Abstract: The invention pertains to a compound of formula (I), (II) or (III) wherein R1 and R2 are independently of each other hydrogen, C1-C18alkyl, C3-C18alkenyl, C3-C18alkinyl or phenyl which are unsubstituted or substituted by NO2, halogen, amino, hydroxy, cyano, carboxy, C1-C4alkoxy, C1-C4alkylthio, C1-C4alkylamino or di(C1-C4alkyl)amino; A is a group capable of forming a stable free nitroxyl radical A*, which is bound via its oxygen atom to the carbon atom; Y is O, NR3 or CHR3—Xa, wherein Xa is O, S or NR3; R3 is hydrogen, C1-C18alkyl, C3-C18alkenyl, C3-C18alkinyl or phenyl which are unsubstituted or substituted by NO2, halogen, amino, hydroxy, cyano, carboxy, C1-C4alkoxy, C1-C4alkylthio, C1-C4alkylamino or di(C1-C4alkyl)amino; Q1 is an organic or inorganic radical, derived from a compound having at least one functional group being capable of reacting with a hydroxy group; Q2 is an organic radical derived from a mono or polyfunctional alcohol, mono or polyfunctional aminoalcohol, mono or polyfunctional amine

Abstract: A compound of the formula (I): and a compound of the formula (V): as well as a compound of the formula (X): which are each a novel siastatin B derivative having a potent inhibitory activity against a glycosidase, are now synthesized by new processes. The compound of the formula (I), the compound of the formula (V) and the compound of the formula (X) have a potent enzyme-inhibitory activity to a glycosidase, which is particularly N-acetyl-galactosaminidase, galactosidase, glucosidase and mannosidase.

Abstract: The present invention provides an alkaloid compound that is an inhibitor of mycotoxin biosynthesis. The alkaloid is an alkenyl piperidine amide wherein the alkenyl is a C18 alkenyl with one or more double bonds. The alkaloid inhibits transcription of the fungus genes nor-1, tri5 and ipnA. The present invention further provides a method for identifying compounds, which inhibit biosynthesis of aflatoxin in Aspergillus spp. and deoxynivalenol in Gibberella spp. without inhibiting growth of the fungus in vitro.

Abstract: A compound of formula Id and pharmaceutically acceptable salts and esters thereof, wherein the substituent designations are as provided in the specification. Compounds of the invention are useful for treating reperfusion injury.

Abstract: Described herein are compounds that are useful as caspase inhibitors having the formula: wherein Ring A is an optionally substituted piperidine, tetrahydroquinoline or tetrahydroisoquinoline ring; R1 is hydrogen, CN, CHN2, R, or CH2Y; R is an optionally substituted group selected from an aliphatic group, an aryl group, or an aralkyl group; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; and R3 is hydrogen, an optionally substituted aryl group, an optionally substituted aralkyl group, or an optionally substituted C1-6 aliphatic group, R4 is an optionally substituted group selected from an aryl group or a heterocyclyl group, or R3 and R4 taken together with the nitrogen to which they are attached optionally form a substituted or unsubstituted monocyclic, bicyclic or tricyclic ring.

Abstract: A compound of formula (I) wherein R2 is arylene or heterocyclene; or R and R2 together with the nitrogen atom to which they are attached form non-aromatic heterocyclene; and the other residues have various meanings, useful as pharmaceuticals, e.g. antimicrobials.

Abstract: Compounds of formula (I) in which R2, X, Y, Cy, L and Lp(D)n have the meanings given in the specification, are inhibitors of the serine protease, factor Xa and are useful in the treatment of cardiovascular disorders.

Abstract: The invention relates to new therapeutically active and selective inhibitors of the enzyme dipeptidyl peptidase-IV, pharmaceutical compositions comprising the compounds and the use of such compounds for treating diseases that are associated with proteins that are subject to processing by DPP-IV, such as Type 2 diabetes mellitus, hyperglycemia, impaired glucose tolerance, metabolic syndrome (Syndrome X or insulin resistance syndrome), glucosuria, metabolic acidosis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, Type 1 diabetes, obesity, conditions exacerbated by obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, infertility due to polycystic ovary syndrome, short bowel syndrome, anxiety, depression, insomnia, chronic fatigue, epilepsy, eating disorders, chronic pain, alcohol addiction, diseases associated with intestinal motility, ulcers, irritable bowel syndrome, in

Abstract: There is disclosed an advantageous mixed acid anhydride production method of formula (1): R1C(O)OY(O)n(R2)p  (1) wherein R1, R2 and Y denote the same as defined below, n and p denote an integer of 1 or 2, which is characterized by adding a carboxylic acid of formula (2); R1COOH  (2) wherein R1 denotes a hydrogen atom, an optionally substituted alkyl group or the like, an organic base to a solution of a carboxylic acid activating agent of formula (3); (R2)pY(O)nX  (3) wherein R2 denotes an optionally substituted aliphatic hydrocarbyl group or the like, Y denotes a carbon atom, a phosphorus atom, or a sulfur atom, and X denotes a chlorine atom or the like.

Abstract: The present invention is generally drawn to novel isolated therapeutic agents, termed resolving, generated from the interaction between a dietary omega-3 polyunsaturated fatty acid (PUFA) such as eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), cyclooxygenase-II (COX-2) and an analgesic, such as aspirin (ASA). Surprisingly, careful isolation of compounds generated from the combination of components in an appropriate environment provide di- and tri-hydroxy EPA or DHA compounds having unique structural and physiological properties. The present invention therefore provides for many new useful therapeutic di- or tri-hydroxy derivatives of EPA or DHA (resolvins) that diminish, prevent, or eliminate inflammation or PMN migration, for example. The present invention also provides methods of use, methods of preparation, and packaged pharmaceuticals for use as medicaments for the compounds disclosed throughout the specification.

Abstract: Disclosed are cathepsin S reversible inhibitory compounds of the formulas (I),(Ia) and (II),(IIa) as defined herein. The compounds are useful for treating autoimmune diseases. Also disclosed are processes, for making such novel compounds.

Abstract: Objects of the present invention are to create compounds having urea structure as basic structure and having a sulfur atom and an amide bond in side chains and to find pharmacological effects thereof, particularly TNF-&agr; production inhibitory effects. The present invention provides compounds represented by the following formula [I] wherein R1 is H, alkyl, aromatic, RA—CO—, RC—S— or the formula [II]; R2, R3 and R4 are H, alkyl, alkenyl, cycloalkyl, cycloalkenyl or aromatic; R5 and R6 are H, alkyl, alkenyl, cycloalkyl, cycloalkenyl or aromatic; R5 and R6 can together form a nonaromatic heterocyclic ring; R7 is H, alkyl, cycloalkyl, hydroxy, mercapto, phenyl, RB—O—, RC—S—, RD—COS—, RE—OCO—, RF—N(RG)— or —CONHOH; and A1 and A2 are alkylene.

Abstract: Drugs or reagents containing as the active ingredient N-acyloxylated cycloalkyl compounds represented by general formula (I): wherein A is optionally substituted C4 or C5 cycloalkyl which may have one double bond in the ring; and R is C1-C3 alkyl or phenyl). The above compounds are hydroxyamine derivatives functioning as spin trapping agents and can rapidly react with free radicals or active oxygen in an objective organ in spite of their being excellent in stability during the preparation or administration thereof.

Abstract: The invention relates to new therapeutically active and selective inhibitors of the enzyme dipeptidyl peptidase-IV, pharmaceutical compositions comprising the compounds and the use of such compounds for treating diseases that are associated with proteins that are subject to processing by DPP-IV, such as Type 2 diabetes mellitus, hyperglycemia, impaired glucose tolerance, metabolic syndrome (Syndrome X or insulin resistance syndrome), glucosuria, metabolic acidosis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, Type 1 diabetes, obesity, conditions exacerbated by obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, infertility due to polycystic ovary syndrome, short bowel syndrome, anxiety, depression, insomnia, chronic fatigue, epilepsy, eating disorders, chronic pain, alcohol addiction, diseases associated with intestinal motility, ulcers, irritable bowel syndrome, in

Abstract: Hindered amine compounds which are substituted by a long hydrocarbon chain are useful in a number of applications where the solubility or compatibility afforded by said substitution is needed. This is seen particularly for example with white, dyed, dipped, unscented and/or scented candle wax which is effectively stabilized against discoloration and fading by the incorporation therein of a long chain hindered amine alone or in combination with a UV absorber and/or an antioxidant.

