4167-77-5Relevant articles and documents
Helianthus-like cucurbit[4]uril and cucurbit[5]uril analogues
Wu, Yufan,Xu, Lixi,Shen, Yenan,Wang, Yang,Wang, Qiaochun
, p. 6991 - 6994 (2017)
A new glycoluril-like molecule, cyclopentanopropanediurea (CyP-TD), was prepared by malonic ester synthesis. Its condensation with paraformaldehyde resulted in two Helianthus-like cucurbituril analogues, CyP4TD[4] and CyP5TD[5], with cyclopentano groups evenly distributed on the equators. The structures of the two macrocycles were confirmed by 1H-NMR, HRMS-ES and single-crystal X-ray diffraction. CyP4TD[4] and CyP5TD[5] both exhibit excellent thermal stability, and CyP5TD[5] has better solubility in water and organic solvents, while CyP4TD[4] can hardly dissolve in them.
Asymmetric Cyclization/Nucleophilic Tandem Reaction of o-Alkynylacetophenone with (Diazomethyl)phosphonate for the Synthesis of Functional Isochromenes
Cai, Liu,Chen, Yuan,Cao, Hao,Wei, Qi,Yang, Yi,Ouyang, Qin,Peng, Yungui
supporting information, p. 7597 - 7601 (2019/10/02)
An efficient asymmetric reaction between (diazomethyl)phosphonate with o-alkynylacetophenone has been established by employing different stereocontrol strategy. A variety of isochromenes bearing tetrasubstituted stereocenters and (diazomethyl)phosphonate at the 1-position were prepared in yield up to 99% with enantioselectivity up to 94% enantiomeric excess (ee) for the first time. These functional isochromenes could be transformed to important structural motifs in biologically active compounds. Moreover, density functional theory calculations were conducted to gain insight into the process and the stereoselectivity.
Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity
Wei, Binqing,Gunzner-Toste, Janet,Yao, Hui,Wang, Tao,Wang, Jing,Xu, Zijin,Chen, Jinhua,Wai, John,Nonomiya, Jim,Tsai, Siao Ping,Chuh, Josefa,Kozak, Katherine R.,Liu, Yichin,Yu, Shang-Fan,Lau, Jeff,Li, Guangmin,Phillips, Gail D.,Leipold, Doug,Kamath, Amrita,Su, Dian,Xu, Keyang,Eigenbrot, Charles,Steinbacher, Stefan,Ohri, Rachana,Raab, Helga,Staben, Leanna R.,Zhao, Guiling,Flygare, John A.,Pillow, Thomas H.,Verma, Vishal,Masterson, Luke A.,Howard, Philip W.,Safina, Brian
supporting information, p. 989 - 1000 (2018/01/01)
Antibody-drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity. Here we report the structure-guided discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B while the valine-citrulline dipeptide linker is not. ADCs bearing the nonpeptidic linker are as efficacious and stable in vivo as those with the dipeptide linker. Our results strongly support the application of the peptidomimetic linker and present new opportunities for improving the selectivity of ADCs.
