13772-94-6Relevant articles and documents
Monna, a potent and selective blocker for transmembrane protein with unknown function 16/anoctamin-1
Oh, Soo-Jin,Hwang, Seok Jin,Jung, Jonghoon,Yu, Kuai,Kim, Jeongyeon,Choi, Jung Yoon,Hartzell, H. Criss,Roh, Eun Joo,Justin Lee
, p. 726 - 735 (2013/11/06)
Transmembrane protein with unknown function 16/anoctamin-1 (ANO1) is a protein widely expressed in mammalian tissues, and it has the properties of the classic calcium-activated chloride channel (CaCC). This protein has been implicated in numerous major physiological functions. However, the lack of effective and selective blockers has hindered a detailed study of the physiological functions of this channel. In this study, we have developed a potent and selective blocker for endogenous ANO1 in Xenopus laevis oocytes (xANO1) using a drug screening method we previously established (Oh et al., 2008). We have synthesized a number of anthranilic acid derivatives and have determined the correlation between biological activity and the nature and position of substituents in these derived compounds. A structure-activity relationship revealed novel chemical classes of xANO1 blockers. The derivatives contain a-NO2 group on position 5 of a naphthyl group-substituted anthranilic acid, and they fully blocked xANO1 chloride currents with an IC 5050 of 0.08 μM for xANO1. Selectivity tests revealed that other chloride channels such as bestrophin-1, chloride channel protein 2, and cystic fibrosis transmembrane conductance regulator were not appreciably blocked by 10～30 μM MONNA. The potent and selective blockers for ANO1 identified here should permit pharmacological dissection of ANO1/CaCC function and serve as potential candidates for drug therapy of related diseases such as hypertension, cystic fibrosis, bronchitis, asthma, and hyperalgesia.
Organocatalytic aryl-aryl bond formation: An atroposelective [3,3]-rearrangement approach to BINAM derivatives
Li, Gong-Qiang,Gao, Hongyin,Keene, Craig,Devonas, Michael,Ess, Daniel H.,Kürti, László
, p. 7414 - 7417 (2013/06/27)
Herein we disclose an organocatalytic aryl-aryl bond-forming process for the regio- and atroposelective synthesis of 2,2′-diamino-1,1′- binaphthalenes (BINAMs). In the presence of catalytic amounts of axially chiral phosphoric acids, achiral N,N′-binaphthyl hydrazines undergo a facile [3,3]-sigmatropic rearrangement to afford enantiomerically enriched BINAM derivatives in good to excellent yield. This transformation represents the first example of a metal-free, catalytic C(sp2)-C(sp2) bond formation between two aromatic rings with concomitant de novo atroposelective installation of an axis of chirality. Density functional calculations reveal that, in the transition state for C-C bond formation, the phosphoric acid proton of the catalyst is fully transferred to one of the N-atoms of the substrate, and the resulting phosphate acts as a chiral counterion.
Raf inhibitor compounds and methods of use thereof
-
Page/Page column 93, (2010/11/26)
Compounds of Formula I are useful for inhibiting Raf kinase and for treating disorders mediated thereby. Methods of using compounds of Formula I, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