Abstract: A process for resolving a racemic mixture into its (R) and (S) enantiomers. The racemic mixture is reacted with a resolving agent selected from the group consisting of di-benzoyl-L-tartaric acid, di-benzoyl-D-tartaric acid, (S)-mandelic acid and (R)-mandelic acid in a solvent. The reaction is carried out under conditions sufficient to form soluble diastereomeric salts comprising the (R) enantiomer and the resolving agent, and the (S) enantiomer and the resolving agent, respectively. One of the diastereomeric salts is then isolated from the mixture. The free base of the isolated salt may then be generated in situ, and directly reacted with other compounds to synthesize useful chiral compounds.

Abstract: A method of synthesizing pure enantiomers of acylanalides such as Casodex® (bicalutamide) and its derivatives includes contacting a compound having a ring structure that, when opened, provides a substituent having the structure of Formula I: 1

Abstract: The invention relates to methods of synthesizing libraries of diverse and complex highly substituted 2,4-dioxopiperidine compounds of the general formula: wherein R1, R2 and R3 are as herein described, novel intermediates useful for synthesizing such 2,4-dioxopiperidine compounds and methods for identifying and isolating the compounds.

Abstract: A process for preparing an &agr;-haloketone of the formula (1) where R1 is an optionally heteroatom-containing and optionally substituted hydrocarbon radical, R2 is a hydrogen, alkyl, aralkyl or aryl radical, and X is a halogen radical, by reacting a carboxylic acid derivative of the general formula (2) where L is a leaving group, with a mono- or dienolate of a silyl ester of the formula (3) where R3 and R4 are identical or different alkyl, aryl, alkenyl or aralkyl radicals; and hydrolyzing the reaction product immediately afterwards by adding acid and decarboxylating to (1). The product &agr;-haloketone may be reduced to the corresponding &agr;-haloalcohol.

Abstract: The present invention provides methods for the asymmetric synthesis of (S,S,R)-(−)-actinonin and its analogs and the compounds thereby synthesized having a structural formula: where R1 is an optionally substituted or halogenated alkyl, aryl, heteroalkyl or heteroaryl amine, said R1 further comprising a cyclic or bicyclic structure; R2 is methyl, CH2CH3, (CH2)2CH3, C(CH3)3, phenyl, 3,4-dichiorophenyl, biphenyl, benzyl, 4-hydroxybenzyl, piperidine, N-Boc-4-piperidine, CH2-(N-Boc-4-piperidine), 4-tetrahydropyran, CH2-4-tetrahydropyran, 3-methyl indolyl, 2-naphthyl, 3-pyridyl, 4-pyridyl, 3-thienyl; R3 is R2 or C3-8alkyl, R4 is C1-3alkyl; and R5 is NH2, OH, NHOH, NHOCH3, N(CH3)OH, N(CH3)OCH3, NHCH2CH3, NH(CH2CH3), NHCH2(2,4-(OCH3)2Ph, NHCH2(4-NO2)Ph, NHN(CH3)2, proline, or 2-hydroxymethyl pyrrolidine.

Abstract: Phenylalanine derivatives of the following formula and analogues thereof have an antagonistic activity to &agr;4&bgr;7 integrin and a selectivity toward &agr;4&bgr;1 integrin. They are used as therapeutic agents for various diseases to which &agr;4&bgr;7 integrin relates.

Abstract: A compound of the formula wherein R1, R2 R3, R4 R5, R6, R7, R8, R9 and Q are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, tissue ulceration, macular degeneration, restenosis, periodontal disease, epidermolysis bullosa, scleritis, and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock and other diseases involving the production of TNF. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAID'S) and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.

Abstract: Selected heterocyclecarbonyl 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 preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

Abstract: A 6-aminocarbonylmethyl-4H-2,3-dioxin-4-one compounds can be produced by reacting a 6-halomethyl-4H-2,3-dioxin-4-one compound with a primary or secondary amine and carbon monoxide. The reaction may be carried out in the presence of a catalyst comprising a platinum group metal. 3-oxopentanedicarboxylic acid monoamides and 3-oxopentanedicarboxylic acid amide esters can be are produced by reacting 6-aminocarbonylmethyl-4H-2,3-dioxin-4-one compound with an alcohol or water. Using such intermediates, 6-aminocarbonylmethyl-4H-2,3-dioxin-4-one compound, 3-oxopentanedicarboxylic acid amide esters can provide in an easy and simple and efficient manner.

Abstract: Hindered amine compounds which are substituted by a long hydrocarbon chain are useful in a number of applications where the solubility or compatibility afforded by said substitution is needed. This is seen particularly for example with white, dyed, dipped, unscented and/or scented candle wax which is effectively stabilized against discoloration and fading by the incorporation therein of a long chain hindered amine alone or in combination with a UV absorber and/or an antioxidant.

Abstract: Hindered amine compounds which are substituted by a long hydrocarbon chain are useful in a number of applications where the solubility or compatibility afforded by said substitution is needed. This is seen particularly for example with white, dyed, dipped, unscented and/or scented candle wax which is effectively stabilized against discoloration and fading by the incorporation therein of a long chain hindered amine alone or in combination with a UV absorber and/or an antioxidant.

Abstract: Hexasubstituted guanidinium chlorides are prepared by a method which affords them in high yield as aqueous solutions, optionally also containing alkali metal chlorides. The solutions may be employed as sources of hexasubstituted guanidinium salts useful as phase transfer catalysts for the reaction of alkali metal salts of dihydroxyaromatic compounds with substituted imides to form polyetherimides or their intermediates.

Abstract: The compound of the formula (I) 1

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: One aspect of the present invention relates to novel heterocyclic compounds. A second aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for various cellular receptors, including opiate receptors, other G-protein-coupled receptors, and ion channels. An additional aspect of the present invention relates to the use of the novel heterocyclic compounds as analgesics.

Abstract: Novel amines of formulas 1D and 1E are disclosed and are useful as agents in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, inflammatory diseases, and gastrointestinal disorders, especially IBS. Processes for the preparation and intermediates useful in the preparation are also disclosed.

Abstract: Y—X—C(R′)═C(R″)COOR″′  (A1)

Abstract: This invention relates to neurotrophic low molecular weight, small molecule N-oxides of heterocyclic esters amides, thioesters, and ketones having an affinity for FKBP-type immunophilins, and their use as inhibitors of the enzyme activity associated with immunophilin proteins, particularly peptidyl-prolyl isomerase, or rotamase, enzyme activity.

Abstract: New secondary amines are described which are prepared from inexpensive, commercially available raw materials, are stable at room temperature, and are reactive toward electrophiles. The secondary amines are prepared by the addition of one or more primary amines with one or more male (amide/ester) and fumar (amide/ester) Michael receptors. The above amines can be used as coreactants with aliphatic polyisocyanates for polyurea coatings. The novel secondary amines are also described as particularly useful as part of a two-part liquid pavement marking composition for pavement markings.

Abstract: Piperidines are prepared in an advantageous manner by catalytic hydrogenation of activated pyridines in the presence of palladium catalysts if the palladium catalyst is palladium-on-carbon and the solvents are aromatic hydrocarbons.

Abstract: An inhibitor mixture containing, as components, a) at least one nitroxyl radical (derivative), b) at least one phenol (derivative) and c) at least one chemical compound which contains at least one phosphorus atom which has the oxidation state +3 is preferably used for stabilizing compounds capable of free radical polymerization.

