2345-34-8Relevant articles and documents
Study on the synthesis of sulfonamide derivatives and their interaction with bovine serum albumin
Zhang, Xuehong,Lin, Yijie,Liu, Lina,Lin, Cuiwu
, p. 269 - 279 (2015)
Three sulfonamide derivatives (SAD) were first synthesized from p-hydroxybenzoic acid and sulfonamides (sulfadimidine, sulfamethoxazole and sulfachloropyridazine sodium) and were characterized by elemental analysis, 1H NMR and MS. The interaction between bovine serum albumin (BSA) and SAD was studied using UV/vis absorption spectroscopy, fluorescence spectroscopy, time-resolved fluorescence spectroscopy and circular dichroism spectra under imitated physiological conditions. The experimental results indicated that SAD effectively quenched the intrinsic fluorescence of BSA via a static quenching process. The thermodynamic parameters showed that hydrogen bonding and van der Waal's forces were the predominant intermolecular forces between BSA and two SADs [4-((4-(N-(4,6-dimethylpyrimidin-2-yl)sulfamoyl)phenyl)carbamoyl)phenyl acetate and 4-((4-(N-(5-methylisoxazol-3-yl)sulfamoyl)phenyl)carbamoyl)phenyl acetate], but hydrophobic forces played a major role in the binding process of BSA and 4-((4-(N-(6-chloropyridazin-3-yl)sulfamoyl)phenyl) carbamoyl)phenyl acetate. In addition, the effect of SAD on the conformation of BSA was investigated using synchronous fluorescence spectroscopy and circular dichroism spectra. Molecular modeling results showed that SAD was situated in subdomain IIA of BSA.
Discovery of β-Adrenergic Receptors Blocker-Carbonic Anhydrase Inhibitor Hybrids for Multitargeted Antiglaucoma Therapy
Nocentini, Alessio,Ceruso, Mariangela,Bua, Silvia,Lomelino, Carrie L.,Andring, Jacob T.,McKenna, Robert,Lanzi, Cecilia,Sgambellone, Silvia,Pecori, Riccardo,Matucci, Rosanna,Filippi, Luca,Gratteri, Paola,Carta, Fabrizio,Masini, Emanuela,Selleri, Silvia,Supuran, Claudiu T.
, p. 5380 - 5394 (2018)
The combination of a β-adrenergic receptors (AR) blocker and a carbonic anhydrase (CA, EC 4.2.1.1) inhibitor in eye drops formulations is one of the most clinically used treatment for glaucoma. A novel approach consisting of single-molecule, multitargeted compounds for the treatment of glaucoma is proposed here by designing compounds which concomitantly interact with the β-adrenergic and CA targets. Most derivatives of the two series of benzenesulfonamides incorporating 2-hydroxypropylamine moieties reported here exhibited striking efficacy against the target hCA II and XII, whereas a subset of compounds also showed significant modulation of β1- and β2-ARs. X-ray crystallography studies provided rationale for the observed hCA inhibition. The best dual-agents decreased IOP more effectively than clinically used dorzolamide, timolol, and the combination of them in an animal model of glaucoma. The reported evidence supports the proof-of-concept of β-ARs blocker-CAI hybrids for antiglaucoma therapy with an innovative mechanism of action.
Identification of Novel Resorcinol Amide Derivatives as Potent and Specific Pyruvate Dehydrogenase Kinase (PDHK) Inhibitors
Cho, Hanna,Cho, Kyungseon,Kim, Mi-Jin,Kim, Nam Doo,Lee, In-Kyu,Park, Sungmi,Shin, Injae,Sim, Taebo,Yoo, Eun Kyung,Yoon, Hojong
, (2019)
Pyruvate dehydrogenase kinases (PDHKs) promote abnormal respiration in cancer cells. Studies with novel resorcinol amide derivatives based on VER-246608 (6) led to the identification of 19n and 19t containing five-membered heteroaromatic rings as unique structural features. These substances possess single-digit nanomolar activities against PDHKs. 19t exhibits higher potencies against PDHK1/2/4 than does 6 and inhibits only PDHKs among 366 kinases. Moreover, 19g, 19l, and 19s were found to be isotype-selective PDHK inhibitors. Molecular dynamics simulations provide a better understanding of how the heteroaromatic rings affect the activities of 19n and 19t on PDHK1/2/3/4. Moreover, 19n possesses a much higher antiproliferative activity against cancer cells than does 6. We demonstrated that the results of PDH assays better correlate with cellular activities than do those of PDHK kinase assays. Furthermore, 19n induces apoptosis of cancer cells via mitochondrial dysfunction, suppresses tumorigenesis, and displays a synergistic effect on satraplatin suppression of cancer cell proliferation.
Photo-induced deep aerobic oxidation of alkyl aromatics
Wang, Chang-Cheng,Zhang, Guo-Xiang,Zuo, Zhi-Wei,Zeng, Rong,Zhai, Dan-Dan,Liu, Feng,Shi, Zhang-Jie
, p. 1487 - 1492 (2021/07/10)
Oxidation is a major chemical process to produce oxygenated chemicals in both nature and the chemical industry. Presently, the industrial manufacture of benzoic acids and benzene polycarboxylic acids (BPCAs) is mainly based on the deep oxidation of polyalkyl benzene, which is somewhat suffering from environmental and economical disadvantage due to the formation of ozone-depleting MeBr and corrosion hazards of production equipment. In this report, photo-induced deep aerobic oxidation of (poly)alkyl benzene to benzene (poly)carboxylic acids was developed. CeCl3 was proved to be an efficient HAT (hydrogen atom transfer) catalyst in the presence of alcohol as both hydrogen and electron shuttle. Dioxygen (O2) was found as a sole terminal oxidant. In most cases, pure products were easily isolated by simple filtration, implying large-scale implementation advantages. The reaction provides an ideal protocol to produce valuable fine chemicals from naturally abundant petroleum feedstocks. [Figure not available: see fulltext.].
Aryl alkyl ether compound as well as derivative, preparation method, pharmaceutical composition and application thereof
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Paragraph 0261; 0262; 0265; 0266, (2021/05/12)
The invention discloses an aryl alkyl ether compound as well as a derivative, a preparation method, a pharmaceutical composition and application thereof. The structure of the aryl alkyl ether compound is shown as a formula (I). The aryl alkyl ether compound derivative relates to a stereoisomer, a tautomer, a metabolite, a metabolic precursor, a prodrug, a solvate, a salt of the solvate, a crystal, a pharmaceutically acceptable salt or a mixture of the stereoisomer, the tautomer, the metabolite, the metabolic precursor, the prodrug and the solvate of the aryl alkyl ether compound. The aryl alkyl ether compound and the derivative thereof have a remarkable inhibition effect on indoleamine 2, 3-dioxygenase 1, and can be used for preparing a medicine for treating indoleamine 2, 3-dioxygenase 1 mediated immunosuppression related diseases, and the prepared medicine can exert the medicine effect at the molecular level and is wide in application.
Structure-Activity Study of Nitazoxanide Derivatives as Novel STAT3 Pathway Inhibitors
Lü, Zirui,Li, Xiaona,Li, Kebin,Wang, Cong,Du, Tingting,Huang, Wei,Ji, Ming,Li, Changhong,Xu, Fengrong,Xu, Ping,Niu, Yan
supporting information, p. 696 - 703 (2021/05/04)
We identified nitazoxanide (NTZ) as a moderate STAT3 pathway inhibitor through immunoblot analysis and a cell-based IL-6/JAK/STAT3 pathway activation assay. A series of thiazolide derivatives were designed and synthesized to further validate the thiazolide scaffold as STAT3 inhibitors. Eight out of 25 derivatives displayed potencies greater than that of NTZ, and their STAT3 pathway inhibitory activities were found to be significantly correlated with their antiproliferative activities in HeLa cells. Derivatives 15 and 24 were observed to be more potent than the positive control WP1066, which is under phase I clinical trials. Compared with NTZ, 15 also exhibited much improved in vivo pharmacokinetic parameters in rats and efficacies against proliferations in multiple cancer cell lines, indicating a broad-spectrum effect of these thiazolides as antitumor agents targeted on STAT3.
PROCESSES FOR PREPARING AN S1P-RECEPTOR MODULATOR
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Page/Page column 33, (2021/05/07)
This application relates to processes for preparing an S1P-receptor modulator "Compound 1", which is useful in the treatment of diseases or disorders associated with activity of S1P, including CNS disorders. The process comprises reacting "compound 2" with "compound 3" in the presence of a reducing agent.
Synthesis and antioxidant activities of berberine 9-: O -benzoic acid derivatives
Liu, Yanfei,Long, Shuo,Zhang, Shanshan,Tan, Yifu,Wang, Ting,Wu, Yuwei,Jiang, Ting,Liu, Xiaoqin,Peng, Dongming,Liu, Zhenbao
, p. 17611 - 17621 (2021/05/29)
Although berberine (BBR) shows antioxidant activity, its activity is limited. We synthesized 9-O-benzoic acid berberine derivatives, and their antioxidant activities were screened via ABTS, DPPH, HOSC and FRAP assays. The para-position was modified with halogen elements on the benzoic acid ring, which led to an enhanced antioxidant activity and the substituent on the ortho-position was found to be better than the meta-position. Compounds 8p, 8c, 8d, 8i, 8j, 8l, and especially 8p showed significantly higher antioxidant activities, which could be attributed to the electronic donating groups. All the berberine derivatives possessed proper lipophilicities. In conclusion, compound 8p is a promising antioxidant candidate with remarkable elevated antioxidant activity and moderate lipophilicity.
Heterogeneous vanadium-catalyzed oxidative cleavage of olefins for sustainable synthesis of carboxylic acids
Upadhyay, Rahul,Rana, Rohit,Sood, Aakriti,Singh, Vikash,Kumar, Rahul,Srivastava, Vimal Chandra,Maurya, Sushil K.
supporting information, p. 5430 - 5433 (2021/06/09)
The development of green and sustainable processes to synthesize active pharmaceutical ingredients and key starting materials is a priority for the pharmaceutical industry. A green and sustainable protocol for the oxidative cleavage of olefins to produce pharmaceutically and biologically valuable carboxylic acids is achieved. The developed protocol involves 70% aq. TBHP as an oxidant over a heterogeneous vanadium catalyst system. Notably, the synthesis of industrially important azelaic acid from various renewable vegetable oils is accomplished. The catalyst could be recycled for up to 5 cycles without significant loss in yield and the protocol was successfully demonstrated at the gram-scale.
1,2-Dibutoxyethane-Promoted Oxidative Cleavage of Olefins into Carboxylic Acids Using O2 under Clean Conditions
Ou, Jinhua,Tan, Hong,He, Saiyu,Wang, Wei,Hu, Bonian,Yu, Gang,Liu, Kaijian
, p. 14974 - 14982 (2021/10/25)
Herein, we report the first example of an effective and green approach for the oxidative cleavage of olefins to carboxylic acids using a 1,2-dibutoxyethane/O2 system under clean conditions. This novel oxidation system also has excellent functional-group tolerance and is applicable for large-scale synthesis. The target products were prepared in good to excellent yields by a one-pot sequential transformation without an external initiator, catalyst, and additive.
