1, A2, A3 and A4 represents a carbon, and R1 binds to a carbon represented by A1, A2, A3 or A4.

Abstract: Provided is a compound which is useful as a therapeutic agent for chronic renal insufficiency and a therapeutic agent for diabetic nephropathy. The present inventors have made extensive studies on an ornithine derivative having an antagonistic action against an EP4 receptor, and as a result, they have found that by introducing cycloalkanediyl at a C terminal of the ornithine part of the compound of the present invention, the physicochemical properties such as solubility, and the like can be improved, thereby giving further preferred properties as a pharmaceutical. Therefore, they have completed the present invention. The compound of the present invention exhibits a good antagonistic action against an EP4 receptor, and thus, it is useful as a therapeutic agent for chronic renal insufficiency and diabetic nephropathy.

Abstract: Heteroaryl amide derivatives are provided, of the Formula: wherein variables are as described herein. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using such compounds to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

Abstract: Compounds of formula I: in free or salt or solvate form, where R1, R2, R3 and R20 have the meanings as indicated in the specification, are useful for treating diseases mediated by the ALK-5 and/or ALK-4 receptor. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described. These compounds are useful for the treatment of inflammatory or obstructive airways diseases such as pulmonary hypertension, pulmonary fibrosis, liver fibrosis, cancer, muscle diseases such as muscle atrophies and muscle dystrophies, and systemic skeletal disorders such as osteoporosis.

Abstract: The invention provides fluorinated compounds of formula (I): The compounds may be used in diagnosis or treatment of a disorder in a mammal characterised by an abnormal density of peripheral benzodiazepine receptors.

Abstract: This invention provides a compound of the formula (I): or a pharmaceutically acceptable salt thereof, and compositions containing such compounds and the use of such compounds for the manufacture of medicament for gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders, cardiac failure, heart arrhythmia, diabetes and apnea syndrome. These compounds have 5-HT4 receptor agonistic activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans.

Abstract: Provided are certain chemical entities, pharmaceutical compositions, and methods of treatment of a member of the flaviviradae family of viruses such as hepacivirus (Hepatitis C or HCV).

Abstract: The present invention provides a novel compound having an excellent corticotrophin-releasing-factor receptor antagonistic activity. That is, it provides a compound represented by the following formula or a salt thereof. Wherein R1 denotes a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group and the like; R2 denotes a halogen atom, a cyano group, a nitro group, a C1-10 alkyl group, a C2-10 alkenyl group, C2-10 alkynyl group and the like; R3 denotes a C6-14 aromatic hydrocarbon cyclic group or a 5- to 14-membered aromatic heterocyclic group, each of which may have a substituent; and X, Y and X are independent of each other and each denotes N or CR4 (wherein R4 denotes a hydrogen atom, a halogen atom, a cyano group, a nitro group, an optionally halogenated C1-6 alkyl group and the like) and, in this case, at least two of X, Y and Z denote CR4.

Abstract: There are provided compounds according to formula I wherein the substitutents are as described herein. Further provided are methods of using such compounds for the treatment of nuclear hormone receptor-associated conditions, such as age related diseases, for example sarcopenia. Also provided are pharmaceutical compositions containing such compounds and processes for preparing some of the compounds of the invention. Other embodiments are also disclosed.

Abstract: Phosphatidylinositol (PI) 3-kinase inhibitor compounds, their pharmaceutically acceptable salts, and prodrugs thereof; compositions of the new compounds, either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases characterized by the abnormal activity of growth factors, protein serine/threonine kinases, and phospholipid kinases.

Abstract: Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, and/or AP-1 and/or NF-?B activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I): its enantiomers, diastereomers, or a pharmaceutically-acceptable salt, or hydrate, thereof, wherein the group X is O or (Rx)(Ry); is heterocyclo or heteroaryl; E is —N—, —NR1—, —O—, —C(?O), —S—, —SO2—, or —CR2—; F is —N—, —NR1a, —O—, —C(?O), —S—, —SO2—, or —CR2a—; G is independently N, —NR1b—, —O—, —C(?O), —S—, —SO2— or —CR2b— provided that the heterocyclic ring formed does not contain a S—S or S—O bond and at least one of E, F and G is a hetero atom; and Ma, Rx, Ry, R1, R1a, R1b, R2, R2a, R2b, R4, R5a, R6, R7, X, Za and Z are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases employing said compounds.

Abstract: Compounds of formula I active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases. Formula (I) wherein Ar is optionally substituted heteroaryl; R2 is hydrogen, lower alkyl or halogen; U is selected from the group consisting of —S(O)2—, —C(X)—, —C(X)—N(R10)—, and —S(O)2—N(R10)—; R3 is optionally substituted lower alkyl, optionally substituted C3.6 cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl; and wherein R1, R3, R4, m, L1, X R10 are as described herein.

Abstract: The present invention relates to acylated indanyl amines according to the general formula (I) wherein R1-R4 have the meanings given in the description, A is CH2, CHOH or CH—(C1-C3-alkyl), B is CH2 or CH—(C1-C3-alkyl), and R5 is an aryl or heteroaryl group, possibly substituted by the substituents listed in the description.

Abstract: The disclosure provides compounds of formula I, II, III, IV, and V, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

Abstract: Provided are certain chemical entities, and methods of use to modulate diskeletal myosin, skeletal actin, skeletal tropomyosin, skeletal troponin C, skeletal troponin I, skeletal troponin T, and skeletal muscle, including fragments and isoforms thereof, as well as the skeletal sarcomere, and methods of use in the treatment of obesity, sarcopenia, wasting syndrome, frailty, muscle spasm, neuromuscular disease, and other indications.

Abstract: The present invention discloses and claims a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I). Wherein R, R1, R2, R3 and R4 are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted N-phenyl-bipyrrolidine carboxamides and intermediates therefor.

Abstract: The present invention is directed to compounds which contain substituted napthyridines which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention.

Abstract: The present invention provides a compound represented by the formula (I): or a pharmacologically acceptable salt thereof, wherein Ar1 represents an imidazolyl group that may be substituted with a C1-6 alkyl group, or the like, Ar2 represents a phenyl group that may be substituted with a C1-6 alkoxy group, or the like, X1 represents a double bond or the like, and Het represents an imidazolyl group that may be substituted with a C1-6 alkyl group, or the like, which is effective as a therapeutic or prophylactic agent for a disease caused by A?.

Abstract: The present invention provides compounds of formula (I), their use as PARP inhibitors as well as pharmaceutical compositions comprising said compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, R7, n, m and X have defined meanings.

Abstract: [Problems] To provide a useful compound as an active ingredient for a preventing and/or treating agent for rejection in the transplantation of an organ, bone marrow, or a tissue, an autoimmune disease, or the like, which has an excellent S1P1 agonist activity.

Abstract: The invention is directed to Compounds of Formula I: as well as methods of making and using the compounds.

Abstract: The invention provides a compound of the formula (I): for use in medicine: or salts or tautomers or N-oxides or solvates thereof; wherein R1 is an optionally substituted heterocyclic group having from 3 to 12 ring members provided that the cyclic group joined to the pyrazole contains at least one heteroatom selected from N, O or S; A is a bond or —Y—(B)n—; B is C?O, NRg(C?O) or O(C?O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; n is 0 or 1; Y is a bond or an alkylene chain of 1,2 or 3 carbon atoms in length; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from optionally substituted carbocyclic and heterocyclic groups having from 3 to 12 ring members or an optionally substituted C1-8 hydrocarbyl group; with the proviso that R1 is not formula (II): where X, R3? and R4? are defined in the claims.

Abstract: The present invention provides transient receptor potential vanilloid (TRPV) modulators of formula (I). In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPV3. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPV3.

Abstract: In its many embodiments, the present invention provides a novel class of 4-cyano, 4-amino, and 4-aminomethyl derivatives of pyrazolo[1,5-a]pyridine, pyrazolo[1,5-c]pyrimidine, and 2H-Indazole compounds and 5-cyano, 5-amino, and 5-aminomethyl derivatives of imidazo[1,2-a]pyridine and imidazo[1,5-a]pyrazine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

Abstract: Compounds of Formula (I): are receptor tyrosine inhibitors useful in the treatment of diseases mediated by class (3) and class (5) receptor tyrosine kinases. Particular compounds of this invention have also been found to be inhibitors of Pim-1.

Abstract: The present invention provides compounds and amyloid probes thereof that allow for an antemortem method of diagnosing AD and quantitating the extent or progression of amyloid deposits (plaques) by in vivo imaging of amyloid and/or amyloid deposits in the regions of the brain. Preferably, an amyloid probe of the invention can cross the blood-brain barrier and distinguish AD brain from normal brain. An amyloid probe can be administered to a patient in amounts suitable for in vivo imaging of amyloid deposits. Amyloid probes of the invention can also be used to detect and quantitate amyloid deposits in diseases including, without limitation, Down's syndrome, familial AD and homozygotes for the apolipoprotein E4 allele. In one aspect, the compounds may be used in the treatment or prophylaxis of diseases that include, without limitation, AD and type 2 diabetes mellitus.

Abstract: In its many embodiments, the present invention provides a novel class of 4-cyano, 4-amino, and 4-aminomethyl derivatives of pyrazolo[1,5-a]pyridine, pyrazolo[1,5-c]pyrimidine, and 2H-Indazole compounds and 5-cyano, 5-amino, and 5-aminomethyl derivatives of imidazo[1,2-a]pyridine and imidazo[1,5-a]pyrazine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

Abstract: Radiolabeled tracers for sulfotransferases (SULTs), their synthesis, and their use are provided. Included are substituted phenols, naphthols, coumarins, and flavones radiolabeled with 18F, 123I, 124I, 125I, or 11C. Also provided are in vivo techniques for using these and other tracers as analytical and diagnostic tools to study sulfotransferase distribution and activity, in health and disease, and to evaluate therapeutic interventions.