20397-57-3Relevant academic research and scientific papers
Face Selection in Reactions of 5,7-Diazaadamantan-2-one Derivatives: Mutual Influence of Remote Substituents
Gonikberg, Elena M.,Noble, William J. le
, p. 7751 - 7755 (1995)
When one of the nitrogen atoms in 5,7-diazaadamantan-2-one (4) is quaternized, for example, as in 3-O, carbonyl reduction occurs principally at the zu face to give alcohol (E)-6-O, in accord with Cieplak-type transition state hyperconjugation.The ratio in this reduction is somewhat less than in that of the previously reported monoaza N-oxide 2-O, which is attributed to the effect of hyperconjugation in the initial state of 3-O.If the parent diaza ketone 4 is reduced first to the corresponding diaza alcohol 5 and if this is then oxidized to 6-O, the Z-isomer is the principal product.The stereochemistry of this latter reaction is also considered to be a result of extended hyperconjugation.Virtually identical data are obtained with the methyl iodide salts.It is concluded that the effect of remote substituents is mutual and that this fact can be exploited to influence, even reverse, the stereochemical outcome of a synthesis by manipulation of the sequence of the individual steps.
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.
