Discovery and SAR Evolution of Pyrazole Azabicyclo[3.2.1]octane Sulfonamides as a Novel Class of Non-Covalent N-Acylethanolamine-Hydrolyzing Acid Amidase (NAAA) Inhibitors for Oral Administration was written by Di Fruscia, Paolo;Carbone, Anna;Bottegoni, Giovanni;Berti, Francesco;Giacomina, Francesca;Ponzano, Stefano;Pagliuca, Chiara;Fiasella, Annalisa;Pizzirani, Daniela;Ortega, Jose Antonio;Nuzzi, Andrea;Tarozzo, Glauco;Mengatto, Luisa;Giampa, Roberta;Penna, Ilaria;Russo, Debora;Romeo, Elisa;Summa, Maria;Bertorelli, Rosalia;Armirotti, Andrea;Bertozzi, Sine Mandrup;Reggiani, Angelo;Bandiera, Tiziano;Bertozzi, Fabio. And the article was included in Journal of Medicinal Chemistry in 2021.Application In Synthesis of tert-Butyl (4-hydroxycyclohexyl)carbamate This article mentions the following:
Inhibition of intracellular N-acylethanolamine-hydrolyzing acid amidase (NAAA) activity is a promising approach to manage the inflammatory response under disabling conditions. In fact, NAAA inhibition preserves endogenous palmitoylethanolamide (PEA) from degradation, thus increasing and prolonging its anti-inflammatory and analgesic efficacy at the inflamed site. In the present work, we report the identification of a potent, systemically available, novel class of NAAA inhibitors, featuring a pyrazole azabicyclo[3.2.1]octane structural core. After an initial screening campaign, a careful structure-activity relationship study led to the discovery of endo-ethoxymethyl-pyrazinyloxy-8-azabicyclo[3.2.1]octane-pyrazole sulfonamide 50 (ARN19689), which was found to inhibit human NAAA in the low nanomolar range (IC50 = 0.042μM) with a non-covalent mechanism of action. In light of its favorable biochem., in vitro and in vivo drug-like profile, sulfonamide 50 could be regarded as a promising pharmacol. tool to be further investigated in the field of inflammatory conditions. In the experiment, the researchers used many compounds, for example, tert-Butyl (4-hydroxycyclohexyl)carbamate (cas: 224309-64-2Application In Synthesis of tert-Butyl (4-hydroxycyclohexyl)carbamate).
tert-Butyl (4-hydroxycyclohexyl)carbamate (cas: 224309-64-2) belongs to alcohols. The oxygen atom of the strongly polarized O―H bond of an alcohol pulls electron density away from the hydrogen atom. This polarized hydrogen, which bears a partial positive charge, can form a hydrogen bond with a pair of nonbonding electrons on another oxygen atom. A multistep synthesis may use Grignard-like reactions to form an alcohol with the desired carbon structure, followed by reactions to convert the hydroxyl group of the alcohol to the desired functionality.Application In Synthesis of tert-Butyl (4-hydroxycyclohexyl)carbamate
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