1586-00-1Relevant articles and documents
Negishi cross-coupling with functionalised organozinc compounds prepared by lithium-zinc transmetallation
Yus, Miguel,Gomis, Joaquín
, p. 5721 - 5724 (2001)
The reaction of some functionalised organolithium compounds 2 (easily prepared by DTBB-catalysed lithiation of isochroman, phthalan and 2,3-dihydrobenzofuran) with an equimolecular amount of zinc bromide followed by reaction with an aryl or alkenyl bromide in the presence of a catalytic amount of Pd(PPh3)4 or Pd(PPh3)2(OAc)2 (5 mol%) under THF reflux overnight gave the expected cross-coupling compounds. These arylation or alkenylation processes, which work also with iodinated substrates, are not possible in the absence of the zinc or palladium compounds under the same reaction conditions.
Synthesis of Benzoazepine Derivatives via Azide Rearrangement and Evaluation of Their Antianxiety Activities
Lapmanee, Sarawut,Palavong, Nitwaree,Reamtong, Onrapak,Ruchirawat, Somsak,Thongsornkleeb, Charnsak,Tummatorn, Jumreang
supporting information, p. 1449 - 1458 (2021/09/13)
A new synthetic method for the construction of benzoazepine analogues has been developed employing ortho-arylmethylbenzyl azide derivatives as precursors using an azide rearrangement reaction. In this work, 14 benzoazepine compounds were successfully synthesized in moderate to excellent yields. All synthetic benzoazepines were evaluated for their cytotoxicity against normal human kidney cell line (HEK cell). The results showed that compound 18c had the lowest cytotoxicity (IC50 = 65.68 μM) among tested compounds, which was comparable with the antianxiety drug diazepam (IC50 = 87.90 μM). Based on the cytotoxicity results, five benzoazepine analogues (compounds 18c, 18h, 18j, 18n, and 18p) were selected to determine the antianxiety effect on stressed rats using elevated plus maze (EPM) and open field test (OFT) methods. Interestingly, compound 18c showed better anxiolytic activity than diazepam without a sedative effect by showing superior hyperlocomotor activity. Therefore, this discovery could pave the way for drug development to treat patients with anxiety disorder.
Cyclic analogue of S-benzylisothiourea that suppresses kynurenine production without inhibiting indoleamine 2,3-dioxygenase activity
Fukuda, Miwa,Sasaki, Tomomi,Hashimoto, Tomoko,Miyachi, Hiroyuki,Waki, Minoru,Asai, Akira,Takikawa, Osamu,Ohno, Osamu,Matsuno, Kenji
supporting information, p. 2846 - 2849 (2018/07/30)
Kynurenine is biosynthesised from tryptophan catalysed by indoleamine 2,3-dioxygenase (IDO). The abrogation of kynurenine production is considered a promising therapeutic target for immunological cancer treatment. In the course of our IDO inhibitor programme, formal cyclisation of the isothiourea moiety of the IDO inhibitor 1 afforded the 5-Cl-benzimidazole derivative 2b-6, which inhibited both recombinant human IDO (rhIDO) activity and cellular kynurenine production. Further derivatisation of 2b-6 provided the potent inhibitor of cellular kynurenine production 2i (IC50 = 0.34 μM), which unexpectedly exerted little effect on the enzymatic activity of rhIDO. Elucidation of the mechanism of action revealed that compound 2i suppresses IDO expression at the protein level by inhibiting STAT1 expression in IFN-γ-treated A431 cells. The kynurenine-production inhibitor 2i is expected to be a promising starting point for a novel approach to immunological cancer treatment.
Effect of mesoporosity on selective benzylation of aromatics with benzyl alcohol over mesoporous ZSM-5
Jin, Hailian,Ansari, Mohd Bismillah,Jeong, Eun-Young,Park, Sang-Eon
experimental part, p. 55 - 62 (2012/08/13)
The effect of mesoporosity on product distribution in benzylation of aromatics such as benzene, toluene, anisole and mesitylene with benzyl alcohol was investigated over various ZSM-5 catalysts with different degree of mesoporosity, which were prepared by microwave-induced assembly via ionic interaction between sulfonic acid-functionalized or non-functionalized ZSM-5 nanozeolites and counter cationic surfactant, and hydrothermal synthesis with or without sulfonic acid functionalization and surfactant. The product distribution of the aromatic benzylation was found to vary with the different mesoporosity. The selectivity of desired monobenzylated aromatic was increased from 19.8% to 75.5% with increasing mesopore volume from 0.11 to 0.75 cm 3/g. Meso ZSM-5 (SO3H-CTAB)-MW with the highest external acid sites and mesopore volume showed better conversion as well as much higher selectivity of desired bulky monobenzylated aromatics than those of other catalysts, whereas microporous ZSM-5 mainly showed dibenzyl ether as major product due to diffusion limitation of bulky product.
