13599-22-9Relevant articles and documents
Acid- and base-catalyzed modifications of 3-[aryl(hetaryl)hydrazinylidene]-3H-furan-2-ones
Maksimov,Mayorova,Yegorova, A. Yu.
, p. 1305 - 1307 (2015)
3-[Aryl(hetaryl)hydrazinylidene]furan-2(3H)-ones tend to undergo rearrangements involving different reaction centers and accompanied by opening of the furan ring. The reaction direction is determined by the conditions and nature of substituent in the hydr
Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors
Baev, Dmitriy,Belenkaya, Svetlana,Chirkova, Varvara,Dalinger, Alexander,Kalinin, Mikhail,Khvostov, Aleksei,Krut'Ko, Dmitry,Maksyutov, Rinat,Medved'Ko, Aleksei,Salakhutdinov, Nariman,Shanshin, Daniil,Sharlaeva, Elena,Shcherbakov, Dmitriy,Tolstikova, Tatyana,Vatsadze, Sergey,Volosnikova, Ekaterina,Yarovaya, Olga
supporting information, (2021/10/21)
For the first time, derivatives of 3,7-diazabicyclo[3.3.1]nonane (bispidine) were proposed as potential inhibitors of the SARS-CoV-2 main viral protease (3-chymotrypsin-like, 3CLpro). Based on the created pharmacophore model of the active site of the protease, a group of compounds were modeled and tested for activity against 3CLpro. The 3CLpro activity was measured using the fluorogenic substrate Dabcyl-VNSTLQSGLRK(FAM)MA; the efficiency of the proposed approach was confirmed by comparison with literature data for ebselen and disulfiram. The results of the experiments performed with bispidine compounds showed that 14 compounds exhibited activity in the concentration range 1-10 μM, and 3 samples exhibited submicromolar activity. The structure-activity relationship studies showed that the molecules containing a carbonyl group in the ninth position of the bicycle exhibited the maximum activity. Based on the experimental and theoretical results obtained, further directions for the development of this topic were proposed.
Bcl-2/MDM2 Dual Inhibitors Based on Universal Pyramid-Like α-Helical Mimetics
Wang, Ziqian,Song, Ting,Feng, Yingang,Guo, Zongwei,Fan, Yudan,Xu, Wenjie,Liu, Lu,Wang, Anhui,Zhang, Zhichao
, p. 3152 - 3162 (2016/05/19)
No α-helical mimetic that exhibits Bcl-2/MDM2 dual inhibition has been rationally designed due to the different helicities of the α-helixes at their binding interfaces. Herein, we extracted a one-turn α-helix-mimicking ortho-triarene unit from o-phenylene foldamers. Linking benzamide substrates with a rotatable C-N bond, we constructed a novel semirigid pyramid-like scaffold that could support its two-turn α-helix mimicry without aromatic stacking interactions and could adopt the different dihedral angles of the key residues of p53 and BH3-only peptides. On the basis of this universal scaffold, a series of substituent groups were installed to capture the key residues of both p53TAD and BimBH3 and balance the differences of the bulks between them. Identified by FP, ITC, and NMR spectroscopy, a compound 6e (zq-1) that directly binds to Mcl-1, Bcl-2, and MDM2 with balanced submicromolar affinities was obtained. Cell-based experiments demonstrated its antitumor ability through Bcl-2/MDM2 dual inhibition simultaneously.
