Ring-expansion synthesis and crystal structure of dimethyl 4-ethyl-1,4,5,6,7,8-hexahydroazonino[5,6-b]indole-2,3-dicarboxylate

The title compound, C20H24N2O4, is the product of a ring-expansion reaction from a seven-membered hexahydroazepine to a nine-membered azonine. The azonine ring of the molecule adopts a chair–boat conformation. In the crystal, molecules are linked by bifurcated N—H...(O,O) hydrogen bonds, generating [010] zigzag chains. The title compound shows inhibitory activity against acetylcholinesterase and butyrylcholinesterase, and might be considered as a candidate for the design of new types of anti-Alzheimer's drugs

Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase Activity

Transformations of 1-methoxymethylethynyl substituted isoquinolines triggered by termi- nal alkynes in alcohols were studied and new 3-benzazecine-containing compounds synthesized, such as 6-methoxymethyl-3-benzazecines incorporating an endocyclic C6–C8 allene fragment and the -ylidene derivatives 6-methoxymethylene-3-benzazecines. The reaction mechanisms were inves- tigated and a preliminary in vitro screening of their potential inhibitory activities against human acetyl- and butyrylcholinesterases (AChE and BChE) and monoamine oxidases A and B (MAO-A and MAO-B) showed that the allene compounds were more potent than the corresponding -ylidene ones as selective AChE inhibitors. Among the allenes, 3e (R3 = CH2OMe) was found to be a competitive AChE inhibitor with a low micromolar inhibition constant value (Ki = 4.9 μM), equipotent with the corresponding 6-phenyl derivative 3n (R3 = Ph, Ki = 4.5 μM), but 90-fold more water-soluble