735-60-4Relevant academic research and scientific papers
Novel KV7 ion channel openers for the treatment of epilepsy and implications for detrusor tissue contraction
Seefeld, Mark A.,Lin, Hong,Holenz, Joerg,Downie, Dave,Donovan, Brian,Fu, Tingting,Pasikanti, Kishore,Zhen, Wei,Cato, Matthew,Chaudhary, Khuram W.,Brady, Pat,Bakshi, Tania,Morrow, Dwight,Rajagopal, Sridharan,Samanta, Swapan Kumar,Madhyastha, Naveena,Kuppusamy, Bharathi Mohan,Dougherty, Robert W.,Bhamidipati, Ravi,Mohd, Zainuddin,Higgins, Guy A.,Chapman, Mark,Rouget, Céline,Lluel, Philippe,Matsuoka, Yasuji
supporting information, p. 3793 - 3797 (2018/10/20)
Neuronal voltage-gated potassium channels, KV7s, are the molecular mediators of the M current and regulate membrane excitability in the central and peripheral neuronal systems. Herein, we report novel small molecule KV7 openers that demonstrate anti-seizure activities in electroshock and pentylenetetrazol-induced seizure models without influencing Rotarod readouts in mice. The anti-seizure activity was determined to be proportional to the unbound concentration in the brain. KV7 channels are also expressed in the bladder smooth muscle (detrusor) and activation of these channels may cause localized undesired effects. Therefore, the impact of individual KV7 isoforms was investigated in human detrusor tissue using a panel of KV7 openers with distinct activity profiles among KV7 isoforms. KCNQ4 and KCNQ5 mRNA were highly expressed in detrusor tissue, yet a compound that has significantly reduced activity on homomeric KV7.4 did not reduce detrusor contraction. This may suggest that the homomeric KV7.4 channel plays a less significant role in bladder contraction and further investigation is needed.
Efficient Aryl Migration from an Aryl Ether to a Carboxylic Acid Group To Form an Ester by Visible-Light Photoredox Catalysis
Wang, Shao-Feng,Cao, Xiao-Ping,Li, Yang
, p. 13809 - 13813 (2017/10/24)
We have developed a highly efficient aryl migration from an aryl ether to a carboxylic acid group through retro-Smiles rearrangement by visible-light photoredox catalysis at ambient temperature. Transition metals and a stoichiometric oxidant and base are avoided in the transformation. Inspired by the high efficiency of this transformation and the fundamental importance of C?O bond cleavage, we developed a novel approach to the C?O cleavage of a biaryl ether to form two phenolic compounds, as demonstrated by a one-pot, two-step gram-scale reaction under mild conditions. The aryl migration exhibits broad scope and can be applied to the synthesis of pharmaceutical compounds, such as guacetisal. Primary mechanistic studies indicate that the catalytic cycle occurs by a reductive quenching pathway.
