36 results about "Thrombin receptor" patented technology

A method is provided for measuring inhibition of platelet aggregation by a thrombin receptor antagonist. First, a blood sample is obtained from a patient treated with a thrombin receptor antagonist. The blood sample is mixed in combination with particles including an immobilized GPIIb / IIIa receptor ligand and a thrombin receptor activator. The combination is then incubated under conditions suitable for agglutinating the particles, and platelet-mediated agglutination is assessed in the mixture. The absence of agglutination indicates that the patient has reduced ability to form platelet thrombi in response to the thrombin receptor antagonist treatment. Also provided is a kit for measuring inhibition of platelet aggregation by a thrombin receptor antagonist that includes a GPIIb / IIIa receptor ligand immobilized on a particle, a thrombin receptor activator, an anticoagulant, and a buffer to maintain the anticoagulated blood in a condition suitable for platelet aggregation.

Disclosed is a method of stimulating bone growth at a site in a subject in need of osteoinduction. The method comprises the step of administering a therapeutically effective amount of an agonist of the non-proteolytically activated thrombin receptor to the site.

The invention relates to a type of 5,5-disubstituted-2-iminopyrrolidine derivatives, a preparation method thereof, and medical applications thereof. Specifically, the invention relates to novel 5,5-disubstituted-2-iminopyrrolidine derivatives represented by a general formula (I), and medicinal salts of the derivatives. The invention also relates to applications of the derivatives and the salts as therapeutic agents, especially thrombin receptor antagonists. Each substituent in the general formula (I) is defined as that in the specification.

Disclosed is a method of stimulating bone growth at a site in a subject in need of osteoinduction. The method comprises the step of administering a therapeutically effective amount of an agonist of the non-proteolytically activated thrombin receptor to the site.

Disclosed are pharmaceutical compositions comprising a thrombin peptide derivatives and a chelating agent and / or a pharmaceutically acceptable thiol-containing compound. The pharmaceutical compositions optionally further comprise an antioxidant. Also, disclosed are methods for activating the non-proteolytically activated thrombin receptor in a subject in need of such treatment. The methods comprise the step of administering an effective amount of a thrombin peptide derivative in the pharmaceutical composition described above.

The invention is directed to novel benzimidazolone peptidomimetic compounds which are useful as thrombin receptor antagonists for the treatment of diseases associated with thrombosis, restenosis, hypertension, heart failure, arrhythmia, inflammation, angina, stroke, atherosclerosis, ischemic conditions, Angiogenesis related disorders, cancer, and neurodegenerative disorders. Pharmaceutical compositions comprising the substituted benzimidazolone peptidomimetics of the present invention and methods of treating conditions mediated by the thrombin receptor are also disclosed.

A method is provided for measuring inhibition of platelet aggregation by a thrombin receptor antagonist. First, a blood sample is obtained from a patient treated with a thrombin receptor antagonist. The blood sample is mixed in combination with particles including an immobilized GPIIb / IIIa receptor ligand and a thrombin receptor activator. The combination is then incubated under conditions suitable for agglutinating the particles, and platelet-mediated agglutination is assessed in the mixture. The absence of agglutination indicates that the patient has reduced ability to form platelet thrombiin response to the thrombin receptor antagonist treatment. Also provided is a kit for measuring inhibition of platelet aggregation by a thrombin receptor antagonist that includes a GPIIb / IIIa receptorligand immobilized on a particle, a thrombin receptor activator, an anticoagulant, and a buffer to maintain the anticoagulated blood in a condition suitable for platelet aggregation.

The invention is directed to novel benzimidazolone peptidomimetic compounds which are useful as thrombin receptor antagonists for the treatment of diseases associated with thrombosis, restenosis, hypertension, heart failure, arrhythmia, inflammation, angina, stroke, atherosclerosis, ischemic conditions, Angiogenesis related disorders, cancer, and neurodegenerative disorders. Pharmaceutical compositions comprising the substituted benzimidazolone peptidomimetics of the present invention and methods of treating conditions mediated by the thrombin receptor are also disclosed.

Endothelial dysfunction (ED) is associated with a number of diseases and disorders. Agonists of the non-proteolytically activated thrombin receptor can be used in methods to treat ED or ED-related diseases and disorders.

Disclosed are thrombin peptide derivatives comprising a polypeptide having the amino acid sequence SEQ ID NO. 2: Arg-Gly-Asp-Ala-Xaa-Glu-Gly-Asp-Ser-Gly-Gly-Pro-Phe-Val, or a C-terminal truncated fragment of the polypeptide having at least six amino acids. Xaa is alanine, glycine, serine, or an S-protected cysteine. Zero, one, two, or three amino acids in the polypeptide or polypeptide fragment differ from the corresponding position of SEQ ID NO. 2. Also disclosed are methods of treating a subject in need of treatment with a thrombin receptor agonist. The methods comprise the step of administering an effective amount of the thrombin peptide derivative described above.

The present invention relates to a thrombin receptor antagonist containing a compound represented by the formula (I)wherein R1a, R1b and R2 are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted alkoxy, R3 is a group represented by the formula —NHCOR4, —NHSO2R5, —NHCON(R6a)(R6b), —NHCOOR7 or —CONHR8 wherein R4, R5, R6a, R6b, R7 and R8 are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like), ring A is monocyclic aromatic ring optionally further having substituent(s), R1a and R1b are optionally bonded to each other to form an optionally substituted nitrogen-containing non-aromatic heterocycle, or a salt thereof or a prodrug thereof. The thrombin receptor antagonist of the present invention has a thrombin receptor (particularly PAR-1) antagonistic action and is useful for the prophylaxis or treatment of PAR-1 mediated pathological condition or disease.

Endothelial dysfunction (ED) is associated with a number of diseases and disorders. Agonists of the non-proteolytically activated thrombin receptor can be used in methods to treat ED or ED-related diseases and disorders.

The invention is directed to substituted heterocyclic acyl-tripeptides useful as thrombin receptor modulators, their use in wound healing and preventing platelet aggregation. Pharmaceutical compositions comprising the substituted heterocyclic acyl-tripeptides of the present invention and methods of treating conditions mediated by the thrombin receptor are also disclosed.

This application discloses a novel process for the preparation of phosphonate esters useful as intermediates in the preparation of himbacine analogs, themselves useful as thrombin receptor antagonists. The chemistry taught herein can be exemplified by the following scheme:wherein R9 is selected from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms, and R11 is selected independently for each occurrence from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms and hydrogen, X2 is Cl, Br, or I; X3 is selected from Cl and Br; and PdLn is a supported palladium metal catalyst or a soluble heterogeneous palladium catalyst. The L-derivatizing reagent is a moiety which converts the alcohol functional group of compound 137D to any leaving group which can be displaced by a triorgano-phosphite phosphonating agent.

The present disclosure is directed to human protease activated receptor 4 (PAR4) binding proteins (e.g. antibodies). In particular, anti-PAR4 binding proteins which are antagonists of human PAR4, as well as methods and uses thereof.

The present invention includes methods of treating acute myocardial infarction in a subject, comprising administering to the subject a therapeutically effective amount of a non-proteolytically activated thrombin receptor agonist.

Disclosed herein are methods of preventing, inhibiting, or ameliorating complications associated with cardiopulmonary bypass surgery by the use of a thrombin receptor antagonist compound. Among the thrombin receptor antagonist compounds useful in these methods are those of Formulas I and II, described herein. Examples of such thrombin receptor antagonists include: