Abstract: Methods of forming camptothecin compounds which are effective anti-tumor compounds are disclosed. These compounds inhibit the enzyme topoisomerase I and may alkylate DNA of the associated topoisomerase I-DNA cleavable complex.

Abstract: A compound, process and method for increasing external auditory canal patency while simultaneously preventing the occurrence of otitis externa is disclosed wherein an aerosolized mixture of lipid crystals comprised of a mixture of one or more lipids surfactants and one or more spreading agents selected from the group consisting of sterols, lipids, fatty acids, cholesteryl esters, phospholipids, carbohydrates, nucleic acids and proteins, in powder form, and one or more fluorocarbon propellants is administered directly to the external auditory canal. Upon administration, the propellant(s) are evaporated from the mixture and the lipid crystals are deposited upon an air/liquid interface resident upon epithelial tissue lining the external auditory canal.

Abstract: A method for treating a living body afflicted with a cancer selected from lung and ovarian carcinoma, comprising the step of administering to the living animal body an amount of a compound selected from those of formula (I): wherein: X and Y represent group selected from hydrogen, halogen, mercapto, cyano, nitro, alkyl, trihaloalkyl, trihaloalkylcarbonylamino, —ORa, —NRaRb, —NRa—C(O)-T1, —O—C(O)-T1, —O-T2-NRaRb, —O-T2-ORa, —NRa-T2-NRaRb, —NRa-T2-ORa and —NRa-T2-CO2Ra wherein Ra, Rb, T1, T2 are as defined in the description, or X and Y together form a methylenedioxy or ethylenedioxy, R1 represents hydrogen or alkyl, R2 represents a group selected from hydrogen, —ORa, —NRaRb, —NRa—C(O)-T1, —O—C(O)-T1, —O-T2-NRaRb, —O-T2-ORa, —NRa-T2-NRaRb, —NRa-T2-ORa and —NRa-T2-CO2Ra wherein Ra, Rb, T1 and T2 are as defined hereinbefore, R3 and R4 represent hydrogen or alkyl, W represents a group of formula —CH(R5)—CH(R6)—, —CH?C(R7)—, —C(R7)?CH— or —C(O)—CH(R8)— wherein R5, R6, R7 and R8 are as defined in the descript

Abstract: A polymorphic form of 9-nitrocamptothecin is provided, the polymorph being characterizable as having, by differential scanning calorimetry, an endotherm at between 273.9 to 275.9° C., and an exotherm at between 279.3 and 281.3° C.

Abstract: The invention relates in particular to the compounds of general formula in which R1, R2, R3, R4, R5, R6 represent various radicals; their use as medicaments and pharmaceutical compositions containing them. These compounds are particularly useful for the treatment of cancer.

Abstract: The use of triaryl acid derivatives of formula (I) and their pharmaceutical compositions as PPAR ligand receptor binders. The PPAR ligand receptor binders of this invention are useful as agonists or antagonists of the PPAR receptor.

Abstract: Compounds of formula (I): wherein: W1 and W2, together with the carbon atoms to which they are bonded, represent a phenyl group or a pyridyl group, and at least one of the groups W1 or W2 represents a pyridyl group, R1 and R2 each represent a group of formula U-V as defined in the description, X and X1 each represent a hydrogen atom or a hydroxy, alkoxy, mercapto or alkylthio group, Y and Y1 each represent a hydrogen atom, or X and Y, X1 and Y1, together with the carbon atom carrying them, represent a carbonyl or thiocarbonyl group, R4 and R5 are as defined in the description, Q1, Q2 represent a hydrogen atom, or Q1 and Q2, together with the carbon atoms carrying them, form an aromatic bond. Medicaments.

Abstract: The specification discloses a method for enhancing the inhibiting action of drugs against multidrug resistant cells, apparently by reversing or inhibiting the glycoprotein “pumps” associated with such cells.

Abstract: New bicyclic based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as in the treatment of diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

Abstract: Spontaneously dispersible pharmaceutical compositions comprising a piperidine, e.g. 1-acylpiperidine Substance P Antagonist and its use in the treatment of CNS disorders, e.g. depression and social phobia, and respiratory diseases, e.g. asthma and chronic bronchitis.

Abstract: The invention pertains to a method for preparing dexchlorpheniramine (“dexchlor”) tannate by reacting dexchlorpheniramine free base at a temperature of about 75 to about 150° C. with tannic acid neat or as an aqueous slurry containing up to about 20 wt. % water. The dexchlorpheniramine free base may be obtained by reacting a commercially available dexchlorpheniramine salt such as dexchlorpheniramine maleate with a base such as aqueous sodium hydroxide. The resultant dexchlor tannate has extended release properties and is useful in pharmaceutical compositions as an antihistamine for human beings.

Abstract: A medicament useful for preventive and/or therapeutic treatment of nerve system diseases which comprises, as an active ingredient, a compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof: wherein, X represents a group represented by the following general formula (II), (III), (IV), (V), or (VI), “A” represents a saturated or unsaturated 3- to 6-membered carbocyclic group and the like, “B” represents CH2 and the like, “n” represents 0 to 2, R1 represents a hydrogen atom, a halogen atom and the like, R2, R3, and R7 to R14 represent a hydrogen atom, a lower alkyl group which may be substituted and the like, R4 represents a hydrogen atom, a lower alkyl group which may be substituted and the like, R5 represents a hydrogen atom, a halogen atom and the like, R6 represents a saturated or unsaturated monocyclic or bicyclic carbocyclic group and the like, and R5 and R6, R7 and R8, R9 and R10, or R11 and R12 may bind to each other to form a cyclic structure.

Abstract: The invention relates to the treatment of an inflammatory disease, especially an inflammatory rheumatoid or rheumatic disease, and/or pain with an inhibitor of the activity of VEGF receptor tyrosine kinase of the formula I, the substituents being defined in the specification; as well as to new phthalazine derivatives; processes for the preparation thereof, the application thereof in a process for the treatment of the human or animal body; the use thereof for the treatment of a disease, especially a disease caused by ocular neovascularization, such as age-related macula degeneration or diabetic retinopathy, or other diseases that respond to the inhibition of tyrosine kinases, such as a proliferative disease; a method for the treatment of such disease in mammals; and the use of such a compound for the manufacture of a pharmaceutical preparation for the treatment especially of a disease as mentioned above.

Abstract: The present invention provides a composition of transdermally administered aconitine alkaloids for ameliorating pain and inflammation. In one aspect, an aconitine alkaloid is delivered in a sufficient amount to achieve and maintain a blood plasma aconitine alkaloid level of about 0.5 ng/mL to about 400 ng/mL. Aconitine alkaloids may be delivered by themselves, or in combination with other elements, such as additional analgesics, other drugs, or positive health promoting substances. Various formulations for the transdermal delivery of aconitine alkaloids are disclosed, and may include selected penetration enhancers.

Abstract: The present invention relates to an improved and economical process for the isolation of anticancer agent Camptothecin from the twigs and stem of Nothapodytes foetida using hot extraction 20(S) Camptothecin is an alkaloid, which contains a pentacyclic ring system that includes a pyrrolo [3,4-b] quinoline moiety (ring A, B and C), the pyridone ring D and a chiral center at C-20 in ring E.

Abstract: The present invention relation to a pharmaceutical composition comprising chelidonine or derivatives thereof, with pharmaceutically acceptable carriers. The compositions according to the present invention can selectively block hKv1.5 channels expressed preferentially in human atrial myocytes, and thus are useful as K+ channel blockers and antiarrhythmic drugs.

Abstract: The present invention describes the use of fumitremorgin A, B and C and a series of diketopiperazines of Formula (I) to resensitize multidrug resistant (MDR) cancer cells to the cytotoxic effects of chemotherapeutic drugs.

Abstract: Methods are provided relating to the enhanced cytoplasmic accumulation of amphipathic weakly basic or amphipathic cationic molecules in prokaryotes and eukaryotes under conditions of high extracellular pH. Furthermore, the methods relate to the unexpected synergistic effects of high extracellular pH and disrupted cellular efflux mechanisms on the cytoplasmic accumulation of amphipathic weakly basic or amphipathic cationic molecules in prokaryotes and eukaryotes. Methods are also provided for increasing the therapeutic potency of amphipathic weakly basic or amphipathic cationic compounds, e.g. antiseptics and disinfectants by using the antiseptic or disinfectant in the presence of a multiple drug resistance inhibitor such as reserpine. Finally, methods also relate to the exploitation of the aforementioned discoveries in the screening of small molecules, and libraries thereof, for biological activity in prokaryotes and eukaryotes.

Abstract: The present invention is directed to novel fused pyrrolocarbazoles and isoindolones, including pharmaceutical compositions, diagnostic kits, assay standards or reagents containing the same, and methods of using the same as therapeutics. The invention is also directed to intermediates and processes for making these novel compounds.

Abstract: The invention relates to insecticidal mixtures for protecting plants against attack by pests comprising (a) compounds of the formula (I) ?in which W, X, Y, Z, A, B, D and G are each as defined in the disclosure, and (b) agonists or antagonists of nicotinic acetylcholine receptors.

Abstract: Oligonucleotide-folate conjugates are described wherein folates are conjugated to one or more sites on an oligonucleotide including the 2?-, 3?-, 5?-, nucleobase and internucleotide linkage sites. The folate can be attached via the ?- or ?-carboxylate, optionally through a linking group. Methods for the regiospecific synthesis of the conjugates are disclosed. Also disclosed are nucleosidic and non-nucleosidic linkers conjugated to folic acid and related folates.

