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.

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyridyl-amino-pyrazine carbonitrile compounds that, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; and (e) ionizing radiation.

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

The present application is directed to solid forms of compounds of formula I: and pharmaceutically acceptable salts thereof, that inhibit bacterial gyrase and/or Topo IV and pharmaceutical compositions comprising said compounds and salts. These compounds and salts are useful in treating bacterial infections.

The invention encompasses compounds having formula I and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases are therapeutically useful.

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 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 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.

Disclosed is a method for preparing optically pure (+)-ambrisentan and (+)-darusentan, comprising: firstly catalyzing the asymmetric epoxidation of a β-unsaturated alkene using a chiral ketone derived from fructose or a hydrate thereof as a catalyst, and then subjecting the product to an epoxy compound ring-opening reaction and substitution reaction successively to obtain optically pure (+)-ambrisentan and (+)-darusentan.

Derivatives of 2,5-piperazinedione of formula (I) are apoptotic peptidase activating factor 1 (Apaf-1) inhibitors, therefore they are useful as active pharmaceutical ingredients for the prophylaxis and/or treatment of a pathological and/or physiological condition associated with an increase of apoptosis.

Formaldehyde-free binder compositions are described that include an aldehyde or ketone, a nitrogen-containing salt of an inorganic acid, and an acidic compound. The acidic compound may be an organic acid, such as maleic acid or citric acid among others. The acidic compound is supplied in quantities that lower the pH of the binder composition to about 5 or less. The binder compositions may be used in methods of binding fiberglass and the resulting fiberglass products have an improved tensile strength due to the addition of the acidic compound.

A composite sheet of the present invention comprises an oxetane-epoxy-based compound, represented by chemical formula 1, as a binder.

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

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.

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.

Injection molded articles and process of forming the same are described herein. The processes generally include providing a polyolefin including one or more propylene heterophasic copolymers, the polyolefin having an ethylene content of at least 10 wt. % based on the total weight of the polyolefin; contacting the polyolefin with a polylactic acid and a reactive modifier to form a compatiblized polymeric blend, wherein the reactive modifier is produced by contacting a polypropylene, a multifunctional acrylate comonomer, and an initiator under conditions suitable for the formation of a glycidyl methacrylate grafted polypropylene (PP-g-GMA) having a grafting yield in a range from 1 wt. % to 15 wt. %; and injection molding the compatibilized polymeric blend into an article.

Plasticizing system which can be used in particular for the plasticizing of a tire diene elastomer composition containing, in combination: a plasticizing hydrocarbon resin, the glass transition temperature of which is greater than 0° C.; anda tri- or pyromellitate ester corresponding to the formula (I): in which the R radicals, which are identical or different, represent a hydrocarbon radical and the R' radical represents hydrogen or COOR group. Also, a rubber composition incorporating the plasticizing system and the use of such a composition for the manufacture of a tire or tire semi-finished product made of rubber, in particular of a tire tread, exhibiting an improved wear resistance without having a detrimental affect on its wet grip.

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

A rubber composition for manufacturing tyres is based on one or more diene elastomers, one or more reinforcing fillers, and a vulcanization system. The vulcanization system includes one or more 1,2,4-triazine compounds chosen from compounds of formula I and compounds of formula II: Certain specific 1,2,4-triazine derivatives are described.

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.

Disclosed are polymeric compositions with improved breakdown strength. The polymeric compositions contain a polyolefin and a voltage stabilizing agent. The voltage stabilizing agent contains a triazine. The triazine may include a substituent that enables keto-enol tautomerism, which provides the voltage stabilizing agent with additional energy dissipation capacity. The present polymeric compositions exhibit improved breakdown strength when applied as an insulating layer for power cable.

The present invention pertains to an additive combination comprising at least two sterically hindered amines, at least one further stabilizer, a dispersing agent and a plasticizer. The present invention also pertains to a composition comprising an organic material susceptible to degradation by light, oxygen and/or heat, and the additive combination and to the use and the process for stabilizing organic material against degradation by light, oxygen and/or heat by the additive combination.

The present invention is directed at a binder for a battery electrode comprising an ethylene oxide-containing copolymer including a first monomer of ethylene oxide (EO) and at least one additional monomer selected from an alkylene-oxide that is different from the first monomer of EO, an alkyl glycidyl ether, or a combination thereof; wherein the ethylene oxide-containing copolymer has a weight average molecular weight less than about 200,000 g/mole (e.g., from about 10,000 to about 100,000), the molar fraction of the first monomer of EO (XEo) in the ethylene oxide-containing copolymer is greater than 0.80 (e.g., from about 0.80 to about 0.995), and the ethylene oxide-containing copolymer has a peak melting temperature (Tp), in ° C., for a selected XEO in the range of about 0.80 to about 0.995, which is below a maximum value of Tpmax, at the selected XEO, which is calculated using the equation Tpmax=(60−150 (1−XEO)).

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.

Non water-soluble polymers with a comb structure and a (meth)acrylic skeleton on which are grafted side chains containing at least one hydrophobic monomer of the styrene or (meth)acrylic ester type on C1 to C4, and at least one hydroxy or methoxy polylakylene glycol monomer. The levels of monomers are such that the polymer is amphiphilic because it is both rich in hydrophobic monomer and polylakylene glycol monomer. These products, used in paper coating dispersions, enable an increase in their Brookfield™ viscosity, a reduction in their ACAV viscosity, and an improvement in their water retention, which makes them particularly well suited for dry extract and/or high deposit speed coatings.

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.

Compounds of formula (I) ##STR1## in which R1 is hydrogen, O°, CN, NO, cyanomethyl, C1 -C12 -alkyl, C3 -C12 -alkenyl or C3 -C12 -alkynyl subject to the proviso that the carbon atom attached to the nitrogen atom is a primary carbon atom, C7 -C12 -aralkyl, C1 -C12 -acyl, 2,3-epoxypropyl, OH-monosubstituted C2 -C6 -alkyl or 2,3-dihydroxypropyl, R2 is hydrogen, C1 -C18 -alkyl, C5 -C18 -cycloalkyl, C6 -C18 -aryl or C7 -C18 -aryalkyl, R3 is C6 -C18 -aryl or a group of the formula (II) ##STR2## in which R1 is as defined above, n is an integer from 1 to 4 and R4 is an organic or inorganic radical of a valency equal to n are useful for stabilizing organic material against oxidative, thermal and/or light induced degradation.

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

The present invention relates to novel heterocycle-substituted diphosphonic acids, and the pharmaceutically-acceptable salts and esters thereof, in which the diphosphonate-substituted carbon atom moiety is attached to a carbon atom in a nitrogen-containing six membered ring heterocycle, preferably a piperidine ring. The heterocycle-substituted diphosphonic acid compounds have the general structure: ##STR1## wherein Z is a nitrogen-containing six membered ring heterocycle moiety selected from piperidinyl, diazinyl and triazinyl; m, n and m+n are from 0 to 10; Q is a covalent bond or a moiety selected from oxygen, sulfur or nitrogen; and R1, R2, R3 and R4 are substituent groups.The present invention further relates to pharmaceutical compositions containing these novel compounds. Finally this invention relates to methods for treating or preventing diseases characterized by abnormal calcium and phosphate metabolism by utilizing a compound or pharmaceutical composition of the present invention.

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

Carbohydrate substituted dibenzo[d,g][1,3,2]dioxaphosphocin compounds of formula I ##STR1## where A is a carbohydrate residue are effective stabilizers for polymers processed at elevated temperatures and subject to thermal or oxidative degradation.

Carbohydrate substituted dibenzo[d,f][1,3,2]dioxaphosphepin compounds of formula I ##STR1## where A is a carbohydrate residue are effective stabilizers for polymers processed at elevated temperatures and subject to thermal or oxidative degradation.

A method of producing a bis(2-carboxyethyl)-alkyl phosphine oxide represented by the following general formula (1) is disclosed. ##STR1## The method comprises the following Steps 1-4: step 1 wherein phosphine is reacted with acrylonitrile to produce bis(2-cyanoethyl)phosphine and then, in step 2, reacted with an alkene to produce a bis(2-cyanoethyl)alkyl phosphine, and in step 3, reacted with an oxidizing agent to produce a bis(2-cyanoethyl)alkyl phosphine oxide, and in step 4, said bis(2-cyanoethyl)alkyl phosphine oxide is reacted with water or a lower alcohol to give a bis(2-carboxyethyl)alkyl phosphine oxide or a derivative thereof.

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.

A process for producing an alkali metal cyclopentadienylide is disclosed which comprises reacting in a solvent an alkali metal hydride with a disubstituted or trisubstituted 1,3-cyclopentadiene. Further, a process for producing a dihalobis(η-substituted-cyclopentadienyl)zirconium is disclosed which comprises reacting a zirconium halide with the above alkali metal cyclopentadienylide. The former process enables performing the reaction between the disubstituted or trisubstituted 1,3-cyclopentadiene and the alkali metal hydride at an easily controllable temperature of room temperature to about 150° C. and also enables obtaining the alkali metal cyclopentadienylide in high yield. The latter process enables obtaining the dihalobis(η-substituted-cyclopentadienyl)zirconium in high yield.

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.

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.

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.

Curable organopolysiloxane compositions comprising a platinum catalyst selected from the group consisting of (PR23)2 Pt(--C.tbd.C--R3)2 (III), (R22 P--R4 --PR22)Pt(--C.tbd.C--R3)2 (IV)and H--C.tbd.C--R5 --C.tbd.C--[--Pt(PR23)2 --C.tbd.C--R5 --C.tbd.C--]e --H (V)where R2, R3, R4, R5 and e are as defined in claim 1.

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 preparation of phosphorescent metalloporphyrin labelling reagents and their use for preparation of phosphorescent conjugates with biomolecules. The labelling reagents obtainable are water soluble monofunctional derivatives of Pt- and Pd-coproporphyrins, where the term “monofunctional” refers to the number of reactive groups in the porphyrin moiety.

A process for obtaining silicon-bridged metallocene compounds comprising the following steps: a) reacting, at a temperature of between −10° C. and 70° C., the starting ligand with about 2 molar equivalents of an alkylating agent;b) after the reaction has been completed, adding at least 2 molar equivalents of an alkylating agent that can be also different from the first one; andc) reacting, at a temperature of between −10° C. and 70° C., the product obtained from step b) with at least 1 molar equivalent of a compound of formula ML's, wherein M is a transition metal; s is an integer corresponding to the oxidation state of the metal; and L' is an halogen atom selected from chlorine, bromine and iodine.