Abstract: The present invention provides methods of parasitic infections, thymoma, and lymphoid malignancies in a subject by administering to the subject a therapeutically effective amount of one or more of the compounds of the invention.

Abstract: The present invention provides compounds having formula (I) (and pharmaceutically acceptable derivatives thereof): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R1-R14 and n are as defined herein.

Abstract: Disclosed is an oxetane-containing vinyl ether compound including one or more aromatic or non-aromatic carbocycles and/or two or more vinyl ether structures, such as a compound of Formula: wherein Ring Z1 is non-aromatic carbocycle; Ra is vinyl group of Formula: wherein each of R1, R2, and R3 is hydrogen or C1-C4 alkyl; Wa is single bond or organic group having a valence of (m+1); X1 is, for example, hydrocarbon; “m” and “q” are each 1 or 2; and “p” is 0 to 5. Also disclosed is an alicyclic epoxy-containing vinyl ether compound of Formula: wherein Ring Z2 is non-aromatic carbocycle; Rb is vinyl group of Formula: wherein R4, R5 and R6 are each hydrogen or C1-C4 alkyl; Wb is single bond or organic group having a valence of (r+1); Rc and Rd are hydrogen or alkyl; and “r” and “s” are 1 or 2.

Abstract: A method of generating light through chemiluminescence involves providing a stable 1,2-dioxetane of the formula: Wherein (a) R1 and R2 are each, individually, a chemical reactive site or when fused together form a chemical reactive site, and R3 and R4 are each, individually, a chemical reactive site or when fused together form a chemical reactive or (b) R1 has at least two hetero atoms with chemical reactive site and R3 and R4 are inactive site and R2 is a chemical reactive site.

Abstract: The present invention is concerned with certain novel derivatives of Formula I, wherein R, R1 to R10 are as described in the specification, and at least one CR5R6, or CR7R8, or CR9R10 is a an optionally substituted azetidine ring or an optionally substituted oxetan ring, which may be useful in the manufacture of pharmaceutical compositions for treating disorders mediated by lipoxygenases. They may also be useful in the manufacture of pharmaceutical formulations for the treatment of lipoxygenase mediated disorders.

Abstract: A method of generating light through chemiluminescence involves providing a stable 1,2-dioxetane of the formula: Wherein (a) R1 and R2 are each, individually, a chemical reactive site or when fused together form a chemical reactive site, and R3 and R4 are each, individually, a chemical reactive site or when fused together form a chemical reactive or (b) R1 has at least two hetero atoms with chemical reactive site and R3 and R4 are inactive site and R2 is a chemical reactive site.

Abstract: Continuous processes comprising: oxidizing a ketone with a solution comprising active oxygen in a reactor in the presence of a buffer substance and a stripping gas to form a gas stream comprising a dioxirane and a liquid stream; and continuously drawing the gas stream comprising the dioxirane and the liquid stream from the reactor; wherein a liquid phase residence time of 1 minute to 4 hours and a normalized condensate mass flow rate of at least 500 g/mol of active oxygen are maintained.

Abstract: In one aspect, the present invention provides compounds having formula I or IV as shown below: as further defined herein. In additional aspects, the present invention provides compositions and kits comprising the compounds of the invention and methods for their use, for example, for the prevention or treatment of a cancer.

Abstract: The present invention relates to conjugates of water-soluble polymers and o(chloracetyl-carbamoyl) fumagillol (TNP-470) and use of those conjugates as specific intracellular carriers of the TNP-470 into tumor vessels. The present invention further relates to use of those conjugates to lower the neurotoxicity of TNP-470. Preferably, the polymer has a molecular weight in the range of 100 Da to 800 kDa. More preferably, the polymer has a molecular weight no greater than 60 kDa. Most preferably, the polymer has a molecular weight in the range of 15 kDa to 40 kDa.

Abstract: A compound for enhancing the light output of a chemiluminescent system and, in particular, a stabilized, triggerable 1,2-dioxetane, is obtained by reacting a polyvinylbenzyl halide and a bilinker with either a trisubstituted amine or trisubstituted phosphine. A fluorescent molecule may be attached to polymer along with the trisubstituted amine or trisubstituted phosphine. Also, the benzyl halide may be reacted with a ?-electron donor, such as a vinyl naphthalene or vinylanthracene to form a co-polymer which is polymerizable with the trisubstituted amine and/or trisubstituted phosphine. By controlling the reaction parameters it is possible to obtain either a water-soluble or partial water soluble or insoluble compound crosslink polymer.

Abstract: The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or more of the angiogenesis inhibitor compounds of the invention.

Abstract: A process for a preparation of Compound (V), a pharmaceutically acceptable salt or a solvate thereof, said process comprising the steps represented by the following formula: wherein R1 and R2 are each independently C1–C8 alkyl.

Abstract: The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or more of the angiogenesis inhibitor compounds of the invention.

Abstract: The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or more of the angiogenesis inhibitor compounds of the invention.

Abstract: The present invention relates to conjugates of water-soluble polymers and o-(chloracetyl-carbamoyl) fumagillol (TNP-470) and use of those conjugates as specific intracellular carriers of the TNP-470 into tumor vessels. The present invention further relates to use of those conjugates to lower the neurotoxicity of TNP-470. Preferably, the polymer has a molecular weight in the range of 100 Da to 800 kDa. More preferably, the polymer has a molecular weight no greater than 60 kDa. Most preferably, the polymer has a molecular weight in the range of 15 kDa to 40 kDa.

Abstract: The present invention relates to conjugates of water-soluble polymers and o-(chloracetyl-carbamoyl) fumagillol (TNP-470) and use of those conjugates as specific intracellular carriers of the TNP-470 into tumor vessels. The present invention further relates to use of those conjugates to lower the neurotoxicity of TNP-470. Preferably, the polymer has a molecular weight in the range of 100 Da to 800 kDa. More preferably, the polymer has a molecular weight no greater than 60 kDa. Most preferably, the polymer has a molecular weight in the range of 15 kDa to 40 kDa.

Abstract: Triptolide analogues are described, including compounds of Formula I: 1

Abstract: The invention relates to novel 1-oxaspiro[2,5]octan-6-ol derivatives of general formula (I): and also to a method for preparing them, and to their use in pharmaceutical compositions for use in human or veterinary medicine, or in cosmetic compositions.

Abstract: Processes for the preparation of Venlafaxine (IX) via the novel epoxy-nitrile intermediate (I), which when subjected to hydrogenation forms compound (X), and may subsequently be reduced to yield the desired product (IX). The epoxy-nitrile intermediate (I) itself may be synthesized via various alternative reaction strategies, from a range of starting materials. E.g. 4-methoxy-benzaldehyde (VI), upon treatment with cyclohexyl magnesium bromide yields compound (V). This in turn may be oxidized to yield compound (III), which forms compound (II) on treatment with an (x-keto-halogenation agent. Cyanation of compound (II), then yields the desired epoxy nitrile intermediate (I), from which Venlafaxine (IX) may be synthesized.

Abstract: Described are novel reversible photochromic indenonaphthopyran compounds, examples of which are 2H-naphtho[1,2-b]pyrans characterized by having a substituted or unsubstituted indeno group fused at the 2,3 positions of the group to the 1 side of the 2H-naphthopyran. The compounds also have substituents at the 3 position of the pyran ring. Substituents may also be present at the number 5, 6, 7, 8, 9, 10, 11, 12, or 13 carbon atoms of the compounds. These compounds may be represented by the following graphic formulae: Also described are various substrates, e.g., paper, glass, organic polymeric materials, etc., that contain or that are coated with such compounds. Optically clear articles such as ophthalmic lenses or other plastic transparencies that incorporate the novel indenonaphthopyran compounds or combinations thereof with complementary photochromic compounds, e.g., indenonaphthopyrans, naphthopyrans, benzopyrans, oxazine-type compounds, etc., are also described.

Abstract: A method of generating light through chemiluminescence involves providing a stable 1,2-dioxetane of the formula: 1

Abstract: Novel chromene compounds having various substituents to exhibit a high color-developing sensitivity and a high density even when dispersed in a high-molecular matrix, and exhibiting a large fading rate, less color when deteriorated, and excellent light resistance in the photochromic properties; photochromic materials containing the chromene compounds; and use thereof.

Abstract: 2,3-Dihydrobenzofuran derivatives of general formula (1): wherein R1 represents a hydrogen atom or an acyl group; R2, R3 and R4 represent a hydrogen atom, a lower alkyl group or a lower alkenyl group; R5 and R6 combine to form a cycloalkyl group or a saturated heterocyclic group containing one or more oxygen atoms or sulfur atoms, provided that R2 and R3 can not simultaneously represent a t-butyl group, or optically active isomers or pharmaceutically acceptable salts thereof are useful as therapeutic or prophylactic agents for various renal diseases and as organ preservatives.

Abstract: The present invention provides a novel bioactive substance having an antiangiogenic effect. The chemical compound represented by the formula (1) (wherein, R1 represents hydrogen atom, aldehyde group or a lower acyl group, R2 and R3 are the same as or different from each other and represent hydrogen atom or a lower alkoxy group or are combined to represent oxygen atom, R4 represents a lower alkyl group and R5 represents hydrogen atom or a lower alkyl group, provided that compounds in which R1 is aldehyde group, R2 and R3are different from each other and are hydrogen atom or methoxy group, R4 is ethyl group and R5 is hydrogen atom are excluded), a salt thereof or a hydrate thereof was isolated from the culture broth of genus Streptomyces and the structure thereof was analyzed.

Abstract: The present invention relates to novel substituted &agr;,&bgr;-fused butyrolactones, to processes for their preparation and to their use for the prevention and/or treatment of disorders caused by hyper- or hypofunction of the glutamatergic system, in particular of cerebral ischaemias, craniocerebral trauma, states of pain or CNS-mediated spasms.

Abstract: The invention relates to novel 1-oxaspiro[2,5]octan-6-ol derivatives of general formula (1): 1

Abstract: The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or more of the angiogenesis inhibitor compounds of the invention.

Abstract: The invention relates to a process for the preparation of Fumagillin by liberation from its salt characterized by reacting Fumagillin dicyclohexylamine salt with an organic acid in alcoholic medium.

Abstract: This invention relates to a method for preparing 1-oxaspiro[2,5]-carbonitriles from ketones using spinning disc reactor technology.

Abstract: This invention relates to a method of preparing a compound type where at least one of R′ or R″ is a carboxyl group (I) by treating a compound of formula (II) with a Group I(a) or Group II(a) metal halide, with an aprotic dipolar amide-based solvent and water.

Abstract: 4-Benzoylpyrazoles of the formula I where: R1 and R2 are each hydrogen, mercapto, nitro, halogen, cyano, thiocyanato, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, —OR10, —OCOR10, —OSO2R10, —S(O)nR10, —SO2OR10, —SO2NR3R10, —NR10SO2R10 or —NR10COR; Q is a pyrazole of the formula II,  which is attached in position 4 and, Substituted 4-benzoylpyralozoles.

Abstract: Chemiluminescent 1,2-dioxetane compounds capable of producing light energy when decomposed, substantially stable at room temperature, represented by the formulas I or II:

Abstract: This invention relates to a method of preparing a compound of the following type by treating a compound of formula (II) with lithium bromide, magnesium bromide and the like.

Abstract: A chemiluminescent assay method and compositions are described which use a dialkyl-substituted dioxetane which is deprotected to trigger a chemiluminescent reaction. Chemiluminescent 1,2-dioxetane compounds substituted on the dioxetane ring with two nonspirofused alkyl groups which can be triggered by a reagent to generate light are disclosed. Dialkyl-substituted dioxetanes are useful for the detection of triggering agents including enzymes. The enzyme may be present alone or linked to a member of a specific binding pair in an immunoassay, DNA probe assay or other assay where the enzyme is bound to a reporter molecule.

Abstract: Novel iridoid derivatives represented by general formula (I): and a vascularization inhibitor having for its active ingredient said derivative are disclosed. This vascularization inhibitor has remarkable vascularization inhibitory effects unaccompanied by serious adverse side effects, which is useful for the treatment and prevention of various diseases accompanied by abnormal acceleration of vascularization.

Abstract: Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.

Abstract: Spiroadamantyl dioxetanes bearing an alkoxy substituent, and an aromatic substituent of phenyl or naphthyl on the dioxetane ring can be activated to chemiluminesce if the aromatic substituent bears a moiety designated OX, wherein the X is cleaved by an enzyme with which the dioxetane is permitted to come in contact with. The T.sub.1/2 kinetics of the chemiluminescent reaction, as well as the signal intensity, or quantum yield of the chemiluminescent reaction, can be altered by selection of an electron-withdrawing or an electron-donating group Z, at positions on the aromatic substituent other than those adjacent the point of attachment to the dioxetane. Signal strength can further be enhanced by recognized chemiluminescent enhancers.

Abstract: A method and compositions including a 1,2-dioxetane and a fluorescent compound is described. In particular, enzymatic triggering of a triggerable 1,2-dioxetane admixed with a surfactant and the fluorescent compound attached to a hydrocarbon to provide a co-surfactant in a micelle or other structure providing close association of these molecules is described. The method and compositions are useful in immunoassays and in DNA probes used for various purposes.

Abstract: Compounds having the formula: ##STR1## wherein T is a polycycloalkylidene group (e.g., adamant-2-ylidene); R is a C.sub.1-20 alkyl, aralkyl or cycloalkyl group; and Y is a fluorescent chromophore (e.g., m-phenylene), produced by reacting a compound having the formula: ##STR2## with an R-ylating agent (e.g., R.sub.2 SO.sub.4) in the presence of an alkali metal alkoxide in a polar aprotic solvent. Also, compounds having the formula: ##STR3## are produced by reacting a compound having the formula: ##STR4## with ##STR5## wherein X is an electronegative leaving group (e.g., a halogen anion such as chloride ion) in the presence of a Lewis base (e.g., a trialkyl-amine) dissolved in an aprotic organic solvent (e.g., benzene or toluene). Also, compounds having the formula ##STR6## are produced by reacting a compound of the formula ##STR7## with a tetra-O-acylated-O-hexopyranoside halide, then hydrolyzing off the protective acyl groups.

Abstract: Compounds useful as angiogenesis inhibiting agents and processes for their preparation are disclosed. In one embodiment, the compounds of the invention are represented by Formula 1: ##STR1## Also disclosed is a pharmaceutical composition for inhibiting angiogenesis in a mammal, said composition comprising a compound of Formula 1, or a pharmaceutically acceptable salt thereof, as an active ingredient.

Abstract: The invention relates to a process for the preparation of vitamin D.sub.3 compounds of formula I. ##STR1## Wherein A is a single or a double bond; B is a single, cis-double, trans double or a triple bond; R.sub.1 and R.sub.2 are independently hydrogen, a lower alkyl, e.g., a C.sub.1 -C.sub.4 alkyl; R.sub.3 and R.sub.4 are independently a lower alkyl, e.g., C.sub.1 -C.sub.4 alkyl, a hydroxyalkyl, and a haloalkyl, e.g., a fluoroalkyl; and X and Y are independently hydrogen or hydroxy in the case when B is a single or a double bond.

Abstract: Stable, enzymatically triggered chemiluminescent 1,2-dioxetanes with improved water solubility and storage stability are provided as well as synthetic processes and intermediates used in their preparation. Dioxetanes further substituted with two or more water-solubilizing groups disposed on the dioxetane structure and an additional fluorine atom or lower alkyl group provide superior performance by eliminating the problem of reagent carryover when used in assays performed on capsule chemistry analytical systems. These dioxetanes display substantially improved stability on storage. Compositions comprising these dioxetanes, a non-polymeric cationic surfactant enhancer and optionally a fluorescer, for providing enhanced chemiluminescence are also provided.

Abstract: Novel iridoid derivatives represented by general formula (I): and a vascularization inhibitor having for its active ingredient said derivative are disclosed. This vascularization inhibitor has remarkable vascularization inhibitory effects unaccompanied by serious adverse side effects, which is useful for the treatment and prevention of various diseases accompanied by abnormal acceleration of vascularization.

Abstract: Spiroadamantyl dioxetanes bearing an alkoxy substituent, and an aromatic substituent of phenyl or naphthyl on the dioxetane ring can be activated to chemiluminesce if the aromatic substituent bears a moiety designated OX, wherein the X is cleaved by an enzyme with which the dioxetane is permitted to come in contact with. The T.sub.1/2 kinetics of the chemiluminescent reaction, as well as the signal intensity, or quantum yield of the chemiluminescent reaction, can be altered by selection of an electron-withdrawing or an electron-donating group Z, at positions on the aromatic substituent other than those adjacent the point of attachment to the dioxetane. Signal strength can further be enhanced by recognized chemiluminescent enhancers.

Abstract: A new class of stable dioxetanes bears a polycyclic stabilizing group and aryloxy moiety, the oxygen atom of which is provided with a protective group which can be removed by an enzymatic or chemical trigger admixed with the dioxetane. The polycyclic stabilizing group is preferably spiroadamantane. The group further bears an alkoxy, aryloxy, aralkyloxy or cycloalkyloxy moiety which is partially or completely substituted with halogens, particularly fluorine and chlorine. Proper selection of electron active groups on the stabilizing moiety, the aryl group and the OR group yields enhanced enzyme kinetics, superior light intensity and excellent detection sensitivity in various assays.

Abstract: A process for producing a stable triggerable dioxetane comprising;(a) reacting a vinyl sulfide compound containing a sulfur-substituent SR.sub.4, wherein R.sub.4 is an organic group containing 1 to 20 carbon atoms and optionally heteroatoms, with oxygen and light in the presence of a photosensitizer to form an intermediate sulfur-substituted dioxetane compound; and(b) reacting the sulfur-substituted dioxetane compound with an electrophilic compound E--Y and a hydroxylic compound R.sub.5 OH selected from the group consisting of alcohols, phenols and carboxylic acids or their salts and containing an OR.sub.5 group to replace the SR.sub.4 group of the dioxetane with the OR.sub.5 group.

Abstract: A 1,2-dioxetane derivative of formula (I) for use as a chemiluminescent substrate for immunoassays: ##STR1## wherein R.sup.1 is an alkyl group or an aryl group, R.sup.2 a hydrogen atom, an alkyl group or an aryl group, and R.sup.3 is a hydroxyl group, an alkoxyl group, aralkyloxy group, a phosphate salt group, or OSi(R.sup.4 R.sup.5 R.sup.6) in which R.sup.4, R.sup.5 and R.sup.6 are each independently an alkyl group which may be the same or different.

Abstract: A process for the manufacture of an optionally protected 4,8,8-trimethyl-1-oxaspiro?2.5!oct-4-en-6-ol (I) starting from protected 4-hydroxy-2,6,6-trimethyl-2-cyclohexen-1-one (II) comprises reacting the protected compound (II) with dihalomethyllithium and, if desired, cleaving off the protecting group from the thus-obtained protected 4,8,8-trimethyl-1-oxaspiro?2.5!oct-4-en-6-ol. The dihalomethyllithium can be produced in situ by reacting a dihalomethane with a lower alkyllithium in the presence of the compound of formula II. Preferably, protected (S)-4-hydroxy-2,6,6-trimethyl-2-cyclohexen-1-one is converted into protected (3S,6S)-4,8,8-trimethyl-1-oxaspiro?2.5!oct-4-en-6-ol in this manner. Both the starting material (II) and the end product (I) of the process in accordance with the invention are known, valuable intermediates for the manufacture of carotenoids.

Abstract: 1,2-dioxetane compounds bearing a proteolytic enzyme specific amino acid or peptide are provided, which amino acid or peptide can be removed by action of the corresponding protease. When the amino acid or peptide is removed, the 1,2-dioxetane decomposes with chemiluminescence, the generation of light providing a rapid, ultra-sensitive and convenient means for detecting the presence of the protease in the sample being inspected. The amount of light generated, or degree of chemiluminescence, can be correlated with the amount of protease present. Immunoassays, as well as DNA hybridization and DNA probe assays are provided.

Abstract: A new class of stable dioxetanes bears a polycyclic stabilizing group and aryloxy moiety, the oxygen atom of which is provided with a protective group which can be removed by an enzymatic or chemical trigger admixed with the dioxetane. The polycyclic stabilizing group is preferably spiroadamantane. The group further bears an alkoxy, aryloxy, aralkyloxy or cycloalkyloxy moiety which is partially or completely substituted with halogens, particularly fluorine and chlorine. Proper selection of electron active groups on the stabilizing moiety, the aryl group and the OR group yields enhanced enzyme kinetics, superior light intensity and excellent detection sensitivity in various assays.