27737-55-9Relevant 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.
Design, synthesis and antifungal activity of isosteric analogues of benzoheterocyclic N-myristoyltransferase inhibitors
Sheng, Chunquan,Xu, Hui,Wang, Wenya,Cao, Yongbing,Dong, Guoqiang,Wang, Shengzheng,Che, Xiaoying,Ji, Haitao,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian
experimental part, p. 3531 - 3540 (2010/09/05)
N-myristoyltransferase (NMT) has been a promising new target for the design of novel antifungal agents with new mode of action. A series of benzoxazole and indole derivatives were designed and synthesized as isosteric analogues of benzoheterocyclic NMT Inhibitors. In vitro antifungal assay indicated that the benzoxazole derivatives were far more potent than the indoles. Molecular docking studies revealed that the hydrogen bonding interaction between the benzoheterocyclic core and NMT might be essential in the orientation of the inhibitor to a proper position. The antifungal activity of benzoxazole derivative 8f was comparable or superior to that of fluconazole, which can serve as a good starting point for further studies of structural diversity of the benzoheterocyclic NMT inhibitors. A series of benzoxazole and indole derivatives were designed and synthesized as isosteric analogues of benzoheterocyclic NMT Inhibitors. The binding mode was investigated by molecular docking.
Cyclization of free radicals at the C-7 position of ethyl indole-2-carboxylate derivatives: An entry to a new class of duocarmycin analogues
Al-Said, Naim H.,Shawakfeh, Khaled Q.,Abdullah, Wasim N.
, p. 1446 - 1457 (2007/10/03)
Aryl free-radicals generated at the C-7 position of ethyl indole-2-carboxylates bearing N-allyl and propargylic groups triggered intramolecular cyclizations to furnish a new class of Duocarmycin analogues, formal ethyl pyrrolo[3,2,1-ij]quinoline-2-carboxylate derivatives, through the less favorable 6-endo-trig cyclization mode.
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.
Formation of Indoles, Isoquinolines, and Other Fused Pyridines from Azidoacrylates
Henn, Lothar,Hickey, Deirde M. B.,Moody, Christopher J.,Rees, Charles W.
, p. 2189 - 2197 (2007/10/02)
Mild thermal decomposition in boiling toluene or xylene of the azidocinnamates (1) - (6), readily prepared from the corresponding aldehyde and ethyl azidoacetate, gives indoles in good yield when there is an unsubstituted ortho position, and dihydroisoquinolines, and hence isoquinolines, when there is an o-methyl or methylene group.In the presence of iodine, which seems to favour a radical type process, the yield of isoquinoline is increased, and isoquinoline formation can compete with the indole-forming cyclisation to a free ortho-position.Iodine also catalyses primary enamine formation by a hydrogen abstraction process.The thiophene (7) and pyrazole (8) are formed and decomposed similarly to give the corresponding c-fused pyridines (28) and (29).The 2,6-dichloro compound (9) thermolyses to the stable 2H-azirine (32) which isomerises to the nitrile (33) on stronger heating.Yields in these azide decompositions are sometimes high, though they can be variable and the reactions, though easily carried out, can be complex
