33992-16-4Relevant academic research and scientific papers
Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen
Cheeseman, Matthew D.,Chessum, Nicola E. A.,Rye, Carl S.,Pasqua, A. Elisa,Tucker, Michael J.,Wilding, Birgit,Evans, Lindsay E.,Lepri, Susan,Richards, Meirion,Sharp, Swee Y.,Ali, Salyha,Rowlands, Martin,O’Fee, Lisa,Miah, Asadh,Hayes, Angela,Henley, Alan T.,Powers, Marissa,Te Poele, Robert,De Billy, Emmanuel,Pellegrino, Loredana,Raynaud, Florence,Burke, Rosemary,Van Montfort, Rob L. M.,Eccles, Suzanne A.,Workman, Paul,Jones, Keith
, p. 180 - 201 (2017/04/26)
Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug discovery. In this article, we describe the discovery of a new chemical probe, bisamide (CCT251236), identified using an unbiased phenotypic screen to detect inhibitors of the HSF1 stress pathway. The chemical probe is orally bioavailable and displays efficacy in a human ovarian carcinoma xenograft model. By developing cell-based SAR and using chemical proteomics, we identified pirin as a high affinity molecular target, which was confirmed by SPR and crystallography.
Acetic Acid Accelerated Visible-Light Photoredox Catalyzed N-Demethylation of N,N-Dimethylaminophenyl Derivatives
Wu, Guolin,Li, Yazhen,Yu, Xuemei,Gao, Yu,Chen, Haijun
supporting information, p. 687 - 692 (2017/02/23)
N,N-Dimethylaminophenyl moiety is a common fragment in medicinal chemistry as several pharmaceuticals bearing this privileged motif are on the market and under clinical evaluation. Oxidative N-demethylation is generally regarded as the major metabolic pathway. However, pharmacokinetics, metabolites studies as well as the further structural modification are precluded by the impracticality of chemical synthesis. Here we report that acetic acid can significantly accelerate visible-light photoredox catalyzed N-demethylation of N,N-dimethylaminophenyl derivatives. This approach is easy for large scale reaction and even for potential industrial manufacture. (Figure presented.).
Observation of a single-pot aromatic reductive denitration
Giumanini, Angelo G.,Verardo, Giancarlo
, p. 469 - 473 (2007/10/03)
4,N,N-Trimethyl-3-nitrobenzenamine gave reductive denitration products (ca. 28%) upon treatment with n-butyl nitrite in the presence of catalytic amounts of ammonium chloride and water in an unprecedented one-reagent single-pot process. The three isomeric N,N-dimethylnitrobenzenamines showed the same behaviour to a much lesser extent; the ortho isomer was partially (7%) transformed into 1-methylbenzotriazole.
