Thrombin antagonist

Bracht F., Schror K. Isolation and identification of aptamers from defibrotide that act as thrombin antagonists in vitro. Biochem Biophys Res Commun 1994 200,933-7. 

Summary of antiplatelet and thrombin antagonist. One molecule of lepirudin binds to one... 

Ximelagatran is a modified thrombin antagonist suitable for oral use. 

Scheme 18 Pilot synthesis of thrombin antagonist CRC 220 (Hochst)...

Hochst [52] described the pilot synthesis of two quite complex a-amino acid derivatives for HMR 2906 (a factor Xa-inhibitor, Scheme 17) and for thrombin antagonist CRC 220 [53] (Scheme 18, formally a diastereoseleclive reaction) using Rh/bpm catalysts. 

The 2(lH)-pyrazinone system has received increased interest in the past two decades by both synthetic and biological research, due to its presence in a variety of natural and non-natural products as well as pharmacologically active compounds. The easy and diverse methods for the generation of this versatile scaffold make it a prime choice for the current pharmaceutical research hke thrombin inhibitors, substance P antagonists, etc. The rich 1,4-azadiene... 

Himbacine (80) Alkaloid SCH 530348 (TRA) (81) Cardiovascular diseases (antiplatelet agent) Thrombin receptor antagonist Phase III (acute coronary syndromes) Schering-Plough 623-626... 

Clasby MC, Chackalamannil S, Czamiecki M, Doller D, Eagen K, Greenlee W, Kao G Lin Y, Tsai H, Xia Y, Ahn HS, Agans-Fantuzzi J, Boykow G Chintala M, Foster C, Smith-Torhan A, Alton K, Bryant M, Hsieh Y, Fan J, Palamanda J. (2007) Metabolism-based identification of a potent thrombin receptor antagonist. J Med Chem 50 129-138. 

Thrombin, a serine protease, cleaves fibrinogen into fibrin to create a fibrous plug and also amplifies its own production through the activation of factor XI and cofactors V and Vlll. Thrombin also plays a crucial role in the activation of platelets through the cleavage of the protease-activated receptors on the platelet surface. Antagonists of G-protein-coupled protease-activated receptor PARi have been synthesised to study the role of thrombin PARi receptor in thrombosis and vascular injury. Thrombosis is the most common cause of death in the industrialised world and, whether through venous thromboembolism, myocardial infarction or stroke, ultimately involves the inappropriate activity of... 

A series of 3,4-dihydro-177-pyrido[2,3- ]pyr3zine-2-ones were found to be very potent receptor antagonists of corticotropin-releasing factor-1 among them, 768 has ICso = 0.7 nM <2004JME5783>. Polysubstituted hexahydro-pyrido[3,4- ]pyrazinone derivatives 769 inhibit human thrombin with Ki <0.1 nM <1999USP5869487>. 

Aplysillin A (527), with unknown double bond geometries was isolated from Aplysina fistularis and is a weak thrombin receptor antagonist [442]. 

Other aptamers under clinical trials are for coagulation factors including thrombin, Factor VIIA, Factor IXA and Factor XII. Additional aptamers are being tested for kidney and lung cancers. A distinct advantage of aptamers is the availability of antidotes for them, which are short complementary sequences to the aptamers that serve as their antagonists and could be used to avert aptamer toxicity. 

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