39 results about "Platelet receptor" patented technology

Novel compounds of formulae (I) to (VIII), which more particularly include sulfonylurea derivatives, sulfonylthiourea derivatives, sulfonylguanidine derivatives, sulfonylcyanoguanidine derivatives, thioacylsulfonamide derivatives, and acylsulfonamide derivatives which are effective platelet ADP receptor inhibitors. These derivatives may be used in various pharmaceutical compositions, and are particularly effective for the prevention and / or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also relates to a method for preventing or treating thrombosis in a mammal comprising the step of administering a therapeutically effective amount of a compound of formulae (I) to (VIII), or a pharmaceutically acceptable salt thereof.

A method is providing for measuring platelet reactivity of a PCI patient that has a (DES). A blood sample is obtained from the patient. The blood sample is mixed in combination with 1) an anticoagulant; 2) sufficient buffer to maintain the pH and salt concentration of the anticoagulated blood within a range suitable for platelet aggregation; 3) a platelet GPIIb / IIIa receptor ligand immobilized on a solid surface; 4) one or more agents to enhance a signal transduction pathway and 5) a receptor activator. The combination is incubated under conditions for agglutinating particles. Platelet-mediated agglutination is assessed in the mixture. The absence of agglutination indicates that the patient has reduced ability to form platelet thrombi.

Novel compounds of formula (I) to (VI), which more particularly include sulfonylurea derivatives, sulfonylthiourea derivatives, sulfonylguanidine derivatives, sulfonylcyanoguanidine derivatives, thioacylsulfonamide derivatives, and acylsulfonamide derivatives which are effective platelet ADP receptor inhibitors. These derivatives may be used in various pharmaceutical compositions, and are particularly effective for the prevention and / or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also relates to a method for preventing or treating thrombosis in a mammal comprising the step of administering a therapeutically effective amount of a compound of formulae (I)-(VI), or a pharmaceutically acceptable salt thereof.

Novel compounds of formula (I) to (VI), which more particularly include sulfonylurea derivatives, sulfonylthiourea derivatives, sulfonylguanidine derivatives, sulfonylcyanoguanidine derivatives, thioacylsulfonamide derivatives, and acylsulfonamide derivatives which are effective platelet ADP receptor inhibitors. These derivatives may be used in various pharmaceutical compositions, and are particularly effective for the prevention and / or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also relates to a method for preventing or treating thrombosis in a mammal comprising the step of administering a therapeutically effective amount of a compound of formulae (I)-(VI), or a pharmaceutically acceptable salt thereof

The present invention provides novel sulfonylurea salts of a salt of formula (I)and polymorph forms thereof. The compounds in their various forms are effective platelet ADP receptor inhibitors and may be used in various pharmaceutical compositions, and are particularly effective for the prevention and / or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also provides a method for preparing such compounds and forms and for preventing or treating thrombosis and thrombosis related conditions in a mammal comprising the step of administering a therapeutically effective amount of a salt of formula (I) or a pharmaceutically acceptable form thereof.

The present invention is directed to pharmaceutical compositions and methods of using combination therapies containing [4-(6-fluoro-7-methylamino-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-phenyl]-5-chloro-thiophen-2-yl-sulfonylurea, or a pharmaceutically acceptable salt thereof, for the treatment of thrombosis diseases.

The present invention provides novel sulfonylurea salts of a salt of formula (I)and polymorph forms thereof. The compounds in their various forms are effective platelet ADP receptor inhibitors and may be used in various pharmaceutical compositions, and are particularly effective for the prevention and / or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also provides a method for preparing such compounds and forms and for preventing or treating thrombosis and thrombosis related conditions in a mammal comprising the step of administering a therapeutically effective amount of a salt of formula (I) or a pharmaceutically acceptable form thereof.

The invention discloses a reagent for detecting anti-platelet surface receptor-specific autoantibodies and a preparation method and application thereof. The reagent has high specificity and sensitivity. The method comprises expressing a human platelet-specific receptor membrane glycoprotein GP Ib-IX and / or GP IIb / IIIa receptor through CHO cells, carrying out co-incubation on the specific membraneglycoprotein receptor expression-positive CHO cells and serum to be detected and adding a fluorescein-labeled anti-human immunoglobulin polyclonal antibody (secondary antibody) for bonding. If there is an anti-platelet receptor-specific antibody in serum or plasma, the CHO-membrane glycoprotein specific antibody-fluorescein-labeled anti-human immunoglobulin polyclonal antibody complex structure isformed, has high CHO cell fluorescence intensity and can be used for flow cytometry or fluorescence microscope examination. The method is easy to operate, has enough specific membrane glycoprotein expression positive CHO cell sources, high specificity and sensitivity and high diagnosis efficiency and can be used for basic research and clinical examination.

Compounds of formula I are provided:wherein Ar1 and Ar2 are substituted aromatic rings and L1 and L2 are independent divalent linking groups. The compounds are useful as platelet ADP receptor inhibitors, for treating thrombosis and for reducing the likelihood and / or severity of a secondary ischemic event in a patient.

The present invention relates to compounds of the formula I,in which R1; R2; R3; R4; R5; R6; R7; R8; R9; R10; R11; R12; R13; A; B, D and E have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong anti-aggregating effect on platelets and thus an anti-thrombotic effect and are suitable e.g. for the therapy and prophylaxis of cardio-vascular disorders like thromboembolic diseases or restenoses. They are reversible antagonists of the platelet ADP receptor P2Y12, and can in general be applied in conditions in which an undesired activation of the platelet ADP receptor P2Y12 is present or for the cure or prevention of which an inhibition of the platelet ADP receptor P2Y12 is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

The present invention relates to compounds of the formula I,whereinR1; R2; Z; A; B; D; Q; J; V; G and M have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong anti-aggregating effect on platelets and thus an anti-thrombotic effect and are suitable, e.g., for the therapy and prophylaxis of cardio-vascular disorders like thromboembolic diseases or restenoses. They are reversible antagonists of the platelet ADP receptor P2Y12, and can in general be applied in conditions in which an undesired activation of the platelet ADP receptor P2Y12 is present or for the cure or prevention of which an inhibition of the platelet ADP receptor P2Y12 is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

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.

The present invention provides engineered platelets with chimeric platelet receptors (CPR) with a desired target specificity. Additionally, the engineered platelets may comprise cargo which may be released upon activation of the platelet. Additionally, the platelets may be generated in vitro from megakaryocytes engineered to generate non-thrombogenic platelets.

Methods and cells or cell lines for identifying antibodies or fragments thereof that activate heparin-induced thrombocytopenia (HIT) are described. The methods comprise contacting a hematopoietic cell or cell line that comprises, in operative association, the platelet receptor FcyRIIA under the control of a suitable promoter, and a reporter construct comprising a reporter gene under the control of a promoter and transcription factor, which transcription factor is regulated downstream of the signaling cascade of activated FcyRIIA, with a test sample from a mammalian subject; a platelet factor 4 (PF4), a wild-type or variant of PF4 or a fragment thereof; and heparin; and detecting or measuring the level of reporter gene expression.

The invention discloses application of glabridin in preparation of drugs to treat thrombotic diseases and belongs to the technical field of medicine. Experiments show that glabridin can significantlyinhibit platelet activating factor receptors, and can significantly reduce, in vivo, p-selectin, vWF, GPIIb / IIIa and TXB2 levels in serum of a thrombosis model rat due to external application of FeCl3solution. venous injection of glabridin can significantly inhibit the rise of whole blood PAF (platelet activating factor) concentration induced by artery thrombosis and can significantly reduce IP3content in platelets and the expression of platelet IP3 receptors; it is indicated that glabridin can inhibit platelet PAF-IP3-IP3R-[Ca2+]i signal transduction pathway, and the inhibition is one of mechanisms of glabridin to inhibit platelet activating and gathering. Glabridin can inhibit thrombosis via multiple targets and multiple pathways, and is functional in and worthy of treating thromboticdiseases.

The invention relates to novel compounds of formula (I) containing fused heterocyclic ring systems which are effective platelet ADP receptor inhibitors:In formula (I), W is carbon or nitrogen, wherein at least one W is a carbon; and Y is nitrogen, oxygen, or sulfur. Such compounds including pharmaceutically acceptable salts are useful in various pharmaceutical compositions for the prevention and / or treatment of cardiovascular disease particularly those related to thrombosis.

The present invention relates to compounds of the formula I, in which R1, R2, A, B, D, F, n, m and o have the meanings indicated herein. The compounds of the formula I are valuable pharmacologically active compounds. They are reversible inhibitors of the interaction between the plasma protein von Willebrand factor (vWF) and the blood platelet receptor glycoprotein Ib-IX-V complex (GPIb). They exhibit an antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of atherothrombotic diseases

The invention provides a method for detecting enzyme digestion of the extracellular fragment of a platelet receptor GPIba based on flow cytometry. The method comprises the following concrete steps: (1) preparation and treatment of samples; (2) detection with a flow cytometer; and (3) data analysis with Weasel software. According to the invention, two different fluorescently-labeled antibodies are used, i.e., an anti-GPIba extracellular fragment antibody and an anti-GPIba intracellular fragment antibody; and the relative value of bonding of the extracellular fragment antibody and the intracellular fragment antibody is analyzed by using flow cytometry, so the degree of enzyme digestion of the GPIba extracellular fragment can be reflected. The detection method provided by the invention is independent on the changes of the number of platelets and applicable to the situation of reduction in the number of platelets, and has high reliability and good stability.

Adhesion of platelets to blood vessel walls is the first step that promotes arrest of bleeding by interaction of the platelet receptors with various extracellular matrix proteins that become exposed on vascular injury. A flow chamber is provided for use in analyzing or studying platelet function, in whole blood, either as part of a batch process or in real time. In the flow chambers, an inert polydimethylsiloxane (PDMS) surface is plasma-activated and a homobifunctional cross-linker is used to immobilize platelet-binding proteins onto a chamber wall surface. Immobilized collagen and fibrinogen may thus be assayed by continuously monitoring the adhesion of ADP and Ca2+ activated platelets from a subject, such as a patient having normal or type 2 diabetes (T2D). The flow chamber provides a simplified and robust method for the construction flow chambers which enable the kinetic monitoring of platelet adhesion in whole blood.

Provided is an anticoagulant and platelet GPⅡb / Ⅲa receptor multi-target compound, its general formula is as follows: A-L-B-L'-C, wherein A and B are binding sites for thrombin, and C is For the platelet GPⅡb / Ⅲa receptor binding site, L is the first linking group, and L' is the second linking group. Preparation methods and uses of the above compounds are also provided. The compound has in vitro human thrombin inhibitory activity, in vitro platelet GPIIb / IIIa receptor inhibitory activity, in vitro / in vivo antiplatelet aggregation, in vivo anticoagulant and antithrombotic effects.

The invention discloses a method for detecting the enzyme cleavage of the extracellular segment of platelet receptor GPIba based on flow cytometry. The specific steps are: (1) sample preparation and processing; (2) flow cytometry detection; (3) Weasel Software data analysis. The present invention uses two different fluorescently labeled antibodies, respectively anti-GPIba extracellular segment antibody and anti-GPIba intracellular segment antibody, and analyzes the relative value of the combination of the extracellular segment antibody and the intracellular segment antibody by flow cytometry, namely It can reflect the degree of cleavage of the extracellular segment of GPIba. The detection method of the invention does not depend on the change of the number of platelets, is suitable for the situation of reduced number of platelets, and has high reliability and good stability.

Methods of modulating the conformation of vWF are provided. One embodiment provides a method for linearizing globular vWF by contacting globular vWF proteins with an effective amount of negatively charged nanoparticles that interact with the globular vWF proteins to induce a conformational change in the globular vWF proteins such that the change in conformation inhibits or reduces the ability of the vWF proteins to bind to platelet receptors. Preferred negatively charged nanoparticles are non-functionalized.

Diagnostic systems, methods, polypeptides and antibodies for detecting the presence of C-terminal hGPIIb fragment of the platelet receptor GPIIb-IIIa in a body fluid sample are disclosed.

The invention provides a traditional Chinese medicine decoction for treating thrombotic diseases, which is characterized in that its active ingredients are prepared from the following raw materials in proportions: 5-30 g of ginseng, 20-50 g of astragalus, 10-30 g of angelica, and 10-30 g of chuanxiong , 10-30g of paeonol cortex, 10-30g of safflower, 10-30g of red peony or white peony, 10-30g of cinnamon, 20-60g of silver flower or silver flower vine, 10-30g of berberine or skullcap, 10-30g of Alisma, Licorice 10-30g, pangolin 10-30g. Among them, ginseng and astragalus can invigorate qi and help yang, play a role in maintaining righteousness and keeping evil from being dry; angelica, chuanxiong, powder paeonol, safflower, red peony or white peony have the effect of promoting blood circulation and removing stasis; cinnamon, silver flower or Yinhuateng, Coptis chinensis, Alisma, and pangolin play the role of warming meridian and dredging collaterals, and licorice plays the role of reconciling various medicines, so as to improve the excitability of platelet blood cell surface receptors, stabilize surface charge, and promote the regulation of cell membrane ion channels so that platelets, blood cells The formed thrombus disintegrates quickly, so as to achieve the purpose of complete cure. The treatment effect is remarkable and the recurrence rate is low. It is currently the best medicine for treating thrombotic diseases.

The invention discloses a class of anti-platelet aggregation peptidomimetic drugs and a preparation method and application thereof. This compound is a platelet GPIIb / IIIa receptor antagonist. It uses scutellarin, an active substance of traditional Chinese medicine, to modify the RGD peptide structure of GPⅡb / Ⅲa receptors, which can not only improve the GPⅡb / Ⅲa receptors of RGD peptides Specificity, but also improve the solubility of scutellarin. The compound has the pharmacological effect of anti-platelet aggregation, and can be used clinically to prevent myocardial oxygen supply artery occlusion, heart attack, unstable angina, no Q wave myocardial infarction, sudden death caused by coronary intervention, or can be used for acute coronary Syndrome patients.

The invention relates to a general formula and physiologically acceptable salts thereof: A-L-B-L'-C, wherein A and B are binding sites with thrombin, C is a binding site with a platelet GPIIb / IIIa receptor, L is a first linking group, and L' is a second linking group. The invention also relates to a preparation method and application of the compound. The invention provides an anticoagulant and antiplatelet GPIIb / IIIa receptor multi-target compound, which has good in-vitro human thrombin inhibition activity, in-vitro platelet GPIIb / IIIa receptor inhibition effect, in-vitro / in-vivo anti-platelet aggregation, in-vivo anticoagulant and antithrombotic effects; and the multi-target compound can be clinically used for preventing and treating peripheral artery thrombosis and arteriovenous bypass thrombosis, treating thrombosis in acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI), and preventing and treating cerebral arterial thrombosis.