35 results about "Thrombin receptor" patented technology

The present invention relates to a thrombin receptor antagonist containing a compound represented by the formula (I)

wherein R^1a, R^1b 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(R^6a)(R^6b), —NHCOOR⁷ or —CONHR⁸ wherein R⁴, R⁵, R^6a, R^6b, 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), R^1a and R^1b 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.

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:

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 PdL_n 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.

Disclosed is a method of promoting healing of a chronic dermal skin ulcer, such as a diabetic ulcer, on a subject. The method comprises the step of contacting the chronic dermal skin ulcer with an effective amount of an agonist of the non-proteolytically activated thrombin receptor.

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.

Disclosed is a method of promoting healing of a chronic dermal ulcer, such as a diabetic ulcer, in a subject. The method comprises administering to the subject a combination one or more agonists of the non-proteolytically activated thrombin receptor and one or more angiogenic growth factors.

The present invention features pharmaceutical compositions and methods to inhibit angiogenesis, with implications to cancer therapy. These methods are based on the discovery that activated thrombin has antiangiogenic activity and that this antiangiogenic activity is at least in part, mediated through the activation of a class of thrombin receptors termed, Protease Activated Receptor (PAR). Pharmaceutical compositions and methods are also directed to a class of proteases which mediate this activation, particularly the urokinase plasminogen activator (uPA) polypeptide.

Disclosed is a hemostatic material, wherein a thrombin receptor activating agent is covalently coupled to a biocompatible matrix.

The invention provides a P2Y12 receptor platelet aggregation detection reagent card and a production method thereof. The P2Y12 receptor platelet aggregation detection reagent card comprises four detection channels, the first channel contains a lyophilized reagent coated with BSA and fibrinogen and contains no activators, the second channel contains a lyophilized reagent coated with the BSA and fibrinogen and also contains a platelet maximum activator iso-TRAP (thrombin receptor activating peptide), the third channel contains no lyophilized reagents, and the fourth channel contains the lyophilized reagent coated with the BSA and fibrinogen, and also contains a platelet P2Y12 receptor activator ADP (adenosine diphosphate) and a P2Y1 receptor antagonist PGE1 (prostaglandin E1). The patient'sP2Y12 receptor pathway-correlated platelet aggregation function is rapidly and effectively detected through optical nephelometry by using the detection reagent card. The card has the advantages of high sensitivity, strong specificity, easiness in operation, and suitableness for bedside fast detection, and can well predict the future thrombus or bleeding risk in patients treated with the P2Y12 receptor antagonists.

An agonist of a non-proteolytically activated thrombin receptor can be used in a method for treating peripheral arterial disease. The agonist can be a thrombin peptide derivative. In some embodiments, the peripheral arterial disease is characterized by intermittent claudication. The thrombin peptide derivatives to be used in the methods can have amino acid sequences similar to a region of thrombin. Usually, the thrombin peptide derivatives are 12-23 amino acid residues in length. In some cases, the thrombin peptide derivatives are dimers, and in particular, dimers that result from formation of a disulfide bond between two cysteine residues of peptide monomers.

Disclosed is a method of stimulating cartilage growth, repair or regeneration at a site in a subject in need of such growth, repair or regeneration. The method comprises the step of administering a therapeutically effective amount of an agonist of the non-proteolytically activated thrombin receptor to the site. Also disclosed is a method of stimulating the proliferation and expansion of chrondrocytes in vitro. The method comprises culturing chrondrocytes in the presence of a stimulating amount of an NPAR agonist.

A compound represented by the structural formula and pharmaceutically acceptable salts and solvents thereof are disclosed, wherein: the single-dashed line between the ring carbons to which R<10> and R<34> are attached represents either a single bond or a double bond; the double-dashed line between X and the carbon to which Y is attached represents either a single bond or an absent bond; X is -O- or -NR<6>- when the double-dashed line represents a single bond; X is H, -OH or -NHR<20> when the double-dashed line represents an absent bond; and other parameters are as defined herein. Also disclosed are pharmaceutical compositions and combinations containing said compounds and their uses as thrombin receptor antagonists and binders to cannabinoid receptors.