137352-78-4Relevant articles and documents
Selective Fatty Acid Amide Hydrolase Inhibitors as Potential Novel Antiepileptic Agents
Grillo, Alessandro,Fezza, Filomena,Chemi, Giulia,Colangeli, Roberto,Brogi, Simone,Fazio, Domenico,Federico, Stefano,Papa, Alessandro,Relitti, Nicola,Di Maio, Roberto,Giorgi, Gianluca,Lamponi, Stefania,Valoti, Massimo,Gorelli, Beatrice,Saponara, Simona,Benedusi, Mascia,Pecorelli, Alessandra,Minetti, Patrizia,Valacchi, Giuseppe,Butini, Stefania,Campiani, Giuseppe,Gemma, Sandra,Maccarrone, Mauro,Di Giovanni, Giuseppe
, p. 1716 - 1736 (2021)
Temporal lobe epilepsy is the most common form of epilepsy, and current antiepileptic drugs are ineffective in many patients. The endocannabinoid system has been associated with an on-demand protective response to seizures. Blocking endocannabinoid catabolism would elicit antiepileptic effects, devoid of psychotropic effects. We herein report the discovery of selective anandamide catabolic enzyme fatty acid amide hydrolase (FAAH) inhibitors with promising antiepileptic efficacy, starting from a further investigation of our prototypical inhibitor 2a. When tested in two rodent models of epilepsy, 2a reduced the severity of the pilocarpine-induced status epilepticus and the elongation of the hippocampal maximal dentate activation. Notably, 2a did not affect hippocampal dentate gyrus long-term synaptic plasticity. These data prompted our further endeavor aiming at discovering new antiepileptic agents, developing a new set of FAAH inhibitors (3a-m). Biological studies highlighted 3h and 3m as the best performing analogues to be further investigated. In cell-based studies, using a neuroblastoma cell line, 3h and 3m could reduce the oxinflammation state by decreasing DNA-binding activity of NF-kB p65, devoid of cytotoxic effect. Unwanted cardiac effects were excluded for 3h (Langendorff perfused rat heart). Finally, the new analogue 3h reduced the severity of the pilocarpine-induced status epilepticus as observed for 2a.
Palladium-Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide
Bismuto, Alessandro,Boehm, Philip,Morandi, Bill,Roediger, Sven
supporting information, p. 17887 - 17896 (2020/08/19)
An efficient palladium-catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high-value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl-containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.
L-(+)-Tartaric acid and choline chloride based deep eutectic solvent: An efficient and reusable medium for synthesis of N-substituted pyrroles via Clauson-Kaas reaction
Wang, Ping,Ma, Fei-Ping,Zhang, Zhan-Hui
, p. 259 - 262 (2014/11/07)
l-(+)-Tartaric acid-choline chloride based deep eutectic solvent has been found to be an effective promoted medium for Clauson-Kaas reaction of aromatic amines and 2,5-dimethoxytetrahydrofuran. Structurally diverse N-substituted pyrroles were obtained in high to excellent yields under mild conditions. The deep eutectic solvent is inexpensive, non-toxic, reusable and biodegradable.
