Visseq, Alexia; Descheemaeker, Amelie; Herault, Karine; Giraud, Francis; Abrunhosa-Thomas, Isabelle; Artola, Alain; Anizon, Fabrice; Dallel, Radhouane; Moreau, Pascale published an article in 2021. The article was titled 《Improved potency of pyridin-2(1H)one derivatives for the treatment of mechanical allodynia》, and you may find the article in European Journal of Medicinal Chemistry.Synthetic Route of C5H4IN The information in the text is summarized as follows:
Mech. allodynia, a painful sensation caused by innocuous touch, is a major chronic pain symptom, which often remains without an effective treatment. There is thus a need for new anti-allodynic treatments based on new drug classes. We recently synthesized new 3,5-disubstituted pyridin-2(1H)-one derivatives By substituting the pyridinone at the 3-position by various aryl/heteroaryl moieties and at the 5-position by a phenylamino group, we discovered that some derivatives exhibited a strong anti-allodynic potency in rats. Here, we report that varying the substitution of the pyridinone 5-position, the 3-position being substituted by an indol-4-yl moiety, further improves such anti-allodynic potency. Compared with 2, one of the two most active compounds of the first series, eleven out of nineteen newly synthesized compounds showed higher anti-allodynic potency, with two of them completely preventing mech. allodynia. In the first series, hit compounds 1 and 2 (I and II) appeared to be inhibitors of p38α MAPK, a protein kinase known to underlie pain hypersensitivity in animal models. Depending on the substitution at the 5-position, some newly synthesized compounds were also stronger p38α MAPK inhibitors. Surprisingly, though, anti-allodynic effects and p38α MAPK inhibitory potencies were not correlated, suggesting that other biol. target(s) is/are involved in the analgesic activity in this series. Altogether, these results confirm that 3,5-disubstituted pyridine-2(1H)-one derivatives are of high interest for the development of new treatment of mech. allodynia. In the experiment, the researchers used many compounds, for example, 4-Iodopyridine(cas: 15854-87-2Synthetic Route of C5H4IN)
4-Iodopyridine(cas: 15854-87-2) is used as a reagent in the synthesis of indazolylamides as glucocorticoid receptor agonists. 4-Iodopyridine is a halogenated heterocycle that is a building block for proteomics research.Synthetic Route of C5H4IN
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com