Heterocyclic compounds of formula (I) useful as imaging probes of Tau pathology in Alzheimer's disease are described. Compositions and methods of making such compounds are also described.

The present invention provides: an uracil derivative represented by general formula (I) or a physiologically acceptable salt thereof (in the formula, R1 represents a hydrogen atom, a C1-10 alkyl group, a C2-6 alkene group or a 3- to 6-membered saturated or 4- to 6-membered unsaturated aliphatic ring group which may contain 1 to 2 hetero atoms independently selected from the group consisting of N, O and S; R2 represents a hydrogen atom, a halogen atom, a cyano group, —NRcRd, —N═CHN(CH3)2, or an C1-3 alkyl group; Ar1 and Ar2 independently represent a 5- to 6-membered aromatic ring group which may contain 1 to 3 hetero atoms independently selected from the group consisting of N, O and S; and L represents a 6-membered aromatic ring group which may contain 1 to 4 nitrogen atoms, a pyrazole group, a triazole group, or an imidazole group); and a therapeutic agent or prophylactic agent for various inflammatory diseases associated with elastase, comprises the compound or the like as an active ingredient.

The present application describes modulators of MCP-1 or CCR-2 of formula or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein m, n, W, X, R1 and R6, are defined herein. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and transplant rejection using modulators of formula (I) are disclosed.

The invention relates compounds of general formula (I) and pharmaceutically acceptable salts and solvates thereof wherein R1 is halogen, vinylene-aryl, substituted aryl, heteroaryl or a benzo[1,3]dioxolil group,W is a group of formula —NH—SO2—R2 or heteroaryl group or NHR3 group where R3 is hydrogen or heteroaryl; and n is 1, 2, 3 or 4. Furthermore, the present invention is directed to pharmaceutical composition containing at least one compound of general formula (I) and/or pharmaceutically acceptable salts or solvates thereof and for the use of them for the preparation of pharmaceutical compositions for the prophylaxis and/or the treatment of protein kinase related, especially CDK9-related diseases e.g. cell proliferative disease, infectious disease, pain, cardiovascular disease and inflammation.

The invention discloses quinoxaline derivatives or salts thereof having PDE9-inhibiting activity and being useful as treating agent of dysuria and the like, which are represented by the formula (I) in the formula, R1 and R2 each independently stands for hydrogen, halogen, alkyl, alkoxy, acyl, amino and the like,R3 stands for alkyl, aryl, saturated carbocyclic group, saturated heterocyclic group, acyl and the like,R4 stands for hydrogen, hydroxy, alkyl or amino,R5 and R8 each independently stands for hydrogen, halogen, alkyl, alkenyl, alkoxy, cyano or nitro,R6 and R7 each independently stands for hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, carbocyclic group, heterocyclic group, COR9 or SO2R9,R9 stands for hydrogen, hydroxy, alkyl, amino, pyrrolidin-1-yl, piperidin-1-yl, pyperazin-1-yl or the like,X stands for S or O, andA1, A2 and A3 each independently stands for N or C.

The present invention relates to pyridazine compounds of formulae I or II and the salts thereof, the N-oxides thereof and the salts of the N-oxides thereof, where the radical A is of the formula A, wherein # denotes the point of attachment to the remainder of formulae I or II, and wherein A1 is N or C—RA1, A2 is N or C—RA2, A3 is N or C—RA3, A4 is N or C—RA4 and A5 is N or C—RA5, provided that one or two of the variables A1, A2, A3, A4 or A5 is N; RA1, RA5, if present, are H, halogen, CN, NO2, C1-C6-alkyl, C1-C6-haloalkyl and the like; RA2, RA4, if present, are H, halogen, CN, NO2, C1-C10-alkyl, C1-C10-haloalkyl and the like; RA3, if present, is H, halogen, CN, NO2, C1-C10-alkyl, C1-C10-haloalkyl and the like; where W is N or C—RW and V is N or C—RV, provided that one of the variables W or V is N; Rt and Rw, if present, are H, halogen, methyl, C1-haloalkyl and the like; Ru and Rv, if present, are H, halogen, C1-C4-alkyl, C1-C3-haloalkyl and the like; X1 is S, O or NR1a, wherein R1a is H, C1-C10-alkyl and the like; X2 is OR2a, NR2bR2c, S(O)mR2d, wherein m is 0, 1 or 2, R2a is C1-C4-alkyl, C1-C4-haloalkyl and the like, R2b, R2c are H, C1-C4-alkyl, C1-C4-haloalkyl and the like, or R2b and R2c together with the nitrogen atom to which they are bound form a heterocycle, and R2d is C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl and the like; and R1 is H, CN, C1-C10-alkyl and the like. The present invention further relates to a method for controlling invertebrate pests, to a method for protecting plant propagation material and/or the plants which grow therefrom, to plant propagation material, comprising at least one compound according to the present invention, to a method for treating or protecting an animal from infestation or infection by parasites and to an agricultural composition containing at least one compound according to the present invention.

A process for the preparation of a chiral compound, in particular posaconazole, wherein the process comprises mixing and reacting the compounds of formula (I) Y3—NH2; of formula (IIa) 0=C═N—Y0 and/or of formula (IIb) and of formula (III) in a solvent in any order to obtain a reaction mixture containing a chiral compound of formula (IV) and/or formula (V).

The present invention provides 4,6-disubstituted pyrimidine compounds useful as kinase inhibitors, pharmaceutically acceptable compositions thereof, and methods of using the same.

The invention relates to oxazolopyrimidine compounds of formula I, where A, R1 and R2 are defined as stated in the claims. The compounds of formula I are suitable, for example, for wound healing.

The present invention relates to compounds of formula (I) wherein X1 to X5, Y, Z1 to Z3, and R have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Q, T, V, W, X, Y, Z, ring A, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 and m are defined herein. There novel pyrrolopyrimidine and purine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; R1 represents halogeno or C1-3alkyl; X1 represents —O—; R2 is selected from one of the following three groups: 1) C1-5alkylR3, wherein R3 is piperidinyl-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy; 2) C2-5alkenylR3, wherein R3 is as defined herein; 3) C2-5alkynylR3, wherein R3 is as defined herein; and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation; pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.

The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades.

The present invention provides a compound of formula I: a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

This invention relates to novel 5-[(hydroxymethyl)aryl]-substituted pyrrolo[2,1-f][1,2,4]triazin-4-amines of formula (I), to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for treating angiogenesis-related disorders, in particular angiogenesis-related ocular disorders.

4,6-dichloro-2-methyl-5-(1-acyl-2-imidazolin-2-yl)-aminopyrimidine is reacted with methanol in the presence of a non-ionic organic base, and moxonidine is obtained directly from the reaction mixture.

Disclosed are oil-extended olefin block copolymer compositions with precipitated silica. The precipitated silica reduces oil-bleed while maintaining composition softness.

Polyamide molding materials for transparent molding parts. The materials comprise transparent copolyamides that contain: (A) 40 to 100 wt % of at least one transparent copolyamide with a glass transition temperature (Tg) of at least 80° C. and not more than 150° C., composed of at least two diamines that are different from each other, wherein the at least two diamines are a mixture of (a) 50 to 90 mol % bis-(4-amino-3-methylcyclohexyl)methane (MACM) and/or bis-(4-amino-3-ethylcyclohexyl)methane (EACM) and/or bis-(4-amino-3,5-dimethylcyclohexyl)methane (TMACM) and b) 10 to 50 mol % aliphatic diamine having 9 to 14 carbon atoms, in particular decandiamine, particularly preferably at least 20 mol % decandiamine, each relative to the total amount of diamines, and of one or more aliphatic dicarboxylic acids, having 6 to 36 carbon atoms, (B) 0 to 60 wt % of at least one further polymer, (C) 0 to 10 wt % of additives, the sum of the components (A), (B) and (C) totaling 100% by weight.

Formulations comprising an isosorbide-modified unsaturated polyester comprising maleic acid, fumaric acid, itaconic acid or maleic anhydride and isosorbide and one or more low profile additives. The formulations exhibit better shrink control in molding compound formulations with standard low profile additives than their non-isosorbide-modified analogues. These isosorbide-modified unsaturated polyester resins may be applied in molding compounds like sheet molding compounds or bulk molding compounds and may be components of fiber reinforced composites or other composite materials.

An ion-conductive thermoplastic compositions contains a partially acetalated polyvinyl alcohol, at least one support electrolyte and at least one plasticizer. The partially acetalated polyvinyl alcohol contains two different acetal units. Electrochromic laminated glass systems produced using the ion-conductive compositions and a method for producing the systems are also provided.

The invention relates to radiation curable coating systems on the basis of aqueous polyurethane dispersions, to a method for the production thereof, to the use of the coating systems as paints and/or adhesives, and to objects and substrates provided with said paints and/or adhesives.

Disclosed is an adhesive for a polarizing plate that comprises a polyvinyl alcohol-based resin with an acetoacetyl group and an amine-based metal compound crosslinking agent, and a method of manufacturing the same.

Disclosed are oil-extended olefin block copolymer compositions with microcrystalline wax. The microcrystalline wax reduces oil-bleed while maintaining composition softness.

An aqueous dispersion includes particles at least partially encapsulated in a microgel where the microgel is prepared from a hyperbranched acrylic polymer. In addition, a method for making an aqueous dispersion includes: (1) mixing in an aqueous medium: (a) particles, (b) at least one ethylenically unsaturated monomer, and (c) a water-dispersible hyperbranched acrylic polymer having ethylenic unsaturation; and (2) polymerizing the at least one ethylenically unsaturated monomer and water-dispersible hyperbranched acrylic polymer having ethylenic unsaturation to at least partially encapsulate the particles in a microgel.

A primer solution for enhanced adhesion to a rigid substrate for aviation and aerospace applications includes an aminosilane-capped polyurethane prepolymer and a first solvent. The first solvent reacts with or modifies the surface of the rigid substrate, enabling the primer solution including the aminosilane-capped polyurethane prepolymer to become a part of the surface of the rigid substrate.

A rubber composition that can be used in applications such as automotive tires and can improve the fuel efficiency performance and driving stability of automobiles and the like, a method for producing a rubber composition, and a tire using the same are provided. A rubber composition comprising: (A) a conjugated diene rubber which is obtained by polymerizing a conjugated diene compound or polymerizing a conjugated diene compound and an aromatic vinyl compound and has a group having an active hydrogen and a group capable of chemically binding to a silica, (B) a silica, (C) a silane coupling agent (I) capable of reacting with a carbon-carbon double bond of the conjugated diene in the conjugated diene rubber, and (D) a silane coupling agent (II) capable of reacting with the group having an active hydrogen; a method for producing a rubber composition, which comprises mixing the above-mentioned composition; and a tire which is obtained by crosslinking and molding the rubber composition obtained by the method for production.

A long-fiber-reinforced resin composition including (A) a long-fiber-reinforced thermoplastic resin pellet including a thermoplastic resin, a modified polyolefin-based resin modified with an unsaturated carboxylic acid or its derivative and reinforcing fiber and satisfying (A-1) the melt index of the thermoplastic resin is 100-250 g/10 min, (A-2) the relaxation time λ of the thermoplastic resin is 0.1 (sec) or less, (A-3) the content of the reinforcing fiber is 40-70 wt %, and (A-4) the content of the modified polyolefin-based resin is 1-5 wt %; and (B) a polyolefin-based resin satisfying (B-1) the melt index of the polyolefin-based resin is 20-70 g/10 min, and (B-2) the relaxation time λ of the polyolefin-based resin is 0.23 (sec) or less; wherein the content of reinforcing fiber contained in (A) is 20-60 wt % relative to the total amount of the fiber-reinforced resin composition.

Titanocenes containing two 5-membered cyclodienyl groups, for example cyclopentadienyl, and one or two 6-membered carbocyclic or 5- or 6-membered heterocyclic aromatic rings which are substituted by a fluorine atom in at least one of the two ortho-positions to the titanium-carbon bond and contain, as a further substituent, unsubstituted or substituted 1-pyrryl, are suitable as photoinitiators for radiation-induced polymerization of ethylenically unsaturated compounds.

The invention relates 6-acyl-(6H)-dibenz[c,e][1,2]oxaphosphorin-6-oxides of the formula ##STR1## wherein each of R1, R2 and R3 may be present one or more times and R1, R2 and R3 represent halogen having an atomic number of from 9 to 35, alkyl or alkoxy each having from 1 to 6 carbon atoms and wherein Ar represents an aromatic hydrocarbon group having from 6 to 10 carbon atoms.The invention further relates to a process for the preparation of the afore-mentioned compounds and polymerizable compositions containing them as an essential ingredient as a photo-initiator. Finally the invention relates to 6-alkoxy-(6H)-dibenz[c,e][1,2]oxaphosphorin of the formula II ##STR2## wherein each of R1 and R2 may be present once or more times and R1 and R2 represent halogen having an atomic number of from 9 to 35, alkyl or alkoxy each having from 1 to 6 carbon atoms, at least one R1 being, however, halogen and wherein R4 represents alkyl having from 1 to 6 carbon atoms.

Beta-lactamase inhibiting compounds of the formula ##STR1## or a pharmaceutically acceptable acid addition or carboxylate salt thereof; where n is zero, 1 or 2; X3 is H or Br, R1 is H, the residue of certain carboxy-protecting groups or the residue of an ester group readily hydrolyzable in vivo; one of R12 and R13 is H and the other is vinyl, certain aryl, alkylthio, alkylsulfonyl or certain heterocyclyl, aminomethyl, thiocarboxyamido or amidino groups; one of R2 and R3 is H and the other is as disclosed for the other of R12 and R13, or is Cl or CH2 OH, and R18 is H or certain acyl groups; intermediates useful in their production, methods for their preparation and use, and pharmaceutical compositions containing them.

1,4-Dihydropyridine-3-carboxylate derivatives are produced having vasodilating and hypotensive action.

Herbicidally active 5-amino-1-phenyl-pyrazoles, most of which are new, of the formula ##STR1##

The invention relates to a process for the preparation of oligonucleotides by the following steps: reaction of a nucleoside with a phosphine derivative, reaction of the nucleotide derivative thus obtained with a nucleoside bonded to a polymeric carrier, oxidation of the carrier-bound nucleoside-nucleotide thus obtained with formation of phosphotriester groups, blocking of free primary 5'--OH groups, elimination of a protective group from the terminal 5'--OH group, where appropriate single or multiple repetition of the abovementioned steps to introduce further nucleoside phosphate or oligonucleoside phosphate units, and cleavage of the nucleoside-carrier bond and, where appropriate, elimination of all protective groups present in the oligonucleoside phosphates. The phosphine derivative used is a compound of the general formula III ##STR1## in which X and L can react with OH groups of the sugar units in the oligonucleotides, and R3 is a protective group which can be liberated by β-elimination.

A diphosphite is provided derived from phosphorous trihalide, tetra alkyl hindered bisphenol, and a neoalkyl diol. The phosphites exhibit improved stability and are useful as thermal oxidative stabilizers for thermoplastic compositions.

A diphosphite is provided derived from phosphorous trihalide, tetra alkyl hindered bisphenol, and a neoalkyl diol. The phosphites exhibit improved stability and are useful as thermal oxidative stabilizers for thermoplastic compositions.

A diphosphite is provided derived from phosphorous trihalide, tetra alkyl hindered bisphenol, and a neoalkyl diol. The phosphites exhibit improved stability and are useful as thermal oxidative stabilizers for thermoplastic compositions.

Antivirally active compounds of formula (I), wherein R1 is hydrogen, hydroxy, mercapto or amino; R2 is hydrogen, hydroxy, fluoro, chloro or amino; R3 and R4 are independently selected from (II), (III), amino, hydroxy or an ether or ester residue thereof, or R3 together with R4 is (IV), wherein M is hydrogen or a pharmaceutically acceptable counterion; and n is 1 or 2; with the proviso that, when R2 is amino and R3 and R4 are hydroxy, R1 is not hydroxy and in addition, when n=1, R1 is not hydrogen, and pharmaceutically acceptable salts thereof; processes for preparation of said compounds, a pharmaceutical composition comprising said compounds, methods for treatments of virus infections as well as use of compounds of formula (I) without the proviso for the manufacture of a medicament for treatment of AIDS. ##STR1##

Catalyst compositions comprising metallocene complexes having polymerisable olefinic groups substituent on an organic group containing a cyclopentadienyl nucleus may be used for the preparation of polyolefins. The catalyst compositions may be in the form of polymers comprising the metallocene complex and may be suitably supported on inorganic supports. Polymers having a broad range of density and melt indices as well as low hexane extractables and excellent powder morphology and flowability may be obtained by use of the catalyst compositions. Preferred metallocene complexes are zirconium complexes in which the polymerisable olefinic group is vinyl.

A diphosphite is provided derived from phosphorous trihalide, tetra alkyl hindered bisphenol, and a neoalkyl diol. The phosphites exhibit improved stability and are useful as thermal oxidative stabilizers for thermoplastic compositions.

A class of pyridine phosphonate compounds is disclosed that are useful as ligands in the one manufacture of oxidation-reduction catalysts. In particular, pyridine-2,6-disphosphonic acid is a specie of the pyridine phosphonate ligands that can be combined with a polyvalent metal to produce a catalyst to convert hydrogen sulfide to solid sulfur.

This invention relates to a process for polymerizing ethylene comprising contacting ethylene and optional comonomers with a catalyst system comprising an activator and a transition metal compound represented by the formula: ##STR1## Wherein R1 and R2 are independently hydrogen or a group having up to 100 carbon atoms, Cp1 is a bulky ligand; Cp2 is a bulky ligand or a heteroatom optionally bound to a C1 to C50 hydrocarbyl group, n is the valence state of the transition metal, Tm is a Group 3 to 10 metal, and each X is independently an anionic leaving group.

Metallocene compounds having two fluorenyl ligands bridged with a single silicon or germanium atom, said atom having two substituent groups containing a total of at least four carbon atoms, are useful as catalyst components for the polymerization of olefins. Particularly, it is possible to prepare high molecular weight atactic polypropylene with improved yields with respect to the known catalysts.

Compositions and methods for the solid phase synthesis of organic compounds are provided. The compositions are solid supports having an attached traceless linker precursor and are represented by the formula: ##STR1## In this formula, S0 is a solid support; B is a connecting group; M is a transition metal, for example ruthenium, chromium, iron, molybdenum and manganese; each L is independently a transition metal ligand; the letter n represents an integer of from 1 to 4, such that M has a sufficient number of ligands to fill the available valences; and X- represents an anion which is typically a non-nucleophilic anion.

Polysubstituted cyclopentadiene compound wherein at least two different substituents are present from the group consisting of linear, branched and cyclic alkyls, aralkyls and alkenyls, and a process for the preparation of a cyclopentadiene compound substituted with at least two different groups chosen from the group consisting of linear, branched, cyclic and aromatic alkyls and alkenyls, characterized in that it comprises the reacting of a halide of a first substituting group in a mixture of the cyclopentadiene compound and an aqueous solution of a base, in which the quantity of the base relative to the cyclopentadiene compound is between 5 and 30 mol/mol, in the presence of a phase transfer catalyst, followed by the addition of a halide of a second or optionally a third substituting group to the reaction mixture.

Disclosed is a process for preparing bridged Group 4 metal complexes containing a neutral diene ligand starting from the corresponding novel, metal diene containing complexes by reaction thereof with the divalent derivative of a bridged bidentate ligand compound. The novel, intermediate metal diene complexes, their formation from tetravalent metal salts and an integrated process combining both process steps are claimed.

Methods for removing parasites and in particular ectoparasites of vertebrates, in particular of mammals, and compositions for the implementation of this method.Methods for removing parasites of vertebrates, and in particular arthropods, mainly insects and Arachnida, wherein an effectively parasiticidal amount of a compound of formula (I) ##STR1## in particular of fipronil, is administered to the animal via an administration route which makes possible systemic distribution and good absorption.

A metallocene compound is provided wherein to a transition metal compound is bonded a multidentate compound wherein a substituted cycloalkadienyl ring CA1 having therein a heteroaromatic group Ra containing an oxygen, sulfur or nitrogen atom on a cycloalkadienyl ring, preferably the five-membered ring thereof, and an unsubstituted or substituted cycloalkadienyl group CA2 or --(R1)N--, --O--, --S-- or --(R1)P--, preferably CA2, more preferably a substituted cycloalkadienyl group identical with CA1 are bonded through a divalent linking group. The metallocene compound is suitable as a principal ingredient of a catalyst for the polymerization of olefins, particularly achieving a very high effect in making the molecular weight of a polypropylene higher.

A number of process steps are provided that can be combined to produce bridged cyclopentadienyl-fluorenyl metallocenes. The process steps include production of a cyclopentadiene compound from dicyclopentadiene; production and recovery of a fulvene compound using the cyclopentadiene compound; production of a raw metallocene product using the fulvene compound; and recovery of the pure metallocene from the raw product.

The present invention relates to a process for preparing a methylene-bridged biscyclopentadienyl compound having the formula I ##STR1##where L are, independently of one another, identical or different and are each a cyclopentadienyl group, by reacting one or two cyclopentadienyl compounds LH with formaldehyde in monomeric, oligomeric or polymeric form or formaldehyde-generating reagents in the presence of at least one base and at least one phase transfer catalyst.

The invention provides an improved process for the synthesis of compounds carrying at least one phosphate group, especially polyalkylene glycol phosphate compounds, said process comprising the steps of: (a) reacting a compound containing at least one primary alcohol moiety with a diaryl- or diaralkyl-halophosphate whereby to form the corresponding diaryl- or diaralkyl-phosphate ester; (b) reductively cleaving the resulting product; and (c) if desired, repeating steps (a) and (b) with the product of step (b) whereby to produce a compound carrying two or more phosphate groups. Advantages of the process in accordance with the invention are that this avoids the production of by-products and results in products which are low in impurities. Also provided are novel diaryl- and diaralkyl-phosphate ester compounds, in particular polyethylene glycol diphenylphosphate ester and derivatives thereof.