Strategies toward optimization of the metabolism of a series of serotonin-4 partial agonists: investigation of azetidines as piperidine isosteres was written by Obach, Ronald Scott;LaChapelle, Erik A.;Brodney, Michael A.;Vanase-Frawley, Michelle;Kauffman, Gregory W.;Sawant-Basak, Aarti. And the article was included in Xenobiotica in 2016.Recommanded Product: 1-Boc-Azetidine-3-yl-methanol This article mentions the following:
The first generation 5HT-4 partial agonist, 4-{4-[4-Tetrahydrofuran-3-yloxy-benzo[d]isoxazol-3-yloxymethyl]-piperidin-1-ylmethyl}-tetrahydropyran-4-ol, PF-4995274 (TBPT), was metabolized to N-dealkylated (M1) and an unusual, cyclized oxazolidine (M2) metabolites. and demonstrated pharmacol. activity at 5HT receptor subtypes warranting further investigation into their dispositional properties in humans; was a minor component in vitro but was the pre-dominant metabolite identified in human plasma. To shift metabolism away from the piperidine ring of TBPT, a series of heterocyclic replacements were designed, synthesized, and profiled. Groups including azetidines, pyrrolidines, as well as functionalized piperidines were evaluated with the goal of identifying an alternative group that maintained the desired potency, functional activity, and reduced turnover in human hepatocytes. Activities of 4-substituted piperidines or pyrrolidine analogs at the pharmacol. target were not significantly altered, but the same metabolic pathways of N-dealkylation and oxazolidine formation were still observed Altering these to bridged ring systems lowered oxazolidine metabolite formation, but not N-dealkylation. The effort concluded with identification of azetidines as second-generation 5HT4 partial agonists. These were neither metabolized via N-dealkylation nor converted to cyclized oxazolidine metabolites rather oxidized on the isoxazole ring. The use of azetidine as a replacement for aliphatic aza-heterocyclic rings in drug design to alter drug metabolism and pharmacol. is discussed. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Recommanded Product: 1-Boc-Azetidine-3-yl-methanol).
1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. Alkyl halides are often synthesized from alcohols, in effect substituting a halogen atom for the hydroxyl group. Tertiary alcohols cannot be oxidized at all without breaking carbon-carbon bonds, whereas primary alcohols can be oxidized to aldehydes or further oxidized to carboxylic acids.Recommanded Product: 1-Boc-Azetidine-3-yl-methanol
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