Abstract: It has been found that sampangine and related analogs such as benzo[4,5]sampangine, 4-bromosampangine and 4-methoxysampangine may be used as effective fungicidal agents for plants. Fungicidal plant compositions and methods of using the materials for such a purpose are also provided.

Abstract: The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, and cancer, in particular of the breast, uterus and prostate.

Abstract: Methods of forming camptothecin compounds which are effective anti-tumor compounds are disclosed. These compounds inhibit the enzyme topoisomerase I and may alkylate DNA of the associated topoisomerase I-DNA cleavable complex.

Abstract: Camptothecin analogs having an E-ring ketone are effective anti tumor compounds. These compounds inhibit the enzyme topoisomerase I and may alkylate DNA of the associated topoisomerase I DNA cleavable complex.

Abstract: A compound selected from those of formula (I): 1

Abstract: This invention is directed to macroheterocyclic compounds useful as kinase or dual-kinase inhibitors, methods for producing such compounds and methods for treating or ameliorating a kinase or dual-kinase mediated disorder.

Abstract: Camptothecin compounds which are effective anti-tumor compounds are disclosed. These conjugates inhibit the enzyme topoisomerase I and enhance the stability of the topoisomerase I-DNA cleavable complex.

Abstract: Certain non-nucleoside compounds that will selectively inhibit telomerase by targeting the nucleic add structures, such as G-quadruplexes, that may be associated with human telomeres or telomerase have been identified. Inhibition of human telomerase by two perylenetetracarboxylic acid diimides and a carbocyanine has been demonstrated. 1H-NMR studies have evidenced the stabilization of a G-quadruplex by the perylenetetracarboxylic acid diimide compounds and provided evidence that these and structurally related compounds inhibit the telomerase enzyme by a mechanism consistent with interaction with G-quadruplex structures.

Abstract: The present invention relates to novel heteroaryl-diazabicycloalkanes which are found to be cholinergic ligands at the nicotinic Acetyl Choline Receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neurodegeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

Abstract: A compound has the formula in racemic form, enantiomerically enriched form or enantiomerically pure form. R6 is preferably —Si(R8R9R10) or —(R7)Si(R8R9R10), wherein R7 is an alkylene group, an alkenylene group, or an alkynylene group; and R8, R9 and R10 are independently a C1-10 alkyl group, a C2-10 alkenyl group, a C2-10 alkynyl group, an aryl group or a —(CH2)NR11 group, wherein N is an integer within the range of 1 through 10 and R11 is a hydroxy group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group, —SRc or a nitro group. R1-R4 can be broadly substituted. R5 is preferably a C1-10 alkyl group, an alkenyl group, an alkynyl group, or a benzyl group. R13 is preferably H, F or —CH3. R16 is R16 is —C(O)Rf or H. The E-ring (the lactone ring) may be opened. A method of synthesis of compound (1) and intermediates in the synthesis thereof are provided.

Abstract: New analgesic compounds, which are prepared by the hydrolysis of N-acylated 4-hydroxyphenylamine derivatives, their synthesis and pharmaceutical compositions containing them are disclosed. These compounds surprisingly possess high analgesic activity with little hepatotoxic effect, making them more useful than conventional non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of chronic pain.

Abstract: Disclosed are prodrugs and analogs of buprenorphine.

Abstract: The present invention relates to a drug composition containing the non-sedating H1 antihistamines cetirizine, loratadine, mixtures or pharmaceutically acceptable salts thereof for topical application in the form of a gel.

Abstract: This invention relates to novel structural analogues and derivatives of compounds with general analgesic or related pharmacological activity. In particular the invention relates to derivatives of opioid compounds, particularly morphine and related compounds, in which an opioid compound is linked via the nitrogen at position 17 to a spacer group, which in turn is linked to a charged group, or a pharmaceutically acceptable salt thereof. In particularly preferred embodiments the opioid compound is morphine, codeine, or buprenorphine.

Abstract: This invention relates to: an indole derivative or a pharmaceutically acceptable salt thereof represented by formula (I): wherein R1 is, for example, hydrogen or C1-5 alkyl; R2 is, for example, hydrogen or hydroxy; R3 is, for example, hydrogen or hydroxy; —Z— is a crosslinkage having 2 to 5 carbon atoms; m is an integer from 0 to 3; n is an integer from 0 to 10; R4 and R5 are, for example, fluoro or hydroxy; R9 is, for example, hydrogen or C1-5 alkyl; and R10 and R11 are bound to each other to form, for example, —O—; and a pharmaceutical composition comprising the same, particularly a drug acting on &dgr; opioid receptor.

Abstract: One aspect of the present application relates to a method for limiting damage to neuronal cells by ischemic or epoxic conditions, e.g., such as may be manifest by a reduction in brain infarct volume, by administering to an individual a hedgehog therapeutic or ptc therapeutic in an amount effective for reducing cerebral infarct volume.

