Marcin, Lawrence R.; Higgins, Mendi A.; Zusi, F. Christopher; Zhang, Yunhui; Dee, Michael F.; Parker, Michael F.; Muckelbauer, Jodi K.; Camac, Daniel M.; Morin, Paul E.; Ramamurthy, Vidhyashankar; Tebben, Andrew J.; Lentz, Kimberley A.; Grace, James E.; Marcinkeviciene, Jovita A.; Kopcho, Lisa M.; Burton, Catherine R.; Barten, Donna M.; Toyn, Jeremy H.; Meredith, Jere E.; Albright, Charles F.; Bronson, Joanne J.; Macor, John E.; Thompson, Lorin A. published an article in Bioorganic & Medicinal Chemistry Letters. The title of the article was 《Synthesis and SAR of indole- and 7-azaindole-1,3-dicarboxamide hydroxyethylamine inhibitors of BACE-1》.Recommanded Product: 3-Formyl-1H-indole-6-carbonitrile The author mentioned the following in the article:
Heterocyclic replacement of the isophthalamide Ph ring in hydroxyethylamine (HEA) BACE-1 inhibitors was explored. A variety of indole-1,3-dicarboxamide HEAs I (X = CH; R1 = R2 = Et, n-Pr, n-Bu; R1 = n-Bu, R2 = H, Me; R3 = H, F, CN; R4 = H, F, Cl, CF3, CO2H, etc.; R5 = 3-MeOC6H4CH2; R6 = H, F) exhibited potent BACE-1 enzyme inhibition, but displayed poor cellular activity. Improvements in cellular activity and aspartic protease selectivity were observed for 7-azaindole-1,3-dicarboxamide HEAs I (X = N; R1 = Bu, n-pentyl, isopentyl, MeOCH2CH2, R2 = Me; R1 = cyclopropylmethyl, R2 = n-Pr; R1R2N = 2-ethoxymethyl-1-piperidinyl, etc.; R3 = R4 = H; R5 = 3-MeOC6H4CH2, 3-MeOC6H4CO, cyclopropyl, etc.; R6 = H, F). A methylprolinol-bearing azaindole I [X = N; R1R2N = (R)-2-methoxymethyl-1-pyrrolidinyl; R3 = R4 = H; R5 = 3-MeOC6H4CH2; R6 = F] demonstrated robust reductions in rat plasma Aβ levels, but did not lower rat brain Aβ due to poor central exposure. The same compound exhibited a high efflux ratio in a bidirectional Caco-2 assay and was likely a substrate of the efflux transporter P-glycoprotein. X-ray crystal structures are reported for two indole HEAs in complex with BACE-1. In the experiment, the researchers used many compounds, for example, 3-Formyl-1H-indole-6-carbonitrile(cas: 83783-33-9Recommanded Product: 3-Formyl-1H-indole-6-carbonitrile)
3-Formyl-1H-indole-6-carbonitrile(cas: 83783-33-9) is a member of nitriles. Nitriles have been reduced to amines by many methods, especially by catalytic hydrogenation and by metal hydrides. Aliphatic and aromatic nitriles have also been reduced to nitro derivatives using hydrazinium monoformate in the presence of Raney-nickel.Recommanded Product: 3-Formyl-1H-indole-6-carbonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts