Abstract: Optionally substituted chromenoisoquinolines and analogs and derivatives thereof are described herein. In addition, syntheses of these compounds are described herein. In addition, uses of these compounds as dopamine receptor binding compounds are described herein.

Abstract: Cell permeable metal ion indicator compounds and methods of their use and synthesis are described. The compound comprises a metal chelating moiety (Mc), a reporter molecule and two or more lipophilic groups (GL) covalently bonded through a linker to the reporter molecule, wherein the lipophilic groups, when present in a live cell, are cleaved resulting in two or more negatively charged groups.

Abstract: The present invention relates to conjugate comprising a carrier substituted with one or more occurrences of a moiety having the structure: wherein each occurrence of M is independently a modifier having a molecular weight ?10 kDa; denotes direct of indirect attachment of M to linker LM; and each occurrence of LM is independently an optionally substituted succinamide-containing linker, whereby the modifier M is directly or indirectly attached to the succinamide linker through an amide bond, and the carrier is linked directly or indirectly to each occurrence of the succinamide linker through an ester bond. In another aspect, the invention provides compositions comprising the conjugates, methods for their preparation, and methods of use thereof in the treatment of various disorder, including, but not limited to cancer.

Abstract: A four arm-polyethylene glycol-7-ethyl-10-hydroxycamptothecin conjugate, such as, is disclosed. Methods of making the conjugates and methods of treating mammals using the same are also disclosed.

Abstract: The invention offers a method of hydrogenating camptothecin in inert solvent in the presence of nickel catalyst, whereby selective hydrogenation of camptothecin can be very efficiently accomplished using the low-cost catalyst.

Abstract: This invention relates to the fields of pharmaceutics and medicine, and, in particular, relates to the production and use of pharmaceutical substances on the basis of mitochondria-addressed compounds. The invention discloses methods for synthesis, purification and storage of mitochondria-addressed antioxidants, making it possible to produce said substances in a form and quality meeting the demands made on active ingredients of medicinal preparations—the pharmaceutical substances. The invention also discloses methods for design and selection of new mitochondria-addressed antioxidants having specified properties.

Abstract: The invention provides compounds of formula I: (I) wherein A, B, W, Y, Z, R1, R3 and R4 have any of the meanings defined in the specification and their salts as well as additional compounds and their salts. The invention also provides pharmaceutical compositions comprising a compound of the invention, processes for preparing compounds of the invention, intermediates useful for preparing compounds of the invention, and therapeutic methods for treating cancer, a bacterial infection or a fungal infection using compounds of the invention.

Abstract: This invention relates to a process for preparing a crystalline form of (4S)-11(dimethoxymethyl)-4-ethyl-4-hydroxy-1H-pyrano[3?4?:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, also named 7-(dimethoxy-methyl)camptothecin). With the provision of a particular crystallization step, in appropriate way, a new crystalline form of the above compound is obtained. The process for the preparation of the polymorph Form II comprises transforming camptothecin to the corresponding 7-(dimethoxy-methyl)-camptothecin, and crystallizing from methanol.

Abstract: The invention provides novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R7 are as described herein, compositions including the compounds and methods of preparing and using the compounds.

Abstract: To provide a marker for determining sensitivity of a patient to an anti-cancer agent, and novel cancer therapeutic means employing the marker. The marker for determining sensitivity to an anti-cancer agent is formed of one or more substances selected from the group consisting of a substance or a fragment thereof detected as an anion at m/z of 149.05 to 149.06, a substance or a fragment thereof detected as an anion at m/z of 152.99 to 153.00, a substance or a fragment thereof detected as a cation at m/z of 724.34 to 724.35, the peaks being determined by means of a mass spectrometer, glycerol 3-phosphate, dihydrobiopterin, GABA, lactic acid, asparagine, aspartic acid, 2-methylbutyroylcarnitine, 1-methyladenosine, and glutathione, and a substance involved in a metabolic pathway of any of these substances.

Abstract: To provide a marker for determining sensitivity of a patient to an anti-cancer agent, and novel cancer therapeutic means employing the marker. The marker for determining sensitivity to an anti-cancer agent is formed of a protein selected from the group consisting of a protein or a fragment thereof which is detected as a peak at m/z of 16,450 to 16,620, a protein or a fragment thereof which is detected as a peak at m/z of 22,080 to 22,310, and a protein or a fragment thereof which is detected as a peak at m/z of 17,100 to 17,270, the peaks being determined by means of a mass spectrometer.

Abstract: Disclosed is a crystalline form of irinotecan hydrochloride (I) and processes for the preparation thereof from crude irinotecan hydrochloride or another polymorphic form of irinotecan. Said crystalline form is particularly suitable for industrial use, because it is easily filtered and possesses characteristics of high stability and purity.

Abstract: The present invention relates to conjugate comprising a carrier substituted with one or more occurrences of a moiety having the structure: wherein each occurrence of M is independently a modifier having a molecular weight ?10 kDa; denotes direct of indirect attachment of M to linker LM; and each occurrence of LM is independently an optionally substituted succinamide-containing linker, whereby the modifier M is directly or indirectly attached to the succinamide linker through an amide bond, and the carrier is linked directly or indirectly to each occurrence of the succinamide linker through an ester bond. In another aspect, the invention provides compositions comprising the conjugates, methods for their preparation, and methods of use thereof in the treatment of various disorder, including, but not limited to cancer.

Abstract: Organic compounds showing the ability to inhibit viral glycoprotein (GP)-mediated entry of a filovirus into a host cell are disclosed. The disclosed filovirus entry inhibitor compounds are useful for treating, preventing, or reducing the spread of infections by filovirus including the type species Marburg virus (MARV) and Ebola virus (EBOV). Preferred inhibitors of the invention provide therapeutic agents for combating the Ivory Coast, Sudan, Zaire, Bundibugyo, and Reston Ebola virus strains.

Abstract: The present invention relates to bioactive extracts its fractions and isolation of compound from Rauwolfia tetraphylla. The extracts and fractions are useful for the treatment of psychosis based on in-vivo validation on animal model and proportional binding affinities for dopaminergic-D2, Cholinergic (muscarinic) and Serotonergic (5HT2A) receptors for antipsychotic activity. The present invention relates to novel antipsychotic activity in the leaf alkaloids of Formula 1 and 2 named tetrahydroalstonine, 10-methoxytetrahydroalstonine, isoreserpiline, 10-der?ethoxyreserpiline, 11-demethoxyreserpiline, reserpiline and ?-yohimbine. The present invention also relates to processes for obtaining antipsychotic extracts as well as for the isolation of alkabids of formula 1 and 2 from the leaves of Rauwolfia tetraphylla. The present invention particularly relates to significant antipsychotic activity in the MeOH extract, ethylacetate and chloroform fractions of R.

Abstract: Novel camptothecin derivatives having antitumor activity, the processes for the preparation thereof, the use thereof as antitumor drugs and pharmaceutical compositions containing them.

Abstract: The present invention provides methods, compositions and applications for efficient, site-specific drug delivery using pro-drug complexes comprising therapeutic agents and one or more functional groups (e.g., imaging agents, targeting agents, and trigger agents). In particular, the present invention relates to pro-drug complexes comprising one or more functional groups conjugated with a therapeutic agent (e.g., a chemotherapeutic agent), methods of synthesizing the same, as well as systems and methods utilizing the therapeutic and diagnostic compositions (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer) diagnosis and/or therapy, etc.)).

Abstract: Various 14-Nitro, 14-amino, and 14-substituted amino camptothecin derivatives are useful in the treatment of cancer and other hyperproliferative diseases. Various 14-nitro camptothecin derivatives are conveniently prepared by reacting a camptothecin derivative with fuming nitric acid, optionally employing acetic anhydride as a solvent.

Abstract: The present invention relates to a compound comprising an imine bond as an acid-labile trigger group, the use of such an imine bond as an acid-labile trigger group, a process of cleaving the imine bond in said compound, and a pharmaceutical composition comprising said compound.

Abstract: Disclosed is a process for production of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin from a camptothecin composition containing 18,19-dehydrocamptothecin without producing any vinyl form of the compound. The process is characterized by catalytically reducing at least one compound selected from a compound (1) and others in the process of producing a compound (5) from a composition containing the compound (1).

Abstract: Novel compounds and pharmaceutical compositions are provided. In one aspect of the invention the compounds may be utilized in medical practice, for example, in treatment of cancer and immune disorders. In another aspect of the invention there is provided a conjugate, comprising a cytotoxic agent and a modulating moiety, the modulating moiety serving to target apoptotic cells.

Abstract: Novel camptothecin derivatives having antitumor activity, the processes for the preparation thereof, the use thereof as antitumor drugs and pharmaceutical compositions containing them.

Abstract: 13-substituted 5,6-dihydrodibenzo[a,g]quinolizinium salt compounds of the general formula (I): processes for the preparation of said compounds, pharmaceutical compositions containing said compounds and the use of said compounds for the manufacture of medicaments suitable for the treatment of cancerous diseases.

Abstract: The present invention provides two new camptothecin derivatives, which were identified as S,R- and S,S-topotecan lactates, respectively. Both compounds have anticancer activities. Pharmaceutical compositions of the new camptothecin derivatives, and cancer therapies with the new camptothecin derivatives or their pharmaceutical compositions were also provided.

Abstract: The invention provides compounds of formula I: wherein A, B, X, and Y have any of the values defined in the specification, as well as pharmaceutical compositions comprising such compounds, processes for preparing such compounds, and therapeutic methods for treating cancer and other topoisomerase mediated conditions.

Abstract: Disclosed are compounds that are conjugates of ladder frame polyether compounds and biologically active compounds or research compounds, pharmaceutical formulations comprising the conjugates, and methods of transporting the conjugates across biological membranes.

Abstract: The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds which comprise a phosphocholine moiety covalently conjugated with one or more antiviral agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions and kits for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus. Additionally, the invention includes compositions and methods useful for combating a cancer in a mammal and for facilitating delivery of a therapeutic agent to a mammalian cell.

Abstract: A crystalline polymorph of 7-ethyl-10-hydroxycamptothecin exhibiting an X-ray diffraction pattern having peaks at 10.9±0.2, 13.2±0.2, 23.9±0.2, and 26.1±0.2 2-theta degree.

Abstract: A stereoselective process for preparing 7-[(E)-t-butyloxyiminomethyl]-camptothecin (also known as gimatecan) is herein disclosed. With the addition of further dissolution and precipitation steps carried out in appropriate different solvent mixtures, four new crystalline forms of gimatecan are also obtainable by using the same stereoselective process.

Abstract: In order to efficiently supply CPT, which is a starting compound of irinotecan hydrochloride and a variety of camptothecin derivatives, by a practical total synthesis, the invention provides a means of efficiently preparing a tricyclic ketone that corresponds to a CDE ring moiety of a camptothecin (CPT) skeleton.

Abstract: The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.

Abstract: The present invention describes tetracyclic compounds of formula (IA) or (IB), wherein the symbols R, X, A, Y, R2, R3 and D are as defined in the specification, their use in the treatment of certain diseases, e.g. depending on MK-2 or TNF activity, and ways of manufacturing them.

Abstract: The present invention provides compounds of formula I: formula (I) wherein X1-X4 and R1-R12 have any of the values defined in the specification, as well as salts and prodrugs thereof, which inhibit major molecular mechanisms associated with bacterial cell division and proliferation so as to be useful for the treatment and/or prevention of bacterial infections. The invention also provides compositions comprising these compounds as well as methods for using these compounds to inhibit bacterial cell division and proliferation and to treat bacterial infections.

Abstract: A stereoselective process for preparing 7-[(E)-t-butyloxyiminomethyl]-camptothecin (also known as gimatecan) is herein disclosed. With the addition of further dissolution and precipitation steps carried out in appropriate different solvent mixtures, four new crystalline forms of gimatecan are also obtainable by using the same stereoselective process.

Abstract: The present invention provides a novel nitrogen-containing heterocyclic derivative and an organic electronic device using the same. The organic electronic device according to the present invention has excellent properties in terms of efficiency, driving voltage, and a life span.

Abstract: The present invention relates to conjugate comprising a carrier substituted with one or more occurrences of a moiety having the structure: wherein each occurrence of M is independently a modifier having a molecular weight ?10 kDa; denotes direct of indirect attachment of M to linker LM; and each occurrence of LM is independently an optionally substituted succinamide-containing linker, whereby the modifier M is directly or indirectly attached to the succinamide linker through an amide bond, and the carrier is linked directly or indirectly to each occurrence of the succinamide linker through an ester bond. In another aspect, the invention provides compositions comprising the conjugates, methods for their preparation, and methods of use thereof in the treatment of various disorder, including, but not limited to cancer.

Abstract: The present technology relates to compounds of Formulas (V) and (VI) and methods of making and using such compounds. Methods of use include prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, and metabolic syndrome. Compounds disclosed herein also lower total cholesterol, LDL-cholesterol, and triglycerides and increase hepatic LDL receptor expression, inhibit PCSK9 expression, and activate AMP-activated protein kinase.

Abstract: A 5(S)-(2?-hydroxyethoxy)-20(S)-camptothecin diasterisomer is described which is a better inhibitor of topoisomerase I than either the diastereoisomeric mixture 5(RS)-(2?-hydroxyethoxy)-20(S)-camptothecin, or the 5(R)-(2?-hydroxyethoxy)-20(S)-camptothecin diastereoisomer. Pharmaceutical compositions of the 5(S)-(2?-hydroxyethoxy)-20(S)-camptothecin diastereoisomer are also described as are methods of using the compound for the inhibition of topoisomerase I and for the treatment of cancer.

Abstract: The present invention is directed to antioxidant derivatives of camptothecin and antioxidant derivatives of camptothecin analogs and the preparation of nanometer-sized camptothecin prodrugs. Methods of synthesizing the antioxidant derivatives of camptothecin and antioxidant derivatives of camptothecin analogs, spontaneous emulsification or nanoprecipitation thereof to produce antioxidant camptothecin nanosphere prodrugs and their use in treating cancerous diseases are also provided. A further aspect of this invention is the use of these antioxidant camptothecin nanosphere prodrugs for the preparation of delivery devices of other pharmaceuticals and/or drugs. Additionally, methods of treating cancer with the camptothecin and antioxidant derivatives of camptothecin analogs, and nanometer-sized camptothecin prodrugs are also provided.

Abstract: There is provided a composition comprising microspheres which comprise a water-insoluble, water-swellable polymer and associated with the polymer, in releasable form, a chemotherapeutic agent, for use in the treatment of a pancreatic tumour or cyst, wherein the microspheres, when equilibrated in water at 37° C., comprise at least 40 wt % water based on weight of polymer plus water, wherein the polymer is anionically charged at pH7 and the chemotherapeutic agent is cationically charged and electrostatically associated with the polymer. Also provided are methods of treating pancreatic tumours or cysts using this composition.

Abstract: Novel compounds and pharmaceutical compositions are provided. In one aspect of the invention the compounds may be utilized in medical practice, for example, in treatment of cancer and immune disorders.

Abstract: A method for preparing a stable dispersion of a camptothecin, camptothecin prodrug, or analog thereof for administration to a patient in need thereof includes preparing a solution of the camptothecin, wherein the solution has a pH which places substantially an entirety of that camptothecin in a carboxylate form. The camptothecin may be a neutral camptothecin. The solution is next loaded into a liposome including at least one lipid, which may be a phospholipid. An intraliposomal pH is maintained which preserves substantially an entirety of the camptothecin in the carboxylate form. The liposomal dispersion is administered to an individual in need thereof, whereby the liposomes accumulate at and permeate into tumor tissue and an active, lactone form camptothecin is released in situ at the tumor site. Compositions formulated in accordance with the described method for treatment of a cancer in an animal in need thereof are provided also.

Abstract: Provided herein are compounds and methods for achieving a sustained therapeutic effect of small molecule anti-cancer agents when administered in vivo.

Abstract: The method of manufacturing of 7-ethyl-10-hydroxycamptothecin of formula I characterized in that 7-ethyl-1,2,6,7-tetrahydrocampotothecin of formula IV is oxidized with an oxidizing agent selected from the group comprising iodosobenzene, an ester of iodosobenzene, sodium periodate, potassium periodate, potassium peroxodisulfate and ammonium peroxodisulfate, in a solvent formed by a saturated aliphatic monocarboxylic add containing 1 to 3 carbon atoms, and in the presence of water.

Abstract: The present application describes deuterium-enriched topotecan, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.

Abstract: Novel crystalline forms of topotecan hydrochloride and processes of making the same are disclosed.

Abstract: The present invention relates to anti-flavivirus compounds, including lycorine and derivatives thereof, and their use in treating a subject infected by a flavivirus. The present invention also relates to the use of the anti-flavivirus compounds for the prophylaxis of flavivirus infection. The present invention further relates to a method of suppressing viral RNA synthesis of a flavivirus. Also described is a method of preparing an anti-flavivirus compound for use in the treatment or prophylaxis of flavivirus infection.

Abstract: Compositions comprising extracts or isolated or purified compounds from plants of the genus Corydalis provide prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, and metabolic syndrome. Corydalis compounds and their derivatives of natural and synthetic origins lower total cholesterol, LDL-cholesterol, and triglycerides and increase hepatic LDL receptor expression and activate AMP-activated protein kinase. Specific stereoisomers of Corydalis compounds with lipid lowering activity include 14R-(+)-corypalmine, 14R,13S-(+)-corydaline, 14R-(+)-tetrahydropalmatin, (+)-corlumidin, d-(+)-bicuculline, and (+)-egenine.

Abstract: To provide a central nervous system tissue-labeling composition labeling the central nervous tissue system. Also, another object of the present invention is to provide a method for non-invasively labeling the central nervous tissue system. Further, another object of the present invention is to provide a screening method using the above central nervous system tissue-labeling composition. A central nervous system tissue-labeling composition containing, as an active ingredient, at least one of compounds represented by the general formula (1) or (7).

Abstract: The invention concerns the production of quinoline compounds containing sulfonic acid groups, the said quinoline compounds and their conversion into dyes containing sulfonic acid groups. The dyes according to the invention are used especially to label analytes, for example to label biomolecules.