Abstract: Hepatitis C virus inhibitors having the general formula (I) are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

Abstract: A process for preparing a crystalline rapamycin analog includes: combining the rapamycin analog with an organic medium to form a mixture; incubating the mixture until the rapamycin analog crystallizes; and recovering the crystalline rapamycin analog. The organic medium can be a solvent, and the process can include causing the rapamycin analog to dissolve into the solvent, and incubating the solvent until the rapamycin analog crystallizes. The following can also be performed: forming a slurry of crystalline rapamycin analog; stirring the rapamycin analog mixture until the rapamycin analog crystallizes; saturating the rapamycin analog solution; forming a supersaturated rapamycin analog solution; combining an antisolvent with the rapamycin analog and the solvent to form a biphasic mixture, and incubating the biphasic mixture to cause a liquid-liquid phase split.

Abstract: The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of diseases.

Abstract: Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt, solvate or ester thereof, wherein U, W, X, L, Y, M, Z, c, d, e, f, g, h, s, t, R1, R2, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 and R18 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Abstract: A process for preparing an o-alkylated rapamycin derivative represented by the following general formula (1) is provided. The process includes the steps of reacting rapamycin with an alkyl triflate, purifying the resulting reaction product with a normal phase chromatograph and further purifying a purified product, which has been purified with the normal phase chromatograph, with a reverse phase chromatography wherein R represents an alkyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, acyloxyalkyl, aminoalkyl, alkylaminoalkyl, alkoxycarbonylaminoalkyl, acylaminoalkyl, or aryl.

Abstract: A rapamycin analog composition includes a crystalline form of a rapamycin analog. The crystal can be a hydrate, dehydrate, solvate, or desolvate.

Abstract: The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. Therefore in aspect the present invention provides 17-desmethylrapamycin and analogues thereof, methods for their production, including recombinant strains, and isolation and uses of the compounds of the invention. In a further aspect the present invention provides for the use of 17-desmethylrapamycin and analogues thereof in the induction or maintenance of immunosuppression, the stimulation of neuronal regeneration or the treatment of cancer, B-cell malignancies, fungal infections, transplantation rejection, graft vs. host disease, autoimmune disorders, diseases of inflammation vascular disease and fibrotic diseases, and in the regulation of wound healing.

Abstract: The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to compounds that are polo-like kinase (PLKs) inhibitors useful for the treatment of disease states mediated by PLK, especially PLK4, in particular such compounds that are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumour growth, rheumatoid arthritis, restenosis and atherosclerosis.

Abstract: A single-step, one-pot process to obtain zotarolimus and other rapamycin derivatives on large scale is presented, which improves currently available synthesis schemes. In one embodiment, dried rapamycin is dissolved in isopropylacetate (IPAc). The solution is cooled, and 2,6-Lutidine is added, followed slowly adding triflic anhydride at ?30° C. Salts are then removed by filtration. Tetrazole, followed by a tert-base diisopropylethylamine (DIEA) is added to the triflate solution. After incubation at room temperature, the product is concentrated and purified by a silica gel column using THF/heptane as eluant. The fractions containing the product are collected, concentrated, and purified again using an acetone/heptane column. The product containing fractions are concentrated. The product is dissolved in t-BME and precipitated with heptane. The solids are dissolved in acetone, treated with butylated-hydroxy toluene (BHT), and the solution concentrated.

Abstract: There is provided a series of macrocyclic diaminopropanes of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, m, n, W, X, Y, Z and L as defined herein, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein (APP) by ?-secretase and, more specifically, inhibit the production of A?-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to ?-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.

Abstract: This invention concerns a new family of phosphorus-containing compounds containing a moiety JQA- in which: A is absent or is —O—, —S— or —NR2—; Q is absent or (if A is —O—, —S— or —NR2—) Q may be —V—, —OV—, —SV—, or —NR2V—, where V is an aliphatic, heteroaliphatic, aryl, or heteroaryl moiety, such that J is linked to the cyclohexyl ring directly, through A or through VA, OVA, SVA or NR2VA; K is O or S; each occurrence of Y is independently —O—, —S—, —NR2—, or a bond linking a R5 moiety to P; each occurrence of R2 and R5 is independently an aliphatic, heteroaliphatic, aryl, or heteroaryl moiety, or H; and each occurrence of R6 is independently —PK(YR5)(YR5), —SO2(YR5) or —C(O)(YR5); so long as any R2, or R5 moiety linked directly to P is not H; wherein two R2, R5 and/or R6 moieties may be chemically linked to one another to form a ring; each occurrence of G is independently —O—, —S—, —NR2— or (M)x; each occurrence of M is independently a substituted or unsubstituted methylene moiety, and any M-M? m

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

Abstract: The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to certain indolin-2-ones and aza-indolin-2-ones which possess anti-tumour activity and are accordingly useful in methods of treatment of the human or animal body, in particular such compounds are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.

Abstract: A class of macrocyclic compounds of formula (I), wherein R1, R3, R4, Ra, Rb, A, Z, Y, X, M, W, n and m are defined herein, that are useful as inhibitors of viral proteases, particularly the hepatitis C virus (HCV) NS3 protease, are provided. Also provided are processes 5 for the synthesis and use of such macrocyclic compounds for treating or preventing HCV infection.

Abstract: Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of ?-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

Abstract: A compound of the structure is described. This compound and its use for preparing medicines useful in the treatment of neurodegenerative disorders is described.

Abstract: The present invention relates to macrocyclic compounds of formula (Ia) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

Abstract: The invention relates to the stabilization of poly-ene macrolides and to a particular macrolide obtained in crystalline form.

Abstract: The present invention concerns the compounds of formula (I), 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: Compounds, compositions, and methods of using such compounds to modulate apoptosis including IAP antagonists are provided herein. Compositions including mimetics of the invention and, optionally, secondary agents, may be used to treat proliferative disorders such as, cancer and autoimmune diseases.

Abstract: There is provided a series of heterocyclic-containing macrocyclic acyl guanidines of Formula (I) or a stereoisomer; or a nontoxic pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, n and X as defined herein, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein (APP) by ?-secretase and, more specifically, inhibit the production of A?-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to ?-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.

Abstract: The present invention relates generally to novel macrocycles of Formula (I): or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein the variables A, B, C, D, L, M, W, Z1, Z2, Z3, Z4, R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as defined herein. These compounds are selective inhibitors of factor VIIa which can be used as medicaments.

Abstract: A stable amorphous form of rifaximin is disclosed. This form is chemically and polymorphically stable on storage and can be prepared by dissolving rifaximin in a solvent to form a solution, which is precipitated by adding an anti-solvent and isolating of the precipitated amorphous rifaximin as an end product.

Abstract: Novel compounds useful for inhibiting the 90kDa heat shock proteins containing a quinone-like moiety and a di-hydroxy phenol like moiety, similar to geldanamycin and radicicol.

Abstract: The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

Abstract: A single-step, one-pot process to obtain zotarolimus and other rapamycin derivatives on large scale is presented, which improves currently available synthesis schemes. In one embodiment, dried rapamycin is dissolved in isopropylacetate (IPAc). The solution is cooled, and 2,6-Lutidine is added, followed slowly adding triflic anhydride at ?30° C. Salts are then removed by filtration. Tetrazole, followed by a tert-base diisopropylethylamine (DIEA) is added to the triflate solution. After incubation at room temperature, the product is concentrated and purified by a silica gel column using THF/heptane as eluant. The fractions containing the product are collected, concentrated, and purified again using an acetone/heptane column. The product containing fractions are concentrated. The product is dissolved in t-BME and precipitated with heptane. The solids are dissolved in acetone, treated with butylated-hydroxy toluene (BHT), and the solution concentrated.

Abstract: The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

Abstract: Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

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-NR12—C1-5alkyl-, —C1-6alkyl-NH—CO— or —CO—NH—C1-6alkyl-; X1 represents —O—; X2 represents a direct bond, —NR11—C1-2alkyl-, —NR11—CH2—, —C1-2alkyl-, —O—C1-2alkyl, —O— or —O—CH2—; R1 represents hydrogen or halo; R2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C1-4alkyloxycarbonyl-, Het16-carbonyl- or Ar5; R3 represents hydrogen, hydroxy, C1-4alkyloxy-, Ar4—C1-4alkyloxy or R3 represents C1-4alkyloxy substituted with one or where possible two or more substituents selected from C1-4alkyloxy- or Het2-; R10 represents hydrogen; R11 represents hydrogen, C1-4alkyl- or C1-4alkyl-oxy-carbonyl-; R12 represents Het14-C1-4alkyl, in particular morpholinyl-C1-4alkyl; Het2 represents a heterocycle selected from morpholinyl or piperidinyl optionally substituted with C1-4alkyl-, preferab

Abstract: A rapamycin analog with an antioxidant moiety or a pharmaceutically acceptable salt or prodrug thereof, is an immunomodulatory agent and is useful in the treatment of restenosis and immune and autoimmune diseases. Also disclosed are cancer-, 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. One particular preferred application of such antioxidant moiety containing rapamycin analog is in medicated devices wherein the stability and resistance to oxidative processes are essential to the success of rapamycin containing combination devices.

Abstract: Substituted rifamycin derivatives in which a nitroimidazole, nitrothiazole or nitrofuran pharmacophore is covalently bonded to a rifamycin, methods of using the rifamycin derivatives, and pharmaceutical compositions containing the rifamycin derivatives are disclosed. Methods of synthesizing these substituted rifamycin derivatives are also disclosed. The rifamycin derivatives possess antibacterial activity, and are effective against a number of human and veterinary pathogens in the treatment of bacterial diseases.

Abstract: There is provided a series of oxime-containing macrocyclic acyl guanidines of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof wherein R1, R2, R3, R4, n and X as defined herein, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein (APP) by ?-secretase and, more specifically, inhibit the production of A?-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to ?-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.

