- Deadly KCN and pricey metal free track for accessing β-ketonitriles employing mild reaction conditions
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A one pot synthesis of β-ketonitriles from readily accessible 3-chloropropenals using economically benign iodine, aqueous ammonia and sodium hydroxide solution, employing mild reaction conditions have been described. This report presents a convenient, inexpensive, highly toxic-matter-free and eco-friendly approach for β-ketonitriles.
- Sharma, Pawan K.,Kumar, Rajiv,Ram, Sita,Chandak, Navneet
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supporting information
p. 1847 - 1856
(2021/04/26)
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- Identification and Optimization of Novel Small c-Abl Kinase Activators Using Fragment and HTS Methodologies
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Abelson kinase (c-Abl) is a ubiquitously expressed, nonreceptor tyrosine kinase which plays a key role in cell differentiation and survival. It was hypothesized that transient activation of c-Abl kinase via displacement of the N-terminal autoinhibitory "myristoyl latch", may lead to an increased hematopoietic stem cell differentiation. This would increase the numbers of circulating neutrophils and so be an effective treatment for chemotherapy-induced neutropenia. This paper describes the discovery and optimization of a thiazole series of novel small molecule c-Abl activators, initially identified by a high throughput screening. Subsequently, a scaffold-hop, which exploited the improved physicochemical properties of a dihydropyrazole analogue, identified through fragment screening, delivered potent, soluble, cell-active c-Abl activators, which demonstrated the intracellular activation of c-Abl in vivo.
- Simpson, Graham L.,Bertrand, Sophie M.,Borthwick, Jennifer A.,Campobasso, Nino,Chabanet, Julien,Chen, Susan,Coggins, Julia,Cottom, Josh,Christensen, Siegfried B.,Dawson, Helen C.,Evans, Helen L.,Hobbs, Andrew N.,Hong, Xuan,Mangatt, Biju,Munoz-Muriedas, Jordi,Oliff, Allen,Qin, Donghui,Scott-Stevens, Paul,Ward, Paris,Washio, Yoshiaki,Yang, Jingsong,Young, Robert J.
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supporting information
p. 2154 - 2171
(2019/02/26)
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- Novel small molecule inhibitors targeting the "switch region" of bacterial RNAP: Structure-based optimization of a virtual screening hit
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Rising resistance against current antibiotics necessitates the development of antibacterial agents with alternative targets. The "switch region" of RNA polymerase (RNAP), addressed by the myxopyronins, could be such a novel target site. Based on a hit can
- Sahner, J. Henning,Groh, Matthias,Negri, Matthias,Haupenthal, J?rg,Hartmann, Rolf W.
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supporting information
p. 223 - 231
(2013/10/01)
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- The discovery and optimization of pyrimidinone-containing MCH R1 antagonists
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Optimization of a series of constrained melanin-concentrating hormone receptor 1 (MCH R1) antagonists has provided compounds with potent and selective MCH R1 activity. Details of the optimization process are provided and the use of one of the compounds in
- Hertzog, Donald L.,Al-Barazanji, Kamal A.,Bigham, Eric C.,Bishop, Michael J.,Britt, Christy S.,Carlton, David L.,Cooper, Joel P.,Daniels, Alex J.,Garrido, Dulce M.,Goetz, Aaron S.,Grizzle, Mary K.,Guo, Yu C.,Handlon, Anthony L.,Ignar, Diane M.,Morgan, Ronda O.,Peat, Andrew J.,Tavares, Francis X.,Zhou, Huiqiang
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p. 4723 - 4727
(2007/10/03)
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