Abstract: The invention provides glucocorticoid receptor antagonists for treatment of infection, neoplasia, and fatty liver disease.

Abstract: The invention provides glucocorticoid receptor antagonists for treatment of infection, neoplasia, and fatty liver disease.

Abstract: This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups. This conjugation method provides in high yields conjugates of high purity and homogeneity that are without inter-chain cross-linking and inactivated linker residues.

Abstract: The present invention relates to macrolactam compounds, intermediates useful in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing and modifying macrolactams. One use of the compounds and methods described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. An example of an HCV inhibitory compound that can be synthesized using the procedures described herein is Compound A and derivative thereof.

Abstract: Embodiments relate to Rifaximin polymorphic, salt, and hydrate forms, methods of producing polymorphic forms and to their use in medicinal preparations and to therapeutic methods using them.

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: The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.

Abstract: The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.

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: Diazonamide analogs having anti-mitotic activity, useful for the treatment of cancer and other proliferative disorders, and related pharmaceutical compositions are provided.

Abstract: Diazonamide analogs having anti-mitotic activity, useful for the treatment of cancer and other proliferative disorders, and related pharmaceutical compositions are provided.

Abstract: The present invention relates to phosphonated Rifamycins, and methods of making and using such compounds. These compounds are useful as antibiotics for prophylaxis and/or the treatment of bone and joint infections, especially for the prophylaxis and/or treatment of osteomyelitis.

Abstract: The present invention relates to phosphonated Rifamycins, and methods of making and using such compounds. These compounds are useful as antibiotics for prophylaxis and/or the treatment of bone and joint infections, especially for the prophylaxis and/or treatment of osteomyelitis.

Abstract: Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein Y, R1, R2, R4 and n have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in HCV therapy.

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-tumor 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: Indoline compounds having anti-mitotic activity, useful for the treatment of cancer and other proliferative disorders are provided.

Abstract: The present invention relates to oral pharmaceutical compositions with controlled and/or programmed release containing at least one active ingredient having antimicrobial and/or anti-infectious activity for the treatment of infections of the large intestine, in particular the colon.

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 tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.

Abstract: The present invention discloses compounds of formula I or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. 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: Methods for fluorinating organic compounds are described herein.

Abstract: The present invention relates to phosphonated Rifamycins, and methods of making and using such compounds. These compounds are useful as antibiotics for prophylaxis and/or the treatment of bone and joint infections, especially for the prophylaxis and/or treatment of osteomyelitis.

Abstract: Indoline compounds having anti-mitotic activity, useful for the treatment of cancer and other proliferative disorders are provided.

Abstract: Compounds of the formula: where X and Y are each independently H, halo, or C1-C6 straight or branched chain substituted or unsubstituted alkyl.

Abstract: Compounds of the formula (I): wherein A, B, D, M, Ar, W, X, Y, Z and R1 are as defined herein, are useful in the prevention and treatment of hepatitis C infections. The compounds, their preparation, pharmaceutical compositions containing them and their use in medicine are disclosed.

Abstract: New compounds belonging to the structural formula (I) are described. in which R1, R2, A, Y and X are specified in the description, useful in the treatment of cholestasis and substantially devoid of antibacterial activity. The synthesis process of said compounds, the pharmaceutical compositions containing them and their use in therapy are also described.

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: The present invention is directed to novel 3-(substituted ethyl) rifamycin derivatives, pharmaceutical compositions containing them and the use of said derivatives and pharmaceutical compositions as antimicrobial agents against pathogenic microorganisms, particularly against resistant microbes.

Abstract: The present invention features rifamycin analogs and methods of using these compounds to treat a variety of microbial infections.

Abstract: The present invention features rifamycin analogs that can be used as therapeutics for treating or preventing a variety of microbial infections. In one form, the analogs are acetylated at the 25-position, as is rifamycin. In another form, the analogs are deacetylated at the 25-position. In yet other forms, benzoxazinorifamycin, benzthiazinorifamycin, and benzdiazinorifamycin analogs are derivatized at various positions of the benzene ring, including 3?-hydroxy analogs, 5?-halo and/or alkoxy analogs, and various 4?- and/or 6?-substituents that incorporate a cyclic amine moiety.

Abstract: The invention relates to a process for the recovery of a macrolide in substantial pure form including: a) treating an impure or crude macrolide with water immiscible solvent to form a mixture, b) optionally concentrating the mixture, c) treating with ammonia gas to phase out impurities, d) separating impurities, e) optionally concentrating a phase containing the macrolide, f) loading on silica gel chromatography, optionally reversed phase or pretreated with silver, and eluting the macrolide, g) affording the macrolide in the substantially pure form, h) optional repetition of steps f and g to afford the macrolide in the substantially pure form. The macrolide is preferably tacrolimus, immunomycin or sirolimus.

Abstract: Compounds of the formula: where X and Y are each independently H, halo, or C1-C6 straight or branched chain substituted or unsubstituted alkyl.

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: The present invention discloses a one-step process for the production of cytotoxic conjugates of maytansinoids and cell binding agents. Maytansinoids having a disulfide linker that bears a reactive moiety are linked to cell binding agents, such as antibodies, without prior modification of the cell binding agent. These conjugates are useful as therapeutic agents which are delivered specifically to target cells and are cytotoxic.

Abstract: The present invention features rifamycin analogs that can be used as therapeutics for treating or preventing a variety of microbial infections. In one form, the analogs are acetylated at the 25-position, as is rifamycin. In another form, the analogs are deacetylated at the 25-position. In yet other forms, benzoxazinorifamycin, benzthiazinorifamycin, and benzdiazinorifamycin analogs are derivatized at various positions of the benzene ring, including 3?-hydroxy analogs, 4?- and/or 6? halo and/or alkoxy analogs, and various 5? substituents that incorporate a cyclic amine moiety.

Abstract: The invention is related to phosphorus substituted anti-infective compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Abstract: The present invention features rifamycin analogs that can be used as therapeutics for treating or preventing a variety of microbial infections. In one form, the analogs are acetylated at the 25-position, as is rifamycin. In another form, the analogs are deacetylated at the 25-position. In yet other forms, benzoxazinorifamycin, benzthiazinorifamycin, and benzdiazinorifamycin analogs are derivatized at various positions of the benzene ring, including 3?-hydroxy analogs, 4?- and/or 6? halo and/or alkoxy analogs, and various 5? substituents that incorporate a cyclic amine moiety.

Abstract: Rifamycin derivatives having the following structure of general formula I (both hydroquinone and corresponding quinone (C1-C4) forms): or its salts, hydrates or prodrugs thereof; wherein a preferred R1 comprises hydrogen or acetyl and a prefered R2 comprises hydrogen, methyl or other lower alkyls; wherein asterik (*) denotes the carbon bearing the chiral center, wherein absolute configuration is assigned as R or S. Methods of preparation of the aforementioned rifamycin derivatives are also described. The compounds exhibit antimicrobial activities, including activities against drug-resistant microorganisms.

Abstract: The present invention features rifamycin analogs that can be used as therapeutics for treating or preventing a variety of microbial infections. In one form, the analogs are acetylated at the 25-position, as is rifamycin. In another form, the analogs are deacetylated at the 25-position. In yet other forms, benzoxazinorifamycin, benzthiazinorifamycin, and benzdiazinorifamycin analogs are derivatized at various positions of the benzene ring, including 3?-hydroxy analogs, and/or various fused ring systems with the benzene ring at the 4?,5? or 5?,6? positions.

Abstract: Provided is a method of purifying a macrolide, especially tacrolimus, that includes loading macrolide onto a bed of sorption resin and elting with a suitable eluent such as a combination of water and tetrahydrofuran.

Abstract: The invention features a method of delivering a drug to a diseased cell by linking the drug to a rifamycin derivative, compositions that include drug-rifamycin conjugates of the invention, and methods for treating disease using those compositions.

Abstract: Laulimalide compounds, intermediates thereto and methods for their preparation, and methods for their use in the treatment of diseases characterized by cellular hyperproliferation.

Abstract: Provided is a method for obtaining a macrolide, especially tacrolimus, from biomatter.

