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 published the artcile< Development of macrocyclic peptides containing epoxyketone with oral availability as proteasome inhibitors>, Electric Literature of 22717-55-1, the main research area is macrocyclic peptide synthesis methylpyrazole imidazole pyrazole oral availability; pharmacokinetic structure activity 20S proteasome inhibition; amino acid coupling iodination alkenylation substitution reaction Stille coupling; peptide ring closing metathesis mol docking human 20S proteasome.
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, imidazole, and pyrazole as their resp. 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, pyrazole-containing compound (I), 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 administration at a comparatively low dose, thereby representing a promising candidate for further development.
Journal of Medicinal Chemistry published new progress about Alkenylation. 22717-55-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, Electric Literature of 22717-55-1.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics