Abstract: The present invention relates compounds of Formula (A) as H3R antagonists, as well as their preparation and uses, and further relates pharmaceutical compositions comprising these compounds and their uses as modulators of Histamine 3 Receptor (H3R) functions. The present invention also relates to the uses of the compounds or pharmaceutical compositions in treating or preventing certain disorders and diseases which relate to H3R functions in humans.

Abstract: The present invention relates to compositions and methods for reducing cell proliferation and/or promoting cell death. It is based, at least in part, on the discovery that in platinum drug-resistant cell lines, certain compounds, together with a second antiproliferative agent (e.g., cisplatin), act synergistically to promote apoptosis. Accordingly, the present invention provides for novel anticancer strategies.

Abstract: This invention provides novel guanylate cyclase C (GC-C) agonists and their therapeutic use. The agonists may be used either alone or in combination with one or more additional agents.

Abstract: Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, salts, and solvates thereof, wherein R and R? have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HCV inhibitors, in HCV therapy.

Abstract: The invention relates to novel heterocyclic compounds which are pyrazolopyridine derivatives that induce FGFR dimerization, having the general formula: M-L-M2 in which M and M2, which may be identical or different, each represent, independently of one another, a monomer unit M and L represents a linker group which links M1 and M2 covalently with the monomer unit which follows (Formula M). Process for the preparation thereof and therapeutic use thereof.

Abstract: The present invention provides analogs and derivatives of thalidomide which inhibit cancer and angiogenesis. The present invention further provides compounds which disrupt microtubule polymerization. The present further provides methods of treating cancers comprising mutant p53.

Abstract: HslVU is the proteasome-related system composed of HslV peptidase and HslU chaperone. It is involved in intracellular proteolysis. The presence of HslVU homologs in pathogenic microbes and its absence in human makes it an antimicrobial drug target. The functional HslVU complex forms when HslV dodecamer is flanked at both ends by HslU hexamers. In the HslVU complex, intercalation of C-termini residues of HslU subunits into the clefts between adjacent HslV subunits results in allosteric activation of HslV. We identified small molecules capable of activating HslV peptidase in the absence of its natural activator HslU. Quinazoline and chromone derivatives were suggested by ligand docking to bind at the HslU C-termini intercalation pockets in the HslV. This was confirmed by HslV activation assays with these compounds that gave ED50 in sub-micromolar range. The results showed that small, extracellular non-peptidic molecules can activate the HslV peptidase which in turn would initiate intracellular proteolysis.

Abstract: The use of BETi as a potential treatment for FSHD is provided. Specifically, the use of BETi, and particularly selective BETi for BRD4, are shown to inhibit DUX4 expression which is expected to result in a decrease in the severity of symptoms of FSHD. Further, the treatments are shown to work when pulsed as opposed to continuous. This allows for a BETi to be supplied to a human in a pulse, and then allows the human to not need any additional treatment for a window at least as long as the one of the treatment pulse.

Abstract: The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.

Abstract: HslVU is the proteasome-related system composed of HslV peptidase and HslU chaperone. It is involved in intracellular proteolysis. The presence of HslVU homologs in pathogenic microbes and its absence in human makes it an antimicrobial drug target. The functional HslVU complex forms when HslV dodecamer is flanked at both ends by HslU hexamers. In the HslVU complex, intercalation of C-termini residues of HslU subunits into the clefts between adjacent HslV subunits results in allosteric activation of HslV. We identified small molecules capable of activating HslV peptidase in the absence of its natural activator HslU. Quinazoline and chromone derivatives were suggested by ligand docking to bind at the HslU C-termini intercalation pockets in the HslV. This was confirmed by HslV activation assays with these compounds that gave ED50 in sub-micromolar range. The results showed that small, extracellular non-peptidic molecules can activate the HslV peptidase which in turn would initiate intracellular proteolysis.

Abstract: The present invention provides analogs and derivatives of thalidomide which inhibit cancer and angiogenesis. The present invention further provides compounds which disrupt microtubule polymerization. The present further provides methods of treating cancers comprising mutant p53.

