99532-45-3Relevant articles and documents
Design, synthesis, and bioevaluation of pyrazolo[1,5-a]pyrimidine derivatives as tubulin polymerization inhibitors targeting the colchicine binding site with potent anticancer activities
Chen, Jianjun,Deng, Xin,Li, Gang,Li, Ling,Liu, Jin,Liu, Shuwen,Luo, Meihua,Ren, Yichang,Wang, Wei,Wang, Yuxi
, (2020/07/08)
A series of Pyrazolo[1,5-a]Pyrimidine analogs were designed and synthesized as novel tubulin inhibitors. Among them, compounds 1a and 1b showed the highest antiproliferative activity against a panel of cancer cell lines with average IC50 values
N - benzenesulfonyl -3 - acetyl indole naked eye compound, preparation method and application
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Paragraph 0046; 0047; 0048, (2019/03/10)
The invention discloses an N-benzenesulfonyl-3-acetyl indole acyl hydrazone compound, a preparation method and application and belongs to the technical field of organic synthesis. An N-benzenesulfonyl-3-acetyl indole acyl hydrazone derivative uses benzpyr
2-Aminoimidazole-based antagonists of the 5-HT6 receptor – A new concept in aminergic GPCR ligand design
Hogendorf, Adam S.,Hogendorf, Agata,Kurczab, Rafa?,Kalinowska-T?u?cik, Justyna,Popik, Piotr,Nikiforuk, Agnieszka,Krawczyk, Martyna,Sata?a, Grzegorz,Lenda, Tomasz,Knutelska, Joanna,Bugno, Ryszard,Staroń, Jakub,Pietru?, Wojciech,Mat?oka, Miko?aj,Dubiel, Krzysztof,Moszczyński-P?tkowski, Rafa?,Pieczykolan, Jerzy,Wieczorek, Maciej,Pilarski, Bogus?aw,Zajdel, Pawe?,Bojarski, Andrzej J.
supporting information, p. 1 - 15 (2019/06/24)
A new strategy in the design of aminergic GPCR ligands is proposed – the use of aromatic, heterocyclic basic moieties in place of the evergreen piperazine or alicyclic and aliphatic amines. This hypothesis has been tested using a benchmark series of 5-HT6R antagonists obtained by coupling variously substituted 2-aminoimidazole moieties to the well established 1-benzenesulfonyl-1H-indoles, which served as the ligands cores. The crystallographic studies revealed that upon protonation, the 2-aminoimidazole fragment triggers a resonance driven conformational change leading to a form of higher affinity. This molecular switch may be responsible for the observed differences in 5-HT6R activity of the studied chemotypes with different amine-like fragments. Considering the multiple functionalization sites of the embedded guanidine fragment, diverse libraries were constructed, and the relationships between the structure and activity, metabolic stability, and solubility were established. Compounds from the N-(1H-imidazol-2-yl)acylamide chemotype (10a–z) exhibited high affinity for 5-HT6R and very high selectivity over 5-HT1A, 5-HT2A, 5-HT7 and D2 receptors (negligible binding), which was attributed to their very weak basicity. The lead compound in the series 4-methyl-5-[1-(naphthalene-1-sulfonyl)-1H-indol-3-yl]-1H-imidazol-2-amine (9i) was shown to reverse the cognitive impairment caused by the administration of scopolamine in rats indicating procognitive potential.
