Abstract: 3-Phenyl-pyrones of the formula in which x represents pyrid-2-yl and Y represents fluorine, or x represents 4-fluoro-phenyl and Y represents chlorine, are highly suitable for use as pesticides, fungicides and herbicides.

Abstract: The invention provides a compound of formula (I): wherein R1, R2, R3, and Y have any of the meanings defined in the specification; as well a pharmaceutical composition comprising a compound of formula I; intermediates and methods useful for preparing a compound of formula I; and therapeutic methods for treating drug addiction, Parkinson's disease or depression comprising administering a compound of formula I, to a mammal in need of such treatment.

Abstract: Novel &agr;-pyrones are described. The &agr;-pyrones are useful in a method for controlling &agr;-pyrone responsive states in a mammal. The method includes administering to a mammal a therapeutically effective amount of an &agr;-pyrone such that control of &agr;-pyrone responsive states in a mammal occurs. &agr;-Pyrone responsive states can be associated with undesirable cell proliferation such as bacteria or cancer. Packaged pharmaceuticals and pharmaceutical compositions including the novel &agr;-pyrones are also described.

Abstract: This invention comprises methods of treating cardiovascular disorders and lowering blood LDL levels comprising administration of a statin and compound of the formulae I or II: wherein Z is a moiety selected from the group of: wherein: R1 is selected from H, OH or the C1-C12 esters or C1-C12 alkyl ethers thereof, benzyloxy, or halogen; or C1-C4 halogenated ethers including trifluoromethyl ether and trichloromethyl ether; R2, R3, R4, R5, and R6 are H, OH or C1-C12 esters or C1-C12 alkyl ethers thereof, halogens, or C1-C4 halogenated ethers, cyano, C1-C6 alkyl, or trifluoromethyl, with the proviso that, when R1 is H, R2 is not OH; Y is the moiety: R7 and R8 are alkyl or concatenated together to form an optionally substituted, nitrogen-containing ring; or a pharmaceutically acceptable salt thereof.

Abstract: The present invention provides water-soluble polymer conjugates of the anti-malarial drug, artelinic acid, using water soluble and non-peptidic polymer backbones, such as poly(ethylene glycol). The invention includes conjugates made using mPEG, bifunctional PEG and multi-arm PEG. The invention further includes a method of forming such conjugates and a method of treating malaria using the conjugates.

Abstract: A method of modifying or altering the structure of a 1&agr;-hydroxylated vitamin D compound to increase its biological activity by altering the conformational equilibrium of the A-ring to favor a chair conformation that presents the 1&agr;-hydroxyl in the axial orientation. This is accomplished by either locking the A-ring chair conformation in a geometry having an axially orientated 1&agr;-hydroxyl, or by the addition of one or more substituents to the A-ring which interact with other substituents in the molecule or on the A-ring to provide a driving force to the A-ring to adopt a chair conformation which presents the 1&agr;-hydroxyl in the axial orientation.

Abstract: A method for enhancing activity of enzyme at an elevated temperature which comprises adding a substance exhibiting chaperone function such as a saccharide to a reaction mixture containing the enzyme. The method can improve activity of enzymes more easily and more effectively and hence afford increased enzyme activity at an elevated temperature.

Abstract: Methods for treating viral infections are disclosed. The methods of the invention are useful for inhibiting viral infection in a subject and for preventing reducing tissue damage associated with viral infections. The method can include the step of administering to a subject in need thereof a therapeutically effective amount of a deprenyl compound, such that treatment of a viral infection occurs.

Abstract: The present invention focuses upon a method for inhibiting bone resorption. This method involves administering a 5-lipoxygenase inhibitor to a subject in an amount inhibiting the effects of an osteoclast-stimulating factor. When the production of the osteoclast-stimulating factors such as PTH, PTHrp, IL-1, TNF, LT, 1,25(OH)2D3 or other factors which may stimulate the production of 5-LO metabolites via the 5-lipoxygenase pathway is inhibited, bone resorption markedly declines. The direct osteoclast-stimulating factors include leukotriene, peptidoleukotriene and 5-hydroxyeicosatetraenoic acid. Other factors yet to be identified or previously known may also be 5-lipoxygenase metabolites that stimulate bone resorption. While 5-lipoxygenase inhibitors may be substrate analogs or allosteric inhibitors, a substance which inhibits the activity of this enzyme may utilize other mechanisms (e.g., inhibition of 5-LO biosynthesis) and nevertheless function to inhibit bone resorption.

Abstract: The invention provides novel non-&bgr;-lactam inhibitors of &bgr;-lactamases. In particular, the invention provides such inhibitors which are boronic acids of formula (1) which is set forth in the specification. These compounds may be used with &bgr;-lactam antibiotics to treat &bgr;-lactam-antibiotic-resistant bacterial infections. These compounds are also antibacterial by themselves. Finally, the invention provides a pharmaceutical composition comprising these compounds.

Abstract: The invention relates to novel heteroethynylenic compounds having the general formula (I): as well as to the use of these compounds in pharmaceutical compositions intended for use in human or veterinary medicine (dermatological, rheumatic, respiratory, cardiovascular and ophthalmological complaints in particular), or alternatively in cosmetic compositions.

Abstract: An intimal thickening inhibitory agent comprising, as an active ingredient, a compound represented by formula (1): wherein x represents an oxygen atom or a group of formula (2) —S—(O)n  (2) wherein n represents an integer of from 0 to 2, R1 represents a hydrogen atom or an acyl group; R2 represents a hydrogen atom, a lower alkyl group or a lower alkenyl group; R3 represents a lower alkyl group; and R4, R5, and R6, which may be the same or different, each represent a hydrogen atom or a substituted or unsubstituted alkyl group; or R3 and R4 may be taken together to form a 5-membered ring; or R5 and R6 may be taken together to form a cycloalkyl group; provided that R6 is nil when R3 and R4 are taken together to form benzofuran or benzo[b]thiophene.

Abstract: Free radical-scavenging olive oil polyphenols are topically applied to treat skin damage, such as contact dermatitis (particularly diaper area dermatitis), atopic dermatitis, xerosis, eczema (including severe hand and foot eczema), rosacea, seborrhea, psoriasis, thermal and radiation burns, other types of skin inflammation, and aging. Typical compositions contain from about 0.25% to about 10% of a polyphenol preparation obtained from olive oil.

Abstract: Compounds of the formula: 1

Abstract: The present invention relates to therapeutic protocols and pharmaceutical compositions designed to target HBx mediated activation of Src kinase, members of the Src tyrosine kinase family and components of the Src kinase family signal transduction pathways for the treatment of HBV infection and related disorders and diseases, such as HCC. The invention further relates to pharmaceutical compositions for the treatment of HBV infection targeted to HBx and its essential activities required to sustain HBV replication. The invention is based, in part, on the Applicants' discovery that activation of Src kinase signaling cascades play a fundamental role in mammalian hepadnavirus replication. Applicants have demonstrated that HBx mediates activation of the Src family of kinases and that this activation is a critical function provided by HBx for mammalian hepadnavirus replication.

Abstract: The invention provides novel non-&bgr;-lactam inhibitors of &bgr;-lactamases. In particular, the invention provides such inhibitors which are boronic acids of formula (1) which is set forth in the specification. These compounds may be used with &bgr;-lactam antibiotics to treat 62 -lactam-antibiotic-resistant bacterial infections. These compounds are also antibacterial by themselves. Finally, the invention provides a pharmaceutical composition comprising these compounds.

Abstract: A method of inhibiting the proliferation of a hyperproliferative mammalian cell having a multiple drug resistant phenotype utilizing an amount of a laulimalide compound effective to disrupt the dynamic state of microtubule polymerization and depolymerization to arrest cell mitosis is disclosed, together with laulimalide compounds which find use in such method.

Abstract: A food or food supplement which comprises a compound that enhances bone growth in vertebrates is described wherein the food or foodstuff is formulated so as to provide the desired bone growth enhancing effect.

Abstract: The present invention relates to novel Pyrrole-Type compounds, compositions comprising Pyrrole-Type compounds, and methods useful for treating or preventing cancer or a neoplastic disorder comprising administering a composition comprising a Pyrrole-Type compound. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The present invention also relates to novel Pyrrole-Type compounds, compositions, and methods useful for treating or preventing a viral infection. The compounds, compositions, and methods of the invention are also useful for inhibiting the replication and/or infectivity of a virus.

Abstract: The instant invention involves a combination therapy and pharmaceutical compositions comprised of a therapeutically effective amount of a cholesterol reducing agent such as an HMG-CoA reductase inhibitor in combination with a platelet aggregation inhibitor which is useful for inhibiting platelet aggregation, for inhibiting the formation of thrombotic occlusions, and for treating, preventing and reducing the risk of occurrence of cardiovascular and cerebrovascular events and related vaso-occlusive disorders.

Abstract: Methods for inactivating matrix metalloproteinases in a vertebrate cell are disclosed. The methods comprise administering to the cell an agent which causes increased endocytosis of the matrix metalloproteinase. Methods for treating vertebrates with disorders mediated by matrix metalloproteinases are also disclosed. These methods comprise administering the above-described agents to the vertebrate. Also disclosed is the use of HMG-CoA reductase inhibitors, also known as statins, as an agent which causes increased endocytosis of matrix metalloproteinases. Assays for determining whether an agent is effective in treating a disorder are also disclosed. These assays comprise testing the agent for activity in increasing endocytosis of a matrix metalloproteinase which mediates the disorder.

Abstract: A sulfonyl divalent aromatic or heteroaromatic ring hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a treatment process that comprises administering a contemplated sulfonyl divalent aromatic or heteroaromatic ring hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

Abstract: Methods for modulating the endocrine system of a mammal are provided. In the subject methods, a positive allosteric modulator of AMPA receptors of the hypothalamus are administered to the host. The subject methods find use in applications where it is desired to increase the circulatory level of a hormone in a mammalian host, such as diseased states characterized by abnormally depressed circulatory levels of the hormone.

Abstract: Spirolaxine, the compound of formula (I) wherein R is H, and the novel compounds of formula (I) wherein R is (C1-C5) alkyl or CH3(CH2)nCO and n is 1, 2, 3 or 4 are useful in treating gastroduodenal diseases such as gastric ulcers, duodenal ulcers and gastric cancer caused by Helicobacter pylori. Spirolaxine and spirolaxine methyl ether are isolated from the fermentation of Sporotrichum pruinosum ATCC 74278. Spirolaxine and the compounds of formula (I) are also useful in combination with H2 antagonist, colloidal bismuth subcitrate and other antibiotics.

Abstract: A method of modifying or altering the structure of a 1&agr;-hydroxylated vitamin D compound to increase its biological activity by altering the conformational equilibrium of the A-ring to favor a chair conformation that presents the 1&agr;-hydroxyl in the axial orientation. This is accomplished by either locking the A-ring chair conformation in a geometry having an axially orientated 1&agr;-hydroxyl, or by the addition of one or more substituents to the A-ring which interact with other substituents in the molecule or on the A-ring to provide a driving force to the A-ring to adopt a chair conformation which presents the 1&agr;-hydroxyl in the axial orientation.

Abstract: A hair growth formulation. The two basic main ingredients are castor oil and a special lemon extract. The special lemon extract is made from fresh lemon peel. The peel, including the bioflavonoids membrane, is blended with purified water until it is liquidified. Then the mixture is filtered through a sanitized cloth. Other ingredients that have been found helpful include: inositol, choline (from bitartate), niacinamide or nicotinic acid, manganese in chelated form, bioflavonoids, and folic acid. Finally perfume and sodium benzoate (as a preservative) can be added.

Abstract: The present invention relates to non-psychoactive derivatives of tetrahydro-cannabinol, which exhibit anti-inflammatory, analgesic and leukocyte antiadhesion activities. The invention includes novel derivatives of (3R,4R)-&Dgr;8-tetrahydrocannabinol-11-oic acids [hereinafter referred to as (3R,4R)-&Dgr;8-THC-11-oic acid], as well as pharmaceutical compositions containing the (3R,4R)-&Dgr;8-THC-11-oic acid derivatives. The invention further covers methods of administering the novel derivatives and pharmaceutical compositions as therapeutic agents in the treatment of pain and tissue inflammation. Non-psychoactive derivatives of &Dgr;8-THC-11-oic acid are described which have analgesic and anti-inflammatory properties.

Abstract: A process for producing a food material having a high concentration of eriocitrin, which comprises extracting a juice, a peel and a squeezed juice refuse of a citrus fruit with a polar solvent, applying the extract to a synthetic adsorption resin, and separating and recovering the food material having the high concentration of eriocitrin using an organic solvent such as hydrous alcohol. A food material having a high concentration eriocitrin as an antioxidant ingredient can industrially be produced quite efficiently without entraining an ingredient of a bitter taste, and drink and food having a high antioxidant effect can be produced.

Abstract: Compounds of the formula where R1 and R2, independently are alkyl groups having 2 to 8 carbons; R3 is hydrogen or lower alkyl; X is S, O or N—R4 where R4 is hydrogen or lower alkyl; Y is phenyl or pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl, and pyrazinyl; A is (CH2)n where n is 0-5, or lower branched chain alkyl, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and 1 or 2 triple bonds; B is hydrogen, COOH or a salt thereof, COOR5, CONR6R7, —CH2OH, CH2OR8, CH2OCOR8, CHO, CH(OR9)2, CHOR10O, —COR11, CR11(OR9)2, or CR11OR10O, where R5 is alkyl of 1 to 10 carbons, or cycloalkyl of 5 to 10 carbons, or R5 is phenyl or lower alkylphenyl, R6 and R7 independently are hydrogen, alkyl of 1 to 10 carbons, or cycloalkyl of 5 to 10 carbons, or phenyl or lower alkylphenyl, R8 is alkyl of 1 to 10 carbons, phenyl or lower alkylphenyl, R9 is lower alkyl, R10 is divalent alkyl radical of 2-5 carbons and R11 is alkyl, cycloalkyl or alkenyl containing 1

