306 results about "Kinin" 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.

The present invention is concerned with new compounds, and particularly those having a fused bicyclic ring substituted with an amidine moiety. These compounds are each potent inhibitors of Factor D of the alternate pathway of complement, C1s of the classical pathway of complement, Factors Xa, XIIa, VIIa and thrombin of the coagulation pathway, plasmin in the fibrinolytic pathway, and kallikrein and high molecular weight kininogen in the inflammatory pathways. These proteases, which have serine in their active site, are called serine proteases and they are pivotal to most of the processes of inflammation and coagulation. In fact, these various systems are interactive with one another and it is difficult to activate one pathway without it influencing the others.

The present invention provides compounds of Formula (I):

or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, B, L₁, L₂, X¹, X², X³, X⁴, X⁵, R⁴, 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.

The invention relates to a method for preserving an organ or tissue comprising contacting the organ or tissue with an effective amount of a kallikrein inhibitor and solutions useful for such a method. Also provided is a method for reducing reperfusion injury of an organ during surgery and/or following removal of the organ from a subject comprising placing the organ in an organ storage and preservative solution, wherein the solution comprises a kallikrein inhibitor.

This invention provides: novel protein homologous of a Kunitz domain, which are capable of binding kallikrein; polynucleotides that encode such novel proteins; and vectors and transformed host cells containing these polynucleotides.

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.

A activator for prekallikrein includes isolated, purified, or substantially purified heat shock protein 90, a phosphate ion, and mixtures thereof. The prekallikrein activator is part of an in vitro system for activating prekallikrein in the absence of FXIIa. The system includes the activator, high-molecular weight kininogen, and zinc ions. A method for activating prekallikrein to produce kallikrein in the absence of FXIIa includes mixing prekallikrein with the activator and a composition comprising high molecular weight kininogen and zinc ions. A method for evaluating the activity of a test drug for the production of kallikrein comprises activating prekallikrein and determining the kallikrein produced. The activity (promoting or inhibiting ability) of the tested drug against the production of kallikrein in the absence of FXIIa can be easily measured. The test drug may be an analgesic, anti-allergy, anti-inflammatory drug.

The present invention provides bradykinin peptide analogs, compositions, and methods of inhibiting thrombin-induced platelet and other cell activation. The bradykinin analogs comprise single or multiple peptide segments. The invention also provides a method for identifying compounds that selectively inhibit thrombin-induced platelet and other cell activation.

A pharmaceutical or veterinary composition, comprises a first active agent selected from a dehydroepiandrosterone and/or dehydroepiandrosterone-sulfate, or a salt thereof, and a second active agent comprising a tyrosine kinase inhibitor, delta opioid receptor antagonist, neurokinin receptor antagonist, or VCAM inhibitor for the treatment of asthma, chronic obstructive pulmonary disease, or other respiratory diseases. The composition is provided in various formulations and in the form of a kit. The products of this patent are applied to the prophylaxis and treatment of asthma, chronic obstructive pulmonary disease, or other respiratory diseases.

Methods for diagnosing and monitoring ovarian cancer in a subject comprising measuring a plurality of kallikrein polypeptides, and optionally CA125, or nucleic acids encoding the polypeptides in a sample from the subject. The kallikrein polypeptides include kallikrein 5, kallikrein 6, kallikrein 7, kallikrein 8, kallikrein 10 and kallikrein 11.

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.

There are provided inter alia multisubstituted aromatic compounds useful for the inhibition of thrombin and/or kallikrein, which compounds include substituted triazolyl. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing certain diseases or disorders, which diseases or disorders are amenable to treatment or prevention by the inhibition of thrombin and/or kallikrein.

Provided herein are methods of treating Parkinson's disease, dementia with Lewy bodies, and conditions associated with Parkinson's disease and dementia with Lewy bodies. These methods include administering to a subject in need thereof a therapeutically effective amount of a tissue kallikrein (KLK1) polypeptide, including active variants and fragments thereof.

Pharmaceutical compositions for intravenous administration comprising the compound of Formula I

or pharmaceutically acceptable salts, hydrates or prodrugs thereof are described herein. Methods of preparing the pharmaceutical compositions and methods for treating nausea and/or emesis with the pharmaceutical compositions are also described herein.

The present invention provides inhibitors and/or antagonists of plasma kallikrein. Also provided are methods of utilizing the inhibitors as therapeutics.

The present invention provides compounds of formula (I): (I) compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease or condition in which plasma kallikrein activity is implicated); and methods of treating patients with such compounds; wherein R5, R6, R7, A, B, W, X, Y and Z are as defined herein.