6742-53-6Relevant articles and documents
Catalytic Synthesis of 1 H-2-Benzoxocins: Cobalt(III)-Carbene Radical Approach to 8-Membered Heterocyclic Enol Ethers
De Bruin, Bas,De Zwart, Felix J.,Li, Zirui,Mathew, Simon,Wolzak, Lukas A.,Zhou, Minghui
supporting information, p. 20501 - 20512 (2021/12/03)
The metallo-radical activation of ortho-allylcarbonyl-aryl N-arylsulfonylhydrazones with the paramagnetic cobalt(II) porphyrin catalyst [CoII(TPP)] (TPP = tetraphenylporphyrin) provides an efficient and powerful method for the synthesis of novel 8-membered heterocyclic enol ethers. The synthetic protocol is versatile and practical and enables the synthesis of a wide range of unique 1H-2-benzoxocins in high yields. The catalytic cyclization reactions proceed with excellent chemoselectivities, have a high functional group tolerance, and provide several opportunities for the synthesis of new bioactive compounds. The reactions are shown to proceed via cobalt(III)-carbene radical intermediates, which are involved in intramolecular hydrogen transfer (HAT) from the allylic position to the carbene radical, followed by a near-barrierless radical rebound step in the coordination sphere of cobalt. The proposed mechanism is supported by experimental observations, density functional theory (DFT) calculations, and spin trapping experiments.
Revisiting Bromohexitols as a Novel Class of Microenvironment-Activated Prodrugs for Cancer Therapy
Johansson, Henrik,Hussain, Omar,Allison, Simon J.,Robinson, Tony V.,Phillips, Roger M.,Sejer Pedersen, Daniel
supporting information, p. 228 - 235 (2019/12/11)
Bromohexitols represent a potent class of DNA-alkylating carbohydrate chemotherapeutics that has been largely ignored over the last decades due to safety concerns. The limited structure?activity relationship data available reveals significant changes in cytotoxicity with even subtle changes in stereochemistry. However, no attempts have been made to improve the therapeutic window by rational drug design or by using a prodrug approach to exploit differences between tumour physiology and healthy tissue, such as acidic extracellular pH and hypoxia. Herein, we report the photochemical synthesis of highly substituted endoperoxides as key precursors for dibromohexitol derivatives and investigate their use as microenvironment-activated prodrugs for targeting cancer cells. One endoperoxide was identified to have a marked increased activity under hypoxic and low pH conditions, indicating that endoperoxides may serve as microenvironment-activated prodrugs.
Synthesis and biological evaluation of pyridazinone derivatives as potential anti-inflammatory agents
Barberot, Chantal,Moniot, Aurélie,Allart-Simon, Ingrid,Malleret, Laurette,Yegorova, Tatiana,Laronze-Cochard, Marie,Bentaher, Abderrazzaq,Médebielle, Maurice,Bouillon, Jean-Philippe,Hénon, Eric,Sapi, Janos,Velard, Frédéric,Gérard, Stéphane
supporting information, p. 139 - 146 (2018/02/09)
Cyclic nucleotide phosphodiesterase type 4 (PDE4), that controls intracellular level of cyclic nucleotide cAMP, has aroused scientific attention as a suitable target for anti-inflammatory therapy in respiratory diseases. Here we describe the development of two families of pyridazinone derivatives as potential PDE4 inhibitors and their evaluation as anti-inflammatory agents. Among these derivatives, 4,5-dihydropyridazinone representatives possess promising activity, selectivity towards PDE4 isoenzymes and are able to reduce IL-8 production by human primary polymorphonuclear cells.