24297-59-4Relevant articles and documents
Novel hits for acetylcholinesterase inhibition derived by docking-based screening on ZINC database
Doytchinova, Irini,Atanasova, Mariyana,Valkova, Iva,Stavrakov, Georgi,Philipova, Irena,Zhivkova, Zvetanka,Zheleva-Dimitrova, Dimitrina,Konstantinov, Spiro,Dimitrov, Ivan
, p. 768 - 776 (2018)
The inhibition of the enzyme acetylcholinesterase (AChE) increases the levels of the neurotransmitter acetylcholine and symptomatically improves the affected cognitive function. In the present study, we searched for novel AChE inhibitors by docking-based virtual screening of the standard lead-like set of ZINC database containing more than 6 million small molecules using GOLD software. The top 10 best-scored hits were tested in vitro for AChE affinity, neurotoxicity, GIT and BBB permeability. The main pharmacokinetic parameters like volume of distribution, free fraction in plasma, total clearance, and half-life were predicted by previously derived models. Nine of the compounds bind to the enzyme with affinities from 0.517 to 0.735 μM, eight of them are non-toxic. All hits permeate GIT and BBB and bind extensively to plasma proteins. Most of them are low-clearance compounds. In total, seven of the 10 hits are promising for further lead optimisation. These are structures with ZINC IDs: 00220177, 44455618, 66142300, 71804814, 72065926, 96007907, and 97159977.
TOTAL SYNTHESIS AND STEREOCHEMICAL REASSIGNMENT OF THE INDOLE ALKALOID VINOXINE
Bosch, Joan,Bennasar, M.-Lluisa,Zulaica, Ester,Feliz, Miguel
, p. 3119 - 3122 (1984)
The first total synthesis of the indole alkaloid vinoxine and the reassignment of the relative configuration at carbon-16 in this alkaloid is reported.
Br?nsted Acid-Promoted Cyclodimerization of Indolyl Ketones: Construction of Indole Fused-Oxabicyclo[3.3.1]nonane and -Cyclooctatetraene Ring Systems
Zhao, Lang,Yan, Zhi-Hua,Tang, Shuai,Wei, Zhong-Lin,Liao, Wei-Wei
, p. 166 - 171 (2021)
A Br?nsted acid-promoted cyclodimerization of C(3)-, C(2)-, or N(1)-substituted indole ketone derivatives is described. A wide range of structurally diverse bisindole fused-9-oxabicyclo[3.3.1]nonane and bisindole fused-cyclooctatetraene (COT) derivatives can be prepared in good to high yields with high efficiency.
Chemospecific Cyclizations of α-Carbonyl Sulfoxonium Ylides on Aryls and Heteroaryls
Clare, Daniel,Dobson, Benjamin C.,Inglesby, Phillip A.,A?ssa, Christophe
, p. 16198 - 16202 (2019/11/03)
The functionalization of aryl and heteroaryls using α-carbonyl sulfoxonium ylides without the help of a directing group has remained so far a neglected area, despite the advantageous safety profile of sulfoxonium ylides. Described herein are the cyclizations of α-carbonyl sulfoxonium ylides onto benzenes, benzofurans and N-p-toluenesulfonyl indoles in the presence of a base in HFIP, whereas pyrroles and N-methyl indoles undergo cyclization in the presence of an iridium catalyst. Significantly, these two sets of conditions are chemospecific for each groups of substrates.