Bagal, Sharan K.; Omoto, Kiyoyuki; Blakemore, David C.; Bungay, Peter J.; Bilsland, James G.; Clarke, Philip J.; Corbett, Matthew S.; Cronin, Ciaran N.; Cui, J. Jean; Dias, Rebecca; Flanagan, Neil J.; Greasley, Samantha E.; Grimley, Rachel; Johnson, Eric; Fengas, David; Kitching, Linda; Kraus, Michelle L.; McAlpine, Indrawan; Nagata, Asako; Waldron, Gareth J.; Warmus, Joseph S. published an article on January 10 ,2019. The article was titled 《Discovery of Allosteric, Potent, Subtype Selective, and Peripherally Restricted TrkA Kinase Inhibitors》, and you may find the article in Journal of Medicinal Chemistry.SDS of cas: 866837-96-9 The information in the text is summarized as follows:
Tropomyosin receptor kinases (TrkA, TrkB, TrkC) are activated by hormones of the neurotrophin family: nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4). Moreover, the NGF antibody tanezumab has provided clin. proof of concept for inhibition of the TrkA kinase pathway in pain leading to significant interest in the development of small mol. inhibitors of TrkA. However, achieving TrkA subtype selectivity over TrkB and TrkC via a Type I and Type II inhibitor binding mode has proven challenging and Type III or Type IV allosteric inhibitors may present a more promising selectivity design approach. Furthermore, TrkA inhibitors with minimal brain availability are required to deliver an appropriate safety profile. Herein, we describe the discovery of a highly potent, subtype selective, peripherally restricted, efficacious, and well-tolerated series of allosteric TrkA inhibitors that culminated in the delivery of candidate quality compound 23. In the experiment, the researchers used many compounds, for example, Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9SDS of cas: 866837-96-9)
Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate(cas: 866837-96-9) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.SDS of cas: 866837-96-9
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics