Lee, Min Jae; Bhattarai, Deepak; Jang, Hyeryung; Baek, Ahreum; Yeo, In Jun; Lee, Seongsoo; Miller, Zachary; Lee, Sukyeong; Hong, Jin Tae; Kim, Dong-Eun; Lee, Wooin; Kim, Kyung Bo published their research in Journal of Medicinal Chemistry on August 12 ,2021. The article was titled 《Macrocyclic Immunoproteasome Inhibitors as a Potential Therapy for Alzheimer’s Disease》.Category: amides-buliding-blocks The article contains the following contents:
Previously, we reported that immunoproteasome (iP)-targeting linear peptide epoxyketones improve cognitive function in mouse models of Alzheimer’s disease (AD) in a manner independent of amyloid β. However, these compounds’ clin. prospect for AD is limited due to potential issues, such as poor brain penetration and metabolic instability. Here, we report the development of iP-selective macrocyclic peptide epoxyketones prepared by a ring-closing metathesis reaction between two terminal alkenes attached at the P2 and P3/P4 positions of linear counterparts. We show that a lead macrocyclic compound DB-60 (20) effectively inhibits the catalytic activity of iP in ABCB1-overexpressing cells (IC50: 105 nM) and has metabolic stability superior to its linear counterpart. DB-60 (20) also lowered the serum levels of IL-1α and ameliorated cognitive deficits in Tg2576 mice. The results collectively suggest that macrocyclic peptide epoxyketones have improved CNS drug properties than their linear counterparts and offer promising potential as an AD drug candidate. In the experimental materials used by the author, we found (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Category: amides-buliding-blocks)
(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6) belongs to amides.Category: amides-buliding-blocksAmides are pervasive in nature and technology. Proteins and important plastics like Nylons, Aramid, Twaron, and Kevlar are polymers whose units are connected by amide groups (polyamides); these linkages are easily formed, confer structural rigidity, and resist hydrolysis.
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics