Výsledky vyhledávání - "Thomas Dineen"

Sulfonamides as Selective NaV1.7 Inhibitors: Optimizing Potency, Pharmacokinetics, and Metabolic Properties to Obtain Atropisomeric Quinolinone (AM-0466) that Affords Robust in Vivo Activity

Publikováno v: Journal of Medicinal Chemistry. 60:5990-6017

Because of its strong genetic validation, NaV1.7 has attracted significant interest as a target for the treatment of pain. We have previously reported on a number of structurally distinct bicyclic heteroarylsulfonamides as NaV1.7 inhibitors that demo

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::bb6062704d531ce83c1a6122ecc44600
https://doi.org/10.1021/acs.jmedchem.6b01850

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Sulfonamides as Selective NaV1.7 Inhibitors: Optimizing Potency and Pharmacokinetics While Mitigating Metabolic Liabilities

Publikováno v: Journal of Medicinal Chemistry. 60:5969-5989

Several reports have recently emerged regarding the identification of heteroarylsulfonamides as NaV1.7 inhibitors that demonstrate high levels of selectivity over other NaV isoforms. The optimization of a series of internal NaV1.7 leads that address

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::3616b7030b42538cb45a4828f9c4821e
https://doi.org/10.1021/acs.jmedchem.6b01851

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Correction to 'Sulfonamides as Selective NaV1.7 Inhibitors: Optimizing Potency and Pharmacokinetics to Enable in Vivo Target Engagement'

Human genetic evidence has identified the voltage-gated sodium channel Na

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5e82bfc2625ad2b8c686cc56a8b01002
https://europepmc.org/articles/PMC5346988/

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Inhibitors of β-Site Amyloid Precursor Protein Cleaving Enzyme (BACE1): Identification of (S)-7-(2-Fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (AMG-8718)

Autor: Paul H. Wen, Robert C. Wahl, Ryan White, Oleg Epstein, Stephen J. Wood, Katayoun Derakhchan, Douglas A. Whittington, Chuck E. Kreiman, Isaac E. Marx, Thomas Dineen, Dean Hickman, Kui Chen, Matthew Weiss, Joel Esmay, Vinod F. Patel, Alan C. Cheng, Robert T. Fremeau

Publikováno v: Journal of Medicinal Chemistry. 57:9811-9831

We have previously shown that the aminooxazoline xanthene scaffold can generate potent and orally efficacious BACE1 inhibitors although certain of these compounds exhibited potential hERG liabilities. In this article, we describe 4-aza substitution o

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c9b3095ff7f5efcf8cbc5e633bdfc8f
https://doi.org/10.1021/jm5012676

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Sulfonamides as Selective NaV1.7 Inhibitors: Optimizing Potency and Pharmacokinetics to Enable in Vivo Target Engagement

Human genetic evidence has identified the voltage-gated sodium channel NaV1.7 as an attractive target for the treatment of pain. We initially identified naphthalene sulfonamide 3 as a potent and selective inhibitor of NaV1.7. Optimization to reduce b

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a45d3cf7f30dc5240f9068aa183a1600
https://europepmc.org/articles/PMC5150675/

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Design and Preparation of a Potent Series of Hydroxyethylamine Containing β-Secretase Inhibitors That Demonstrate Robust Reduction of Central β-Amyloid

Publikováno v: Journal of Medicinal Chemistry. 55:9009-9024

A series of potent hydroxyethyl amine (HEA) derived inhibitors of β-site APP cleaving enzyme (BACE1) was optimized to address suboptimal pharmacokinetics and poor CNS partitioning. This work identified a series of benzodioxolane analogues that posse

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::282a471f56ccce495f911c58f29307ea
https://doi.org/10.1021/jm300119p

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Design and Synthesis of Potent, Orally Efficacious Hydroxyethylamine Derived β-Site Amyloid Precursor Protein Cleaving Enzyme (BACE1) Inhibitors

Publikováno v: Journal of Medicinal Chemistry. 55:9025-9044

We have previously shown that hydroxyethylamines can be potent inhibitors of the BACE1 enzyme and that the generation of BACE1 inhibitors with CYP 3A4 inhibitory activities in this scaffold affords compounds (e.g., 1) with sufficient bioavailability

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8863b7dd3a68852600abaa1a5773f2a
https://doi.org/10.1021/jm300118s

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Ring opening of aziridines with ortho-bromophenyl metal reagents: synthesis of 2-substituted indolines

Autor: David J. Michaelis, Thomas Dineen

Publikováno v: Tetrahedron Letters. 50:1920-1923

Stabilized ortho-bromo phenyllithium reagents, generated via lithium-halogen exchange of aryl iodides, undergo regioselective ring opening of mono-substituted N-Boc, N-Cbz, and N-tosyl-protected aziridines in good to excellent yields. The resulting o

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::3b0d65f85156d92a9e87d8739ec8ceb1
https://doi.org/10.1016/j.tetlet.2009.02.047

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Total Synthesis of Cochleamycin A

Autor: William R. Roush, Thomas Dineen

Publikováno v: Organic Letters. 6:2043-2046

[reaction: see text] Cochleamycin A (1) was synthesized in 2.4% overall yield via a 23-step linear sequence starting from 3-butene-1-ol. Key features of the synthesis include the synthesis of (Z)-1,3-diene 21 via a Stille coupling of 4 and 5 and a tr

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6ebc54383ff9381b546bed643a384596
https://doi.org/10.1021/ol049331x

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