Abstract: The present invention relates to pyridine, pyrimidine, pyrazine, and pyridazine compounds, and pharmaceutically acceptable compositions thereof, useful as BTK inhibitors.

Abstract: The invention relates to compounds of the formula or a pharmaceutically acceptable salt thereof, wherein R?, R1 through R7 and Ar are as defined herein. These compounds are useful as inhibitors of phosphodiesterase 10 (PDE10A) which are useful in treating central nervous system diseases such as psychosis and also in treating, for example, obesity, type II diabetes, metabolic syndrome, glucose intolerance, pain and ophthalmic diseases.

Abstract: The present invention is concerned with the formation of amide bonds. More specifically, the present invention, relates to processes for the manufacture of organogellant compounds (OG) as depicted below wherein L is selected from C2-C20 alkyl, C6-C20 aryl, C7-C20 alkylaryl, R1 are side chain substituents and one of X1, X2 is nitrogen and the other two are carbon. Processes of the present invention employ reaction mixtures with beneficial flow characteristics allowing sufficient agitation of all parts of these reaction mixtures and thus achieving adequate mixing of reaction partners and/or dissipation of heat. The beneficial flow characteristics are achieved by using suitable activation for coupling the terminal pyridine-carboxylic acid.

Abstract: The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, in duce cellular apoptosis and/or inhibit transcription in the subject.

Abstract: The present invention provides novel compounds of Formula (I) and Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

Abstract: Disclosed are 2,2?-bipyridyl compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein R1, Z and n are as described herein. In certain embodiments, a compound disclosed herein inhibits GDF8, and can be used to treat disease by blocking GDF8 signaling.

Abstract: The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma, lung cancer), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g.

Abstract: The present invention provides a quinazoline derivative represented by the following formula (I): wherein R1 and R2 represent a hydrogen atom, a halogen atom, or a lower alkyl group optionally having a substituent; Z represents a cycloalkyl group having a substituent or a cycloalkenyl group having a substituent; and Q represents a bicyclic heteroaryl group optionally having a substituent, or a pharmaceutically acceptable salt thereof. Since the compound has an inhibitory effect on the Wnt/?-catenin signaling pathway and exhibits an antitumor effect, it is useful as a medicine.

Abstract: Provided herein are Itraconazole analogs. Also provided herein are methods of inhibition of Hedgehog pathway, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, angiogenesis and treatment of disease with Itraconazole analogs.

Abstract: The present invention relates to novel compounds having ?2 adrenergic agonist and M3 muscarinic antagonist dual activity, to pharmaceutical compositions containing them, to the process for their preparation and to their use in respiratory therapies.

Abstract: A fluorogenic compound comprising a biologically active component and a hypoxia-activated protecting group which is fluorogenic. The biologically active component is bound to the fluorogenic component at an active binding position such that activity of the biologically active compound is suppressed until the protecting group is released. The protecting group is cleaved under hypoxic conditions, releasing the active compound and a fluorescent compound. The compounds can therefore be used in the treatment of hypoxia-related disease and disorder, such as tumour, and enable imaging of the release of the biologically active compound.

Abstract: A fumarate salt and a maleate salt of compound (I) represented by the following structural formula, as well as their corresponding pharmaceutical compositions, are disclosed. Particular single crystalline forms of 1:1 compound (I) fumarate and 1:1 compound (I) maleate are characterized by a variety of properties and physical measurements. Methods of preparing specific crystalline forms of 1:1 compound (I) fumarate and 1:1 compound (I) maleate are also disclosed. The present invention also provides methods of treating a subject with a cancer.

Abstract: This invention provides small molecule Myc-inhibitors. Also provided in the invention are therapeutic applications of these compounds for treating Myc-driven cancer and other related methods.

Abstract: A compound of formula (I) wherein R1 is a C5 to C39 alkyl or alkenyl group and R2 is (c) wherein A is an anion.

Abstract: The present invention refers to processes for preparing a dihydropyrimidine compound having Formula (I), or a tautomer thereof having Formula (la), as well as a intermediate thereof. The process of the invention has simple operation, high optical purity of product, high yield and convenient work-up, which is suitable for industrial production.

Abstract: The present invention refers to processes for preparing a dihydropyrimidine compound having Formula (I), or a tautomer thereof having Formula (Ia), as well as a intermediate thereof. The process of the invention has simple operation, high optical purity of product, high yield and convenient work-up, which is suitable for industrial production.

Abstract: This application features pyrazol-3-one compounds that activate pro-apoptotic BAX. Also featured are methods of using such compounds, e.g., for the treatment or prevention of diseases, disorders, and conditions associated with deregulated apoptosis of cells (e.g., insufficient apoptosis of diseased or damaged cells or essentially the absence of apoptosis of diseased or damaged cells).

Abstract: The present invention relates to a process for preparation of crystalline Form-SDI of Dasatinib (I). Said crystalline Form-SDI of Dasatinib is characterized by X-ray powder diffraction pattern comprising of at least seven 2?° peaks selected from the XRPD peak set of 5.8, 11.5, 12.7, 13.2, 17.3, 17.5, 18.1, 20.1, 20.5, 22.1, 25.4, 26.6, 26.8±0.20 2?°; IR spectrum having at least five absorption peaks selected from about 3390 cm?1, 2923 cm?1, 1621 cm?1, 1615 cm?1, 1537 cm?1, 1316 cm?1, 1061 cm?1, 815 cm?1 and 783 cm?1; and DSC isotherm comprising at least two endothermic peaks ranging between ?130° C. to 150° C., 160° C. to 175° C. or 280° C. to 290° C. The pharmaceutical compositions of the crystalline Form-SDI of Dasatinib or its hydrate thereof may be useful as an anti-cancer agent.

Abstract: Provided herein, inter alia, are methods and compositions for inhibiting ?v?1 integrin and for treating fibrosis.

Abstract: The invention is concerned with the compounds of formula I: and salts thereof and other compounds of formulas II-IX as disclosed herein. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formulas I-IX as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain or asthma.

Abstract: The present invention relates to substituted triazolopyridine compounds of general formula (I), in which R1, R2, R3, R4, and R5 are as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

Abstract: 7-(3-Aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate and hydrates thereof, processes for their preparation, pharmaceutical compositions comprising them, and their use in antibacterial therapy.

Abstract: The invention provides a method of blocking transmission of a Plasmodium parasite and a method of treating or preventing malaria comprising administering to an animal an effective amount of a first compound of formula I: wherein A, B, R1, R2, R10, and R11 are described herein, either alone or in combination with a second compound selected from elesclomol, NSC 174938, NVP-AUY922, Maduramicin, Narasin, Alvespimycin, Omacetaxine, Thiram, Zinc pyrithione, Phanquinone, Bortezomib, Salinomycin sodium, Monensin sodium, Dipyrithione, Dicyclopentamethylene-thiuram disulfide, YM155, Withaferin A, Adriamycin, Romidepsin, AZD-1 152-HQPA, CAY10581, Plicamycin, CUDC-101, Auranofin, Trametinib, GSK-458, Afatinib, and Panobinostat.

Abstract: A fluorophore and methods of detecting cations and hydrophobic environments using the fluorophore are disclosed. The fluorophore includes an imidazo[1,5-a]pyridinium ion core and has the formula where R1, R2, R3 and X? are as defined in the specification, and n is an integer from 1 to 4.

Abstract: The present application relates to a series of substituted pyrazolo[1,5-a]pyridine compounds, their use as tropomyosin receptor kinase (Trk) family protein kinase inhibitors, method of making and pharmaceutical compositions comprising such compounds.

Abstract: A process for producing a diazabicyclooctane derivative represented by Formula (IV) and intermediates thereof by carrying out the following steps: wherein P is an NH protecting group capable of being removed with acid; R1 is 2,5-dioxopyrrolidin-1-yl, 1,3-dioxo-3a,4,7,7a-tetrahydro-1H-isoindol-2(3H)-yl, 1,3-dioxohexahydro-1H-isoindol-2(3H)-yl, or 3,5-dioxo-4-azatricyclo[5.2.1.02.6]dec-8-en-4-yl; R2 is hydrogen, ClCO— or Cl3COCO—; R3 is C1-6 alkyl or heterocyclyl, or forms a 3- to 7-membered heterocyclic ring together with the —O—NH— to which it is attached; and OBn is benzyloxy.

Abstract: This disclosure relates, at least in part, to a method of treatment. In one embodiment, the method of treatment comprises administering to a subject in need of such treatment a first therapeutic agent including compound (1): (structurally represented) or a pharmaceutically acceptable salt thereof in combination with a second therapeutic agent, wherein the first therapeutic agent and the second therapeutic agent are administered either simultaneously or sequentially.

Abstract: Described herein are compounds that are autotaxin inhibitors, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with autotaxin activity.

Abstract: The purinone derivative 6-amino-9-[(3R)-1-(2-butynoyl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one hydrochloride has Btk-selective inhibitory activity and, in addition to having excellent metabolic stability, it is a compound that exhibits a high level of solubility and absorption with respect to the free base and can be crystallized, hence it can serve as a therapeutic agent for diseases involving B cells and mast cells.

Abstract: The disclosure relates to Compounds of Formulae (IA) and (IB), and pharmaceutically acceptable salts thereof wherein Z1, Z2, Z3, Xa, Xb, Xc, Xd, Y, X2, and X4 are as defined herein, compositions comprising an effective amount of a Compound of Formula (IA) and/or (IB), and methods to treat or prevent a condition, such cancer which overexpresses Her-kinases, comprising administering to an patient in need thereof a therapeutically effective amount of a Compound of Formula (IA) or (IB). The disclosure further relates to compounds of Formulae (IA) and (IB) in which X2 is a leaving for introducing a radiolabeled atom, such as 124I or 131I and to methods of using such compounds in the preparation of radiolabeled compounds, particularly for use in imaging.

Abstract: Pyrazolopyrimidone and pyrrolotriazone derivatives, methods of preparation thereof, and pharmaceutical uses thereof are described. Specifically, pyrazolopyrimidone and pyrrolotriazone derivatives represented by the general formula (I) and pharmaceutically acceptable salts thereof are described. The pyrazolopyrimidone and pyrrolotriazone derivatives are useful as gonadotropin releasing hormone (GnRH) antagonists, such as for therapeutic agents for endometriosis. The definitions of the substituents in the general formula (I) are the same as the definitions in the specification.

Abstract: A compound represented by the general formula (1) has a pyridone ring structure introduced into a pyrrolo pyrimidine skeleton, so that the compound has a strong Axl inhibitory activity. Consequently, the compound can be used as a therapeutic agent for Axl-related diseases including cancers such as acute myeloid leukemia, melanoma, breast cancer, pancreatic cancer, and glioma, kidney diseases, immune system diseases, and circulatory system diseases.

Abstract: The present invention provides bicyclic azaheterocyclobenzylamines of Formula I: wherein the variables are defined herein, that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.

Abstract: Disclosed herein are aza-pyridone compounds, pharmaceutical compositions that include one or more aza-pyridone compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an orthomyxovirus infection, with an aza-pyridone compound. Examples of an orthomyxovirus viral infection include an influenza infection.

Abstract: Compounds of formula (I) and pharmaceutically acceptable salts, esters, amides, or radiolabelled forms thereof, wherein GAr, L1, Z1 and Z2 are as defined in the specification, are useful in treating conditions or disorders prevented by or ameliorated by voltage-gated sodium channels, e.g., Nav 1.7 and/or Nav 1.8. Methods for making the compounds are disclosed. Also disclosed are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.

Abstract: The present invention relates to compounds of formula (I) and to compositions comprising the same and to the use of the compounds and their compositions in treatment, for example in the treatment of inflammatory diseases, in particular respiratory inflammatory disease. The invention also extends to methods of making said compounds.

Abstract: Provided is a method for preparing Ibrutibin (I), and steps of preparing same comprise: 4-benzyloxybenzoyl chloride (II) is used as a raw material, condensation and methoxidation reactions occur among 4-benzyloxybenzoyl chloride (II), malononitrile, and dimethyl sulfate to generate 4-benzyloxyphenyl(methoxy)vinylidenedicyanomethane (III), pyrazole cyclization occurs between the intermediate (III) and 1-(3R-hydrazino-1-piperidino)-2-propylene-1-ketone (IV) to acquire 1-[(3R)-[3-(4-benzyloxyphenyl)-4-nitrile-5 -amino-1H-pyrazole]-1-piperidino]-2 propylene-1-ketone (V), and pyrimidine cyclization occurs between an intermediate (V) and a cyclizing agent to prepare Ibrutinib (I). In the preparation method, the raw material is readily available, and the process is simple, economical, environmentally friendly, and is suitable for industrial production.

Abstract: The present invention relates to compounds of formula (I), wherein A, B, R1 and R2 are as defined herein before useful for the treatment of psychiatric disorders.

Abstract: The invention provides novel compounds having the general formula (I) wherein R1, Y and R2 are as described herein, compositions including the compounds and methods of using the compounds.

Abstract: The present invention includes compositions that are useful in preventing or treating metastasis in a subject diagnosed with cancer. The present invention also includes methods of preventing or treating metastasis in a subject diagnosed with cancer, wherein the method comprises administering to the subject in need thereof an effective amount of a pharmaceutical formulation comprising at least one pharmaceutically acceptable carrier and at least one CX3CR1 or fractalkine antagonist.

Abstract: In certain embodiments the invention is directed to a process for preparing an oxycodone hydrochloride composition having less than 25 ppm of 14-hydroxycodeinone.

Abstract: This invention relates to opioid ketal compounds of Formula (I), Formula (II), or Formula (III): or a pharmaceutically acceptable salts thereof, wherein R1 is H or CH3, R2 is H or OH, n is 0, 1, 2 or 3, R3 and R4 are independently H or optionally substituted C1-C4 alkyl, or when n is 0, then R3 and R4 and the carbon atoms to which they are attached together form six, or seven membered ring, which is optionally mono or disubstituted by C1-C4 alkyl. The invention also relates to oxycodone ketal compounds of Formula (IV) or (V): or a pharmaceutically acceptable salts thereof. The invention also relates to the use of such compounds for the treatment, prevention, or amelioration of pain.

Abstract: The present invention relates to a method for the synthesis of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (i.e. iriniotecan), comprising: (a) preparing 10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptotecin; and (b) selectively ethylating the compound of step (a) at the 7-position, thus resulting in the preparation of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin. The present invention is further directed to the use of 10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (i.e. 7-des-ethyl-irinotecan) as intermediate in a method for the synthesis of irinotecan as described.

Abstract: Disclosed are chiral dopants of general formula (I) below as well as uses thereof involving chiral liquid crystal polymers and markings comprising these polymers: wherein R1, R2, R3, R4, A1 and A2, m, n, o and p are as defined in the claims.

Abstract: The present invention discloses a sulfur-substituted podophyllotoxin derivative, synthesis method thereof, and use thereof. The present invention introduces a rigid aromatic heterocyclic compound, as well as a further sulfonamidated product of 3-amino-5-mercapto-1,2,4-triazole, 2-amino-5-mercapto-1,3,4-thiadiazole, 4-methylbenzenesulfonyl chloride, or 4-methoxybenzenesulfonyl chloride as a substituent group, into position 4 of the C-ring of podophyllotoxin or 4?-demethylepipodophyllotoxin to obtain the podophyllotoxin derivative shown in formula (V), said derivative having significantly increased antitumor activity and reduced toxic side effects. Experiments on in vitro tumor cell inhibition indicate that the antitumor activity of the compound of formula (V) of the present invention is significantly higher than the antitumor activity of podophyllotoxin or 4?-demethylepipodophyllotoxin.

Abstract: The present invention provides a method for in vivo delivery of endothal to a target cell in a subject, the method comprising administering to the subject a compound having the structure: Formula (I).

Abstract: The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Homer-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

Abstract: One class of blue thiophene electrochromic compounds include 3,4-(2,2-bis(2-oxo-3-phenylpropyl))propylenedioxythiophene, 3,4-(2,2-bis(2-oxo-3-phenylbutyl))propylenedioxythiophene, and 3,4-(2,2-bis(2-oxo-3-phenylamyl))propylenedioxythiophene. The thiophene electrochromic compounds can change color between blue and transparency. The thiophene compounds can be electropolymerized on the surface of the ITO glass to form a film. The film has characteristics of low driving voltage (within ±1V), fast response time, and large transmittance difference between colored-state and bleached-state (up to 77.5%). The thiophene electrochromic compounds can be used in the electrochromic window, rearview mirror, electrochomeric display, and the like.

Abstract: The invention relates to compounds of formula wherein R, R1, R2, X, and Y are as defined herein and to a pharmaceutically suitable acid addition salt thereof. Compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds can be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

Abstract: Disclosed are compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein Ring B, A1, A2, R6, w and n1 are defined and described herein; compositions thereof; and methods of use thereof. These compounds are useful for treating a variety of neurological and psychiatric disorders, such as those described herein.