Synthetic Route of C6H3ClFNO2On October 31, 2021 ,《Ligand-based substituent-anchoring design of selective receptor-interacting protein kinase 1 necroptosis inhibitors for ulcerative colitis therapy》 appeared in Acta Pharmaceutica Sinica B. The author of the article were Zhu, Jing; Xin, Meng; Xu, Congcong; He, Yuan; Zhang, Wannian; Wang, Zhibin; Zhuang, Chunlin. The article conveys some information:
Receptor-interacting protein (RIP) kinase 1 is involved in immune-mediated inflammatory diseases including ulcerative colitis (UC) by regulating necroptosis and inflammation. Our group previously identified TAK-632 (5) as an effective necroptosis inhibitor by dual-targeting RIP1 and RIP3. In this study, using ligand-based substituent-anchoring design strategy, we focused on the benzothiazole ring to obtain a series of TAK-632 analogs showing significantly improving on the anti-necroptosis activity and RIP1 selectivity over RIP3. Among them, a conformational constrained fluorine-substituted derivative (25) exhibited 333-fold selectivity for RIP1 (Kd = 15 nmol/L) than RIP3 (Kd > 5000 nmol/L). This compound showed highly potent activity against cell necroptosis (EC50 = 8 nmol/L) and systemic inflammatory response syndrome (SIRS) induced by TNF-α in vivo. Especially, it was able to exhibit remarkable anti-inflammatory treatment efficacy in a DSS-induced mouse model of UC. Taken together, the highly potent, selective, orally active anti-necroptosis inhibitor represents promising candidate for clin. treatment of UC. The experimental part of the paper was very detailed, including the reaction process of 3-Chloro-4-fluoronitrobenzene(cas: 350-30-1Synthetic Route of C6H3ClFNO2)
3-Chloro-4-fluoronitrobenzene(cas: 350-30-1) belongs to organochlorine compounds. Many organochlorine compounds have been isolated from natural sources ranging from bacteria to humans. Synthetic Route of C6H3ClFNO2 Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics