38212-33-8Relevant articles and documents
Microwave assisted rapid synthesis of 1-arylpiperazines
Jaisinghani, Harsha G.,Chowdhury, Boudhayan Roy,Khadilkar
, p. 1175 - 1178 (1998)
1-Arylpiperazines, an important class of compounds were synthesized rapidly under Microwave irradiation from diethanolamine and substituted anilines using Pollard's method of synthesis. The yields obtained were comparable with the conventional yields and drastic reduction in reaction time was observed.
Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents
Blackmore, Timothy R.,Jacobson, Jonathan,Jarman, Kate E.,Lewin, Sharon R.,Nguyen, William,Purcell, Damian F.,Sabroux, Helene Jousset,Sleebs, Brad E.
, (2020/04/08)
A persistent latent reservoir of virus in CD4+ T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC50s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents.
Understanding Flavin-Dependent Halogenase Reactivity via Substrate Activity Profiling
Andorfer, Mary C.,Grob, Jonathan E.,Hajdin, Christine E.,Chael, Julia R.,Siuti, Piro,Lilly, Jeremiah,Tan, Kian L.,Lewis, Jared C.
, p. 1897 - 1904 (2017/08/17)
The activity of four native FDHs and four engineered FDH variants on 93 low-molecular-weight arenes was used to generate FDH substrate activity profiles. These profiles provided insights into how substrate class, functional group substitution, electronic activation, and binding affect FDH activity and selectivity. The enzymes studied could halogenate a far greater range of substrates than have been previously recognized, but significant differences in their substrate specificity and selectivity were observed. Trends between the electronic activation of each site on a substrate and halogenation conversion at that site were established, and these data, combined with docking simulations, suggest that substrate binding can override electronic activation even on compounds differing appreciably from native substrates. These findings provide a useful framework for understanding and exploiting FDH reactivity for organic synthesis.
