Abstract: It is presently accepted that the mechanism of action for all anti-tumor tubulin ligands involves the perturbation of microtubule dynamics during the G2/M phase of cell division and subsequent entry into apoptosis (1). In this invention, we report a novel tubulin ligands which have a unique mechanism of action. These compounds, halogenated derivatives of acetamido benzoyl ethyl ester (HAABE), arrest cancer cells in S-phase and cause cell death by a combination of apoptosis (DNA ladder) and necrosis (DNA degradation) type mechanisms. Normal cells are not affected at the same concentrations of compound. The ligands bind covalently to tubulin in vitro and in vivo and shows potent cancericidal activity in tissue culture assays and in animal tumor models. These compounds target early S-phase at the G1/S transition rather than the G2/M phase and mitotic arrest.

Abstract: Tropolone derivatives represented by the formula (I), which have retinoid actions and are useful as active ingredients of medicaments [R1 to R4 represent hydrogen atom, an alkyl group, or an alkoxyl group; the ring represented by Ar represents an aryl ring or a heteroaryl ring; X represents a single bond, —N?N—, —CON(R5)—, —(C?C)nCON(R6)—, —N(R7)CON(R8)—, —SO2N(R9)—, —N(R10)— (R5 to R9 represent hydrogen atom or an alkyl group, n represents 1 to 3, R10 represents hydrogen atom, an alkyl group, or an acyl group), an alkylene group, an aryldiyl group, or a heterocyclic diyl group; Y represents hydrogen atom, —OR11 (R11 represents hydrogen atom, an alkyl group, or an acyl group), —NHR12 (R12 represents hydrogen atom, an alkyl group, an acyl group, or amino group), or a halogen atom

Abstract: The present invention relates generally to amino acid derivatives and to methods of making the same. In particular, the invention relates to compounds bearing a stereochemical identity, that is, the same stereochemistry, with the chiral ?-carbon of D-?-amino acids and their use in methods of therapy, including the treatment of inflammatory diseases, and to compositions and enantiomeric mixtures containing them.

Abstract: Amide compounds of the formula: wherein R1 and R2 are taken together to form lower alkenylene, etc., R3 is aryl, etc., X is N, etc., Y is a single bond, etc., and Q is and salt thereof, which are useful as medicament.

Abstract: Novel compounds and compositions including those compounds, as well as methods of using and making the compounds are herein described. The compounds are useful in therapeutic applications, including modulation of disease or disease symptoms in a subject (e.g., mammal, human, dog, cat, horse). The compounds are useful as modulators of the mu opioid receptor (MOR) through their binding affinity with that receptor.

Abstract: Compounds of formula I in which R1, R2, R3, each X, L, Y, Cy, Lp, D and n have the meanings as set out in the specification, and corresponding compounds in which the unsubstituted or substituted amidine group is replaced with an unsubstituted or substituted aminomethyl group, are useful as serine protease inhibitors.

Abstract: Novel inhibitors of polyamine transport having inhibition constants two orders of magnitude lower than those of known compounds are disclosed. These polyamine analogues are useful pharmaceutical agents for treating diseases where it is desired to inhibit polyamine transport or other polyamine binding proteins, for example cancer and post-angioplasty injury. Novel chemical synthetic methods to obtain polyamine analogues are disclosed, including the production of a combinational polyamine library. These approaches yield analogues with desirable activities both for diagnostic and research assays and therapy. The assays of the invention are useful for high throughput screening of targets in the discovery of drugs that interact with the polyamine system.

Abstract: Novel compounds useful for inhibiting the 90 kDa heat shock proteins containing a quinone-like moiety and a di-hydroxy phenol like moiety, similar to geldanamycin and radicicol.

Abstract: A diene production stream comprising a solvent recovery blend from diene production comprising one or more fouling agent, one or more extractive distillation solvent, and from about 1 ppm to about 1000 ppm of N,N-disubstituted amide.

Abstract: A pharmaceutical composition an inclusion complex and methods for treating patients and preparing said complex disclosed for transmucosal delivery comprising an inclusion complex of (a) alprazolam and (b) a water soluble 2-hydroxypropyl-beta-cyclodextrin, and a pharmaceutically acceptable carrier therefor, wherein all the alprazolam is present in ring-closed form.

Abstract: Z-substituted acrylamides of formula (I), where the substituents have the following meanings: X?H, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, with X in the 3- or 4-position, n=1 or 2, where X can be different if n=2, R1=alkyl, haloalkyl, cycloalkyl, alkoxy, haloalkoxy, aziridine and oxirane and R2?H, alkyl, haloalkyl, allyl, propargyl or CH2C?C-alkyl. Methods for production thereof, agents comprising the above and the use thereof for the treatment of plant-pathogenic fungal pests.

Abstract: Novel mono- and dihydroxy phenylethylamine derivatives useful in treating melanoma are provided having the formulae (Ia, Ib or Ic). In the above formulae, Ra is hydrogen or —COORb, Rb is hydrogen or C1-6 alkyl; Re and Re independently represent hydrogen and hydroxy, Rf is hydrogen, C1–4? alkyl or halogen, X is —CHOH—, —CH2-oxygen or sulphur, m is zero or 1, W is oxygen or sulphur, and —ODrug, —NHDrug and —N(Drug)2 each represent a residue of a therapeutically active agent. The above compounds are prodrugs which are inactive until metabolised by enzymes expressed by host melanoma cells.

Abstract: The invention concerns compounds of formula (1): R-A-R? wherein: A is as defined in the description; R represent a group (V), (VI), (VII), or (VIII), where E, Q, R1, R2, R3, v and R4 are as defined in the description; R? represents a —(CH2)t—R5 group wherein t and R5 are as defined in the description, and medicaments containing the same

Abstract: The invention relates to copper complexes of phosphorus compounds, to a process for their preparation and to their use in catalytic coupling reactions.

Abstract: A drug based on a metabolite of fenretinide, or N-(4hydroxyphenyl) retinamide (4-HPR), specifically 4-oxo-N-(4-hydroxyphenyl) retinamide (4-oxo-4-HPR), is used in the treatment of different kinds of tumors, in particular in the treatment of ovarian carcinoma, breast tumor and neuroblastoma. The drug is more potent than fenretinide alone, and enhances the effects of fenretinide when administered together with fenretinide.

Abstract: Novel inhibitors of polyamine transport having inhibition constants two orders of magnitude lower than those of known compounds are disclosed. These polyamine analogues are useful pharmaceutical agents for treating diseases where it is desired to inhibit polyamine transport or other polyamine binding proteins, for example cancer and post-angioplasty injury. Novel chemical synthetic methods to obtain polyamine analogues are disclosed, including the production of a combinatiorial polyamine library. These approaches yield analogues with desirable activities both for diagnostic and research assays and therapy. The assays of the invention are useful for high throughput screening of targets in the discovery of drugs that interact with the polyamine system.

Abstract: The present invention provides crystalline biphenyl-4-carboxylic acid (R)-(6-(1-((4-fluorobenzyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amide hemihydrate, compositions thereof, methods of using the same, processes for making the same, and processes for making intermediates thereof.

Abstract: The present invention relates to a phthalamide derivative represented by the general formula (I): wherein R1, R2, R3, X, Y, m, and n are as defined in the disclosure, which can be used as the active ingredient in an agricultural or horticultural insecticide that exhibits an excellent insecticidal effect even when used in a small active-ingredient amount.

Abstract: Novel urea and urethane derivatives of general formula (I) in which R1, R2, R3, R5, R5?, X, Y, B, m, n and o are as defined in Patent Claim 1, and physiologically acceptable salts or solvates thereof are integrin inhibitors and can be employed for combating thromboses, cardiac infarction, coronary heart disease, arteriosclerosis, inflammation, tumors. Osteoporosis, infections and restenosis after angioplasty or in pathological processes maintained or propagated by antiogenesis.

Abstract: From compounds of formula II wherein R1 and R2 are independently of one another H, C1–C6alkyl, C1–C6halogenalkyl, C1–C6alkoxy, C1–C6alkoxy-C1–C6alkyl, or C1–C6alkoxy-C1–C6alkyloxy, R3 is C1–C6alkyl, R4 is C1–C6alkyl, and R5 is C1–C6alkyl, C1–C6hydroxyalkyl, C1–C6alkoxy-C1–C6-alkyl, C1–C6alkanoyloxy-C1–C6alkyl, C1–C6aminoalkyl, C1–C6alkylamino-C1–C6-alkyl, C1–C6-dialkylamino-C1–C6-alkyl, C1–C6-alkanoylamido-C1–C6-alkyl, HO(O)C—C1–C6-alkyl, C1–C6alkyl-O—(O)C—C1–C6alkyl, H2N—C(O)—C1–C6alkyl, C1–C6alkyl-HN—C(O)—C1–C6alkyl or (C1–C6alkyl)2N—C(O)—C1–C6-alkyl, R6 is C1–C6alkyl, R7 is C1–C6alkyl or C1–C6alkoxy, or R6 and R7 together are tetramethylene, pentamethylene, 3-oxa-1,5-pentylene or —CH2CH2O— substituted, if necessary, with C1–C4-Alkyl, phenyl or benzyl, it is possible—through halolactonization, azidation of the halogen group, ring opening with an amine R5—NH2, and reduction of the azide group to form the amino group—to prepare compounds of formula I wherein R5 is C1–C6alkyl, C1–C6hydroxyalkyl, C1–C6

Abstract: Compounds comprising are disclosed, wherein Y, A, X, R, D, and n are as described. A compound comprising a prostaglandin EP2 selective agonist wherein the ?-chain comprises a substituted phenyl, wherein at least one substituent consists of hydrocarbyl or non-linear hydroxyhydrocarbyl is also disclosed herein. Methods, compositions, and medicaments related thereto are also disclosed.

Abstract: The present invention provides compounds that are inducers or inhibitors of apoptosis or apoptosis preceded by cell-cycle arrest. In addition, the present invention provides pharmaceutical compositions and methods for treating mammals with leukemia or other forms of cancer or for treating disease conditions caused by apoptosis of cells.

Abstract: The present invention relates to novel phenyl-substituted 2-enamino-ketonitriles of the formula (I): in which Ar, X, Z, Y and K are each as defined in the description, to a plurality of processes for their preparation and to their use as herbicides and pesticides.

Abstract: This invention is directed to a [di(ether or thioether)heteroaryl or fluoro substituted aryl] compound or an N-oxide thereof or a pharmaceutically acceptable salt thereof, which is useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. The present invention is therefore directed to their pharmacological use for inhibiting TNF and/or cyclic AMP phosphodiesterase, pharmacological compositions comprising the compounds and methods for their preparation.

Abstract: The present invention relates to pharmaceutically acceptable compounds, including acylguanidine compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are particularly useful for the treatment or prophylaxis of neurological injury and neurodegenerative disorders.

Abstract: Amide compounds of the formula: wherein R1 and R2 are taken together to form lower alkenylene, etc., R3 is aryl, etc., X is N, etc., Y is a single bond, etc., and Q is and salt thereof, which are useful as medicament.

Abstract: The present invention provides a new fluorine-containing acetophenone derivative useful as a photo initiator, and a surface layer material containing the fluorine-containing acetophenone derivative. The present invention provides inexpensively an article with a hard coat excellent in anti-staining property, lubricity, scratch resistance and abrasion resistance, and provides a method for forming the hard coat. A fluorine-containing acetophenone derivative represented by the following general formula (I): wherein R1, R2 and R3 each independently represent an organic group other than aryl group, a hydrogen atom, a halogen atom or a hydroxyl group, provided that the following case does not take place: all of R1, R2 and R3 are simultaneously hydrogen atoms; and any two of R1, R2 and R3 may be linked to each other to form a ring, and R4 represents a fluorine-containing organic group.

Abstract: From compounds of formula II wherein R1 and R2 are independently of one another H, C1–C6alkyl, C1–C6halogenalkyl, C1–C6alkoxy, C1–C6alkoxy-C1–C6alkyl, or C1–C6alkoxy-C1–C6alkyloxy, R3 is C1–C6alkyl, R4 is C1–C6alkyl, and R5 is C1–C6alkyl, C1–C6hydroxyalkyl, C1–C6alkoxy-C1–C6-alkyl, C1–C6alkanoyloxy-C1–C6alkyl, C1–C6aminoalkyl, C1–C6alkylamino-C1–C6-alkyl, C1–C6-dialkylamino-C1–C6-alkyl, C1–C6-alkanoylamido-C1–C6-alkyl, HO(O)C—C1–C6-alkyl, C1–C6alkyl-O—(O)C—C1–C6alkyl, H2N—C(O)—C1–C6alkyl, C1–C6alkyl-HN—C(O)—C1–C6alkyl or (C1–C6alkyl)2N—C(O)—C1–C6-alkyl, R6 is C1–C6alkyl, R7 is C1–C6alkyl or C1–C6alkoxy, or R6 and R7 together are tetramethylene, pentamethylene, 3-oxa-1,5-pentylene or —CH2CH2O— substituted, if necessary, with C1–C4-Alkyl, phenyl or benzyl, it is possible—through halolactonization, azidation of the halogen group, ring opening with an amine R5—NH2, and reduction of the azide group to form the amino group—to prepare compounds of formula I wherein R5 is C1–C6alkyl, C1–C6hydroxyalkyl, C1–C6a

