In 2018,Mizojiri, Ryo; Asano, Moriteru; Tomita, Daisuke; Banno, Hiroshi; Nii, Noriyuki; Sasaki, Masako; Sumi, Hiroyuki; Satoh, Yoshihiko; Yamamoto, Yukiko; Moriya, Takeo; Satomi, Yoshinori; Maezaki, Hironobu published 《Discovery of Novel Selective Acetyl-CoA Carboxylase (ACC) 1 Inhibitors》.Journal of Medicinal Chemistry published the findings.Product Details of 18621-18-6 The information in the text is summarized as follows:
The authors initiated structure-activity relationship (SAR) studies for selective ACC1 inhibitors from 1a (N-(1-(2-(3-(3-methylphenoxy)azetidin-1-yl)-1,3-benzoxazol-6-yl)ethyl)acetamide) as a lead compound SAR studies of bicyclic scaffolds revealed many potent and selective ACC1 inhibitors represented by 1f (N-(1-(2-(4-(3-(Cyclopropylmethoxy)phenoxy)phenyl)-1,3-benzoxazol-6-yl)ethyl)acetamide), however most of them had physicochem. issues, particularly low aqueous solubility and potent CYP inhibition. To address these two issues and improve the drug-likeness of this chem. series, the authors converted the bicyclic scaffold into a monocyclic framework. Ultimately, this lead the authors to discover a novel monocyclic derivative 1q (1-((2S)-1-((2-(4-(3-(Cyclopropylmethoxy)phenoxy)phenyl)-1,3-oxazol-5-yl)oxy)propan-2-yl)urea) as a selective ACC1 inhibitor, which showed highly potent and selective ACC1 inhibition as well as acceptable solubility and CYP inhibition profiles. Since compound 1q displayed favorable bioavailability in mouse cassette dosing testing, the authors conducted in vivo PD studies of this compound Oral administration of 1q significantly reduced the concentration of malonyl-CoA in HCT-116 xenograft tumors at doses of more than 30 mg/kg. Accordingly, the authors’ novel series of selective ACC1 inhibitors represents a set of useful orally-available research tools, as well as potential therapeutic agents for cancer and fatty acid related diseases. In the experiment, the researchers used many compounds, for example, Azetidin-3-ol hydrochloride(cas: 18621-18-6Product Details of 18621-18-6)
Azetidin-3-ol hydrochloride(cas:18621-18-6) is one of azetidine.Azetidines (azacyclobutanes) constitute a well-known class of heterocyclic compounds. Azetidine scaffold has been discovered in several natural products.Product Details of 18621-18-6 Several pharmacologically important synthetic compounds also contain azetidine ring. Because of inherent ring strain, the synthesis of azetidines is a challenging endeavor.
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