《Design and synthesis of tripeptidyl furylketones as selective inhibitors against the β5 subunit of human 20S proteasome》 was written by Sun, Qi; Zhou, Tongliang; Xi, Dandan; Li, Xiaona; Lu, Zirui; Xu, Fengrong; Wang, Chao; Niu, Yan; Xu, Ping. Product Details of 87694-50-6 And the article was included in European Journal of Medicinal Chemistry on April 15 ,2020. The article conveys some information:
A series of tripeptidic proteasome inhibitors with furylketone as C-terminus were designed and synthesized. Biochem. evaluations against β1, β2 and β5 subunits revealed that they acted selectively on β5 subunit with IC50s against chymotrypsin-like (CT-L) activity in micromolar range. LC-MS/MS anal. of the ligand-20S proteasome mixture showed that the most potent compound (I) (IC50 = 0.18μM) made no covalent modification on 20S proteasome. However, it was identified acting in a slowly reversible manner in wash-out assay and the reversibility was much lower than that of MG132, suggesting the possibility of these tripeptidic furylketones forming reversible covalent bonds with 20S proteasome. Several compounds were selected for anti-proliferative assay towards multiple cancer cell lines, and compound I displayed comparable potency to pos. control (MG132) in all cell lines tested. Furthermore, the pharmacokinetic (PK) data in rats indicated I behaved similarly (Cmax, 2007μg/L; AUC0-t, 680μg/L·h; Vss, 0.66 L/kg) to the clin. used agent carfilzomib. All these data suggest I is a good lead compound to be developed to novel anti-tumor agent. The experimental process involved the reaction of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Product Details of 87694-50-6)
(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6) belongs to amides. Because of the greater electronegativity of oxygen, the carbonyl (C=O) is a stronger dipole than the N–C dipole. The presence of a C=O dipole and, to a lesser extent a N–C dipole, allows amides to act as H-bond acceptors.Product Details of 87694-50-6 In primary and secondary amides, the presence of N–H dipoles allows amides to function as H-bond donors as well.
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics