Pyrazoles are synthesized by the reaction of α,β-unsaturated aldehydes with hydrazine and subsequent dehydrogenation. 2075-46-9, formula is C3H3N3O2, Name is 4-Nitro-1H-pyrazole. Substituted pyrazoles are prepared by condensation of 1,3-diketones with hydrazine (Knorr-type reactions). For example, acetylacetone and hydrazine gives 3,5-dimethylpyrazole. Category: pyrazoles-derivatives.
Shah, Rishi R.;Redmond, Joanna M.;Mihut, Andrei;Menon, Malini;Evans, John P.;Murphy, John A.;Bartholomew, Michelle A.;Coe, Diane M. research published 《 Hi-JAK-ing the ubiquitin system: The design and physicochemical optimisation of JAK PROTACs》, the research content is summarized as follows. PROTACs have recently emerged as a novel paradigm in drug discovery. They can hijack existing biol. machinery to selectively degrade proteins of interest, in a catalytic fashion. Here we describe the design, optimization and biol. activity of a set of novel PROTACs targeting the Janus kinase family (JAK1, JAK2, JAK3 and TYK2) of proximal membrane-bound proteins. The JAK family proteins display membrane localisation by virtue of their association with cytoplasmic tails of cytokine receptors, and there are no reports of a successful PROTAC strategy being deployed against this class of proteins. JAK PROTACs from two distinct JAK chemotypes were designed, optimizing the physicochem. properties for each template to enhance cell permeation. These PROTACs are capable of inducing JAK1 and JAK2 degradation, demonstrating an extension of the PROTAC methodol. to an unprecedented class of protein targets. A number of known ligase binders were explored, and it was found that PROTACs bearing an inhibitor of apoptosis protein (IAP) ligand induced significantly more JAK degradation over Von Hippel-Lindau (VHL) and Cereblon (CRBN) PROTACs. In addition, the mechanism of action of the JAK PROTACs was elucidated, and it was confirmed that JAK degradation was both IAP- and proteasome-dependent.
Category: pyrazoles-derivatives, 4-Nitro-1H-pyrazole, also known as 4-Nitropyrazole, is a useful research compound. Its molecular formula is C3H3N3O2 and its molecular weight is 113.08 g/mol. The purity is usually 95%.
4-Nitropyrazole, is a building block for the synthesis of various pharmaceutical compounds, including inhibitors, and therapeutic agents. It can be used for the synthesis of highly selective, brain-penetrant aminopyrazole LRRK2 Inhibitor, as a potentially viable treatment for Parkinson’s disease., 2075-46-9.
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics