HCV NS5A Replication Complex Inhibitors. Part 4.1 Optimization for Genotype 1a Replicon Inhibitory Activity
摘要:
A series of symmetrical E-stilbene prolinamides that originated from the library-synthesized lead 3 was studied with respect to HCV genotype 1a (G-1a) and genotype 1b (G-1b) replicon inhibition and selectivity against BVDV and cytotoxicity. SAR emerging from an examination of the prolinamide cap region revealed 11 to be a selective HCV NS5A inhibitor exhibiting submicromolar potency against both G-1a and G-1b replicons. Additional structural refinements resulted in the identification of 30 as a potent, dual G-1a/1b HCV NS5A inhibitor.
HCV NS5A replication complex inhibitors. Part 3: discovery of potent analogs with distinct core topologies
摘要:
In a recent disclosure,(1) we described the discovery of dimeric, prolinamide-based NS5A replication complex inhibitors exhibiting excellent potency towards an HCV genotype 1b replicon. That disclosure dealt with the SAR exploration of the peripheral region of our lead chemotype, and herein is described the SAR uncovered from a complementary effort that focused on the central core region. From this effort, the contribution of the core region to the overall topology of the pharmacophore, primarily vector orientation and planarity, was determined, with a set of analogs exhibiting < 10 nM EC50 in a genotype 1b replicon assay. (c) 2012 Elsevier Ltd. All rights reserved.
[EN] HEPATITIS C VIRUS INHIBITORS<br/>[FR] INHIBITEURS DU VIRUS DE L'HÉPATITE C
申请人:BRISTOL MYERS SQUIBB CO
公开号:WO2011082077A1
公开(公告)日:2011-07-07
The present disclosure is generally directed to antiviral compounds, and more specifically directed to compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such compounds, and methods for inhibiting the function of the NS5A protein.
Transition-Metal-Free<i>N</i>-Arylation of Pyrazoles with Diaryliodonium Salts
作者:Zsombor Gonda、Zoltán Novák
DOI:10.1002/chem.201502995
日期:2015.11.16
developed for the N‐arylation of pyrazoles using diaryliodoniumsalts. The transformation does not require any transition‐metal catalyst and provides the desired N‐arylpyrazoles rapidly under mild reaction condition in the presence of aqueous ammonia solution as a mild base without the use of inert atmosphere. The chemoselectivity of unsymmetric diaryliodoniumsalts was also explored with large number
Stereoselective Direct
<i>N</i>
‐Trifluoropropenylation of Heterocycles with a Hypervalent Iodonium Reagent
作者:János T. Csenki、Ádám Mészáros、Zsombor Gonda、Zoltán Novák
DOI:10.1002/chem.202102840
日期:2021.11.11
E-selective trifluoropropenylation of versatile N-heterocycles was developed with the utilization of trifluoropropenyliodonium salts. The procedure enables the straightforward direct introduction of the trifluoroalkenyl moiety into heterocyclic scaffolds under simple and mild reaction conditions.
A convenient one pot procedure for the synthesis of 3,5-disubstituted pyrazoles by condensation of chalcones, hydrazine hydrate and sulfur in ethanol under microwave irradiation and conventional heating method is reported. The hydrogen sulfide is produced during the reaction. The pyrazoles are obtained in good yields and excellent state of purity. The structures of new compounds were confirmed by IR
据报道,在微波辐射和常规加热方法下,通过查耳酮,水合肼和硫在乙醇中的缩合反应,可以方便地一锅法合成3,5-二取代的吡唑。在反应过程中产生硫化氢。以良好的产率和优异的纯度获得吡唑。通过IR,1 H和13 C NMR,MS和元素分析确认了新化合物的结构。
Hepatitis C Virus Inhibitors
申请人:Lopez Omar D.
公开号:US20110294819A1
公开(公告)日:2011-12-01
The present disclosure is generally directed to antiviral compounds, and more specifically directed to compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such compounds, and methods for inhibiting the function of the NS5A protein.