106367-88-8Relevant academic research and scientific papers
Synthesis and Structure-Activity Relationships of 3-Arylisoquinolone Analogues as Highly Specific hCES2A Inhibitors
Zhao, Yitian,Xiong, Yuan,Dong, Sanfeng,Guan, Xiaoqing,Song, Yunqing,Yang, Yanqing,Zou, Kun,Li, Zhao,Zhang, Yong,Fang, Shengquan,Li, Bo,Zhu, Weiliang,Chen, Kaixian,Jia, Qi,Ge, Guangbo
, p. 388 - 398 (2020/10/26)
Mammalian carboxylesterases (CES) are key enzymes that participate in the hydrolytic metabolism of various endogenous and exogenous substrates. Human carboxylesterase 2A (hCES2A), mainly distributed in the small intestine and colon, plays a significant ro
Exploration of the 2,3-dihydroisoindole pharmacophore for inhibition of the influenza virus PA endonuclease
Rogolino, Dominga,Naesens, Lieve,Bartoli, Jennifer,Carcelli, Mauro,De Luca, Laura,Pelosi, Giorgio,Stokes, Ryjul W.,Van Berwaer, Ria,Vittorio, Serena,Stevaert, Annelies,Cohen, Seth M.
, (2021/10/14)
Seasonal influenza A and B viruses represent a global concern. Antiviral drugs are crucial to treat severe influenza in high-risk patients and prevent virus spread in case of a pandemic. The emergence of viruses showing drug resistance, in particular for the recently licensed polymerase inhibitor baloxavir marboxil, drives the need for developing alternative antivirals. The endonuclease activity residing in the N-terminal domain of the polymerase acidic protein (PAN) is crucial for viral RNA synthesis and a validated target for drug design. Its function can be impaired by molecules bearing a metal-binding pharmacophore (MBP) able to coordinate the two divalent metal ions in the active site. In the present work, the 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one scaffold is explored for the inhibition of influenza virus PA endonuclease. The structure-activity relationship was analysed by modifying the substituents on the lipophilic moiety linked to the MBP. The new compounds exhibited nanomolar inhibitory activity in a FRET-based enzymatic assay, and a few compounds (15–17, 21) offered inhibition in the micromolar range, in a cell-based influenza virus polymerase assay. When investigated against a panel of PA-mutant forms, compound 17 was shown to retain full activity against the baloxavir-resistant I38T mutant. This was corroborated by docking studies providing insight into the binding mode of this novel class of PA inhibitors.
Discovery of dihydrooxazolo[2,3-: A] isoquinoliniums as highly specific inhibitors of hCE2
Ding, Lixia,Wang, Lu,Zou, Kun,Li, Bo,Song, Yunqing,Zhang, Qihua,Zhao, Yitian,Xu, Zhijian,Ge, Guangbo,Zhao, Bo,Zhu, Weiliang
, p. 35904 - 35912 (2019/11/16)
Human carboxylesterase 2 (hCE2) is one of the most abundant esterases distributed in human small intestine and colon, which participates in the hydrolysis of a variety of ester-bearing drugs and thereby affects the efficacy of these drugs. Herein, a new c
6,7-Dihydroxy-1-oxoisoindoline-4-sulfonamide-containing HIV-1 integrase inhibitors
Zhao, Xue Zhi,Maddali, Kasthuraiah,Smith, Steven J.,Métifiot, Mathieu,Johnson, Barry C.,Marchand, Christophe,Hughes, Stephen H.,Pommier, Yves,Burke Jr., Terrence R.
, p. 7309 - 7313 (2013/02/21)
Although an extensive body of scientific and patent literature exists describing the development of HIV-1 integrase (IN) inhibitors, Merck's raltegravir and Gilead's elvitegravir remain the only IN inhibitors FDA-approved for the treatment of AIDS. The em
HYDRAZIDE, AMIDE, PHTHALIMIDE AND PHTHALHYDRAZIDE ANALOGS AS INHIBITORS OF RETROVIRAL INTEGRASE
-
Page/Page column 34; 35, (2009/04/25)
The present invention provides catechol-containing hydrazides, amides, phthalimide and phthalhydrazide analogs. These compounds are inhibitors of retroviral integrase, an essential enzyme for the proliferation of retroviruses such as HIV-1. Also provided are pharmaceutical compositions comprising at least one of the catechol-containing hydrazides, amides, phthalimide or phthalhydrazide analogs and a method of using the hydrazide, amide, phthalimide and phthalhydrazide analogs to inhibit retroviral proliferation and as therapeutics for the treatment of AIDS.
2,3-Dihydro-6,7-dihydroxy-1H-isoindol-1-one-based HIV-1 integrase inhibitors
Xue, Zhi Zhao,Semenova, Elena A.,Vu, B. Christie,Maddali, Kasthuraiah,Marchand, Christophe,Hughes, Stephen H.,Pommier, Yves,Burke Jr., Terrence R.
, p. 251 - 259 (2008/09/19)
The bis-salicylhydrazides class of HIV-1 integrase (IN) inhibitors has been postulated to function by metal chelation. However, members of this series exhibit potent inhibition only when Mn2+ is used as cofactor. The current study found that bis-aroylhydrazides could acquire inhibitory potency in Mg2+ using dihydroxybenzoyl substituents as both the right and left components of the hydrazide moiety. Employing a 2,3-dihydro-6,7-dihydroxy-1H- isoindol-1-one ring system as a conformationally constrained 2,3-dihydroxybenzoyl equivalent provided good selectivity for IN-catalyzed strand transfer versus the 3′-processing reactions as well as antiviral efficacy in cells using HIV-1 based vectors.
A Simple Total Synthesis of the Isoindolobenzazepine Alkaloids Lennoxamine and Chilenamine
Napolitano, Elio,Spinelli, Guido,Fiaschi, Rita,Marsili, Antonio
, p. 785 - 788 (2007/10/02)
Lennoxamine (8) and chilenamine (9) have been synthesized from 3-(3,4-methylenedioxybenzylidene)-6,7-dimethoxyphthalide (1) in four and five high-yielding steps, respectively.The key step of the process is the cyclization, by intramolecular alkylation, of 3-(3,4-methylenedioxybenzyl)-6,7-dimethoxyphthalimidin-2-ylacetaldehyde dimethyl acetal (3) to 13,13a-dihydro-3,4-dimethoxy-10,11-methylenedioxyisoindolobenzazepin-5-one (7).Attempts to prepare (3) by base-catalysed cyclization of 3,4-dimethoxy-3',4'-methylenedioxystilbene-2-(2,2-dimethoxyethyl)carboxamide (15) were unsuccesful.
