106050-92-4Relevant academic research and scientific papers
A SUPERIOR SYNTHETIC METHOD FOR THE BROMINATION OF INDOLES AND BENZIMIDAZOLES.
Mistry, Anil G.,Smith, Keith,Bye, Martin R.
, p. 1051 - 1054 (1986)
Brominated indoles and benzimidazoles are formed in very high yields and with substantial regioselectivity by use of a reagent system consisting of N-bromosuccinimide (NBS) and silica gel in dichloromethane.
New MKLP-2 inhibitors in the paprotrain series: Design, synthesis and biological evaluations
Labrière, Christophe,Talapatra, Sandeep K.,Thoret, Sylviane,Bougeret, Cécile,Kozielski, Frank,Guillou, Catherine
supporting information, p. 721 - 734 (2016/02/09)
Members of the kinesin superfamily are involved in key functions during intracellular transport and cell division. Their involvement in cell division makes certain kinesins potential targets for drug development in cancer chemotherapy. The two most advanc
Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors
Shultz, Michael D.,Cao, Xueying,Chen, Christine H.,Cho, Young Shin,Davis, Nicole R.,Eckman, Joe,Fan, Jianmei,Fekete, Alex,Firestone, Brant,Flynn, Julie,Green, Jack,Growney, Joseph D.,Holmqvist, Mats,Hsu, Meier,Jansson, Daniel,Jiang, Lei,Kwon, Paul,Liu, Gang,Lombardo, Franco,Lu, Qiang,Majumdar, Dyuti,Meta, Christopher,Perez, Lawrence,Pu, Minying,Ramsey, Tim,Remiszewski, Stacy,Skolnik, Suzanne,Traebert, Martin,Urban, Laszlo,Uttamsingh, Vinita,Wang, Ping,Whitebread, Steven,Whitehead, Lewis,Yan-Neale, Yan,Yao, Yung-Mae,Zhou, Liping,Atadja, Peter
experimental part, p. 4752 - 4772 (2011/09/20)
Histone deacetylase (HDAC) inhibitors have shown promise in treating various forms of cancer. However, many HDAC inhibitors from diverse structural classes have been associated with QT prolongation in humans. Inhibition of the human ether a-go-go related gene (hERG) channel has been associated with QT prolongation and fatal arrhythmias. To determine if the observed cardiac effects of HDAC inhibitors in humans is due to hERG blockade, a highly potent HDAC inhibitor devoid of hERG activity was required. Starting with dacinostat (LAQ824), a highly potent HDAC inhibitor, we explored the SAR to determine the pharmacophores required for HDAC and hERG inhibition. We disclose here the results of these efforts where a high degree of pharmacophore homology between these two targets was discovered. This similarity prevented traditional strategies for mitigating hERG binding/modulation from being successful and novel approaches for reducing hERG inhibition were required. Using a hERG homology model, two compounds, 11r and 25i, were discovered to be highly efficacious with weak affinity for the hERG and other ion channels.
2-arylindole-3-acetamides: FPP-competitive inhibitors of farnesyl protein transferase
Trotter,Quigley, Amy G.,Lumma, William C.,Sisko, John T.,Walsh, Eileen S.,Hamann, Christian S.,Robinson, Ronald G.,Bhimnathwala, Hema,Kolodin,Zheng, Wei,Buser, Carolyn A.,Huber, Hans E.,Lobell, Robert B.,Kohl, Nancy E.,Williams, Theresa M.,Graham, Samuel L.,Dinsmore, Christopher J.
, p. 865 - 869 (2007/10/03)
A series of 2-arylindole-3-acetamide farnesyl protein transferase inhibitors has been identified. The compounds inhibit the enzyme in a farnesyl pyrophosphate-competitive manner and are selective for farnesyl protein transferase over the related enzyme geranylgeranyltransferase-I. A representative member of this series of inhibitors demonstrates equal effectiveness against HDJ-2 and K-Ras farnesylation in a cell-based assay when geranylgeranylation is suppressed.
