Výsledky vyhledávání - "Brent V. Mischke"

Design, Synthesis, and Biological Evaluation of 3-[4-(2-Hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a Potent, Orally Active, Brain Penetrant Inhibitor of Phosphodiesterase 5 (PDE5)

Publikováno v: Journal of Medicinal Chemistry. 53:2656-2660

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-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::892c7788c8aa398973abd4f8bb5a78a5
https://doi.org/10.1021/jm901781q

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Identification, synthesis and SAR of amino substituted pyrido[3,2b]pyrazinones as potent and selective PDE5 inhibitors

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 19:4088-4091

A new class of potent and selective PDE5 inhibitors is disclosed. Guided by X-ray crystallographic data, optimization of an HTS lead led to the discovery of a series of 2-aryl, (N8)-alkyl substituted-6-aminosubstituted pyrido[3,2b]pyrazinones which s

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5005db6742e606fdadbf520ea66a63a9
https://doi.org/10.1016/j.bmcl.2009.06.012

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Design of potent inhibitors of human β-secretase. Part 1

Autor: John N. Freskos, Yvette M. Fobian, Timothy E. Benson, Michael J. Bienkowski, David L. Brown, Thomas L. Emmons, Robert Heintz, Alice Laborde, Joseph J. McDonald, Brent V. Mischke, John M. Molyneaux, Joseph B. Moon, Patrick B. Mullins, D. Bryan Prince, Donna J. Paddock, Alfredo G. Tomasselli, Gregory Winterrowd

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 17:73-77

We describe a novel series of potent inhibitors of human beta-secretase. These compounds possess the hydroxyethyl amine transition state isostere. A 2.5A crystal structure of inhibitor 32 bound to BACE is provided.

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48e643373fd67faba63c23379fdd0447
https://doi.org/10.1016/j.bmcl.2006.09.092

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MMP-13 selective alpha-sulfone hydroxamates: Identification of selective P1′ amides

Autor: James R. Kiefer, Barta Thomas E, Heintz Robert M, Yvette M. Fobian, Daniel P. Becker, Grace E. Munie, Patrick B. Mullins, John M. Molyneaux, Brent V. Mischke, Darren J. Kassab, Louis J. Bedell, John N. Freskos

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 21:2823-2825

Continuing our interest in designing compounds preferentially potent and selective for MMP-13, we report on a series of hydroxamic acids with a flexible amide P1' substituents. We identify an amide which spares both MMP-1 and -14, and shows >500 fold

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d64fc828c6eacfa443f80cdc71c9f154
https://doi.org/10.1016/j.bmcl.2011.03.095

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Design, synthesis, and biological evaluation of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a potent, orally active, brain penetrant inhibitor of phosphodiesterase 5 (PDE5)

Publikováno v: Journal of medicinal chemistry. 53(6)

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=pmid________::88c2de53db53a1f8525bbef66ae6a7e3
https://pubmed.ncbi.nlm.nih.gov/20196613

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Optimization of the aminopyridopyrazinones class of PDE5 inhibitors: discovery of 3-[(trans-4-hydroxycyclohexyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one

Publikováno v: Bioorganicmedicinal chemistry letters. 19(17)

We describe efforts to improve the pharmacokinetic profile of the aminopyridopyrazinone class of PDE5 inhibitors. These efforts led to the discovery of 3-[(trans-4-hydroxycyclohexyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyra

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56bba8721c0b4d57439e25992ba23e4b
https://pubmed.ncbi.nlm.nih.gov/19631533

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Investigation of aminopyridiopyrazinones as PDE5 inhibitors: Evaluation of modifications to the central ring system

Publikováno v: Bioorganicmedicinal chemistry letters. 19(15)

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 an

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c530b519c26bbcf215a387ac7749266
https://pubmed.ncbi.nlm.nih.gov/19539468

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Design of potent inhibitors of human beta-secretase. Part 2

Autor: Donna J. Paddock, Alfredo G. Tomasselli, John N. Freskos, Heintz Robert M, Brown David L, Thomas L. Emmons, Joseph B. Moon, Timothy E. Benson, Yvette M. Fobian, John M. Molyneaux, Alice Laborde, Greg Winterrowd, D. Bryan Prince, Brent V. Mischke, Joseph J. McDonald, Michael J. Bienkowski, Patrick B. Mullins

Publikováno v: Bioorganicmedicinal chemistry letters. 17(1)

We describe an optimized series of acyclic hydroxyethylamine transition state isosteres of beta-secretase that incorporates a variety of P(2) side chains that yield potent inhibitors with excellent cellular activity. A 2.2A crystal structure of compo

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1541d1cca9874f925ad126ae4a925af1
https://pubmed.ncbi.nlm.nih.gov/17049233

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