851322-37-7Relevant academic research and scientific papers
Optimization and SAR research at the piperazine and phenyl rings of JNJ4796 as new anti-influenza A virus agents, part 1
Wang, Aoyu,Li, Yuhuan,Lv, Kai,Gao, Rongmei,Wang, Apeng,Yan, Haiyan,Qin, Xiaoyu,Xu, Shijie,Ma, Chao,Jiang, Jiandong,Wei, Zengquan,Zhang, Kai,Liu, Mingliang
supporting information, (2021/06/15)
JNJ4796, a small molecule fuse inhibitor targeting the conserved stem region of hemagglutinin, effectively neutralized a broad spectrum of group 1 influenza A virus (IAV), and protected mice against lethal and sublethal influenza challenge after oral admi
Structure–Activity Studies of 3,9-Diazaspiro[5.5]undecane-Based γ-Aminobutyric Acid Type A Receptor Antagonists with Immunomodulatory Effect
Bavo, Francesco,de-Jong, Heleen,Petersen, Jonas,Falk-Petersen, Christina Birkedahl,L?ffler, Rebekka,Sparrow, Emma,Rostrup, Frederik,Eliasen, Jannik Nicklas,Wilhelmsen, Kristine S.,Barslund, Kasper,Bundgaard, Christoffer,Nielsen, Birgitte,Kristiansen, Uffe,Wellendorph, Petrine,Bogdanov, Yury,Fr?lund, Bente
, p. 17795 - 17812 (2022/01/03)
The 3,9-diazaspiro[5.5]undecane-based compounds 2027 and 018 have previously been reported to be potent competitive γ-aminobutyric acid type A receptor (GABAAR) antagonists showing low cellular membrane permeability. Given the emerging peripheral application of GABAAR ligands, we hypothesize 2027 analogs as promising lead structures for peripheral GABAAR inhibition. We herein report a study on the structural determinants of 2027 in order to suggest a potential binding mode as a basis for rational design. The study identified the importance of the spirocyclic benzamide, compensating for the conventional acidic moiety, for GABAAR ligands. The structurally simplified m-methylphenyl analog 1e displayed binding affinity in the high-nanomolar range (Ki = 180 nM) and was superior to 2027 and 018 regarding selectivity for the extrasynaptic α4βδ subtype versus the α1- and α2- containing subtypes. Importantly, 1e was shown to efficiently rescue inhibition of T cell proliferation, providing a platform to explore the immunomodulatory potential for this class of compounds.
NOVEL DIAZASPIROALKANES AND THEIR USE FOR TREATMENT OF CCR8 MEDIATED DISEASES
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Page/Page column 45, (2008/06/13)
The invention provides compounds of general formula. wherein A, B, W, X, Y, Z, D, E, R1 and n are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
