52488-29-6Relevant articles and documents
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.
Decarboxylative Halogenation and Cyanation of Electron-Deficient Aryl Carboxylic Acids via Cu Mediator as Well as Electron-Rich Ones through Pd Catalyst under Aerobic Conditions
Fu, Zhengjiang,Li, Zhaojie,Song, Yuanyuan,Yang, Ruchun,Liu, Yanzhu,Cai, Hu
, p. 2794 - 2803 (2016/04/26)
Simple strategies for decarboxylative functionalizations of electron-deficient benzoic acids via using Cu(I) as promoter and electron-rich ones by employing Pd(II) as catalyst under aerobic conditions have been established, which lead to smooth synthesis of aryl halides (-I, Br, and Cl) through the decarboxylative functionalization of benzoic acids with readily available halogen sources CuX (X = I, Br, Cl), and easy preparation of benzonitriles from decarboxylative cyanation of aryl carboxylic acids with nontoxic and low-cost K4Fe(CN)6 under an oxygen atmosphere for the first time.
Methyltriphenylphosphonium peroxydisulfate and iodine as mild reagents for the iodination of activated aromatic compounds
Hajipour, Abdol R.,Ruoho
, p. 279 - 283 (2007/10/03)
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