{"id":11647,"date":"2022-12-01T06:38:33","date_gmt":"2022-11-30T22:38:33","guid":{"rendered":"https:\/\/www.pyrazoles-derivatives.com\/?p=11647"},"modified":"2022-12-01T06:38:33","modified_gmt":"2022-11-30T22:38:33","slug":"tarr-james-c-s-team-published-research-in-acs-chemical-neuroscience-in-3-cas-763120-58-7","status":"publish","type":"post","link":"https:\/\/www.pyrazoles-derivatives.com\/?p=11647","title":{"rendered":"Tarr, James C.&#8217;s team published research in ACS Chemical Neuroscience  in 3 | CAS: 763120-58-7"},"content":{"rendered":"<p>Tarr, James C. published the artcile<b><i>Targeting Selective Activation of M<sub>1<\/sub> for the Treatment of Alzheimer&#8217;s Disease: Further Chemical Optimization and Pharmacological Characterization of the M<sub>1<\/sub> Positive Allosteric Modulator ML169<\/i><\/b>,  <a href=\"https:\/\/www.ambeed.com\/products\/763120-58-7.html\">Computed Properties of  763120-58-7<\/a>,  the publication is  ACS Chemical Neuroscience (2012), 3(11), 884-895, database is CAplus and MEDLINE.<\/p>\n<p>The M<sub>1<\/sub> muscarinic acetylcholine receptor is thought to play an important role in memory and cognition, making it a potential target for the treatment of Alzheimer&#8217;s disease (AD) and schizophrenia. Moreover, M<sub>1<\/sub> interacts with BACE1 and regulates its proteasomal degradation, suggesting selective M<sub>1<\/sub> activation could afford both palliative cognitive benefit as well as disease modification in AD. A key challenge in targeting the muscarinic acetylcholine receptors is achieving mAChR subtype selectivity. Our lab has previously reported the M<sub>1<\/sub> selective pos. allosteric modulator ML169. Herein we describe our efforts to further optimize this lead compound by preparing analog libraries and probing novel scaffolds. We were able to identify several analogs that possessed submicromolar potency, with our best example displaying an EC<sub>50<\/sub> of 310 nM. The new compounds maintained complete selectivity for the M<sub>1<\/sub> receptor over the other subtypes (M<sub>2<\/sub>-M<sub>5<\/sub>), displayed improved DMPK profiles, and potentiated the carbachol (CCh)-induced excitation in striatal MSNs. Selected analogs were able to potentiate CCh-mediated non-amyloidogenic APP\u03b1 release, further strengthening the concept that M<sub>1<\/sub> PAMs may afford a disease-modifying role in the treatment of AD.<\/p>\n<p>ACS Chemical Neuroscience published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C9H5ClO2, <a href=\"https:\/\/www.ambeed.com\/products\/763120-58-7.html\">Computed Properties of  763120-58-7<\/a>.<\/p>\n<p>Referemce:<br \/><a href=\"https:\/\/en.wikipedia.org\/wiki\/Pyrazole\">https:\/\/en.wikipedia.org\/wiki\/Pyrazole<\/a>,<br \/><a href=\"Pyrazole - Wikipedia\">Pyrazoles &#8211; an overview | ScienceDirect Topics<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>ACS Chemical Neuroscience published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C9H5ClO2, <a href=\"https:\/\/www.ambeed.com\/products\/763120-58-7.html\">Computed Properties of  763120-58-7<\/a>.<\/p>\n","protected":false},"author":8,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[802,131],"tags":[732],"class_list":["post-11647","post","type-post","status-publish","format-standard","hentry","category-763120-58-7","category-pyrazoles-derivatives","tag-m-w100-150"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v24.9 - 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