179524-35-7Relevant academic research and scientific papers
Novel thrombin inhibitors incorporating weakly basic heterobicyclic P1-arginine mimetics: optimization via modification of P1 and P3 moieties.
Krajnc, Andreja,Peterlin-Masic, Lucija,Ilas, Janez,Prezelj, Andrej,Stegnar, Mojca,Kikelj, Danijel
, p. 3251 - 3256 (2007/10/03)
Optimization of lead compounds 1 and 2 resulted in novel, selective, and potent thrombin inhibitors incorporating weakly basic heterobicyclic P(1)-arginine mimetics. The design, synthesis, and biological activity of racemic thrombin inhibitors 17-29 and enantiomerically pure thrombin inhibitors 30-33 are described. The arginine side-chain mimetics used in this study are 4,5,6,7-tetrahydro-1,3-benzothiazol-2-amine, 4,5,6,7-tetrahydro-2H-indazole, and 2-imino-4,5,6,7-tetrahydro-1,3-benzothiazol-3(2H)-ylamine.
Non-covalent thrombin inhibitors featuring P3-heterocycles with P1-monocyclic arginine surrogates
Reiner, John E.,Siev, Daniel V.,Araldi, Gian-Luca,Cui, Jingrong Jean,Ho, Jonathan Z.,Reddy, Komandla Malla,Mamedova, Lala,Vu, Phong H.,Lee, Kuen-Shan S.,Minami, Nathaniel K.,Gibson, Tony S.,Anderson, Susanne M.,Bradbury, Annette E.,Nolan, Thomas G.,Semple, J. Edward
, p. 1203 - 1208 (2007/10/03)
Investigations on P2-P3-heterocyclic dipeptide surrogates directed towards identification of an orally bioavailable thrombin inhibitor led us to pursue novel classes of achiral, non-covalent P1-arginine derivatives. The design, synthesis, and biological activity of inhibitors NC1-NC30 that feature three classes of monocyclic P1-arginine surrogates will be disclosed: (1) (hetero)aromatic amidines, amines and hydroxyamidines, (2) 2-aminopyrazines, and (3) 2-aminopyrimidines and 2-aminotetrahydropyrimidines.
Heteroaryl aminoguanidines and alkoxyguanidines and their use as protease inhibitors
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Page column 41, (2010/02/05)
Aminoguanidine and alkoxyguanidine compounds are described, including compounds of the Formula VII: wherein X is O or NR9and Het, R1, R7, R8, R12-R15, Ra, Rb, Rc, Z, and n are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing such compounds. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents. Additionally, the compounds can be detectably labeled and employed for in vivo imaging of thrombi.
Aromatic heterocyclic derivatives as enzyme inhibitors
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Page column 89, (2010/02/04)
The present invention discloses peptide aldehydes which are potent and specific inhibitors of thrombin, their pharmaceutically acceptable salts, pharmaceutically acceptable compositions thereof, and methods of using them as therapeutic agents for disease states in mammals characterized by abnormal thrombosis.
Heteroaryl aminoguanidines and alkoxyguanidines and their use as protease inhibitors
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, (2008/06/13)
Aminoguanidine and alkoxyguanidine compounds are described, including compounds of the Formula VII: wherein X is O or NR9 and Het, R1, R7, R8, R12-R15, Ra, Rb, Rc, Z, and n are set forth in the specification, as well as hydrates, solvates or pharmaceutica
Aromatic heterocyclic derivatives as enzyme inhibitors
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, (2008/06/13)
The present invention discloses peptide aldehydes which are potent and specific inhibitors of thrombin, their pharmaceutically acceptable salts, pharmaceutically acceptable compositions thereof, and methods of using them as therapeutic agents for disease states in mammals characterized by abnormal thrombosis.
AROMATIC HETEROCYCLIC DERIVATIVES AS ENZYME INHIBITORS
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, (2008/06/13)
The present invention discloses peptide aldehydes which are potent and specific inhibitors of thrombin, their pharmaceutically acceptable salts, pharmaceutically acceptable compositions thereof, and methods of using them as therapeutic agents for disease states in mammals characterized by abnormal thrombosis.
Efficacious, orally bioavailable thrombin inhibitors based on 3- aminopyridinone or 3-aminopyrazinone acetamide peptidomimetic templates
Sanderson, Philip E. J.,Lyle, Terry A.,Cutrona, Kellie J.,Dyer, Dona L.,Dorsey, Bruce D.,McDonough, Colleen M.,Naylor-Olsen, Adel M.,Chen, I.-Wu,Chen, Zhongguo,Cook, Jacquelynn J.,Cooper, Carolyn M.,Gardell, Stephen J.,Hare, Timothy R.,Krueger, Julie A.,Lewis, S. Dale,Lin, Jiunn H.,Lucas Jr., Bobby J.,Lyle, Elizabeth A.,Lynch Jr., Joseph J.,Stranieri, Maria T.,Vastag, Kari,Yan, Youwei,Shafer, Jules A.,Vacca, Joseph P.
, p. 4466 - 4474 (2007/10/03)
We have addressed the key deficiency of noncovalent pyridinone acetamide thrombin inhibitor L-374,087 (1), namely, its modest half-lives in animals, by making a chemically stable 3-alkylaminopyrazinone bioisostere for its 3- sulfonylaminopyridinone core.
L-373,890, an anchiral, noncovalent, subnanomolar thrombin inhibitor
Sanderson, Philip E. J.,Dona, L. Dyer,Naylor-Olsen, Adel M.,Vacca, Joseph P.,Gardell, Steven J.,Lewis, S. Dale,Lucas Jr., Bobby J.,Lyle, Elizabeth A.,Lynch Jr., Joseph J.,Mulichak, Anne M.
, p. 1497 - 1500 (2007/10/03)
L-373,890, a highly selective and efficacious pyridinone acetamide thrombin inhibitor was designed using a combination of X-ray crystallography, molecular modeling and empirical structure optimization.
Design and synthesis of a novel class of thrombin inhibitors incorporating heterocyclic dipeptide surrogates
Tamura, Susan Y.,Semple, J. Edward,Reiner, John E.,Goldman, Erick A.,Brunck, Terence K.,Lim-Wilby, Marguerita S.,Carpenter, Stephen H.,Rote, William E.,Oldeshulte, Gerard L.,Richard, Brigitte M.,Nutt, Ruth F.,Ripka, William C.
, p. 1543 - 1548 (2007/10/03)
Several potent and selective inhibitors of thrombin incorporating novel heterocyclic peptide surrogates in the P3-P2 position of peptidyl argininals have been discovered. Illustrated in this article are three classes of heterocycles: pyridones, uracils, and pyrimidinones. The synthesis and biological activities of these unique aromatic heterocyclic derivatives are reported herein.
