Abstract: The present invention relates to novel pyrrolidine derivatives of formula (I): wherein R1, R2, R3, R4, R5 and X are as defined in claim 1, optionally in a zwitterionic form, in the form of a pure optical isomer, or in the form of a mixture of optical isomers in any proportions, or in a form enriched with an optical isomer, as well as their pharmaceutically acceptable salts, solvates or hydrates, and pharmaceutical compositions containing such compounds. These compounds are notably useful for treating, in particular in human beings, epilepsy, ischemia, neurodegenerative diseases such as Parkinson's disease or Huntington's chorea, multiple sclerosis, Devic's disease, Alzheimer's disease, psychiatric diseases such as schizophrenia, depression, addiction, allodynia and hyperalgia.

Abstract: A compound represented by the following formula (a): CH2?CR1—CONJ-CGR2—(CH2)n—COO-Q1-Rf1??(a) is provided. This compound is capable of forming a polymer having an oil repellency equivalent to polymers containing a polyfluoroalkyl group containing at least 8 carbon atoms, although the polyfluoroalkyl group contains up to 6 carbon atoms. In the formula, R1 is hydrogen atom or methyl group, R2 is hydrogen atom or a group represented by —(CH2)m—COO-Q2-Rf2 (r), n and m are independently an integer of 0 to 4, Rf1 and Rf2 are independently a polyfluoroalkyl group or a polyfluoroether group containing 1 to 6 carbon atoms, Q1 and Q2 are independently single bond or a divalent linkage group, J is hydrogen atom or an alkyl group containing 1 to 3 carbon atoms, and G is hydrogen atom or an alkyl group containing 1 to 3 carbon atoms.

Abstract: A flavour composition comprising a compound according to the formula (I) or edible salts thereof, wherein R1 is an alkyl residue containing 6 to 20 carbon atoms, or an alkene residue containing from 9 to 25 carbon atoms with 1 to 6 double bonds, R1 together with the carbonyl group to which it is attached is a residue of a carboxylic acid, and NR2R3, in which R3 is H or together with R2 and the N-atom to which they are attached, a 5-membered ring, is a residue of an amino acid, in particular a proteinogenic amino acid, ornithine, gamma-aminobutyric acid or beta alanine, or a 1-amino cycloalkyl carboxylic acid.

Abstract: A compound useful as a building block for the manufacture of various compounds is represented by Formula A or D. In Formula A and D, z is 0 or 1; Q is a heteroatom; R1 through R11 and Ra through Rf are each independently hydrogen, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom containing hydrocarbyl group, or a functional group; d, e and f are each independently 0 or greater; each of A, B and D is independently a carbon atom or a heteroatom; and two or more of R1 though R11, Ra through Rf and Y optionally combine to form a ring. In some embodiments, R8 and R9 combine to form a carbonyl group. In some embodiments, R2 and Y combine to form a ring with the Q atom. In some embodiments, the ring includes at least one double bond.

Abstract: The present invention aims to provide a compound superior in broad utility and stability, which is useful as a protecting reagent (anchor) of amino acid and/or peptide in liquid phase synthesis and the like of a peptide having a C-terminal etc., which are of a carboxamide (—CONHR)-type, an organic synthesis reaction method (particularly peptide liquid phase synthesis method) using the compound, and a kit for peptide liquid phase synthesis containing the compound, and has found that the object can be achieved by a particular compound having a diphenylmethane skeleton.

Abstract: Among other things, the present invention provides novel isoprenyl compounds capable of effectively modulating inflammatory responses and pharmaceutical, cosmetic, cosmeceutical and topical compositions comprising these isoprenyl compounds. Anti-inflammatory compounds of the present invention are useful in treating or preventing diseases or conditions associated with inflammation. Proinflammatory compounds of the present invention are useful in treating or preventing diseases or conditions associated with suppression of inflammatory responses. Thus, the present invention also provides methods useful in the treatment or prevention of diseases or conditions associated with inflammation as well as methods useful in the treatment or prevention of diseases or conditions associated with suppression of inflammatory responses.

Abstract: The present invention provides an inexpensive and industrially advantageous method for producing an optically active form of an anti-(3S,4R)-3-alkylcarbamoyl-4-hydroxypyrrolidine derivative or it's enantiomer, which is a key intermediate for producing a high-quality optically active form of (3R,4S)-3-alkylaminomethyl-4-fluoropyrrolidine or it's enantiomer useful as an intermediate for producing pharmaceuticals. The present invention relates to a method for producing an optically active anti-(3S,4R)-4-hydroxypyrrolidine-3-carboxamide derivative, or it's enantiomer by carrying out asymmetric hydrogenation using an optically active catalyst of a 4-oxopyrrolidine-3-carboxamide derivative represented by the general formula (I). [in the formula (I), PG1 represents a protective group for an amino group, and R1 represents hydrogen, a C1 to C6 alkyl group which may be substituted, or a C3 to C8 cycloalkyl group which may be substituted].

Abstract: The disclosure relates to hexafluoroisopropyl carbamate derivatives of general formula (I): in which: R, Z, A, m, and n are as defined in the disclosure; in the form of the base or of an addition salt with an acid, and to the preparation process and therapeutic application thereof.

Abstract: The invention relates to a compound of formula (I) wherein A and R1 to R7 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

Abstract: N-(aminoacyl)-amino compound, represented by the following formula Wherein R1 denotes hydrogen, low alkyl or carbonyl, and N1 denotes an NH group and R2 denotes hydrogen or low alkylphenyl or aralkyl or imidazoalkyl or indolylalkyl, R1 and R2 together may complete a pyrrolidine or piperidine or thiazolidine ring and R3 denotes hydrogen or methyl or low alkyl and R4 denotes hydrogen or alkyl or the group remaining on exclusion of R4 from the formula and Z is a straight chain or branched alkylene, which may contain up to 3 carbon atoms. and R5 is nitrogen or sulphur or oxygen or salts thereof and ester compounds, characterised in that A is an ester or amino acid or alternatively sodium or a potassium salt of arginate and/or of ornithate and/or of aspharaginate.

Abstract: A compound useful as a building block for the manufacture of various compounds is represented by Formula A or D. In Formula A and D, z is 0 or 1; Q is a heteroatom; R1 through R11 and Ra through Rf are each independently hydrogen, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom containing hydrocarbyl group, or a functional group; d, e and f are each independently 0 or greater; each of A, B and D is independently a carbon atom or a heteroatom; and two or more of R1 though R11, Ra through Rf and Y optionally combine to form a ring. In some embodiments, R8 and R9 combine to form a carbonyl group. In some embodiments, R2 and Y combine to form a ring with the Q atom. In some embodiments, the ring includes at least one double bond.

Abstract: Methods and compounds for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV are provided.

Abstract: The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a g-amino-d-biphenyl-a-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Abstract: This invention relates to a class of pyrrolidine compounds of formula (I), and pharmaceutically acceptable derivatives thereof, to their use in medicine, to compositions containing them, and to processes for their preparation. It also relates to intermediates used in the preparation of such compounds and derivatives. In particular the compounds of formula (I) are useful for the treatment of EP2-mediated conditions, such as endometriosis, uterine fibroids (leiomyomata), menorrhagia, adenomyosis, primary and secondary dysmenorrhoea (including symptoms of dyspareunia, dyschexia and chronic pelvic pain), chronic pelvic pain syndrome.

Abstract: The invention relates to a process for the preparation of 5-(2-amino-pyrimidin-4-yl)-2-aryl-1H-pyrrole-3-carboxamides and to the useful intermediate compounds of such process. The process allows to obtain the desired products in high yields and purity. The synthesis is starting from the coupling of an acetal with a beta-ketoester; the resultant compound is acetylated and then reacted with a dialkyl acetal of N,N-dimethylformamide to give an intermediate which is cyclized to 5-(2-amino-pyrimidin-4-yl)-2-aryl-1H-pyrrole-3-carboxylic ester; the carboxylic ester is then hydrolyzed and the resultant carboxylic acid is finally condensed with an appropriate form of ammonia to give the desired carboxamide. The compounds prepared according to the process of the invention are endowed with protein kinase inhibiting activity and, more particularly, Cdc7 or Cdc7/Cdks inhibiting activity.

Abstract: The present invention provides an efficient and scalable process to prepare the compound of formula 4 by reduction of the corresponding ?-acyloxy sulfides.

Abstract: The present invention is directed to providing epoxycarboxamide compounds, azide compounds and amino alcohol compounds which serve as manufacturing intermediates that can lead to useful ?-ketoamide compounds, and the present invention is also is directed to processes for preparing ?-ketoamide compounds using the intermediates. The epoxycarboxamide compounds, azide compounds and amino alcohol compounds are represented by the following formulae: wherein R1, R2, R3, R4 and R5, as well as subvariables for one or more of R1, R2, R3, R4 and R5 are as defined herein.

Abstract: The present invention is directed to a method of using compounds of Formula (I) to inhibit Cathepsin B. Specifically the compounds of the present invention are useful as therapeutic agents for the treatment of tumor invasion, metastasis, Alzheimer's Disease, arthritis, inflammatory diseases such as chronic and acute pancreatitis, inflammatory airway disease, and bone and joint disorders, including osteoporosis, osteoarthritis, rheumatoid arthritis, psoriasis, and other autoimmune disorders, liver fibrosis, including liver fibrosis associated with HCV, all types of steatosis (including non-alcoholic steatohepatitis) and alcohol-associated steatohepatitis, non-alcoholic fatty liver disease, forms of pulmonary fibrosis including idiopathic pulmonary fibrosis, pathological diagnosis of interstitial pneumonia following lung biopsy, renal fibrosis, cardiac fibrosis, retinal angiogenesis and fibrosis/gliosis in the eye, schleroderma, and systemic sclerosis.

Abstract: Novel 4-fluoropyrrolidine-2-carbonyl fluoride compounds as useful fluorinated intermediates are disclosed. Their preparative methods are also disclosed. Useful applications of the 4-fluoropyrrolidine-2-carbonyl fluorides are shown.

Abstract: A compound represented by the following formula (a): CH2?CR1—CONJ-CKR2—(CH2)n—COO-Q1-Rf1??(a) is provided. This compound is capable of forming a polymer having an oil repellency equivalent to polymers containing a polyfluoroalkyl group containing at least 8 carbon atoms, although the polyfluoroalkyl group contains up to 6 carbon atoms. In the formula, R1 is hydrogen atom or methyl group, R2 is hydrogen atom or a group represented by —(CH2)m—COO-Q2-Rf2 (r), n and m are independently an integer of 0 to 4, Rf1 and Rf2 are independently a polyfluoroalkyl group or a polyfluoroether group containing 1 to 6 carbon atoms, Q1 and Q2 are independently single bond or a divalent linkage group, J is hydrogen atom or an alkyl group containing 1 to 3 carbon atoms, K is hydrogen atom or an alkyl group containing 1 to 3 carbon atoms, and j and k are independently single bond or an alkylene group containing 1 to 3 carbon atoms with the proviso that j and k are not simultaneously single bond.

Abstract: Novel compounds are continually sought after to treat and prevent diseases and disorders. The invention relates to N-(2-oxo-1-phenylpiperidin-3-yl)sulfonamides useful for being biologically and pharmacologically screened, and to contribute to the exploration and identification of new lead molecules that are capable of modulating the functional activity of a biological target.

Abstract: New compounds are continually being sought for the treatment and prevention of disorders. The invention relates to 1-(sulfonyl)-N-phenyl-pyrrolidine 2-carboxamides which can be used in the search for, and identification of, new lead compounds that could modulate the functional activity of a biological target.

Abstract: New compounds are continually sought after for the treatment and prevention of disorders. The invention relates to 1-(sulfonyl)-N-phenylpyrrolidine-2-carboxamides which can be biologically and pharmacologically traced, in order to be used in the search for, and identification of, new lead compounds that can modulate the functional activity of a biological target.

Abstract: The invention provides a novel class of reactive fluorescent agents that are based on a pyrene sulfonic acid nucleus. The agents are readily incorporated into conjugates with other species by reacting the reactive group with a group of complementary reactivity on the other species of the conjugate. Also provided are methods of using the compounds of the invention to detect and/or quantify an analyte in a sample. In an exemplary embodiment, the invention provides multi-color assays incorporating the compounds of the invention.

Abstract: Provided is a compound useful as a therapeutic drug for pain and inflammation caused by various pathological conditions such as neuropathic pain and rheumatoid arthritis. The compound of the formula (I) or a salt thereof [wherein R1 is a methyl group or a hydrogen atom, R2 represents a hydrogen atom, an alkyl group, an alkylcarbonyl group or an aryl carbonyl group, A represents a cycloalkyl group, a cycloalkenyl group, an aryl group or a heteroaryl group (each group may be substituted with a substituent selected from the group consisting of alkyl, alkenyl, cycloalkyl and halogen), n and m each represent an integer of 1, 2 or 3, and p represents an integer of 0, 1, 2 or 3].

Abstract: New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains. The compounds are of the formula M-L-Q where M is a synthetic ligand for an FKBP protein.

Abstract: The present invention relates to a compound or a pharmacologically acceptable salt thereof having superior glucokinase activating activity, and is a compound represented by general formula (I), or pharmacologically acceptable salt thereof: [wherein, A represents, for example, an oxygen atom or sulfur atom, R1 represents, for example, a C1-C6 alkyl group, a C1-C6 alkoxy group or a C1-C6 halogenated alkyl group, A and R1 together with the carbon atom bonded thereto form a heterocyclic group that may be substituted with 1 to 3 group(s) independently selected from Substituent Group ?, R2 represents a phenyl group that may be substituted with 1 to 5 group(s) independently selected from Substituent Group ? or a heterocyclic group that may be substituted with 1 to 3 group(s) independently selected from Substituent Group ?, R3 represents a hydroxy group or a C1-C6 alkoxy group, and Substituent Group ? consists of, for example, a halogen atom, a C1-C6 alkyl group, a C1-C6 alkyl group substituted with 1 or 2 hyd

Abstract: Novel 4-fluoropyrrolidine-2-carbonyl fluoride compounds as useful fluorinated intermediates are disclosed. Their preparative methods are also disclosed. Useful applications of the 4-fluoropyrrolidine-2-carbonyl fluorides are shown.

Abstract: The invention provides ?-sulfonamide ?-keto esters and amides in which the ?-keto is protected as a 1,3-dithiolane derivative. Also provided are methods for preparing such esters and amides and for incorporating them into peptides.

Abstract: The present invention relates to nitroxide imaging probes that are isotopically modified or unmodified. Such nitroxide imaging probes may be included in liposomes that encapsulate self-quenching concentrations thereof, wherein the liposomes optionally comprise a targeting ligand specific to and having affinity for targeted tissue.

Abstract: Prodrugs of alpha-2-delta ligands, pharmaceutical compositions of prodrugs of alpha-2-delta ligands, methods of making prodrugs of alpha-2-delta ligands, and methods of using prodrugs of alpha-2-delta ligands and pharmaceutical compositions of prodrugs of alpha-2-delta ligands to treat various diseases are disclosed.

Abstract: The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

Abstract: The present invention relates to a process for the preparation of cis substituted cyclic ?-aryl or heteroaryl carboxylic acid derivatives in high diastereo- and enantioselectivity by enantioselective hydrogenation in accordance with the following scheme wherein X, Ar, n, and m are defined hereinand corresponding salts thereof.

Abstract: Methods and compounds for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV are provided.

Abstract: The invention relates to a compound of formula (I) wherein A, R1-R6 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.

Abstract: Compounds are provided that act as potent antagonists of the CCR2 or CCR9 receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR2 and CCR9. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases, CCR9-mediated diseases, as controls in assays for the identification of CCR2 antagonists, and as controls in assays for the identification of CCR9 antagonists.

Abstract: The present invention relates to new, potent DPP-IV enzyme inhibitors of the general formula (I), which contain fluorine atoms.

Abstract: The invention provides a new enantioselective process for the preparation of (S)-pregabalin, or a pharmaceutical acceptable addition acid salt comprising: acid hydrolysis of the dioxolan ring of a chiral compound of general formula (I) to obtain compound of general formula (II); oxidation of compound (II) to obtain a compound of general formula (III) and transforming compound (III) into compound of general formula (IV); subjecting compound (IV) to basic hydrolysis to obtain a compound of general formula (V) which is reduced to obtain enantiomerically pure S-pregabalin. The invention also provides new chiral intermediates involved in the process.

Abstract: The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

Abstract: This invention relates to a class of pyrrolidine compounds of formula (I), and pharmaceutically acceptable derivatives thereof, to their use in medicine, to compositions containing them, and to processes for their preparation. It also relates to intermediates used in the preparation of such compounds and derivatives. In particular the compounds of formula (I) are useful for the treatment of EP2-mediated conditions, such as endometriosis, uterine fibroids (leiomyomata), menorrhagia, adenomyosis, primary and secondary dysmenorrhoea (including symptoms of dyspareunia, dyschexia and chronic pelvic pain), chronic pelvic pain syndrome.

Abstract: The present invention relates to pyrrolidin-2-ones according to the formula (1), or salts thereof, wherein R1 is hydrogen or a nitrogen protecting group, methods for their preparation and their use in the preparation of NEP-inhibitors, particularly in the preparation of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Abstract: The invention relates to nitric oxide donor compounds and their use for treating cardiovascular diseases, inflammation, pain, fever, gastrointestinal disorders, ophthalmic diseases, hepatic disorders, renal diseases, respiratory disorders, immunological diseases, bone metobolismsdysfunctions, central and peripheral nervous system diseases, sexual dysfunctions, infectious diseases, for the inhibition of platelet aggregation and platelet adhesion, for treating pathological conditions resulting from abnormal cell proliferation, vascular diseases. The invention also relates to compositions comprising at least one nitric oxide releasing compounds of the invention and composition comprising at least one nitric oxide releasing compounds according to the invention and at least one 15 therapeutic agent.

Abstract: This invention relates to novel diazabicyclic aryl derivatives which are found to be cholinergic ligands at the nicotinic acetylcholine receptors and modulators of the monoamine receptors and transporters. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

Abstract: An enzymatic ammonolysis process is provided for the preparation of intermediates used in preparing dipeptidyl peptidase IV inhibitors wherein the enzyme Candida antarctica lipase-B is used to catalyze the ammonolysis process.

Abstract: The present invention relates to compounds that are capable of inhibiting, modulating and/or regulating signal transduction of both receptor-type and non-receptor type tyrosine kinases. The compounds of the instant invention possess a core structure that comprises a substituted pyrrole moiety. The present invention is also related to the pharmaceutically acceptable salts, hydrates and stereoisomers of these compounds.

Abstract: An industrially advantageous process for the production of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine or an enantiomer thereof that is useful as an intermediate for the production of novel antimicrobial agents 10-(3-cyclopropylaminomethyl-4-fluoropyrrolidinyl)pyridobenzoxazine carboxylic acid derivatives. Highly stereoselective asymmetric hydrogenation of 1-protected-4-alkoxycarbonyl-3-oxopyrrolidine, followed by ester hydrolysis, followed by amidation with cyclopropylamine gives crude crystals. The crude crystals are purified by recrystallization to give a novel compound (3R,4S)-1-protected-3-cyclopropylcarbamoyl-4-hydroxypyrrolidine or an enantiomer thereof at high optical purity. The use of these intermediates enables industrial production of high-quality products of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine or an enantiomer thereof. The process is highly simple and can produce the desired products at high purity and stable yields.

Abstract: Methods and compounds for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV are provided.

Abstract: The present invention is directed to a novel, high yield method for preparing 2-imidazol-1-yl-4-methyl-6-pyrrolidin-2-yl-pyrimidine, particularly to a method of preparing 4-(1-alkylpyrrolidin-2-yl)-2-(1H-imidazol-1-yl)-6-methylpyrimidine, more particularly, 2-(2-(2-(1H-imidazol-1-yl)-6-methylpyrimidin-4-yl)pyrrolidrn-1-yl)-N-(benzo[d][1,3]dioxol-5-yh-nethyl)-N-methylethanamine. These compounds and pharmaceutical compositions thereof are inhibitors of nitric oxide synthase, are selective for inducible nitric oxide synthase, and are useful in treating diseases and disorders including inflammation and pain.

Abstract: The present invention relates to novel compounds of Formula (I) wherein ‘X’ represents an amino acid group, ‘n’ is an integer between 1 and 4, ‘R1’ represents benzyl, t-butyl or 9-fluorenylmethyl and ‘R2’ represents a tetramethylmercaptoimidazole derivative or —S+R3R4, wherein R3 and R4 each independently represent lower alkyl, or a pharmaceutically and/or veterinarily acceptable derivative thereof. The present invention further relates to pharmaceutical formulations of said compound and the use thereof in the preparation of a medicament for inhibiting diseases in which transglutaminase has been implicated. Advantageously, the medicament is for treating fibrosis, scarring and/or cancer. Additionally, the invention relates to a method of inhibiting autoimmune diseases such as coeliac disease, neurodegeneration and chronic inflammatory diseases (e.g. of the joints including rheumatoid arthritis and osteoarthritis in a subject).

Abstract: Compounds, pharmaceutical compositions, kits and methods are provided for use with MEK that comprise a compound selected from the group consisting of: wherein the variables are as defined herein.