Abstract: Compounds, compositions and methods for altering insulin secretion, particularly in the context of treatment of subjects having, or suspected of being at risk for having, diabetes mellitus. The compounds have the following structure (I): including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein W1, W2, X, R1, R2, R3, R4, m and n are defined herein.

Abstract: A method for synthesizing cyclic polymers using transition metal alkylidene complexes as reaction catalysts is provided, wherein the complexes contain a cyclic group. Polymerization is carried out on the catalyst, using cyclic olefin monomers that undergo ring insertion polymerization, and no linear intermediates are generated. Following completion of polymerization, the cyclic polymer detaches from the complex via an intramolecular chain transfer reaction and the catalytic complex is regenerated. The invention also provides novel transition metal alkylidene complexes useful as catalysts in the aforementioned process, as well as novel cyclic hydrocarbons.

Abstract: The present invention relates to a process for the preparation of ?-chloroketones from readily available alkyl esters by the reaction of a sulfoxonium ylide on said alkyl esters to generate a keto sulfoxonium ylide that is in turn treated with anhydrous HCl.

Abstract: Described are compounds of Formula I and Formula II and their pharmaceutically acceptable salts. The compounds of Formulas I and II are antagonists of NMDA receptor channel complexes useful for treating cerebral vascular disorders such as, for example, cerebral ischemia, cardiac arrest, stroke, and Parkinson's disease.

Abstract: The invention relates to 3-phenyl-propionamido, 3-phenyl-acrylamido and 3-phenyl-propynamido derivatives, for example, deriviatives of the formula wherein A is selected from R1, R3, R4, R5, R6, R7, R21, R22, R23, R24, and n are as defined herein or pharmaceutically acceptable salts thereof. The invention also relates to processes for preparation of such compounds, compositions containing them, and the use of such derivatives as MAO-B inhibitors. The invention further relates to methods for treating or preventing Alzheimer's disease and senile dementia by administering compounds of the invention.

Abstract: An amine derivative, its tautomeric or stereoisomeric form, or a salt thereof which has vanilloid receptor 1 (VR1) antagonistic activity, is disclosed. The amine derivative has an excellent activity as VR1 antagonist and useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, incontinence and/or inflammatory disorders.

Abstract: Compounds of formula (I) are novel P2X3 and P2X2/P2X3 antagonists which are useful in treating pain, urinary incontinence and bladder overactivity.

Abstract: The present invention provides a pharmaceutical composition comprising N-(3-chloro-4-morpholin-4-yl)phenyl-N′-hydroxyimidoformamidine and sulfobutyl ether &bgr;-cyclodextrin or a salt thereof, wherein sulfobutyl ether &bgr;-cyclodextrin increases the solubility of N-(3-chloro-4-morpholin-4-yl)phenyl-N′-hydroxyimidoformamidine and improves the photostability.

Abstract: The invention is directed to the cross-metathesis and ring-closing metathesis reactions between geminal disubstituted olefins and terminal olefins, wherein the reaction employs a Ruthenium or Osmium metal carbene complex. Specifically, the invention relates to the synthesis of &agr;-functionalized or unfunctionalized olefins via intermolecular cross-metathesis and intramolecular ring-closing metathesis using a ruthenium alkylidene complex. The catalysts preferably used in the invention are of the general formula wherein: M is ruthenium or osmium; X and X1 are each independently an anionic ligand; L is a neutral electron donor ligand; and, R, R1R6, R7, R8, and R9 are each independently hydrogen or a substituent selected from the group consisting of C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, aryl, C1-C20 carboxylate, C1-C20 alkoxy, C2-C20 alkenyloxy, C2-C20 alkynyloxy, aryloxy, C2-C20 alkoxycarbonyl, C1-C20 alkylthio, C1-C20 alkylsulfonyl and C1-C20 alkylsulfinyl.

