《Rational design of pyridyl derivatives of vanillin for the treatment of sickle cell disease》 was written by Pagare, Piyusha P.; Ghatge, Mohini S.; Musayev, Faik N.; Deshpande, Tanvi M.; Chen, Qiukan; Braxton, Courtney; Kim, Solyi; Venitz, Jurgen; Zhang, Yan; Abdulmalik, Osheiza; Safo, Martin K.. Electric Literature of C6H7Br2NThis research focused onvanillin pyridyl derivative preparation sickle cell disease treatment Hb; Antisickling; Aromatic aldehyde; Crystal structure; Hemoglobin; Oxygen equilibrium; Polymerization; Relaxed state; Sickle cell disease. The article conveys some information:
Hypoxia-induced polymerization of sickle Hb (Hb S) is the principal phenomenon that underlays the pathophysiol. and morbidity associated with sickle cell disease (SCD). Opportunely, as an allosteric protein, Hb serves as a convenient and potentially critical druggable target. Consequently, mols. that prevent Hb S polymerization (Hb modifiers), and the associated erythrocyte sickling have been investigated-and retain significant interest-as a viable therapeutic strategy for SCD. This group of mols., including aromatic aldehydes, form high oxygen affinity Schiff-base adducts with Hb S, which are resistant to polymerization Here, the authors report the design and synthesis of novel potent antisickling agents (SAJ-009, SAJ-310 and SAJ-270) based on the pharmacophore of vanillin and INN-312, a previously reported pyridyl derivative of vanillin. These novel derivatives exhibited superior in vitro binding and pharmacokinetic properties compared to vanillin, which translated into significantly enhanced allosteric and antisickling properties. Crystal structure studies of liganded Hb in the R2 quaternary state in complex with SAJ-310 provided important insights into the allosteric and antisickling properties of this group of compounds While these derivatives generally show similar in vitro biol. potency, significant structure-dependent differences in their biochem. profiles would help predict the most promising candidates for successful in vivo pre-clin. translational studies and inform further structural modifications to improve on their pharmacol. properties. The experimental part of the paper was very detailed, including the reaction process of 2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8Electric Literature of C6H7Br2N)
2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8) belongs to pyridine. Pyridine-based materials are valued for their optical and physical properties as well as their medical potential. Additionally, pyridine-based natural products continue to be discovered and studied for their properties and to understand their biosynthesis.Electric Literature of C6H7Br2N