Abstract: This invention features ring-substituted pyrrolo-&bgr;-carboline derivatives and ring-substitution and structural derivatives of 3-(1H-indol-3-yl)-1H-pyrrole-2,5-dione of formulas (I-III), which are useful as neuroprotective and anti-proliferative compounds. Also disclosed are methods for the preparation of these compounds, selected biological profiles and uses of these compounds in the treatment of various neurodegenerative and inflammatory diseases of the human nervous system and in the treatment of various other proliferative disorders characterized by loss of growth or cellular differentiation control including, but not limited to, cancer and inflammation.

Abstract: The present invention relation to a pharmaceutical composition comprising chelidonine or derivatives thereof, with pharmaceutically acceptable carriers. The compositions according to the present invention can selectively block hKv1.5 channels expressed preferentially in human atrial myocytes, and thus are useful as K+ channel blockers and antiarrhythmic drugs.

Abstract: The present invention provides compound having the structure: and pharmaceutically acceptable salts or derivatives thereof, as well as compositions including such compounds. The invention also provides methods of (1) preventing pain, (2) treating pain, (3) inducing sedation, (4) treating opiate addiction, (5) treating opiate withdrawal (abstinence syndrome) and/or (6) treating cough in a patient in need thereof by administering a compound or composition of the invention.

Abstract: The present invention provides orally administered pharmaceutical compositions which contains an effective amount of free base or pharmaceutcially acceptable salts of nalbuphine and/or nalbuphine ester, an oily substance, and a solubility-assisting agent. The oily substance is preferably sesame oil. The solubility-assisting agent is preferably benzyl benzoate. The pharmaceutical composition is useful as an analgesic. The compositions achieves a much higher bioavailability rate and yields much longer lasting effects on nalbuphine than other nalbuphine products currently in the market.

Abstract: A use for agents that disrupt actin cytoskeletal organization is provided. In the instant invention, agents that disrupt actin cytoskeletal organization are found to upregulate endothelial cell Nitric Oxide Synthase activity. As a result, agents that disrupt actin cytoskeletal organization are useful in treating or preventing conditions that result from the abnormally low expression and/or activity of endothelial cell Nitric Oxide Synthase. Such conditions include hypoxia-induced conditions. Subjects thought to benefit mostly from such treatments include nonhyperlipidemics and nonhypercholesterolemics, but not necessarily exclude hyperlipidemics and hypercholesterolemics.

Abstract: Novel coordination polymers, their pharmaceutical formulations, useful for treating atheroma, tumors and other neoplastic tissue, as well as other conditions that are responsive to the induction of targeted oxidative stress, are disclosed.

Abstract: A composition in unit dosage form for the inhibition, prevention or treatment of inflammatory bowel disease comprising an effective amount of a compound having the formula: and a pharmaceutically acceptable carrier therefor.

Abstract: The invention relates to the treatment of an inflammatory disease, especially an inflammatory rheumatoid or rheumatic disease, and/or pain with an inhibitor of the activity of VEGF receptor tyrosine kinase of the formula I, the substituents being defined in the specification; as well as to new phthalazine derivatives; processes for the preparation thereof; the application thereof in a process for the treatment of the human or animal body; the use thereof for the treatment of a disease, especially a disease caused by ocular neovascularization, such as age-related macula degeneration or diabetic retinopathy, or other diseases that respond to the inhibition of tyrosine kinases, such as a proliferative disease; a method for the treatment of such disease in mammals; and the use of such a compound for the manufacture of a pharmaceutical preparation for the treatment especially of a disease as mentioned above.

Abstract: A compound or a salt or solvate thereof, of formula (I): 1

Abstract: This invention relates to: an indole derivative or a pharmaceutically acceptable salt thereof represented by formula (I): 1

Abstract: The invention relates to compound of formula (I): wherein: G1 represents an alkylene chain as defined in the description, A represents R2 and R3 represent hydrogen, alkyl, alkoxy or hydroxy or together form oxo, R4 and R5 represent hydrogen, R1 is as defined in the description, and medicinal products containing the same which are useful in treating or preventing melatoninergic disorders.

Abstract: The present invention provides methods of reducing angiogenesis in an individual. The methods generally involve administering to the individual an effective amount of a nicotinic acetyl choline receptor antagonist. The methods are useful to treat conditions associated with or resulting from angiogenesis, particularly pathological angiogenesis. The invention further provides methods of treating a condition associated with or resulting from angiogenesis.

Abstract: The present invention is directed to novel fused pyrrolocarbazoles and isoindolones, including pharmaceutical compositions, diagnostic kits, assay standards or reagents containing the same, and methods of using the same as therapeutics. The invention is also directed to intermediates and processes for making these novel compounds.