Abstract: Compounds having therapeutic utility are of the formula wherein NB2 is heterocycloalkyl and R1 and R2 are each various substituents or a cyclic group.

Abstract: This invention is directed to methods of treating insulin resistance in a mammal which comprise administering an effective amount of a compound of formula I, where the variables are defined in the specification, or the stereoisomeric mixtures, diastereomerically enriched, diastereomerically pure, enantiomerically enriched or enantiomerically pure isomers, or the pharmaceutically acceptable salts and prodrugs thereof to said mammal. The compounds of formula I are growth hormone secretagogues and as such are useful for increasing the level of endogenous growth hormone. In another aspect this invention provides certain intermediates which are useful in the synthesis of the foregoing compounds and certain processes useful for the synthesis of said intermediates and the compounds of formula I.

Abstract: A multifunctional reagent for erythrocytes containing an amount sufficient to produce the lysis of erythrocytes or the sphering of erythrocytes in such a way that they can be detected by a cytometer or an automatic counting device, of a carbamate or of an agent inducing the formation by the erythrocytes, from carbonate and from a nitrogenated heterocycle or ammonium ions, of a carbamate combined with the absorption of CO2 by said erythrocytes, process for lysing or sphering erythrocytes and preparation process for leucocytes.

Abstract: Novel nitroimidazole compounds are provided that have a substituent linked via an ester linkage. The ester linkage may be obtained by derivation of the hydroxyl group of metronidazole. These nitroimidazole ester analogs have anti-microbial activity, with a number of novel compounds having an anti-microbial activity that is significantly improved with respect to metronidazole.

Abstract: The invention relates to heterocyclic derivatives of formula (I) and (Ia), or pharmaceutically-acceptable salts thereof, which possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.

Abstract: The present invention discloses halogenated 2-amino-5,6 heptenoic acid derivatives useful as nitric oxide synthase inhibitors.

Abstract: The present invention relates to prodrug compounds of inhibitors of dipeptidyl peptidase IV (DP IV), which prodrug compounds have the general formula A-B-C, wherein

Abstract: This invention relates to neurotrophic low molecular weight, small molecule N-linked ureas and carbamates of heterocyclic thioesters having an affinity for FKBP-type immunophilins, and their use as inhibitors of the enzyme activity associated with immunophilin proteins, particularly peptidyl-prolyl isomerase, or rotamase, enzyme activity.

Abstract: Hindered amines substituted on the N-atom with an hydroxy-substituted alkoxy moiety are particularly effective in stabilizing organic polymer compositions against the deleterious effects of oxidative, thermal and actinic radiation where the presence of the OH group on the compounds adds important properties not otherwise attainable.

Abstract: The present invention provides novel N-type calcium channel blockers, compositions comprising them, and methods of their use. The compounds of the invention are useful in the treatment of stroke, cerebral ischemia, pain, epilepsy, and head trauma.

Abstract: A method for producing an optically active piperidine carboxylic acid derivative, which comprises subjecting a piperidine carboxylic acid derivative of the formula (1): wherein Z is a protecting group for the carboxyl group, to optical resolution by means of an optical resolution agent of the formula (2): wherein symbol * indicates that the designated carbon atom is asymmetric.

Abstract: Piperidines are prepared in an advantageous manner by catalytic hydrogenation of activated pyridines in the presence of palladium catalysts if the palladium catalyst is palladium-on-carbon and the solvents are aromatic hydrocarbons.

Abstract: A compound of the formula wherein R1, R2 R3, R4 R5, R6, R7, R8, R9 and Ar are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, and other diseases characterized by matrix metalloproteinase or mammalian reprolysin activity. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAID'S), COX-2 inhibitors and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.

Abstract: Libraries of ethylenediamine compounds having the general formula (I): wherein R1 to R6, m, n, o and p are as defined herein, are prepared using solid phase combinatorial chemistry techniques. A heterocyclic alcohol is reacted with an ethylenediamine bound to a solid support to give a scaffold having sites of diversity. Libraries of the invention are useful for screening in biological assays in order to identify pharmaceutically useful compounds.