Abstract: The present invention provides a compound as represented by formula (1) or a pharmaceutically acceptable salt, a solvate, an active metabolite, a polymorph, an isotope label, an isomer or a prodrug thereof. The present invention also provides a pharmaceutical composition containing the same and the use of the compound and the pharmaceutical composition in preparation of drugs for treating tyrosine kinase-mediated diseases. The compound and the pharmaceutical composition comprising same provided by the present disclosure have significant tyrosine kinase inhibitory activity, can overcome tumor drug resistance, and break through blood-brain barrier, also have excellent pharmacokinetic properties and excellent oral bioavailability, and can be administered in a small dosage, thereby reducing treatment costs and possible side effects to a patient. Thus, the application potential is very great.

Abstract: Provided are a compound as represented by formula (D) and a preparation method therefor, where X2 is a halogen, Pg is selected from H and an amino protecting group, such as Cbz, Boc, Fmoc, Alloc, Teoc, methoxycarbonyl or ethoxycarbonyl. Also provided are a synthesized intermediate compound of the formula (D) compound and a preparation method for the intermediate compound.

Abstract: The present disclosure includes compounds, kits, and assay procedures for use in determining the levels of certain types of drugs in samples that contain specific binding proteins for the drugs. The present disclosure includes analog compounds useful for displacing the drugs from their endogenous binding proteins, and kits including same, as well as methods that utilize these displacers as binding competitors in pharmaceutical assays.

Abstract: The present invention provides compounds of formula I, compositions thereof, and methods of using the same as mTORC1 inhibitors.

Abstract: The present invention relates to methods and compositions for anti-aging therapy and for the treatment and prophylaxis of age-related diseases and disorders in a human subject in need of such therapy or treatment, the methods comprising the pulmonary administration to the subject, preferably via inhalation, of composition comprising rapamycin, or a prodrug or derivative thereof.

Abstract: The disclosure provides compounds and salts that show high selectivity and inhibitory activity for mTORC1 and uses thereof for the treatment of disease, such as Formula X: or a pharmaceutically acceptable salt thereof.

Abstract: A novel crystalline form of rifaximin and process for its preparation are described. A pharmaceutical composition comprising crystalline rifaximin is also described.

Abstract: A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O—R, where R is C(O)—(CH2)n-X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH2)) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs.

Abstract: Disclosed herein is a method for treating and/or preventing atrial fibrillation in a subject, comprising administering to the subject a pharmaceutical composition comprising an anti-CD44 neutralizing antibody or an antigen binding portion thereof which specifically binds to the amino-terminal domain of CD44. The anti-CD44 neutralizing antibody is a monoclonal antibody. The pharmaceutical composition further includes a pharmaceutically acceptable carrier.

Abstract: The present invention relates to an epidithiodioxopiperazine derivative represented by the following Chemical Formula 1 or its reduced derivative; a method for preparing a compound represented by Chemical Formula 1 having improved intracellular permeability and mimicking the activity of 2-Cys-Prx in its reduced form in the cells; a pharmaceutical composition for preventing or treating vascular diseases comprising an epidithiodioxopiperazine compound or its derivatives or pharmaceutically acceptable salts thereof as an active ingredient; a drug delivery device for local administration including the pharmaceutical composition; and a pharmaceutical composition for inhibiting melanoma metastasis comprising the epidithiodioxopiperazine compound or its derivatives or pharmaceutically acceptable salts thereof as an active ingredient.

Abstract: The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. One important area is the isolation and potential use of novel FKBP-ligand analogues and host cells that produce these compounds. The invention is particularly concerned with methods for the efficient transformation of strains that produce FKBP analogues and recombinant cells in which cloned genes or gene cassettes are expressed to generate novel compounds such as polyketide (especially rapamycin) FKBP-ligand analogues, and to processes for their preparation, and to means employed therein (e.g. nucleic acids, vectors, gene cassettes and genetically modified strains).

Abstract: The present invention provides improved processes for obtaining rapamycin derivatives including Biolimus A9.

Abstract: A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O—R, where R is C(O)—(CH2)n-X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH2)n) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs.

Abstract: Amorphous rifaximin, methods of making it, and pharmaceutical compositions containing it. Also described are methods of converting amorphous rifaximin to crystalline rifaximin and vice versa.

Abstract: There is provided inter alia a compound of formula (I) or a pharmaceutically acceptable salt thereof and its use in therapy.

Abstract: There is provided compounds of formula I, wherein R1, R2a, R2b, R2c, X, Y, Z, R3 and ring A/B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K, PIM family kinase and/or mTOR) is desired and/or required, and particularly in the treatment of cancer. The invention also relates to combinations containing such compounds.

Abstract: The present invention relates to Rifaximin polymorphic forms, to their use in medicinal preparations and to therapeutic methods using them.

Abstract: A process is described which enables Rifaximin in a completely amorphous form to be obtained. Said process comprises the steps of dissolving crude Rifaximin in absolute ethanol while hot and then collecting after precipitation by—cooling the title compound under amorphous form.

Abstract: The disclosure is in part directed to crystalline forms of an oxalate salt of 6-O-(4-dimethylaminoethoxy)cinnamoyl fumagillol.

Abstract: The present invention includes compounds useful as intermediates in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing macrolactams from the intermediates. One use of the methods and intermediates described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. HCV NS3 inhibitory compounds have therapeutic and research applications.

Abstract: The disclosure provides rifamycin and rifamycin derivative compositions, including rifabutin and rifabutin derivative compositions able to cause drug-sensitization in a cancer cell or inhibition of a cancer cell. The disclosure also provides methods of administering such compositions to cancer cells to sensitize them to drugs, such as chemotherapeutics, or directly inhibit them. The disclosure also provides methods of administering such compositions to increase reactive oxygen species (ROS), particularly superoxides, in cancer cells. The disclosure further provides methods of determining whether a cancer will respond to chemotherapeutics and whether to administer rifamycin or a rifamycin derivative based on ROS levels in cancer cells of a patient.

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: The invention refers to the selective acylation of Rapamycin at the 42-position (I) with an acylating agent of the formula (II) wherein R4 and R5 are the same or different, individually the rest of an acetal, especially tetrahydropyran, or of a carbonate or the rest of a silyl ether or taken together are the rest of a boronate, an acetal or ketal.

Abstract: A method for treating endocrine tumors by administration of an mTOR inhibitor, optionally in combination with another drug.

Abstract: The present invention relates to Rifaximin polymorphic, salt, hydrate, and amorphous forms, to their use in medicinal preparations and to therapeutic methods using them.

Abstract: This disclosure concerns a new family of phosphorus-containing compounds of Formula (I): and pharmaceutically acceptable derivatives thereof. Compositions containing such compounds and uses thereof are also provided.

Abstract: A method for preparing temsirolimus, the method including: using a substituted aromatic aldehyde to protect 2,2-dimethylol propionic acid to produce intermediate II; carrying out reaction between the intermediate II and 2,4,6-trichlorobenzoyl chloride; carrying out condensation reaction between a resulting product and rapamycin to produce intermediate III; and finally using sulfuric acid to remove a protecting group from the intermediate III to yield temsirolimus.

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective Factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: Disclosed is a method of preparing an amino acid ester of maytansinol by reacting maytansinol with an N-carboxyanhydride of an amino acid (NCA) in the presence of a drying agent. Also disclosed is an improved method of preparing an amino acid ester of maytansinol in which a nucleophile is added to the reaction mixture after completion of the reaction between maytansinol and an N-carboxyanhydride of an amino acid.

Abstract: Compounds of formula I: or salts thereof are disclosed. Also disclosed are pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for treating a Retroviridae viral infection including an infection caused by the HIV virus.

