190 results about "Factor XIa" patented technology

The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R3, R4, R6, R11, X1, X2, and X3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

This invention provides aryl and heteroaryl compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention may be useful as antagonists, or partial antagonist of factor IX and / or factor XI and thus, may be used to inhibit the intrinsic pathway of blood coagulation. The compounds may be useful in a variety of applications including the management, treatment and / or control of diseases caused in part by the intrinsic clotting pathway utilizing factor IX and / or XI.

This invention provides aryl and heteroaryl compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention may be useful as antagonists, or partial antagonist of factor IX and / or factor XI and thus, may be used to inhibit the intrinsic pathway of blood coagulation. The compounds may be useful in a variety of applications including the management, treatment and / or control of diseases caused in part by the intrinsic clotting pathway utilizing factor IX and / or XI.

The present invention provides compounds that inhibit Factor XIa and methods of preventing or treating undesired thrombosis by administering a compound of the invention to a mammal. The invention also provides three-dimensional structures of Factor XIa and methods for designing or selecting additional Factor XIa inhibitors using these structures.

The present invention provides compounds that inhibit Factor XIa and methods of preventing or treating undesired thrombosis by administering a compound of the invention to a mammal. The invention also provides three-dimensional structures of Factor XIa and methods for designing or selecting additional Factor XIa inhibitors using these structures.

This invention provides aryl and heteroaryl compounds of formula (X). The compounds of the invention may be useful as antagonists, or partial antagonist of factor IX and / or factor XI and thus, may be used to inhibit the intrinsic pathway of blood coagulation. Formula (X) wherein R102 is selected from the group consisting of —C(O)OH, —C(O)OCH3, —C(O)O-t-butyl, —C(O)NH—OCH2-phenyl, C(O)NHOH, and —C(O)NHSO2CH3; and wherein R101, R103, R104 and Y are as defined herein.

The present invention provides compounds of Formula (I):or a stereoisomer or pharmaceutically acceptable salt or hydrate form thereof, wherein the variables A, B, L1, L2, X1, X2, X3, X4 and W are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

This invention provides aryl and heteroaryl compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention may be antagonists, or partial antagonist of factor IX and / or factor XI and thus, may be useful for inhibiting the intrinsic pathway of blood coagulation. The compounds may be useful in a variety of applications including the management, treatment and / or control of diseases caused in part by the intrinsic clotting pathway.

The present invention provides compounds of Formula (I): or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R3, and ring B are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

The present invention provides compounds of Formula (I):or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, B, R3 and R11 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

The present invention provides methods and compositions for treating bleeding episodes. The methods are carried out by administering to a patient in need thereof a preparation comprising a factor XI polypeptide, in an amount effective for such treatment. The methods of the invention result in one or more of: reduced clotting time; enhancement of hemostasis; increase in clot lysis time; increase in clot strength; and / or increase in overall clot quality (OCQ) in said patient.

Disclosed are novel dipeptide analogs compounds of Formula (I), (II) or (III):or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a solvate, or a prodrug thereof, which are inhibitors of factor XIa and / or plasma kallikrein, compositions containing them, and methods of using them, for example, for the treatment or prophylaxis of thrombotic diseases.

The present invention relates to compositions and methods for inhibiting thrombosis without compromising hemostasis. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The invention further includes pharmaceutical compositions comprising the anti-factor XI monoclonal antibodies of the invention, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier. Methods of the invention comprise administering the compositions described above to a subject in need thereof for the purpose of inhibiting thrombosis, reducing a required dose of an antithrombotic agent in the treatment of thrombosis, treating metastatic cancer, or treating an acute inflammatory reaction. Methods for making an anti-factor XI monoclonal antibody, or epitope-binding fragments, variants, or derivatives thereof, are also provided.

The present invention provides compounds of Formula (I):or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, X1, X2, X3, X4, and X5 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

The present invention relates to a novel pharmaceutical combination for treating thromboembolic and / or inflammatory diseases, wherein the combination has: (a) a first therapeutic agent independently selected from the group consisting of a selective Factor VIIa inhibitor, a selective Factor XIa inhibitor, a combination of the selective Factor VIIa and XIa inhibitors, or pharmaceutically acceptable salt forms thereof; and (b) a second therapeutic agent comprising a selective plasma kallikrein inhibitor or a pharmaceutically acceptable salt form thereof. The instant invention is also directed to a method and composition suitable for treating thromboembolic and / or inflammatory diseases using the novel combinations.

The present invention provides compounds of Formula (I):or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R3, and ring B are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

The present invention provides compounds of Formula (I):or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein the variables A, B, L1, L2, X1, X2, X3, X4, R4, R5, R13, R14, R15 and R16 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

The present invention provides compounds of Formula (I): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, X1, X2, X3, X4, and X5 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

A method of factor XI-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject. A method of factor XI-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising: (i) selecting a subject that is not deficient for factor XI; and (ii) administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject, wherein the NASP enhances blood coagulation in a factor XI-dependent manner. A method of identifying a non-anticoagulant sulfated polysaccharide (NASP) which is capable of enhancing blood coagulation in dependence on FXI, the method comprising: a) combining a blood or plasma sample comprising activation competent FXI with a composition comprising a sulfated polysaccharide and measuring the clotting or thrombin generation parameters of the blood or plasma sample; b) combining a corresponding blood or plasma sample deficient in activation competent FXI with a composition comprising the sulfated polysaccharide and measuring the clotting or thrombin generation parameters of the blood or plasma sample; and c) comparing the clotting or thrombin generation parameters of the blood or plasma samples as determined in steps (a) and (b) with each other, wherein a decrease in the clotting time of the blood sample or an increase in peak thrombin or decrease in peak time of the plasma sample comprising activation competent FXI compared to the clotting time of the blood sample or peak thrombin or peak time of the plasma sample deficient in activation competent FXI is indicative of a NASP which is capable of enhancing blood coagulation in dependence on FXI.

The invention relates to an offshore doubly fed motor stator winding turn-to-turn short circuit early fault identification method, and is used for judging the doubly fed motor stator winding turn-to-turn short circuit and determining the phase of the turn-to-turn short circuit. The method comprises the following steps that 1) the three-phase signals of an offshore doubly fed motor under fault identification are acquired, including the stator three-phase voltage, the rotor three-phase voltage, the stator three-phase current, the rotor three-phase current and the rotor rotating speed; 2) the three-phase signals are converted to a dq axis coordinate system, the motor parameters are acquired, then the three-phase signals are converted to an alphabeta axis coordinate system, the estimated stator current is acquired through an observer, and the estimated current difference is calculated and decomposed so that a fault severity factor xi is obtained; and 3) when the amplitude of the fault severity factor xi caused by the turn-to-turn short circuit fault reaches the fault early warning value, the stator winding turn-to-turn short circuit fault occurs on the offshore doubly fed motor under fault identification. Compared with the methods in the prior art, the offshore doubly fed motor stator winding turn-to-turn short circuit early fault identification method has the advantages that the fault phase can be reliably located and the robustness is high.

This invention provides aryl and heteroaryl compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention may be antagonists, or partial antagonist of factor IX and / or factor XI and thus, may be useful for inhibiting the intrinsic pathway of blood coagulation. The compounds may be useful in a variety of applications including the management, treatment and / or control of diseases caused in part by the intrinsic clotting pathway.

Disclosed are novel dipeptide analogs compounds of Formula (I), (II) or (III):or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a solvate, or a prodrug thereof, which are inhibitors of factor XIa and / or plasma kallikrein, compositions containing them, and methods of using them, for example, for the treatment or prophylaxis of thrombotic diseases.

The invention discloses a local curved surface change factor based scattered point cloud data compaction processing method. The local curved surface change factor based scattered point cloud data compaction processing method comprises the steps of 1 reading measured point cloud data, 2 calculating a central point of a point cloud, 3 searching dynamic K neighborhood points of the central point based on cubic grids and accordingly establishing the topological relation of scattered point cloud, 4 adopting a variance component method to calculate curved surface change factors of a k neighborhood of the central point, 5 determining the compaction rate of each cubic grid in the k neighborhood of the central point and performing even compaction in within a k neighborhood range. The topological relation of the scattered point cloud is established by establishing the dynamic K neighborhood point information of the scattered point cloud. Complicated curvature calculation is replaced by the curved surface change factors. The compaction ratio is adjusted according to the curved surface change factors Xi, even compaction within the k neighborhood range is achieved, the detail characteristic of high curvature can be protected, and planar characteristic of low curvature is also protected when the compaction degree is high. Point cloud data processing and curved surface reconstruction efficiency and accuracy are improved.

The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.