Abstract: Method for identifying a drug lead compound that inhibits binding of target bioogical molecules (TBM) by contacting TBM with members of a library of candidate cross-linked target binding fragments (CXBF), each CXBF having at least two candidate target bindig fragments (CTBF), which are inhibitors of binding, linked to a cross-linker, and selecting CXBF that inhibit the binding of the TBM to a greater extent than either of the individual CTBF linked to said cross-linker, wherein the library of CXBF is produced by: (a) screening a population of CTBF capable of being chemically cross-linked by a cross-linker to identify a subpopulation of the CTBF that inhibit binding of the TBM; and (b) chemically cross-linking members of the subpopulation of CTBF or structurally related analogs thereof with a cross-linker to provide a library of CXBF, wherein at least one linking group comprises an oxime ether linking group.

Abstract: Methods of using prostaglandin agonists for the reduction of intraocular pressure, and accordingly glaucoma.

Abstract: The present invention is directed to novel methods for identifying small molecule ligands that are capable of binding with high affinity to a biological target molecule of interest. High affinity binding ligands identified by the described methods find use, for example, as small molecule lead compounds that may they themselves be, or may give rise to, novel therapeutic drugs. More specifically, the subject invention is directed to methods for identifying a ligand that binds to a target biological molecule of interest, wherein a population of small organic compounds are selected and then “pre-screened” to identify those that are capable of binding to the molecular target.

Abstract: Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or “linker” defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 Å, are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.

Abstract: Compounds of formula (I) or their salts or esters: have excellent sialidase inhibitory activity and are therefore useful for the treatment and prevention of influenza and other viral diseases where the replication of the virus is susceptible to sialidase inhibitors.

Abstract: The present invention provides a protective agent for nervous system structural cells comprising a prostaglandin I derivative, preferably a prostaglandin I2 derivative, particularly beraplost, as an active component. This medicine exhibits excellent effects as a protective agent for nervous system structural cells, and is effective as an excellent agent for preventing or curing cerebrovascular disorder, cerebral nerve cell disorder, ischemic cerebral disorder, dementia, and peripheral nerve disorder due to diabetic or the like.

Abstract: A method and product for treating and preventing diarrhea and scours is provided. The method involves treating a subject who has diarrhea, or scours, or is at risk of getting diarrhea or scours with an aromatic compound of the invention. The products of the invention are a veterinary preparation of the aromatic compound of the invention and an anti-scours agent, and a pharmaceutical preparation of the aromatic compound of the invention and an anti-diarrheal agent.

Abstract: The invention relates to pharmaceutical compositions comprising an aldose reductase inhibitor and an ACE inhibitor, and their use in the treatment of diabetic complications such as diabetic neuropathy, diabetic retinopathy and diabetic nephropathy.

Abstract: Novel tubulin binding compounds (SPIKETS) having potent tubulin depolymerization activity and inhibitory activity against tubulin polymerization. The compounds are effective agents for inhibiting cellular proliferation, for example, in cancer cells. The compounds are adapted to interact favorably with a novel SP binding pocket on tubulin, which pocket is useful for screening of anti-tubulin, anti-proliferation, and anti-cancer drugs.

Abstract: A novel antifungal compound, “CAY-1”, was isolated from the dried fruit of Capsicum frutescens (cayenne pepper), purified to homogeneity, and characterized as a novel sterol glycoside (a saponin) with a molecular mass of 1243.35 Da. CAY-1 demonstrates antifungal activity against a large variety of fungal organisms associated with diseases in plants, animals and humans including, but not limited to, Aspergillus flavus, A. fumigatus, A. parasiticus, A. niger, Pneumocystis carnii and Candida albicans, but has minimal toxic effects on mammalian cells.

Abstract: Selected amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically inhibiting retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

Abstract: A compound of the following formula: and the salts thereof, wherein A is hydrogen, halo, hydroxy, or the like; the broken line represents an optional double bond with proviso that if the broken line is a double bond, then A is absent; Ar1 is optionally substituted phenyl or the like; Ar2 is aryl or heteroaryl selected from phenyl, napththyl, pyridyl, and the like, the aryl or heteroaryl being optionally substituted; R1 is hydrogen, hydroxy, C1-C4 alkyl, or the like; and R2 and R3 are independently selected from optionally substituted C1-C7 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, and the like or R2 and R3, together with the nitrogen atom to which they are attached, form an optionally substituted pyrrolidine, piperidine or morpholine ring. These compounds are useful as kappa agonists.

Abstract: The present invention is directed to an improved synthesis of clasto-lactacystin-&bgr;-lactone, and analogs thereof, that proceeds in fewer steps and in much greater overall yield than syntheses described in the prior art. The synthetic pathway relies upon a novel stereospecific synthesis of an oxazoline intermediate and a unique stereoselective addition of a formyl amide to the oxazoline. Also described are novel clasto-lactacystin-&bgr;-lactones, and analogs thereof and their use as proteosome inhibitors.

Abstract: A novel screening system for detecting a non-antibiotic compound having &bgr;-lactam-sensitivity-inducing activity comprising a non-antibiotic compound and a &bgr;-lactam antibiotic two times serially diluted series and a pharmaceutical composition having anti-MRSA activity comprising a flavone derivative and a &bgr;-lactam antibiotic.

Abstract: The invention concerns novel 6- or 7-substituted derivatives of esculetin (6,7-dihydroxy-2H-1-benzopyran-2-one), their synthesis, and their application as substrates for the detection of micro-organisms in samples where a derivative is enzymatically cleaved to release a colored or fluorogenic marker which has a low tendency to diffuse through agar or other aqueous environments.

Abstract: A process for preventing the transfer of harmful organisms of zooplankton including the epifauna thereof and of phytoplankton including its resting stages, which are taken up with the ballast water of ships and transferred to another locality on discharge. The organisms are substantially destroyed by the addition of an agent containing a water-soluble percarboxylic acid with 1 to 6 carbon atoms, particularly an aqueous solution containing peracetic acid and/or performic acid and hydrogen peroxide, in a quantity of 0.1 to 200 mg of percarboxylic acid per liter of ballast water and allowing it to react before discharge. In a preferred embodiment, cyanide is also added to the ballast water.

Abstract: The present invention is directed to tetrahydronaphthalene derivatives of &agr;-conindendrin, &bgr;-conindendrin, sikkimotoxin, and podophyllotoxin having at least one methyleneoxy bridge wherein the oxygen atom extends to the benzhydrylic carbon atom.

Abstract: A natural method for promoting fat, and weight loss while decreasing food cravings comprising administrating to an individual in need thereof L-carnitine, chromium, coenzyme Q10, creatine, lipoic acid, niacin, pyruvate, riboflavin, and thiamine. Pyruvate is a major promoter of the oxidation of dietary fuels like carbohydrates and fatty acids in the citric acid cycle. L-carnitine allow the transport of fatty acids into the mitochondria were they can be degraded in the citric acid cycle. Lipoic acid is a major intracellular antioxidant, and component of key enzymes in the citric acid cycle. Niacin, riboflavin, and thiamine are key components of enzymes that lead to the breakdown of dietary fuel molecules such as fatty acids, amino acids, and carbohydrates that enter the citric acid cycle. The breakdown of these dietary fuels leads to the production of high energy hydrogen atoms. Coenzyme Q10 accepts these hydrogen atoms and utilizes them for cellular energy production.

Abstract: Disclosed herein is a method for reducing neurodegenerative disease in patients by administration of a therapeutically-effective amount of a compound which can increase ApoE levels.

Abstract: The invention provides a simple and selective method for the deacylation of 4-acylated statins during the preparation of statins from a fermentation broth, more specifically a reduction of impurities from the process, by increasing the pH of the fermentation broth.

Abstract: A method for treating or preventing cardiovascular pathologies by administering a compound of the formula (I): wherein Z is C═O or a covalent bond; Y is H or O(C1-C4)alkyl, R1 and R2 are individually (C1-C4)allyl or together with N are a saturated heterocyclic group, R3 is ethyl or chloroethyl, R4 is H or together with R3 is —CH2—CH2— or —S—, R5 is I, O(C1-C4)alkyl or H and R6 is I, O(C1-C4)alkyl or H with the proviso that when R4F R5, and R6 are H, R3 is not ethyl; or a pharmaceutically acceptable salt thereof, effective to activate or stimulate production of TGF-beta to treat and/or prevent conditions such as atherosclerosis, thrombosis, myocardial infarction, and stroke is provided. Useful compounds include idoxifene and salts thereof. Further provided is a method for identifying a compound that is a TGF-beta activator or production stimulator is provided. Another embodiment of the invention is an assay or kit to determine TGF-beta in vitro.