- Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE)
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Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50000 individuals worldwide. Until recently, prophylactic HAE treatment options were limited to injectables, a burdensome administration route that has driven the need for an oral treatment. A substantial body of evidence has shown that potent and selective plasma kallikrein inhibitors that block the generation of bradykinin represent a promising approach for the treatment of HAE. Berotralstat (BCX7353, discovered by BioCryst Pharmaceuticals using a structure-guided drug design strategy) is a synthetic plasma kallikrein inhibitor that is potent and highly selective over other structurally related serine proteases. This once-daily, small-molecule drug is the first orally bioavailable prophylactic treatment for HAE attacks, having successfully completed a Phase III clinical trial (meeting its primary end point) and recently receiving the U.S. Food and Drug Administration's approval for the prophylactic treatment of HAE attacks in patients 12 years and older.
- Babu, Yarlagadda S,Chambers-Wilson, Ramanda,Chen, Xilin,Chintareddy, Venkat,Davis Parker, Cynthia,Juarez, Luis,Kellogg-Yelder, Debra,Kotian, Pravin L,Lu, Pengcheng,Muppa, Saritha,Polach, Kevin J,Raman, Krishnan,Vadlakonda, Satish,Williams, Jason,Wu, Minwan,Zhang, Weihe
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supporting information
p. 12453 - 12468
(2021/09/13)
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- Synthesis and SAR of novel tricyclic quinoxalinone inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1)
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Based on screening hit 1, a series of tricyclic quinoxalinones have been designed and evaluated for inhibition of PARP-1. Substitutions at the 7- and 8-positions of the quinoxalinone ring led to a number of compounds with good enzymatic and cellular poten
- Miyashiro, Julie,Woods, Keith W.,Park, Chang H.,Liu, Xuesong,Shi, Yan,Johnson, Eric F.,Bouska, Jennifer J.,Olson, Amanda M.,Luo, Yan,Fry, Elizabeth H.,Giranda, Vincent L.,Penning, Thomas D.
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scheme or table
p. 4050 - 4054
(2010/03/30)
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- INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE
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Inhibitors of poly(ADP-ribose)polymerase, ways to make them and methods of treating patients using them are disclosed.
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Page/Page column 32
(2008/12/06)
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- PYRROLOTRIAZINE DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS AND DISEASES ASSOCIATED WITH ANGIOGENESIS
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This invention relates to pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and the use of those compounds and compositions for the prevention and/or treatment of hyper-proliferative disorders and diseases associated with angiogenesis.
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Page/Page column 105; 106
(2008/06/13)
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- KINASE INHIBITORS
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ABSTRACT The present invention provides kinase inhibitors of Formula I: .
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Page/Page column 21;26
(2010/02/13)
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