Property Focused Structure-Based Optimization of Small Molecule Inhibitors of the Protein-Protein Interaction between Menin and Mixed Lineage Leukemia (MLL) was written by Borkin, Dmitry;Pollock, Jonathan;Kempinska, Katarzyna;Purohit, Trupta;Li, Xiaoqin;Wen, Bo;Zhao, Ting;Miao, Hongzhi;Shukla, Shirish;He, Miao;Sun, Duxin;Cierpicki, Tomasz;Grembecka, Jolanta. And the article was included in Journal of Medicinal Chemistry in 2016.Quality Control of 5-Methyl-2-nitrobenzonitrile This article mentions the following:
Development of potent small mol. inhibitors of protein-protein interactions with optimized druglike properties represents a challenging task in lead optimization process. Here, we report synthesis and structure-based optimization of new thienopyrimidine class of compounds, which block the protein-protein interaction between menin and MLL fusion proteins that plays an important role in acute leukemias with MLL translocations. We performed simultaneous optimization of both activity and druglike properties through systematic exploration of substituents introduced to the indole ring of lead compound 1 (MI-136) to identify compounds suitable for in vivo studies in mice. This work resulted in the identification of compound 27 (MI-538), which showed significantly increased activity, selectivity, polarity, and pharmacokinetic profile over 1 and demonstrated a pronounced effect in a mouse model of MLL leukemia. This study, which reports detailed structure-activity and structure-property relationships for the menin-MLL inhibitors, demonstrates challenges in optimizing inhibitors of protein-protein interactions for potential therapeutic applications. In the experiment, the researchers used many compounds, for example, 5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6Quality Control of 5-Methyl-2-nitrobenzonitrile).
5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6) belongs to nitriles. Nitrile compounds can be prepared by the incorporation of a cyanide source through C–C bond formation or by dehydration of primary carboxamides. Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to the CN group.Strong bases are required, such as lithium diisopropylamide and butyl lithium. The product is referred to as a nitrile anion. Quality Control of 5-Methyl-2-nitrobenzonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts