Antimalarial activity enhancement in hydroxymethylcarbonyl (HMC) isostere-based dipeptidomimetics targeting malarial aspartic protease plasmepsin was written by Hidaka, Koushi;Kimura, Tooru;Ruben, Adam J.;Uemura, Tsuyoshi;Kamiya, Mami;Kiso, Aiko;Okamoto, Tetsuya;Tsuchiya, Yumi;Hayashi, Yoshio;Freire, Ernesto;Kiso, Yoshiaki. And the article was included in Bioorganic & Medicinal Chemistry in 2008.COA of Formula: C9H10O4 This article mentions the following:
Plasmepsin (Plm) is a potential target for new antimalarial drugs, but most reported Plm inhibitors have relatively low antimalarial activities. We synthesized a series of dipeptide-type HIV protease inhibitors, which contain an allophenylnorstatine-dimethylthioproline scaffold to exhibit potent inhibitory activities against Plm II. Their activities against Plasmodium falciparum in the infected erythrocyte assay were largely different from those against the target enzyme. To improve the antimalarial activity of peptidomimetic Plm inhibitors, we attached substituents on a structure of the highly potent Plm inhibitor KNI-10006. Among the derivatives, we identified alkylamino compounds such as 44 (KNI-10283) and 47 (KNI-10538) with more than 15-fold enhanced antimalarial activity, to the sub-micromolar level, maintaining their potent Plm II inhibitory activity and low cytotoxicity. These results suggest that auxiliary substituents on a specific basic group contribute to deliver the inhibitors to the target Plm. In the experiment, the researchers used many compounds, for example, 2-(4-Methoxyphenoxy)acetic acid (cas: 1877-75-4COA of Formula: C9H10O4).
2-(4-Methoxyphenoxy)acetic acid (cas: 1877-75-4) belongs to ethers. The oxygen atom in ethers are more electronegative than carbon, thus the hydrogens which are alpha to the ethers are more acidic than the simple hydrocarbons. Ethers can form hydrogen bonds with other molecules (alcohols, amines, etc.) that have O―H or N―H bonds. 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.COA of Formula: C9H10O4
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem