1267478-86-3Relevant academic research and scientific papers
Exploration of novel macrocyclic dipeptide N-benzyl amides as proteasome inhibitors
Yu, Jianjun,Liu, Jieyu,Li, Daqiang,Xu, Lei,Hong, Duidui,Chang, Shan,Li, Jia,Liu, Tao,Zhou, Yubo
, p. 423 - 439 (2019)
As proteasome inhibitors, a series of novel macrocyclic dipeptide N-benzyl amides were designed, synthesized and evaluated. Most of them exhibited potent proteasome inhibition and excellent anti-proliferative activity against RPMI 8226, MM1S, and MV-4-11 cell lines. As the most distinguished one among this series, compound 23h displayed potent and selective proteasome inhibitory potency (IC50: β5c = 29 nM, β5i = 35 nM, β1c, β2c β1i β2i > 10 μM), excellent anti-proliferative activity against RPMI 8226, MM1S, and MV-4-11 cell lines with IC50 values of 18 nM, 15 nM, and 21 nM, respectively, as well as favorable metabolic stability in human liver microsomes (HLMs), highlighting that it is a promising lead compound for further development of proteasome inhibitors.
Photochemical Reaction Cascade from O -Pent-4-enyl-Substituted Salicylates to Complex Multifunctional Scaffolds
Zech, Andreas,Bach, Thorsten
, p. 3069 - 3077 (2018)
The arene ring of the title compounds is cleaved by a reaction cascade which is initiated by an intramolecular ortho photocycloaddition reaction. Tricyclic products were obtained in a highly regio- and diastereoselective fashion via a cyclooctatriene inte
Development of Macrocyclic Peptides Containing Epoxyketone with Oral Availability as Proteasome Inhibitors
Li, Daqiang,Zhang, Xiaotuan,Ma, Xiaodong,Xu, Lei,Yu, Jianjun,Gao, Lixin,Hu, Xiaobei,Zhang, Jiankang,Dong, Xiaowu,Li, Jia,Liu, Tao,Zhou, Yubo,Hu, Yongzhou
, p. 9177 - 9204 (2018/10/24)
Macrocyclization has been frequently utilized for optimizing peptide or peptidomimetic-based compounds. In an attempt to obtain potent, metabolically stable, and orally available proteasome inhibitors, 30 oprozomib-derived macrocyclic peptides with structural diversity in their N-terminus and linker were successively designed and synthesized for structure-activity relationship (SAR) studies. As a consequence, the macrocyclic peptides with N-methyl-pyrazole (24p, 24x), imidazole (24t), and pyrazole (24v) as their respective N-termini exhibited favorable in vitro activity and metabolic stability, which translated into their potent in vivo proteasome inhibitory activity after oral administration. In particular, compound 24v, as the most distinguished one among this series, displayed excellent chymotrypsin-like (ChT-L, β5) inhibitory potency (IC50 = 16 nM), low nanomolar antiproliferative activity against all three of the tested cell lines, and superior metabolic stability in mouse liver microsome (MLM), as well as favorable inhibition against ChT-L compared to that of oprozomib in BABL/c mice following po administration at a comparatively low dose, thereby representing a promising candidate for further development.
Investigating the arenyl-diene double [3 + 2] photocycloaddition reaction
Penkett, Clive S.,Woolford, Jason A.,Read, Timothy W.,Kahan, Rachel J.
supporting information; experimental part, p. 1295 - 1304 (2011/04/26)
The double [3 + 2] photocycloaddition reaction involving arenyl-dienes has been used to assemble seven separate [5.5.5.5] fenestrane structures that include ether and aza variants. The primary photolysis step was a meta photocycloaddition reaction, while