Abstract: A process for preparing an optically active biaryl compound the formula (4): 1

Abstract: Universal supports for oligonucleotide synthesis include a support material represented by the following formula: In this formula, substituent A is selected from H, alkyl, aryl, or a polymeric or silica base material; substituent B is selected from acyl, aroyl, or a polymeric or silica base material; and substituent C is selected from a dimethoxytrityl group or a protecting group removable under acidic or neutral conditions. For the supports, one of substituents A or B constitutes the polymeric or silica base material. In use, an oligonucleotide is attached to the support at substituent C.

Abstract: 1,3-Diarylprop-2-en-1-ones and derivatives, compositions containing them, manufacturing process and use. Substituted 1,3-diarylprop-2-en-1-ones with therapeutic activity may be used in oncology.

Abstract: The present invention relates to compounds according to the general formula (I), wherein R1-R4 have the meanings given in the description, A is CH2, CHOH or CH—(C1-C3-alkyl), B, C and D are independently CH2 or CH—(C1-C3-alkyl), and R5 is an aryl or heteroaryl group, possibly substituted by the substituents listed in the description.

Abstract: The invention provides novel compounds of the Formula (I) that stimulate rates of glucose oxidation in myocardial cells: 1

Abstract: The novel compound 3-amidinobenzoyl-D-phenylglycine-3-phenylanilide is useful as a serine protease inhibitor.

Abstract: A compound of the formula (I):

Abstract: Tropolone derivatives represented by the formula (I), which have retinoid actions and are useful as active ingredients of medicaments [R1 to R4 represent hydrogen atom, an alkyl group, or an alkoxyl group; the ring represented by Ar represents an aryl ring or a heteroaryl ring; X represents a single bond, —N═N—, —CON(R5)—, —(C═C)nCON(R6)—, —N(R7)CON(R8)—, —SO2N(R9)—, —N(R10)— (R5 to R9 represent hydrogen atom or an alkyl group, n represents 1 to 3, R10 represents hydrogen atom, an alkyl group, or an acyl group), an alkylene group, an aryldiyl group, or a heterocyclic diyl group; Y represents hydrogen atom, —OR11 (R11 represents hydrogen atom, an alkyl group, or an acyl group), —NHR12 (R12 represents hydrogen atom, an alkyl group, an acyl group, or amino group), or a halogen atom.

Abstract: Amide compounds of the formula: 1

Abstract: Compounds, compositions and methods for altering insulin secretion, particularly in the context of treatment of subjects having, or suspected of being at risk for having, diabetes mellitus.

Abstract: Compounds of Formula I Each R is independently linear or branched C1 to C8 alkyl, or linear or branched C1 to C8 alkoxy or one R is H and the other R is linear or branched C1 to C8 alkyl, or linear or branched C1 to C8 alkoxy; R1 is selected from the group consisting of COCH3, CO2R3, CONH2, CONH(R4)2, CN, COX(CH2)n-N—(R2)(R4)(R3), and the quaternized salt form of the formula COX(CH2)n-N—(R2)(R4)(R3)+Y−; X is O or NH; n is an integer of 1 to 5; Y is an anion; and R2, R3 and R4 are independently linear or branched C1 to C20. Hair care formulations and other compounds containing compounds of Formula I, and methods for protecting hair and substrates such as polymers, textiles, fabrics, leathers and paints using the compounds herein.

Abstract: PPAR alpha activators, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.

Abstract: The present invention provides the compound having the structure: wherein each of R1 and R2 are independently the same as or different from each other; when R1 and R2 are the same, each is a substituted or unsubstituted arylamino, cycloalkylamino, pyridineamino, piperidino, 9-purine-6-amine, or thiozoleamino group; when R1 and R2 are different, R1=R3—N—R4, wherein each of R3 and R4 are independently the same as or different from each other and are a hydrogen atom, a hydroxyl group, a substituted or unsubstituted, branched or unbranched alkyl, alkenyl, cycloalkyl, aryl, alkyloxy, aryloxy, arylalkyloxy, or pyridine group, or R3 and R4 bond together to form a piperidine group and R2 is a hydroxylamino, hydroxyl, amino, alkylamino, dialkylamino or alkyloxy group; and n is an integer from about 4 to about 8. The present invention also provides a method of selectively inducing terminal differentiation of neoplastic cells and thereby inhibiting proliferation of such cells.