Abstract: Disclosed are oxo-hydroquinazolines that are useful as selective TSHR agonists. The compounds may be used for detecting or treating thyroid cancer, or treating a bone degenerative disorder.

Abstract: Quinazoline derivatives 1-25, (2-[3,4-bis(methyloxy)phenyl]quinazolin-4-(3H)-one) and 2-[2-(ethyloxy)phenyl]quinazoline-4-(3H)-one) are reported as ?-glucuronidase inhibitors useful in the treatment of ?-glucuronidase hyperactivity disorders.

Abstract: This invention relates to substituted bicyclic dihydropyrimidinones of formula 1 and their use as inhibitors of neutrophil elastase activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of pulmonary, gastrointestinal and genitourinary diseases, inflammatory diseases of the skin and the eye and other autoimmune and allergic disorders, allograft rejection, and oncological diseases.

Abstract: A compound for treating protein kinase-related disease or disorder having a structure of formula (A): wherein X is N or CH; Y is NH, O, or CH2; Z is an aryl or a heteroaryl; and R1, R2, R3, and R4 are independently H, halo, nitro, cyano, aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, —ORa, —C(O)Ra, —C(O)NRaRb, —NRaC(O)Rb, —NRaRb, —S(O)2Ra, —S(O)2NRaRb, —NRaS(O)2Rb, —N?CRaRb, or —NRaC(O)NHRb, wherein each of Ra and Rb, independently, is H, alkyl, alkenyl, alkynyl, aryl, aryloxy, alkoxy, hydroxy, heteroaryl, cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, or Ra and Rb, together with the nitrogen atom to which they are bonded, form heteroaryl, heterocycloalkyl, or heterocycloalkenyl; or R3 and R4 are as defined above, and R1 and R2 together with the carbons, to which they are attached, form a heterocycloalkenyl or heteroaryl.

Abstract: Disclosed are oxo-hydroquinazolines that are useful as selective TSHR agonists. The compounds may be used for detecting or treating thyroid cancer, or treating a bone degenerative disorder.

Abstract: The present disclosure relates to compounds, which are useful for inhibition of BET protein function by binding to bromodomains, and their use in therapy.

Abstract: A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.

Abstract: The present invention provides analogs and derivatives of thalidomide which inhibit cancer and angiogenesis. The present invention further provides compounds which disrupt microtubule polymerization. The present further provides methods of treating cancers comprising mutant p53.

Abstract: Provided is a compound of the formula I or a pharmaceutically acceptable salt, solvate or stereoisomer thereof: wherein Ar represents R5, R7, R8, R2?, R4?, R5?, R6?, R7?, R8? independently represent H, OH, F, Cl, Br, methoxyl group, NH2 group or NMe2 group; X represents NH, O or S; and R6 is selected from the group consisting of: pyrrolidinyl group, piperidinyl group, morpholino group, methoxyl group, and dimethylamine group. The present invention also provides a composition comprising the compound of formula I. The compound and the composition in accordance with the present invention are effective on treating or alleviating a disease or disorder, such as malignant glioma.

Abstract: A synergistic combination of a vanilloid receptor VR-1 antagonist and an NSAID or a pharmaceutically acceptable salt or solvate of either or both compounds thereof.

Abstract: A compound of formula (1): wherein R1, R2, R3 and Y are as defined herein, or a pharmaceutically-acceptable and -cleavable ester, or acid addition salt thereof, useful for promoting the release of parathyroid hormone, e.g. for preventing or treating bone conditions which are associated with increased calcium depletion or resorption or in which stimulation of bone formation and calcium fixation in the bone is desirable.

Abstract: The present disclosure provides non-naturally occurring polyphenol compounds that inhibit the bromodomain and extra terminal domain (BET) proteins. The disclosed compositions and methods can be used for treatment and prevention of cancer, including NUT midline carcinoma, Burkitt's Lymphoma, Acute Myelogenous Leukemia, and Multiple Myeloma; autoimmune or inflammatory diseases or conditions, and sepsis.

