95264-30-5Relevant academic research and scientific papers
Synthesis of five libraries of 6,5-fused heterocycles to establish the importance of the heterocyclic core for antiplasmodial activity
Jacobs, Leon,de Kock, Carmen,Taylor, Dale,Pelly, Stephen C.,Blackie, Margaret A.L.
, p. 5730 - 5741 (2018/11/06)
Research has indicated that N-myristoyl transferase, an enzyme that catalyzes the addition of a myristate group to the N-terminal glycine residues of proteins, is involved in the myristoylation of more than 100 proteins. Genetic knockdown of the enzyme proved detrimental for the viability of the parasite P. knowlesi. A crystal structure of P. vivax N-myristoyl transferase (pvNMT), containing a 3-methyl benzofuran ligand has made it possible to assess key amino acid residue-ligand interactions. We synthesized five libraries of 6,5-fused heterocycles to establish the importance of the heterocycles as core scaffolds, as well as introduced various aromatic amides and esters to determine which carbonylic group affects the potency of each heterocyclic antiplasmodial agent.
Novel Indole-2-carboxylates as Ligands for the Strychnine-Insensitive N-Methyl-D-aspartate-Linked Glycine Receptor
Gray, Nancy M.,Dappen, Michael S.,Cheng, Brian K.,Cordi, Alexis A.,Biesterfeldt, John P.,et al.
, p. 1283 - 1292 (2007/10/02)
A series of indole-2-carboxylates were prepared and evaluated for their ability to inhibit the binding at the strychnine-insensitive glycine receptor that is associated with the NMDA-PCP-glycine receptor complex.All of the compounds were selective for the glycine site relative to other sites on the receptor macrocomplex and several of the compounds in this series were found to have submicromolar affinity for this receptor.The lead compound, 2-carboxy-6-chloro-3-indoleacetic acid (Ki = 1.6 μM vsglycine), was also found to noncompetitively inhibit the binding of MK-801, a ligand for the phencyclidine site on the receptor macrocomplex.These latter data suggest that the compound functions as an antagonist at the strychnine-insensitive glycine receptor.The structural activity relationships within this series of indole-2-carboxylates is discussed and several key pharmacophores are identified for this series of glycine ligands.In general, the most potent compounds were the C-3 acetamides, with N-propyl-2-carboxy-6-chloro-3-indoleacetamide having the highest receptor affinity.
