Design and synthesis of cyanamides as potent and selective N-acylethanolamine acid amidase inhibitors was written by Malamas, Michael S.;Farah, Shrouq I.;Lamani, Manjunath;Pelekoudas, Dimitrios N.;Perry, Nicholas Thomas;Rajarshi, Girija;Miyabe, Christina Yume;Chandrashekhar, Honrao;West, Jay;Pavlopoulos, Spiro;Makriyannis, Alexandros. And the article was included in Bioorganic & Medicinal Chemistry in 2020.Synthetic Route of C9H17NO3 This article mentions the following:
N-acylethanolamine acid amidase (NAAA) inhibition represents an exciting novel approach to treat inflammation and pain. NAAA is a cysteine amidase which preferentially hydrolyzes the endogenous biolipids palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). PEA is an endogenous agonist of the nuclear peroxisome proliferator-activated receptor-α (PPAR-α), which is a key regulator of inflammation and pain. Thus, blocking the degradation of PEA with NAAA inhibitors results in augmentation of the PEA/PPAR-α signaling pathway and regulation of inflammatory and pain processes. We have prepared a new series of NAAA inhibitors exploring the azetidine-nitrile (cyanamide) pharmacophore that led to the discovery of highly potent and selective compounds Key analogs demonstrated single-digit nanomolar potency for hNAAA and showed >100-fold selectivity against serine hydrolases FAAH, MGL and ABHD6, and cysteine protease cathepsin K. Addnl., we have identified potent and selective dual NAAA-FAAH inhibitors to investigate a potential synergism between two distinct anti-inflammatory mol. pathways, the PEA/PPAR-α anti-inflammatory signaling pathway,1-4 and the cannabinoid receptors CB1 and CB2 pathways which are known for their antiinflammatory and antinociceptive properties.5-8 Our ligand design strategy followed a traditional structure-activity relationship (SAR) approach and was supported by mol. modeling studies of reported X-ray structures of hNAAA. Several inhibitors were evaluated in stability assays and demonstrated very good plasma stability (t1/2 > 2 h; human and rodents). The disclosed cyanamides represent promising new pharmacol. tools to investigate the potential role of NAAA inhibitors and dual NAAA-FAAH inhibitors as therapeutic agents for the treatment of inflammation and pain. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Synthetic Route of C9H17NO3).
1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. A strong base can deprotonate an alcohol to yield an alkoxide ion (R―O−). For example, sodamide (NaNH2), a very strong base, abstracts the hydrogen atom of an alcohol. Under carefully controlled conditions, simple alcohols can undergo intermolecular dehydration to give ethers. This reaction is effective only with methanol, ethanol, and other simple primary alcohols.Synthetic Route of C9H17NO3
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