18355-73-2Relevant articles and documents
Novel quinazoline derivatives bearing various 6-benzamide moieties as highly selective and potent EGFR inhibitors
Hou, Weijie,Ren, Yan,Zhang, Zhenhua,Sun, Huan,Ma, Yongfen,Yan, Bo
, p. 1740 - 1750 (2018/03/12)
A series of novel quinazoline derivatives bearing various C-6 benzamide substituents were synthesized and evaluated as EGFR inhibitors, and most showed significant inhibitory potency against EGFR kinase. In particular, compound 6g possessed potent inhibitory activity against EGFR wild-type (IC50 = 5 nM), and strong antiproliferative activity against HCC827 and Ba/F3 (L858R) cell lines. Kinase profiling against a panel of 365 kinases showed that 6g was highly selective for EGFR. Furthermore, 6g showed desirable properties in assays of liver microsome metabolic stability and cytochromes P450 inhibition and preliminary pharmacokinetic study. The overall attractive profile of 6g made it an interesting compound for further development.
N -pyridyl and pyrimidine benzamides as KCNQ2/Q3 potassium channel openers for the treatment of epilepsy
Amato, George,Roeloffs, Rosemarie,Rigdon, Greg C.,Antonio, Brett,Mersch, Theresa,McNaughton-Smith, Grant,Wickenden, Alan D.,Fritch, Paul,Suto, Mark J.
supporting information; experimental part, p. 481 - 484 (2011/08/22)
A series of N-pyridyl benzamide KCNQ2/Q3 potassium channel openers were identified and found to be active in animal models of epilepsy and pain. The best compound 12 [ICA-027243, N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide] has an EC50 of 0.38 μM and is selective for KCNQ2/Q3 channels. This compound was active in several rodent models of epilepsy and pain but upon repeated dosing had a number of unacceptable toxicities that prevented further development. On the basis of the structure-activity relationships developed around 12, a second compound, 51, [N-(2-chloro-pyrimidin-5-yl)-3,4-difluoro- benzamide, ICA-069673], was prepared and advanced into a phase 1 clinical study. Herein, we describe the structure-activity relationships that led to the identification of compound 12 and to the corresponding pyrimidine 51.
Synthesis and anti-inflammatory activity of fluorinated isocoumarins and 3,4-dihydroisocoumarins
Qadeer, Ghulam,Rama, Nasim Hasan,Gardu?o-Ramírez
, p. 641 - 646 (2008/01/06)
The synthesis of several fluorinated isocoumarins and 3,4-dihydroisocoumarins are described. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. All synthesized compounds were evaluated for their anti-inflammatory and antioxidant activity. These compounds were found to present antioxidant and anti-inflammatory activities. A few of them were found to be significantly active in vivo against ear edema in mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and also good radical scavengers.