98586-21-1Relevant articles and documents
Temperature-controlled divergent synthesis of 4-alkoxy- or 4-alkenyl-chromanes via inverse electron-demand cycloaddition with in situ generated ortho-quinone methides
Tanaka, Kenta,Kishimoto, Mami,Hoshino, Yujiro,Honda, Kiyoshi
supporting information, p. 1841 - 1845 (2018/04/11)
The temperature-controlled divergent synthesis of 4-alkoxy- or 4-alkenyl-chromanes via inverse electron-demand cycloaddition with in situ generated ortho-quinone methides under identical reaction conditions except for thermal condition has been developed. At room temperature, the reaction generated 4-methoxychromanes, whereas the reaction performed at room temperature to 100 °C gave 4-alkenylchromanes. Trifluoromethanesulfonic acid was efficiently suitable in the reaction to give the 4-substituted chromanes. This divergent synthetic strategy exhibits a new method giving carbon–carbon or carbon–oxygen bond by controlling the reaction temperature.
Kinetics of the solvolyses of fluoro-substituted benzhydryl derivatives: Reference electrofuges for the development of a comprehensive nucleofugality scale
Nolte, Christoph,Mayr, Herbert
supporting information; experimental part, p. 1435 - 1439 (2010/05/18)
A series of m-fluoro-substituted benzhydryl chloridcjs, bromides, mesylates and Losylates 1-X to 5-X were prepared and subjected to solvolysis reactions in various solvents. The observed first-order rate constants ks(25 °C) were found to follow the correlation equation log ks(25 °C) = Sf(Nf + Ef), which allowed us to determine the electrofugalily parameters Ef for these destabilized benzhydrylium cations and the nucleofugality parameters Nf, S f for a series of leaving group/ solvent combinations.
Novel inhibitors of the gardos channel for the treatment of sickle cell disease
McNaughton-Smith, Grant A.,Burns, J. Ford,Stocker, Jonathan W.,Rigdon, Gregory C.,Creech, Christopher,Arlington, Susan,Shelton, Tara,De Franceschi, Lucia
, p. 976 - 982 (2008/12/20)
Sickle cell disease (SCD) is a hereditary condition characterized by deformation of red blood cells (RBCs). This phenomenon is due to the presence of abnormal hemoglobin that polymerizes upon deoxygenation. This effect is exacerbated when dehydrated RBCs experience a loss of both water and potassium salts. One critical pathway for the regulation of potassium efflux from RBCs is the Gardos channel, a calcium-activated potassium channel. This paper describes the synthesis and biological evaluation of a series of potent inhibitors of the Gardos channel. The goal was to identify compounds that were potent and selective inhibitors of the channel but had improved pharmacokinetic properties compared to 1, Clotrimazole. Several triarylamides such as 10 and 21 were potent inhibitors of the Gardos channel (IC50 of 10 nM) and active in a mouse model of SCD. Compound 21 (ICA-17043) was advanced into phase 3 clinical trials for SCD.