Abstract: A method for preventing and/or treating a functional gastrointestinal disorder, comprising administering, to a subject with the functional gastrointestinal disorder, rifaximin as an effective ingredient. The functional gastroinstestinal disorder includes a functional esophageal disorder, a functional gastroduodenal disorder (e.g., a functional dyspepsia), a functional bowel disorder (e.g., a functional bloating, a functional diarrhea), a functional abdominal pain syndrome, a functional gallbladder and Sphincter of Oddi disorder, a functional anorectal disorder (e.g., a functional fecal incontinence, a functional anorectal pain, a functional defecation disorder), a functional disorder in neonates and toddlers (e.g., an infant functional diarrhea), a functional disorder in children and adolescents (e.g., a childhood functional abdominal pain, a childhood nonretentive fecal incontinence), and other diseases.

Abstract: The present invention provides compounds of Formula (Ia): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: The conformationally restricted, spatially defined macrocyclic ring system of formula (I) is constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. Macrocycles described by this ring system I are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), inhibitory activity on enzymes or antimicrobial activity. In particular, these macrocycles show inhibitory activity on endothelin converting enzyme of subtype 1 (ECE-1) and/or the cysteine protease cathepsin S (CatS), and/or act as antagonists of the oxytocin (OT) receptor, thyrotropin-releasing hormone (TRH) receptor and/or leukotriene B4 (LTB4) receptor, and/or as agonists of the bombesin 3 (BB3) receptor, and/or show antimicrobial activity against at least one bacterial strain.

Abstract: A semi-synthetic rapamycin analog with a triazole moiety or a pharmaceutically acceptable salt or prodrug thereof, is a broad-spectrum cytostatic agent and a mTOR inhibitor, and is useful in the treatment of various cancers, or tumors in organs such as kidney, liver, breast, head and neck, lung, prostate, and restenosis in coronary arteries, peripheral arteries, and arteries in the brain, immune and autoimmune diseases. Also disclosed are fungal growth-, restenosis-, post-transplant tissue rejection- and immune- and autoimmune disease-inhibiting compositions and a method of inhibiting cancer, fungal growth, restenosois, post-transplant tissue rejection, and immune and autoimmune disease in a mammal.

Abstract: The present invention relates to a sorbent comprising a solid support material, the surface of which comprises a residue of a general formula (I), wherein the residue is attached via a covalent single bond to a functional group on the surface of either the bulk solid support material itself or of a polymer film on the surface of the solid support material.

Abstract: The invention provides therapeutic particulates including a macrolide, such as rapamycin, in solid state crystalline form, having a size of 20 ?m or less, or 10 ?m or less. The particulates are formed in one method by preparing a composition with a macrolide and first (e.g., xylene) and second (e.g., an alcohol, acetone, or acetonitrile) solvents. In the composition a maximum solubility for the macrolide that is greater than a maximum solubility of the macrolide dissolved in either the first or second solvent individually. The first and second solvents are then evaporated from the composition to provide the macrolide particulates. In another method, the particulates can be formed by a method including sonication and stirring/evaporation steps, and the particulates can be obtained from a supersaturated solution, formed during the process.

Abstract: The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, esters, or prodrugs thereof: Q-G-A-L-B—W??(I), which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The invention provides methods of making and using compounds of the formula shown, which are inhibitors of human plasmin and plasma kallikrein. (Formula I) The compounds are useful for the prevention of blood loss, and as components of fibrin adhesives.

Abstract: This invention relates to repeated administration of antigen-specific immunotherapeutics using protocols, or elements thereof, that do not induce immunosuppression. In some embodiments, the protocol has been previously shown not to induce immunosuppression in a subject.

Abstract: Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

Abstract: The disclosure provides macrolide particulates including a macrolide therapeutic agent such as rapamycin at high concentration in the particulate. In one method the particulates are made by adding a composition containing an polyoxyethylene sorbitan n-acyl ester, poly(ethyleneimine), or alkylated quaternary ammonium salt to a composition including macrolide dissolved in an alcohol such as ethanol. In another method the particulates are made by adding a non-solvent composition to a composition including macrolide and an alkyl-substituted chromanol dissolved in an alcohol such as ethanol. The formed macrolide particulates have one or more desirable properties including sizes in the range of 0.1 ?m to 10 ?m, spherical or near spherical shapes, low polydispersity, and/or stability. The macrolide particulates can be used for therapeutic compositions, or in association with an implantable or insertable medical device, such as associated with a polymeric coating on a device.