Abstract: The present invention provides a novel class of compounds that have the activity of inhibiting HSP90 enzyme and are useful as anti-cancer agents or such, and compounds that are useful as synthetic intermediates thereof. Specifically, the present invention provides compounds represented by the following formula (1), and pharmaceutically acceptable salts thereof: wherein X, R1, R2, R3, R4, R5, R6, R7, L1, L2, and L3 are as defined in the specification.

Abstract: The present invention is directed to synthetic cytoskeletal active compounds that are related to natural Latrunculin A or Latrunculin B. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with actin polymerization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or II, wherein said amount is effective to influence the cytoskeleton, for example by inhibiting actin polymerization.

Abstract: The present invention is directed towards lasonolide derivatives, methods of inducing premature chromosome condensation using lasonolide derivatives, and methods of treating disorders, such as cancer, in a subject, the method comprising administering to the subject a lasonolide derivative.

Abstract: Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.

Abstract: The present invention relates to macrocyclic a compound of formula (I) and its use as inhibitors of the hepatitis C virus (HCV) NS3 protease, and in treating or preventing HCV infections.

Abstract: A polyketide synthase complex composed of polyketide synthase with 15 total modules, a non-ribosomal peptide synthetase with 1 module, and a cytochrome P450 hydroxylase is described. Also provided are novel Streptomyces species and methods of modified Streptomyces species. Further described are novel compounds, C-36-ketomeridamycin, C9-deoxomeridamycin, and C9-deoxoprolylmeridamcyin and uses thereof.

Abstract: The present invention relates to novel 39-desmethoxyrapamycin derivatives, methods for their production, and uses thereof. In a further aspect the present invention provides for the use of these 39-desmethoxyrapamycin derivatives in the treatment of cancer and/or B-cell malignancies, the induction or maintenance of immunosuppression, the treatment of transplantation rejection, graft vs. host disease, autoimmune disorders, diseases of inflammation, vascular disease and fibrotic diseases, the stimulation of neuronal regeneration or the treatment of fungal infections.

Abstract: The present invention provides processes for crystallization of macrolides, specifically pimecrolimus and tacrolimus.

Abstract: Compositions and methods for inhibiting translation using 3-(5-tert-Butyl-2-Hydroxy-phenyl)-3-phenyl-1,3-dihydro-indol-2-one and/or its derivatives are provided. Compositions, methods and kits for treating (1) cellular proliferative disorders, (2) non-proliferative, degenerative disorders, (3) viral infections, and/or (4) disorders associated with viral infections, using 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3-dihydro-indol-2-one and/or its derivatives are described.

Abstract: The disclosure relates to a compound of the formula (I) wherein m and n are independently of one another 0, 1 or 2, obtainable from Actinomadura namibiensis (DSM 6313), its use for the treatment of bacterial infections, viral infections and/or pain, and pharmaceutical composition comprising it.

Abstract: A process for making Biolimus A9 comprises reacting sirolimus (or rapamycin) with alkyl benzene sulfonate under the catalyzing of organic base and in the presence of organic solvent to undergo a nucleophilic substitution reaction to obtain the Biolimus A9 with high yield, not only for small-scale laboratory experiment, but also for rendering reproducibility of high yield even after process amplification.

Abstract: A scalable process for the preparation of a rapamycin 42-ester by reacting a rapamycin 42-ester boronate with a diol and purifying crude rapamycin 42-ester by recrystallization and treatment with a diol is provided. Also provided is a method for isolating and purifying a rapamycin 42-ester boronate from mother liquors comprising acetone and rapamycin contaminants.

Abstract: Isomers and 42-epimers of rapamycin alkyl ether analogs and pharmaceutically acceptable salts or prodrugs thereof, are immunomodulatory agents and are useful in the treatment of restenosis and immune and autoimmune diseases. Also disclosed are cancer-, fungal growth-, restenosis-, post-transplant tissue rejection- and immune- and autoimmune disease-inhibiting compositions and a method of inhibiting cancer, fungal growth, restenosis, post-transplant tissue rejection, and immune and autoimmune disease in a mammal. One particular preferred application of such isomers and 42-epimers of rapamycin alkyl ether analogs is in medicated devices and local vascular delivery wherein the stability and lipid solubility and subsequently diffusion through tissue and cell membranes are essential to the success of rapamycin containing combination devices.

Abstract: The present invention relates generally to novel macrocycles of Formula (I): or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein the variables A, B, L, M, W, Z, R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as defined herein. These compounds are selective inhibitors of the serine protease coagulation factor VIIa which can be used as medicaments.

Abstract: The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and/or variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as antagonists or inverse agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, cardiovascular disorders, obesity and obesity-associated disorders, gastrointestinal disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

Abstract: The present invention relates to a method of extracting tacrolimus in a test blood sample to use in a tacrolimus quantification assay. The method of the present invention extracts tacrolimus in non-precipitating, non-denaturing aqueous environment, avoiding cumbersome manual pretreatment procedures or the use of organic solvents. The method of the present invention permits full automation of tacrolimus quantification assays.

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 provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.