Výsledky vyhledávání - "Matthew T, Loch"

Challenges in the Discovery and Optimization of mGlu2/4 Heterodimer Positive Allosteric Modulators

Autor: Charles David Weaver, Emily Days, Craig W. Lindsley, Alice L. Rodriguez, Paige N. Vinson, Colleen M. Niswender, Anna L. Blobaum, Matthew T. Loch, Caroline Anne Cuoco, P.J. Conn, Krystian A. Kozek, Mark G. Fulton

Publikováno v: Letters in Drug Design & Discovery

Background: This article describes the challenges in the discovery and optimization of mGlu2/4 heterodimer Positive Allosteric Modulators (PAMs). Methods: Initial forays based on VU0155041, a PAM of both the mGlu4 homodimer and the mGlu2/4 heterodime

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::12744d2df7d05c9a81a50373a85b8687
https://doi.org/10.2174/1570180815666181017131349

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Positive allosteric modulators (PAMs) of the group II metabotropic glutamate receptors: Design, synthesis, and evaluation as ex-vivo tool compounds

Autor: Yousuke Yamada, Bruce J. Melancon, Zixiu Xiang, Katherine E. Crocker, Colleen M. Niswender, Craig W. Lindsley, P. Jeffrey Conn, Kristen Gilliland, Alice L. Rodriguez, Matthew T. Loch, Michael L. Schulte, Daniel Haymer

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 50:128342

This letter describes synthesis and evaluation of two series of dual mGlu2/mGlu3 positive allosteric modulators with moderate mGlu3 potency and robust mGlu2 potency in thallium flux assays. These compounds were profiled their ability to modulate mGlu

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::84ec84e58e6cc03d5b185dec786f3488
https://doi.org/10.1016/j.bmcl.2021.128342

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VU6010608, a Novel mGlu7 NAM from a Series of N-(2-(1H-1,2,4-Triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamides

Autor: Colleen M. Niswender, Kevin M. McGowan, Carson W. Reed, Jerri M. Rook, Vincent B. Luscombe, Craig W. Lindsley, Annie L. Blobaum, Darren W. Engers, Matthew T. Loch, Hanna F. Roenfanz, P. Jeffrey Conn, Branden J. Stansley, Alice L. Rodriguez, Paul K. Spearing, Eileen M. Engelberg, Daniel H. Remke

Publikováno v: ACS Medicinal Chemistry Letters. 8:1326-1330

Herein, we report the structure–activity relationships within a series of mGlu7 NAMs based on an N-(2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamide core with excellent CNS penetration (Kp 1.9–5.8 and Kp,uu 0.4–1.4). Analogues in

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::97d6c42ce8acd7d17c8e70f2dbcf2dd5
https://doi.org/10.1021/acsmedchemlett.7b00429

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Discovery of VU6005649, a CNS Penetrant mGlu7/8 Receptor PAM Derived from a Series of Pyrazolo[1,5-a]pyrimidines

Autor: Vincent B. Luscombe, Sichen Chang, Michael Bubser, Craig W. Lindsley, Joel M. Harp, Eileen M. Engelberg, Colleen M. Niswender, Darren W. Engers, P. Jeffrey Conn, Carrie K. Jones, Katrina A. Bollinger, Alice L. Rodriguez, Mabel Seto, Anna L. Blobaum, Rocco G. Gogliotti, Matthew T. Loch, Masahito Abe

Publikováno v: ACS Medicinal Chemistry Letters. 8:1110-1115

Herein, we report the structure–activity relationships within a series of mGlu7 PAMs based on a pyrazolo[1,5-a]pyrimidine core with excellent CNS penetration (Kps > 1 and Kp,uus > 1). Analogues in this series proved to display a range of Group III

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::d798e9b1600c95ed98088deb14dfd238
https://doi.org/10.1021/acsmedchemlett.7b00317

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Discovery and optimization of a novel CNS penetrant series of mGlu4 PAMs based on a 1,4-thiazepane core with in vivo efficacy in a preclinical Parkinsonian model

Autor: Kaylee J. Stillwell, Jonathan W. Dickerson, Matthew T. Loch, Craig W. Lindsley, Mark G. Fulton, Olivier Boutaud, P. Jeffrey Conn, Colleen M. Niswender, Caitlin N. Kent, Alice L. Rodriguez, Jerri L. Rook, Anna L. Blobaum

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 37:127838

A high throughput screen (HTS) identified a novel, but weak (EC50 = 6.2 μM, 97% Glu Max) mGlu4 PAM chemotype based on a 1,4-thiazepane core, VU0544412. Reaction development and chemical optimization delivered a potent mGlu4 PAM VU6022296 (EC50 = 32.

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::8982a8ca4fb9fbb1b11c0095cf87e8fb
https://doi.org/10.1016/j.bmcl.2021.127838

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Synthesis and pharmacological evaluation of bivalent tethered ligands to target the mGlu2/4 heterodimeric receptor results in a compound with mGlu2/2 homodimer selectivity

Autor: Jonathan A. Javitch, Colleen M. Niswender, Alice L. Rodriguez, P. Jeffrey Conn, Matthew T. Loch, Xin Lin, Craig W. Lindsley, Mark G. Fulton

Publikováno v: Bioorg Med Chem Lett

This Letter details our ongoing efforts to develop selective positive allosteric modulators (PAMs) of the mGlu(2/4) heterodimeric receptor that exists in the CNS and may represent a novel drug target to modulate the glutamatergic system. As multiple

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21b3d6f0170e32b132342614e9740e3a
https://doi.org/10.1016/j.bmcl.2020.127212

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