《Biologic-like In Vivo Efficacy with Small Molecule Inhibitors of TNFα Identified Using Scaffold Hopping and Structure-Based Drug Design Approaches》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Xiao, Hai-Yun; Li, Ning; Duan, James J.-W.; Jiang, Bin; Lu, Zhonghui; Ngu, Khehyong; Tino, Joseph; Kopcho, Lisa M.; Lu, Hao; Chen, Jing; Tebben, Andrew J.; Sheriff, Steven; Chang, ChiehYing Y.; Yanchunas, Joseph Jr.; Calambur, Deepa; Gao, Mian; Shuster, David J.; Susulic, Vojkan; Xie, Jenny H.; Guarino, Victor R.; Wu, Dauh-Rurng; Gregor, Kurt R.; Goldstine, Christine B.; Hynes, John Jr.; Macor, John E.; Salter-Cid, Luisa; Burke, James R.; Shaw, Patrick J.; Dhar, T. G. Murali. Recommanded Product: N-Methoxy-N-methylacetamide The article mentions the following:
Scaffold hopping and structure-based drug design were employed to identify substituted 4-aminoquinolines and 4-aminonaphthyridines as potent, small mol. inhibitors of tumor necrosis factor alpha (TNFα). Structure-activity relationships in both the quinoline and naphthyridine series leading to the identification of compound 42 with excellent potency and pharmacokinetic profile are discussed. X-ray co-crystal structure anal. and ultracentrifugation experiments clearly demonstrate that these inhibitors distort the TNFα trimer upon binding, leading to aberrant signaling when the trimer binds to TNF receptor 1 (TNFR1). Pharmacokinetic-pharmacodynamic activity of compound 42 in a TNF-induced IL-6 mouse model and in vivo activity in a collagen antibody-induced arthritis model, where it showed biol.-like in vivo efficacy, will be discussed. In the experiment, the researchers used many compounds, for example, N-Methoxy-N-methylacetamide(cas: 78191-00-1Recommanded Product: N-Methoxy-N-methylacetamide)
N-Methoxy-N-methylacetamide(cas: 78191-00-1) belongs to anime. Nitrous acid converts secondary amines (aliphatic or aromatic) to N-nitroso compounds (nitrosamines): R2NH + HNO2 → R2N―NO. Some nitrosamines are potent cancer-inducing substances, and their possible formation is a serious consideration when nitrites, which are salts of nitrous acid, are present in foods or pharmaceutical preparations. Tertiary amines give rise to nitrosamines more slowly; an alkyl group is eliminated as an aldehyde or ketone, along with nitrous oxide, N2O.Recommanded Product: N-Methoxy-N-methylacetamide
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics