776-34-1Relevant academic research and scientific papers
Synthesis and application of 2-(arylazo)-8-nitronaphtho[1,2-d] thiazole disperse dyes
Rangnekar, Dinesh W.,Maladkar, Gajanan J.
, p. 199 - 205 (2000)
The paper describes the synthesis of 2-amino-8-nitronaphtho[1,2-d]thiazole and its utilization to prepare a range of heterocyclic azo disperse dyes. These arylazo dyes were studied with respect to their color and constitution relationship. These dyes were applied on polyester fibre and their fastness properties were evaluated.
Copper-Catalyzed Regioselective Nitration and Azidation of 1-Naphthylamine Derivatives via Remote C–H Activation
Dou, Yandong,Yin, Biao,Zhang, Pengfei,Zhu, Qing
, p. 4571 - 4576 (2018)
A simple and facile protocols for copper-catalyzed regionselective C4 nitration and azidation of 1-naphthylamines via remote C–H activation that use of pyridyl amide fragment as the removable directing group have been firstly developed. These reactions proceed under mild conditions without any additives, tolerate a wide variety of functional groups, and afford a wide range of products in good to excellent yields. Control experiments suggest that those C–H activation reactions are likely to proceed through a single-electron-transfer (SET) process.
Keap1-Nrf2 PPI inhibitor prodrug and preparation method and application
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Paragraph 0031; 0034-0037; 0040; 0041, (2021/02/06)
The invention discloses a Keap1-Nrf2 PPI inhibitor prodrug and a preparation method and application. According to the prodrug P-168 provided by the invention, a polar carboxylic acid group of an active compound 168 is blocked, so that the fat solubility is improved, and the membrane permeability and druggability are effectively improved; the prodrug P-168 is reduced under the condition of high ROS, a pharmacophore 168 and a fluorophore coumarin are released, expression of Nrf2 and downstream genes of Nrf2 is activated, anti-inflammatory activity is brought into play, and meanwhile fluorescenceis released to achieve visual monitoring.
A hydrogen peroxide responsive prodrug of Keap1-Nrf2 inhibitor for improving oral absorption and selective activation in inflammatory conditions
Jiang, Zhengyu,Lu, Mengchen,You, Qidong,Zhang, Xian,Zhao, Jing
, (2020/05/18)
Transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and its negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (Keap1), control the redox and metabolic homeostasis and oxidative stress. Inhibitors of Keap1-Nrf2 interaction are promising in oxidative stress related inflammatory diseases but now hit hurdles. By utilizing thiazolidinone moiety to shield the key carboxyl pharmacophore in Keap1-Nrf2 inhibitor, a hydrogen peroxide (H2O2)-responsive prodrug pro2 was developed. The prodrug modification improved the physicochemical properties and cell membrane permeability of the parent drug. Pro2 was stable and stayed inactive under various physiological conditions, while became active by stimulation of H2O2 or inflammation derived reactive oxygen species. Moreover, pro2 exhibited proper pharmacokinetic profile suitable for oral administration and enhanced anti-inflammatory efficiency in vivo. Thus, this novel prodrug approach may not only provide an important advance in the therapy of chronic inflammatory diseases with high level of H2O2, but also offer a fresh solution to improve the drug-like and selectivity issues of Keap1-Nrf2 inhibitors.
Unravelling the mechanism of cobalt-catalysed remote C-H nitration of 8-aminoquinolinamides and expansion of substrate scope towards 1-naphthylpicolinamide
Chu, Melody,Planas, Oriol,Company, Anna,Ribas, Xavi,Hamilton, Alex,Whiteoak, Christopher J.
, p. 534 - 542 (2020/01/21)
Previously, an unexpected Co-catalysed remote C-H nitration of 8-aminoquinolinamide compounds was developed. This report provided a novel reactivity for Co which was assumed to proceed through the mechanistic pathway already known for analogous Cu-catalysed remote couplings of the same substrates. In order to shed light into this intriguing, and previously unobserved reactivity for Co, a thorough computational study has now been performed, which has allowed for a full understanding of the operative mechanism. This study demonstrates that the Co-catalysed remote coupling does not occur through the previously proposed Single Electron Transfer (SET) mechanism, but actually operates through a high-spin induced remote radical coupling mechanism, through a key intermediate with significant proportion of spin density at the 5- and 7-positions of the aminoquinoline ring. Additionally, new experimental data provides expansion of the synthetic utility of the original nitration procedure towards 1-naphthylpicolinamide which unexpectedly appears to operate via a subtly different mechanism despite having a similar chelate environment.
A Comparative Assessment Study of Known Small-Molecule Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity
Tran, Kim T.,Pallesen, Jakob S.,Solbak, Sara M.,Narayanan, Dilip,Baig, Amina,Zang, Jie,Aguayo-Orozco, Alejandro,Carmona, Rosa M. C.,Garcia, Anthony D.,Bach, Anders
, p. 8028 - 8052 (2019/10/11)
Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood-brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance - and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1-Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.
Sodium persulfate-promoted site-selective synthesis of mononitroarylamines under transition-metal-free conditions
Xie, De-Xun,Yu, Hui-Juan,Liu, Hui,Xue, Wei-Cai,Qin, Yuan-Shou,Shao, Guang
, p. 1157 - 1165 (2019/01/24)
A practical preparation of nitroarylamines from protected arylamines was herein disclosed. In this system, sodium nitrite acted as a nitration reagent in the presence of sodium persulfate without any transition-metal catalysts. This efficient site-selective protocol took place at room temperature for a short time through a free radical pathway.
Synthesis method of naphthylamine derivative
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Paragraph 0065; 0066; 0067, (2018/08/03)
The invention discloses a preparation method of a naphthylamine derivative. In the presence of a copper-based catalyst and an oxidant, a picolinamide naphthylamine nitrated product is obtained throughreaction of a nitrate source and picolinamide naphthylamine; furthermore, according to the preparation method, the picolinamide naphthylamine nitrated product is further aminated to further modify naphthylamine. According to the preparation method disclosed by the invention, the naphthylamine is modified according to a C-H activation technology to prepare a series of naphthylamine derivatives. Compared with the conventional method, the preparation method is simpler, more convenient and more efficient.
One-scale basicities of diaminobenzenes and diaminonaphthalenes: from aniline to proton sponge
Vlasenko, Marina P.,Ozeryanskii, Valery A.
supporting information, (2017/01/17)
Basicity constants, pKa, for a wide range of mono-protonated diaminobenzenes and diaminonaphthalenes, including dimethylamino derivatives were for the first time uniformly measured in 20% aqueous ethanol (29 compounds) and 80% aqueous dioxane (39 compounds) spanning from aniline to 1,8-bis(dimethylamino)naphthalene (‘proton sponge’). The dioxane system proved to be more versatile and because of better solubility of N-alkylated polyaminoarenes allowed to add to the same scale some superbasic bis(dialkylamino)-, tetrakis(dialkylamino)-, and hexakis(dialkylamino)naphthalenes, thus extending the scale for almost 10 pKa units, revealing possible limits of basicity changes in aromatic amines. The basicity of reference bases, pyridine and triethylamine, was also measured in these solvent systems. A group of N-alkylated compounds was found to be less basic in aqueous dioxane when compared with their NH2-analogs. This anomaly was not observed in aqueous ethanol. Other basicity trends and correlations between different basicity scales were also discussed. Copyright
Co(II)-Catalyzed Regioselective Cross-Dehydrogenative Coupling of Aryl C-H Bonds with Carboxylic Acids
Lan, Jianyong,Xie, Haisheng,Lu, Xiaoxia,Deng, Yuanfu,Jiang, Huanfeng,Zeng, Wei
supporting information, p. 4279 - 4282 (2017/08/23)
A cobalt(II)-catalyzed regioselective aryl C-H bond oxygenation between arenes and aryl or aliphatic carboxylic acids under bidendate-chelation assistance is developed. This method provides an efficient approach to acyoxy-substituted arenes with a broad range of functional group tolerance. Furthermore, this reaction system could be further applied to the preparation of polyfunctional naphthylenes.