Abstract: Sodium salt of 3-(4-cinnamyl-1-piperazinyl)-iminomethyl rifamycin SV was synthesized. The compound shows high activity against Gram-positive and Gram-negative microorganims, Mycobacterium tuberculosis (including atypical and rifampicin resistant) and may be used in the medical practice. The sodium salt has formula (II). The process for preparation of the sodium salt consists of reacting equimolar quantities of 3-(4-cinnamyl-1-piperazinyl)-iminomethyl rifamycin SV and sodium ascorbate with addition of 30% methanol solution of sodium methylate, followed by filtration and removement of the solvent by distillation under reduced pressure. The compound can also be obtained from the sodium salt of 3-formil rifamycin SV, which is reacting with N1-amino-N4-cinnamypiperazin in medium of inert solvent at room temperature.

Abstract: The present invention discloses a one-step process for the production of cytotoxic conjugates of maytansinoids and cell binding agents. Maytansinoids having a disulfide linker that bears a reactive moiety are linked to cell binding agents, such as antibodies, without prior modification of the cell binding agent. These conjugates are useful as therapeutic agents which are delivered specifically to target cells and are cytotoxic.

Abstract: The present invention is directed to peptidomimetic macrocyclic compounds of the formula A: wherein W is a heterocycle, V is a heterocycle or aryl moiety and Z1 is a suitably substituted aryl or heterocycle moiety. The instant compounds inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.

Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.

Abstract: Macrocyclic compounds of formula ##STR1## are potent inhibitors of matrix metalloproteinase and are useful in the treatment of diseases in which matrix metalloproteinase play a role. Also disclosed are matrix metalloproteinase inhibiting compositions and a method of inhibiting matrix metalloproteinase in a mammal.

Abstract: Rifamycin antibiotic derivatives of formulae (I) and (Ia) bearing at the position 36 a substituent selected from (C.sub.1 -C.sub.8)alkyl, halo, hydroxy, (C.sub.1 -C.sub.4)acyloxy, (C.sub.1-C.sub.4)alkoxy, (C.sub.1 -C.sub.4)alkylthio, (C.sub.1 -C.sub.4)alkylamino, di(C.sub.1-C.sub.4)alkylamino and substituted 4-oxo-3-pyridinyl carbonyloxy of formula (1) obtained by reacting rifamycin with suitably substituted malonic acid. The compounds of the invention are antimicrobial agents mainly active against gram positive bacteria and fastidious gram negative bacteria showing the considerable antimicrobial activity against the rifamypicin resistant microbial strains.

Abstract: Automatic dishwashing detergent compositions, comprising particular quaternary-substituted bleach activators, are provided. More specifically, the invention relates to granular automatic dishwashing detergents which provide enhanced cleaning/bleaching benefits through the selection of quaternary-substituted bleach activators having specific features, such as caprolactam or valerolactam leaving groups and/or the ability to form particular cationic aliphatic peracid structures in solution. Preferred automatic dishwashing compositions comprise amylase enzymes. Included are preferred activator compounds and methods for washing tableware in domestic automatic dishwashing appliances using the activators.

Abstract: The present invention provides a process for the preparation and purification of thiol-containing maytansinoids comprising the steps of: (1) reductive hydrolysis of a maytansinoid C-3 ester with a reducing agent selected from the group consisting lithium trimethoxyaluminum hydride (LiAl (OMe)3H), lithium triethoxyaluminum hydride (LiAl(OEt)3H), lithium tripropoxyaluminum hydride (LiAl (OPr)3H), sodium trimethoxyaluminum hydride (NaAl (OMe)3H), sodium triethoxyaluminum hydride (NaAl(OEt)3H) and sodium tripropoxyaluminum hydride (NaAl(OPr)3H) to yield a maytansinol; (2) purifying the maytansinol to remove side products when present; (3) esterifying the purified maytansinol with a carboxylic acid to yield a mixture of an L- and a D-aminoacyl ester of maytansinol; (4) separating the L-aminoacyl ester of maytansinol from the reaction mixture in (3); (5) reducing the L-aminoacyl ester of maytansinol to yield a thiol-containing maytansinoid; and (5) purifying the thiol-containing maytansinoid.