Abstract: The invention relates to substituted nitrogen containing bicyclic heterocycles of the formula (I) wherein Z is CH2 or N—R4 and X, R1, R2, R4, R6, R7 and n are as defined in the description. Such compounds are suitable for the treatment of a disorder or disease which is mediated by the activity of MDM2 and/or MDM4, or variants thereof.

Abstract: The present disclosure provides non-naturally occurring polyphenol compounds that inhibit the bromodomain and extra terminal domain (BET) proteins. The disclosed compositions and methods can be used for treatment and prevention of diseases or disorders that are susceptible to administration of a BET inhibitor.

Abstract: This disclosure is directed to treatment of addictions and primary impulse-control disorders using phosphodiesterase 7 (PDE7) inhibitors, alone or in combination with other therapeutic agents.

Abstract: Screening methods for identifying compounds and compounds and pharmaceutical compositions for treating and preventing cancer are disclosed. The compounds affect signal transduction downstream of the MET receptor.

Abstract: Surprising antiviral activity of 3-amino-2-(4-nitrophenyl)-4-(3H)-quinazolinone (Compound 1) was reported in the treatment or prevention of viral infections, particularly in combination with other antiviral agents such as interferon and/or ribavarin.

Abstract: Use of compound of formula (I), wherein, is, or, and wherein the symbols are as defined, or a pharmaceutically-acceptable and -cleavable ester, or acid addition salt thereof, for the preparation of a medicament for promoting the release of parathyroid hormone, e.g. for preventing or treating bone conditions which are associated with increased calcium depletion or resorption or in which stimulation of bone formation and calcium fixation in the bone is desirable.

Abstract: The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate, and/or modulate kinase receptor, particularly c-Met, KDF, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.

Abstract: The present invention relates to substituted amino-quinazolinones of general formula (I) wherein the groups R1 to R14 and A, are defined as in the specification and claims and the use thereof for the treatment of Alzheimer's disease (AD) and similar diseases.

Abstract: The present invention provides compounds capable of regulating apoptosis, e.g., via regulating mitochondrial fission or fusion. The present invention also provides methods of screening for compounds capable of regulating apoptosis and methods of treating conditions association with apoptosis.

Abstract: The present disclosure relates to novel solid pharmaceutical formulations and process for their preparation. The present disclosure also provides, in part, methods of using the pharmaceutical formulations for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for the treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.

Abstract: Provided is a compound of the formula I or a pharmaceutically acceptable salt, solvate or stereoisomer thereof: wherein Ar represents R5, R6, R7, R8, R1?, R2?, R3?, R4?, R5?, R6?, R7?, R8? independently represent H, OH, F, Cl, Br, C1 to C6 alkyl group, C1 to C6 alkoxy group, C2 to C6 alkenyl group, C2 to C6 alkenoxy group, C2 to C6 alkynyl group, C2 to C6 alkynoxy group, amine group, mono- or di-substituted amino group, cyclic C1 to C5 alkylamino group, imidazolyl group, morpholino group, piperazinyl group, optionally substituted with one or more hydroxy or halo; and X represents NH, O or S. The present invention also provides a composition comprising the compound of formula I. The compound and the composition in accordance with the present invention are effective on treating or alleviating a disease or disorder, such as malignant glioma.

Abstract: The present invention provides an improved and commercially viable process for preparation of erlotinib substantially free of N-methoxyethyl impurity, namely N-[(3-ethynylphenyl)-(2-methoxyethyl)]-6,7-bis(2-methoxyethoxy)-4-quinazolinamine, and its pharmaceutically acceptable acid addition salts thereof in high purity and in high yield. According to the present invention, erlotinib or a pharmaceutically acceptable acid addition salt of erlotinib substantially free of N-methoxyethyl impurity is prepared by isolating erlotinib or a pharmaceutically acceptable salt of erlotinib from a solvent medium comprising dimethyl sulfoxide and an alcoholic solvent.

Abstract: Screening methods for identifying compounds and compounds and pharmaceutical compositions for treating and preventing cancer are disclosed. The compounds affect signal transduction downstream of the MET receptor.

Abstract: This invention generally relates to compositions and methods for cancer treatment and, in particular, to compositions able to interact (e.g., bind to) with MUC1 growth factor receptor or its ligands, and methods for treating the same. The invention also relates to assays or use of such compositions for the treatment of patients susceptible to or exhibiting symptoms characteristic of cancer or tumorigenesis. Other compositions of the present invention useful for the treatment or prevention of cancer or tumorigenesis include homologs, analogs, derivatives, enantiomers or functional equivalents. The present compositions can also be packaged in kits in some cases.

Abstract: TSHR inverse agonists and neutral antagonists that are useful for treating Graves' orbitopathy, Graves' hyperthyroidism and/or thyroid cancer.

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 quinazolinone, 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, hearing and vision loss, Alzheimer's disease, age-related memory loss, learning deficiencies, anxiety 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: Methods for screening for inhibitors of endoplasmic reticulum (ER) stress are provided. These methods involve the addition of thapsigargin, which induces ER stress, and a test agent to mammalian cells in multi-well plates. Cell survival can be readily monitored by measuring intracellular ATP content using a bioluminescent reagent. Screening a commercially available library of 50,000 compounds led to the identification of 93 hit compounds that were subjected to secondary assays to confirm their ability to rescue cells from thapsigargin-induced cell death.

Abstract: 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.

Abstract: The present invention provides analogs and derivatives of thalidomide which inhibit cancer and angiogenesis. The present invention further provides compounds which disrupt microtubule polymerization. The present further provides methods of treating cancers comprising mutant p53.

Abstract: The present invention relates to the use of a series of quinazoline-derived compounds to produce a medicament for the treatment and/or prevention of neurological and/or neurodegenerative diseases, such as Parkinson's disease or Alzheimer's disease. The present invention also relates to a method for the treatment and/prevention of neurological and/neurodegenerative diseases comprising the administration of a therapeutically effective amount of said compounds.

Abstract: The present invention provides analogs and derivatives of thalidomide which inhibit cancer and angiogenesis. The present invention further provides compounds which disrupt microtubule polymerization. The present further provides methods of treating cancers comprising mutant p53.

Abstract: A compound of the general formula (I): (wherein the symbols are as defined in the description), or a non-toxic salt thereof.

Abstract: Disclosed are methods of regulating interleukin-6 (IL-6) and/or vascular cell adhesion molecule-1 (VCAM-1) and methods of treating and/or preventing cardiovascular and inflammatory diseases and related disease states, such as, for example, atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s) by administering a naturally occurring or synthetic quinazolone derivative. The invention provides novel synthetic quinazolone compounds, as well as pharmaceutical compositions comprising those compounds.

Abstract: The present invention relates to the 3-arylquinazolin-4-one compounds of the formula I and the salts thereof, wherein n is 0, 1 or 2; X is O, S or N—R4; Y1 is N or CH; Y2 is N or C—R5; R1 is C1-C10-alkyl, C1-C10-haloalkyl, C2-C10-alkenyl, C2-C10-haloalkenyl, C2-C10-alkynyl, C2-C10-haloalkynyl, C3-C12-cycloalkyl, C5-C12-cycloalkenyl, C3-C12-cycloalkyl-C1-C4-alkyl, C5-C12-cycloalkenyl-C1-C4-alkyl, where the cycloalkyl radical and the cycloalkenyl radical in the last four mentioned radicals are unsubstituted, partially or fully halogenated and/or carry 1, 2, 3, 4, or 5 C1-C4-alkyl radicals; R2 is hydrogen, halogen, CN, C(Z)NH2, C1-C4-alkyl or C1-C4-haloalkyl, wherein Z is O, S or NR6; and the variables k, R, R3, R4, R5 and R6 are as defined in the claims. The invention also relates to the use of novel compounds of formula I for combating invertebrate pests and to a method for controlling invertebrate pests.

Abstract: The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.

Abstract: Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract: Disclosed are novel compounds that are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for the treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis. Also disclosed are pharmaceutical compositions comprising the novel compounds.