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: Provided are efficient methods for direct coupling of a maytansinoid with a carboxylic acid to prepare a maytansinoid C-3 ester in high yield using a rare earth metal-based or trifluoromethanesulfonate-based Lewis acid catalyst and a base together with a coupling reagent. Also provided are compositions used in such methods.

Abstract: The present invention relates to macrocyclic compounds of Formula I: or pharmaceutically acceptable salts thereof or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are JAK/ALK inhibitors useful in the treatment of JAK/ALK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.

Abstract: The present invention relates to macrocylic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of FLT3 (FMS-Related Tyrosine kinase 3). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the treatment of cell proliferative disorders, such as cancer.

Abstract: The present application describes organic compounds of Formula (I) and pharmaceutical compositions thereof, and their use for the treatment, prevention and/or amelioration of diseases, particularly bacterial infections.

Abstract: Crystalline polymorphous forms of rifaximin (INN) antibiotic named rifaximin ? and rifaximin ?, and a poorly crystalline form named rifaximin ?, useful in the production of medicinal preparations containing rifaximin for oral and topical use and obtained by means of a crystallization carried out by hot-dissolving the raw rifaximin in ethyl alcohol and by causing the crystallization of the product by addition of water at a determinate temperature and for a determinate period of time, followed by a drying carried out under controlled conditions until reaching a settled water content in the end product, are the object of the invention.

Abstract: The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR13—C1-5alkyl-, —C1-5alkyl-NR14—CO—C1-5alkyl-, —C1-2alkyl-NR21—H2—CO—NH—C1-3alkyl- or —C1-2alkyl-NR23—CO—CR16R17—NH—; X1 represents O or —O—C1-2alkyl-; X2 represents a direct bond, C1-2alkyl, —CO—C1-2alkyl or NR12—C1-2alkyl; R1 represents hydrogen or halo; R2 represents halo, acetylene or Het1 R3 represents hydrogen or cyano; R4 represents Ar4—C1-4alkyloxy-, C1-4alkyloxy- or C1-4alkyloxy substituted with one or where possible two or more substituents selected from Het2, NR7R8, hydroxy and C1-4alkyloxy-C1-4alkyloxy-; R7 represents hydrogen or C1-4alkyl; R8 represents C1-4alkyl substituted with NR25R26 or C1-4alkylsulfonyl; R12 represents hydrogen or C1-4alkyl-; R13 represents Ar6-sulfonyl or C1-6alkyloxycarbonyl optionally substituted with phenyl; R16 and R17 represents hydr

Abstract: The disclosure relates to compounds and compositions for bone formation, fracture treatment, bone grafting, bone fusion, cartilage maintenance and repair and methods related thereto. In certain embodiments, the disclosure relates to compositions comprising one or more compound(s) disclosed herein, such as clotrimazole, honokiol, magnolol, tacrolimus, pimecrolimus, sirolimus, everolimus, temsirolimus, spironolactone, fluticasone, fluticasone propionate, fluticasone furoate, linezolid, telmisartan, chlorambucil, retinol, isotretinoin, acitretin, etretinate, retinoic acid (tretinoin), teniposide, mitomycin C, cytarabine, decitabine, vinblastine, vincristine, vindesine, vinorelbine, valrubicin, doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxantrone, pixantrone, plicamycin, pazopanib, topotecan, camptothecin, irinotecan, sunitinib, derivatives, or salt thereof, for use in bone growth processes.

Abstract: A method for synthesizing temsirolimus, the method including: using a substituted boric acid to protect 2,2-dimethylol propionic acid to produce intermediate II; carrying out a reaction between the intermediate II and 2,4,6-trichlorobenzoyl chloride; carrying out condensation reaction between a resulting product and rapamycin to produce intermediate III; and finally using a diol to remove a protecting group from the intermediate III to yield temsirolimus.