5302-79-4Relevant articles and documents
Cu(II)-Mediated N-H and N-Alkyl Aryl Amination and Olefin Aziridination
Munnuri, Sailu,Anugu, Raghunath Reddy,Falck, John R.
supporting information, p. 1926 - 1929 (2019/03/11)
Cu(II)-mediated direct NH2 and NH alkyl aryl aminations and olefin aziridinations are described. These room-temperature, one-pot, environmentally friendly procedures replace costly Rh2 catalysts and, in some instances, display important differences with comparable Rh2- and Fe-supported reactions.
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
supporting information, 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.
Novel 3-oxazolidinedione-6-aryl-pyridinones as potent, selective, and orally active EP3 receptor antagonists
Jin, Jian,Morales-Ramos, Angel,Eidam, Patrick,Mecom, John,Li, Yue,Brooks, Carl,Hilfiker, Mark,Zhang, David,Wang, Ning,Shi, Dongchuan,Tseng, Pei-San,Wheless, Karen,Budzik, Brian,Evans, Karen,Jaworski, Jon-Paul,Jugus, Jack,Leon, Lisa,Wu, Charlene,Pullen, Mark,Karamshi, Bhumika,Rao, Parvathi,Ward, Emma,Laping, Nicholas,Evans, Christopher,Leach, Colin,Holt, Dennis,Su, Xin,Morrow, Dwight,Fries, Harvey,Thorneloe, Kevin,Edwards, Richard
scheme or table, p. 316 - 320 (2010/11/18)
High-throughput screening and subsequent optimization led to the discovery of novel 3-oxazolidinedione-6-aryl-pyridinones exemplified by compound 2 as potent and selective EP3 antagonists with excellent pharmacokinetic properties. Compound 2 was orally active and showed robust in vivo activities in overactive bladder models. To address potential bioactivation liabilities of compound 2, further optimization resulted in compounds 9 and 10, which maintained excellent potency, selectivity, and pharmacokinetic properties and showed no bioactivation liability in glutathione trapping studies. These highly potent, selective, and orally active EP3 antagonists are excellent tool compounds for investigating and validating potential therapeutic benefits from selectively inhibiting the EP3 receptor.
