Discovery of potent nucleotide pyrophosphatase/phosphodiesterase3 (NPP3) inhibitors with ancillary carbonic anhydrase inhibition for cancer (immuno)therapy was written by Lee, Sang-Yong;Namasivayam, Vigneshwaran;Boshta, Nader M.;Perotti, Arianna;Mirza, Salahuddin;Bua, Silvia;Supuran, Claudiu T.;Mueller, Christa E.. And the article was included in RSC Medicinal Chemistry in 2021.Synthetic Route of C7H10N2O2S This article mentions the following:
Nucleotide pyrophosphatase/phosphodiesterase3 (NPP3) catalyzes the hydrolysis of extracellular nucleotides. It is expressed by immune cells and some carcinomas, e.g. of kidney and colon. Together with ecto-5′-nucleotidase (CD73), NPP3 produces immunosuppressive, cancer-promoting adenosine, and has therefore been proposed as a target for cancer therapy. Here we report on the discovery of 4-[(4-methylphthalazin-1-yl)amino]benzenesulfonamide (1) as an inhibitor of human NPP3 identified by compound library screening. Subsequent structure-activity relationship (SAR) studies led to the potent competitive NPP3 inhibitor 2-methyl-5-{4-[(4-sulfamoylphenyl)amino]phthalazin-1-yl}benzenesulfonamide (23, Ki 53.7 nM vs. the natural substrate ATP). Docking studies predicted its binding pose and interactions. While 23 displayed high selectivity vs. other ecto-nucleotidases, it showed ancillary inhibition of two proposed anti-cancer targets, the carbonic anhydrases CA-II (Ki 74.7 nM) and CA-IX (Ki 20.3 nM). Thus, 23 may act as multi-target anti-cancer drug. SARs for NPP3 were steeper than for CAs leading to the identification of potent dual CA-II/CA-IX (e.g.34) as well as selective CA-IX inhibitors (e.g.31). In the experiment, the researchers used many compounds, for example, 4-Amino-3-methylbenzenesulfonamide (cas: 53297-70-4Synthetic Route of C7H10N2O2S).
4-Amino-3-methylbenzenesulfonamide (cas: 53297-70-4) belongs to amides. The solubilities of amides and esters are roughly comparable. Typically amides are less soluble than comparable amines and carboxylic acids since these compounds can both donate and accept hydrogen bonds. Tertiary amides, with the important exception of N,N-dimethylformamide, exhibit low solubility in water. Ionic, or saltlike, amides are strongly alkaline compounds ordinarily made by treating ammonia, an amine, or a covalent amide with a reactive metal such as sodium.Synthetic Route of C7H10N2O2S
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics