519166-83-7Relevant articles and documents
Synthesis of 3-nitroindoles by sequential paired electrolysis
Lindsay, Ashley C.,Kilmartin, Paul A.,Sperry, Jonathan
, p. 7903 - 7913 (2021/09/28)
3-Nitroindoles are synthetically versatile intermediates but current methods for the preparation hinder their widespread application. Herein, we report that nitroenamines undergo electrochemical cyclisation to 3-nitroindoles in the presence of potassium iodide. Detailed control experiments and cyclic voltammogram studies infer the reaction proceedsviaa sequential paired electrolysis process, beginning with anodic oxidation of iodide (I?) to the iodine radical (I˙), which facilitates cyclisation of the nitroenamine to give a 3-nitroindolinyl radical. Cathodic reduction and protonation generates a 3-nitroindoline that upon oxidation forms the 3-nitroindole.
The Trifluoromethyl Group as a Bioisosteric Replacement of the Aliphatic Nitro Group in CB1 Receptor Positive Allosteric Modulators
Tseng, Chih-Chung,Baillie, Gemma,Donvito, Giulia,Mustafa, Mohammed A.,Juola, Sophie E.,Zanato, Chiara,Massarenti, Chiara,Dall'Angelo, Sergio,Harrison, William T. A.,Lichtman, Aron H.,Ross, Ruth A.,Zanda, Matteo,Greig, Iain R.
supporting information, p. 5049 - 5062 (2019/05/28)
The first generation of CB1 positive allosteric modulators (e.g., ZCZ011) featured a 3-nitroalkyl-2-phenyl-indole structure. Although a small number of drugs include the nitro group, it is generally not regarded as being "drug-like", and this is particularly true for aliphatic nitro groups. There are very few case studies where an appropriate bioisostere replaced a nitro group that had a direct role in binding. This may be indicative of the difficulty of replicating its binding interactions. Herein, we report the design and synthesis of ligands targeting the allosteric binding site on the CB1 cannabinoid receptor, in which a CF3 group successfully replaced the aliphatic NO2. In general, the CF3-bearing compounds were more potent than their NO2 equivalents and also showed improved in vitro metabolic stability. The CF3 analogue (1) with the best balance of properties was selected for further pharmacological evaluation. Pilot in vivo studies showed that (±)-1 has similar activity to (±)-ZCZ011, with both showing promising efficacy in a mouse model of neuropathic pain.
A versatile synthetic route to 11H-indolo[3,2-c]isoquinolines
Qu, Ji,Kumar, Naresh,Alamgir, Mahiuddin,Black, David StC.
scheme or table, p. 5628 - 5630 (2011/02/22)
A wide variety of indoloisoquinoline derivatives are prepared from the acid-catalyzed cyclization of 3-amido-2-phenylindoles, which in turn were obtained from the Beckmann rearrangement of 2-phenylindole-3-oximes.
