Synthesis and SAR of indole- and 7-azaindole-1,3-dicarboxamide hydroxyethylamine inhibitors of BACE-1 was written by 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.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2011.Formula: C9H6ClNO This article mentions the following:
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, 5-Chloroindole-3-carboxaldehyde (cas: 827-01-0Formula: C9H6ClNO).
5-Chloroindole-3-carboxaldehyde (cas: 827-01-0) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. It is used in perfumery and in making tryptophan, an essential amino acid, and indoleacetic acid (heteroauxin), a hormone that promotes the development of roots in plant cuttings.Formula: C9H6ClNO
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Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles