{"id":11146,"date":"2022-11-21T05:00:35","date_gmt":"2022-11-20T21:00:35","guid":{"rendered":"https:\/\/www.pyrazoles-derivatives.com\/?p=11146"},"modified":"2022-11-21T05:00:35","modified_gmt":"2022-11-20T21:00:35","slug":"van-herk-t-s-team-published-research-in-journal-of-medicinal-chemistry-in-46-cas-890590-91-7","status":"publish","type":"post","link":"https:\/\/www.pyrazoles-derivatives.com\/?p=11146","title":{"rendered":"van Herk, T.&#8217;s team published research in Journal of Medicinal Chemistry  in 46 | CAS: 890590-91-7"},"content":{"rendered":"<p>van Herk, T. published the artcile<b><i>Pyrazole Derivatives as Partial Agonists for the Nicotinic Acid Receptor<\/i><\/b>,  <a href=\"https:\/\/www.ambeed.com\/products\/890590-91-7.html\">Formula: C7H10N2O2<\/a>,  the publication is  Journal of Medicinal Chemistry (2003), 46(18), 3945-3951, database is CAplus and MEDLINE.<\/p>\n<p>Nicotinic acid as a hypolipidemic agent appears unique due to its potential to increase HDL cholesterol levels to a greater extent than other drugs. However, it has some side effects, among which severe skin flushing is the most frequent and often limits patients&#8217; compliance. In a search for novel agonists for the recently identified and cloned G protein-coupled nicotinic acid receptor, we synthesized a series of substituted pyrazole-3-carboxylic acids that proved to have substantial affinity for this receptor. The affinities were measured by inhibition of [<sup>3<\/sup>H]nicotinic acid binding to rat spleen membranes. Potencies and intrinsic activities relative to nicotinic acid were determined by their effects on [<sup>35<\/sup>S]GTP\u03b3S binding to rat adipocyte and spleen membranes. Interestingly, most compounds were partial agonists. In particular, 2-diazabicyclo[3,3,0<sup>4,8<\/sup>]octa-3,8-diene-3-carboxylic acid (4c) and 5-propylpyrazole-3-carboxylic acid (4f) proved active with K<sub>i<\/sub> values of approx. 0.15 \u03bcM and EC<sub>50<\/sub> values of approx. 6 \u03bcM, while their intrinsic activity was only \u223c50% when compared to nicotinic acid. Even slightly more active was 5-butylpyrazole-3-carboxylic acid (4g) with a K<sub>i<\/sub> value of 0.072 \u03bcM, an EC<sub>50<\/sub> value of 4.12 \u03bcM, and a relative intrinsic activity of 75%. Of the aralkyl derivatives, 4q (5-(3-chlorobenzyl)pyrazole-3-carboxylic acid) was the most active with a relatively low intrinsic activity of 39%. Partial agonism of the pyrazole derivatives was confirmed by inhibition of G protein activation in response to nicotinic acid by these compounds The pyrazoles both inhibited the maximum effect elicited by 100 \u03bcM nicotinic acid and concentration dependently shifted nicotinic acid concentration-response curves to the right, pointing to a competitive mechanism of action.<\/p>\n<p>Journal of Medicinal Chemistry published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C11H10O, <a href=\"https:\/\/www.ambeed.com\/products\/890590-91-7.html\">Formula: C7H10N2O2<\/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>Journal of Medicinal Chemistry published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C11H10O, <a href=\"https:\/\/www.ambeed.com\/products\/890590-91-7.html\">Formula: C7H10N2O2<\/a>.<\/p>\n","protected":false},"author":8,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[131],"tags":[717],"class_list":["post-11146","post","type-post","status-publish","format-standard","hentry","category-pyrazoles-derivatives","tag-m-w150-200"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v24.9 - 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