- PIKFYVE KINASE INHIBITORS
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The present invention relates to compounds useful as inhibitors of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) as well as their use for treating diseases and disorders associated with PIKfyve.
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Page/Page column 206-207; 399
(2021/08/20)
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- Carbon-11 and Fluorine-18 Radiolabeled Pyridopyrazinone Derivatives for Positron Emission Tomography (PET) Imaging of Phosphodiesterase-5 (PDE5)
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The cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5) plays an important role in various pathologies including pulmonary arterial hypertension and cardiomyopathy. PDE5 represents an important therapeutic and/or prognostic targ
- Chekol, Rufael,Gheysens, Olivier,Ahamed, Muneer,Cleynhens, Jan,Pokreisz, Peter,Vanhoof, Greet,Janssens, Stefan,Verbruggen, Alfons,Bormans, Guy
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p. 486 - 496
(2017/04/26)
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- Design, synthesis, and biological evaluation of 3-[4-(2-hydroxyethyl) piperazin-l-yl]7-(6-methoxypyridin-3-yl)-l-(2-propoxyethyl)pyrido[3,4-b] pyrazin-2(lH)-one, a potent, orally active, brain penetrant inhibitor of phosphodiesterase 5 (PDE5)
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We recently described a novel series of aminopyridopyrazinones as PDE5 inhibitors. Efforts toward optimization of this series culminated in the identification of 3-[4-(2-hydroxyethyl)piperazin-l-yl]7-(6-methoxypyridin-3-yl)- l-(2-propoxyethyl)pyrido[3,4-è]pyrazin-2(l//)-one, which possessed an excellent potency and selectivity profile and demonstrated robust in vivo blood pressure lowering in a spontaneously hypertensive rat (SHR) model. Furthermore, this compound is brain penetrant and will be a useful agent for evaluating the therapeutic potential of central inhibition of PDE5. This compound has recently entered clinical trials.
- Hughes, Robert O.,Rogier, D. Joseph,Jacobsen, E. Jon,Walker, John K.,Maclnnes, Alan,Bond, Brian R.,Zhang, Lena L.,Yu, Ying,Zheng, Yi,Rumsey, Jeanne M.,Walgren, Jennie L.,Curtiss, Sandra W.,Fobian, Yvette M.,Heasley, Steven E.,Cubbage, Jerry W.,Moon, Joseph B.,Brown, David L.,Acker, Brad A.,Maddux, Todd M.,Tollefson, Mike B.,Mischke, Brent V.,Owen, Dafydd R.,Freskos, John N.,Molyneaux, John M.,Benson, Alan G.,Blevis-Ba, Rhadika M.
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supporting information; experimental part
p. 2656 - 2660
(2010/08/22)
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- Investigation of aminopyridiopyrazinones as PDE5 inhibitors: Evaluation of modifications to the central ring system
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Efforts to improve the potency and physical properties of the aminopyridiopyrazinone class of PDE5 inhibitors through modification of the core ring system are described. Five new ring systems are evaluated and features that impart improved potency and imp
- Hughes, Robert O.,Walker, John K.,Cubbage, Jerry W.,Fobian, Yvette M.,Rogier, D. Joseph,Heasley, Steve E.,Blevis-Bal, Rhadika M.,Benson, Alan G.,Owen, Dafydd R.,Jacobsen, E. Jon,Freskos, John N.,Molyneaux, John M.,Brown, David L.,Stallings, William C.,Acker, Brad A.,Maddux, Todd M.,Tollefson, Mike B.,Williams, Jennifer M.,Moon, Joseph B.,Mischke, Brent V.,Rumsey, Jeanne M.,Zheng, Yi,MacInnes, Alan,Bond, Brian R.,Yu, Ying
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scheme or table
p. 4092 - 4096
(2010/03/30)
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- Pyridine [3,4-b] Pyrazinones
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Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I: wherein R2, R6A, R6B and R8 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, synthetic methods, and intermediates are also disclosed.
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Page/Page column 29; 31-32; 34
(2008/06/13)
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- PYRIDINE [3,4-B] PYRAZINONES
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Compounds, tautomers of the compounds, and pharmaceutically acceptable salts of the compounds or tautomers are disclosed, wherein the compounds have the structure of Formula I: wherein R2, X6, Y6, R6, and R8 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, synthetic methods, and intermediates are also disclosed.
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- PYRIDINE [3 , 4-B] PYRAZINONE COMPOUNDS AS PDE-5 INHIBITORS
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Compounds, tautomers of the compounds, and pharmaceutically acceptable salts of the compounds or tautomers are disclosed, wherein the compounds have the structure of Formula (I), wherein R22, X6, Y6, R6, and R8 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, synthetic methods, and intermediates are also disclosed.
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Page/Page column 58-59
(2010/11/25)
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