In 2016,Rabal, Obdulia; Sanchez-Arias, Juan A.; Cuadrado-Tejedor, Mar; de Miguel, Irene; Perez-Gonzalez, Marta; Garcia-Barroso, Carolina; Ugarte, Ana; Estella-Hermoso de Mendoza, Ander; Saez, Elena; Espelosin, Maria; Ursua, Susana; Haizhong, Tan; Wei, Wu; Musheng, Xu; Garcia-Osta, Ana; Oyarzabal, Julen published 《Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer’s Disease》.Journal of Medicinal Chemistry published the findings.Electric Literature of C7H6BrNO2 The information in the text is summarized as follows:
Simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylases (HDAC) has recently been validated as a potentially novel therapeutic approach for Alzheimer’s Disease (AD). To further extend this concept, the authors designed and synthesized the first chem. series of dual acting PDE5 and HDAC inhibitors, and the authors validated this systems therapeutics approach. Following the implementation of structure- and knowledge-based approaches, initial hits were designed and were shown to validate the hypothesis of dual in vitro inhibition. Then, an optimization strategy was pursued to obtain a proper tool compound for in vivo testing in AD models. Initial hits were translated into mols. with adequate cellular functional responses (histone acetylation and cAMP/cGMP response element-binding (CREB) phosphorylation in the nanomolar range), an acceptable therapeutic window (>1 log unit) and the ability to cross the blood-brain barrier, leading to the identification of 7 as a candidate for in vivo proof-of-concept testing. In the experimental materials used by the author, we found Methyl 5-bromopicolinate(cas: 29682-15-3Electric Literature of C7H6BrNO2)
Methyl 5-bromopicolinate(cas: 29682-15-3) belongs to pyridine. Pyridines form stable salts with strong acids. Pyridine itself is often used to neutralize acid formed in a reaction and as a basic solvent. Electric Literature of C7H6BrNO2