《PEGylated AdipoRon derivatives improve glucose and lipid metabolism under insulinopenic and high-fat diet conditions》 was written by Onodera, Toshiharu; Ghazvini Zadeh, Ebrahim; Xu, Peng; Gordillo, Ruth; Guo, Zheng; Joffin, Nolwenn; Yu, Biao; Scherer, Philipp E.; Li, Wen-hong. Synthetic Route of C9H19NO4 And the article was included in Journal of Lipid Research in 2021. The article conveys some information:
The pleiotropic actions of adiponectin in improving cell survival and metabolism have motivated the development of small-mol. therapeutic agents for treating diabetes and lipotoxicity. AdipoRon is a synthetic agonist of the adiponectin receptors, yet is limited by its poor solubility and bioavailability. In this work, we expand on the protective effects of AdipoRon in pancreatic β-cells and examine how structural modifications could affect the activity, pharmacokinetics, and bioavailability of this small mol. We describe a series of AdipoRon analogs containing amphiphilic ethylene glycol (PEG) chains. Among these, AdipoRonPEG5 induced pleiotropic effects in mice under insulinopenic and high-fat diet (HFD) conditions. While both AdipoRon and AdipoRonPEG5 substantially attenuate palmitate-induced lipotoxicity in INS-1 cells, only AdipoRonPEG5 treatment is accompanied by a significant reduction in cytotoxic ceramides. In vivo, AdipoRonPEG5 can substantially reduce pancreatic, hepatic, and serum ceramide species, with a concomitant increase in the corresponding sphingoid bases and improves insulin sensitivity of mice under HFD feeding conditions. Furthermore, hyperglycemia in streptozotocin (STZ)-induced insulinopenic adiponectin-null mice is also attenuated upon AdipoRonPEG5 treatment. Our results suggest that AdipoRonPEG5 is more effective in reducing ceramides and dihydroceramides in the liver of HFD-fed mice than AdipoRon, consistent with its potent activity in activating ceramidase in vitro in INS-1 cells. Addnl., these results indicate that the beneficial effects of AdipoRonPEG5 can be partially attributed to improved pharmacokinetics as compared with AdipoRon, thus suggesting that further derivatization may improve affinity and tissue-specific targeting. In the experimental materials used by the author, we found tert-Butyl (2-(2-hydroxyethoxy)ethyl)carbamate(cas: 139115-91-6Synthetic Route of C9H19NO4)
tert-Butyl (2-(2-hydroxyethoxy)ethyl)carbamate(cas: 139115-91-6) belongs to ethers.Ethers do have nonbonding electron pairs on their oxygen atoms, and they can form hydrogen bonds with other molecules (alcohols, amines, etc.) that have O―H or N―H bonds. Synthetic Route of C9H19NO4 The ability to form hydrogen bonds with other compounds makes ethers particularly good solvents for a wide variety of organic compounds and a surprisingly large number of inorganic compounds.
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem