145797-86-0Relevant academic research and scientific papers
An allosteric ligand-binding site in the extracellular cap of K2P channels /631/45/269/1151 /631/45/612/1237 /631/92/555 article
Luo, Qichao,Chen, Liping,Cheng, Xi,Ma, Yuqin,Li, Xiaona,Zhang, Bing,Li, Li,Zhang, Shilei,Guo, Fei,Li, Yang,Yang, Huaiyu
, (2017)
Two-pore domain potassium (K2P) channels generate leak currents that are responsible for the maintenance of the resting membrane potential, and they are thus potential drug targets for treating diseases. Here, we identify N-(4-cholorphenyl)-N-(2-(3,4-dihydrosioquinolin-2(1H)-yl)-2-oxoethyl)methanesulfonamide (TKDC) as an inhibitor of the TREK subfamily, including TREK-1, TREK-2 and TRAAK channels. Using TKDC as a chemical probe, a study combining computations, mutagenesis and electrophysiology reveals a K2P allosteric ligand-binding site located in the extracellular cap of the channels. Molecular dynamics simulations suggest that ligand-induced allosteric conformational transitions lead to blockage of the ion conductive pathway. Using virtual screening approach, we identify other inhibitors targeting the extracellular allosteric ligand-binding site of these channels. Overall, our results suggest that the allosteric site at the extracellular cap of the K2P channels might be a promising drug target for these membrane proteins.
Amide compound for prevention and treatment of mental disorders
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Paragraph 0129-0132; 0203-0206, (2019/01/08)
The present invention relates to an amide compound for prevention and treatment of mental disorders, which is shown as a formula (I), a pharmaceutically acceptable salt thereof, a prodrug thereof, a solvate thereof, a deuterated substance or a stereoisomer thereof. Wherein R1, R2, R3, R4, R5, Ar1, Ar2, p and q are as defined in the specification. The invention also relates to a preparation methodof the amide compound, a pharmaceutical composition and a pharmaceutical preparation containing the amide compound, and an application of the compound in preparation of a drug for prevention or treatment of mental disorders such as depression, depression and anxiety, and schizophrenia.
Tetrahydroisoquinoline-2-methylbenzimidazole salt compound and preparation method and application thereof
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Paragraph 0071; 0073, (2018/11/22)
The invention provides a tetrahydroisoquinoline-2-methylbenzimidazole salt compound, and belongs to the field of organic compounds. Two pharmacophores, namely, tetrahydroisoquinoline and 2-methylbenzimidazole are utilized to synthesize a series of tetrahydroisoquinoline-2-methylbenzimidazole salt compounds for bioactivity study, and new molecules with high anti-tumor activity are discovered in thestudy, so that material foundation and new guidance significance are provided to further study the medicinal chemistry. The test data of the embodiment shows that the tetrahydroisoquinoline-2-methylbenzimidazole salt compound with structure as shown in formula I shows obvious in-vitro tumor growing inhibiting activity to five human cancer cells (leukemia, liver cancer, lung cancer, breast cancerand colon cancer cell); and the in-vitro tumor growing inhibiting activity to A-549, MCF-7 and SW480, of some compounds is superior to that of an anticancer drug-cis-platinum (DDP).
Synthesis of novel 1,2,5-oxadiazoles and evaluation of action against Acinetobacter baumannii
Christoff, Rebecca M.,Murray, Gerald L.,Kostoulias, Xenia P.,Peleg, Anton Y.,Abbott, Belinda M.
supporting information, p. 6267 - 6272 (2017/10/13)
With multidrug resistant bacteria on the rise, novel antibiotics are becoming highly sought after. In 2008, eleven compounds were identified by high throughput screening as inhibitors of BasE, a key enzyme of the non-ribosomal peptide synthetase pathway found in Acinetobacter baumannii. Herein, we describe the preparation of four structurally similar heterocyclic lead compounds from that study, including one 1,2,5-oxadiazole. A further library of 30 analogues containing the oxadiazole moiety was then generated. All compounds were screened against Acinetobacter baumannii and their minimum inhibitory concentration data is reported, with (E)-3-(2-hydroxyphenyl)-N-(4-methyl-1,2,5-oxadiazol-3-yl)acrylamide 32 found to have an MIC of 0.5 mM. This work provides the foundation for further investigation of 1,2,5-oxadizoles as novel inhibitors of A. baumannii.
Synthesis and NK1/NK2 receptor activity of substituted-4(Z)-(methoxyimino)pentyl-1-piperazines
Ting, Pauline C.,Lee, Joe F.,Anthes, John C.,Shih, Neng-Yang,Piwinski, John J.
, p. 2333 - 2335 (2007/10/03)
A series of 5-[(3,5-bis(trifluoromethyl)phenyl)methoxy]-3-(3,4-dichlorophenyl)-4(Z)-(meth oxyimino)pentyl-1-piperazines was prepared and their affinity for the NK1 and NK2 receptors investigated. Compounds 7f, 10o, 10r, and 10s were
