69963-46-8Relevant academic research and scientific papers
Synthesis of oxadiazole-2-oxide derivatives as potential drug candidates for schistosomiasis targeting SjTGR
Li, Gongming,Guo, Qingqing,Feng, Chao,Chen, Huan,Zhao, Wenjiao,Li, Shu,Hong, Yang,Sun, Dequn
, (2021/05/03)
Background: Schistosomiasis is a chronic parasitic disease that affects millions of people’s health worldwide. Because of the increasing drug resistance to praziquantel (PZQ), which is the primary drug for schistosomiasis, developing new drugs to treat schistosomiasis is crucial. Oxadiazole-2-oxides have been identified as potential anti-schistosomiasis reagents targeting thioredoxin glutathione reductase (TGR). Methods: In this work, one of the oxadiazole-2-oxides derivatives furoxan was used as the lead compound to exploit a series of novel furoxan derivatives for studying inhibitory activity against both recombinant Schistosoma japonicum TGR containing selenium (rSjTGR-Sec) and soluble worm antigen protein (SWAP) containing wild-type Schistosoma japonicum TGR (wtSjTGR), in order to develop a new leading compound for schistosomiasis. Thirty-nine novel derivatives were prepared to test their activity toward both enzymes. The docking method was used to detect the binding site between the active molecule and SjTGR. The structure–activity relationship (SAR) of these novel furoxan derivatives was preliminarily analyzed. Results: It was found that several new derivatives, including compounds 6a–6d, 9ab, 9bd and 9be, demonstrated greater activity toward rSjTGR-Sec or SWAP containing wtSjTGR than did furoxan. Interestingly, all intermediates bearing hydroxy (6a–6d) showed excellent inhibitory activity against both enzymes. In particular, compound 6d with trifluoromethyl on a pyridine ring was found to have much higher inhibition toward both rSjTGR-Sec (half-maximal inhibitory concentration, IC50,7.5nM) and SWAP containing wtSjTGR (IC50 55.8nM) than furoxan. Additionally, the docking method identified the possible matching sites between 6d and Schistosoma japonicum TGR (SjTGR), which theoretically lends support to the inhibitory activity of 6d. Conclusion: The data obtained herein showed that 6d with trifluoromethyl on a pyridine ring could be a valuable leading compound for further study.
Synthesis and Assessment of Novel Probes for Imaging Tau Pathology in Transgenic Mouse and Rat Models
McMurray, Lindsay,MacDonald, Jennifer A.,Ramakrishnan, Nisha Kuzhuppilly,Zhao, Yanyan,Williamson, David W.,Tietz, Ole,Zhou, Xiaoyun,Kealey, Steven,Fagan, Steven G.,Smolek, Tomá?,Cubinkova, Veronika,?ilka, Norbert,Spillantini, Maria Grazia,Tolkovsky, Aviva M.,Goedert, Michel,Aigbirhio, Franklin I.
, p. 1885 - 1893 (2021/04/07)
Aggregated tau protein is a core pathology present in several neurodegenerative diseases. Therefore, the development and application of positron emission tomography (PET) imaging radiotracers that selectively bind to aggregated tau in fibril form is of importance in furthering the understanding of these disorders. While radiotracers used in human PET studies offer invaluable insight, radiotracers that are also capable of visualizing tau fibrils in animal models are important tools for translational research into these diseases. Herein, we report the synthesis and characterization of a novel library of compounds based on the phenyl/pyridinylbutadienylbenzothiazoles/benzothiazolium (PBB3) backbone developed for this application. From this library, we selected the compound LM229, which binds to recombinant tau fibrils with high affinity (Kd = 3.6 nM) and detects with high specificity (a) pathological 4R tau aggregates in living cultured neurons and mouse brain sections from transgenic human P301S tau mice, (b) truncated human 151-351 3R (SHR24) and 4R (SHR72) tau aggregates in transgenic rat brain sections, and (c) tau neurofibrillary tangles in brain sections from Alzheimer's disease (3R/4R tau) and progressive supranuclear palsy (4R tau). With LM229 also shown to cross the blood-brain barrier in vivo and its effective radiolabeling with the radioisotope carbon-11, we have established a novel platform for PET translational studies using rodent transgenic tau models.
Synthesis of β-heteroaryl carbonyl compounds via direct cross-coupling of allyl alcohols with heteroaryl boronic acids under cooperative bimetallic catalysis
Zhu, Mingxiang,Du, Hongli,Li, Jingya,Zou, Dapeng,Wu, Yusheng,Wu, Yangjie
, p. 1352 - 1355 (2018/03/06)
The eco-friendly cooperative Cu/Pd-catalyzed oxidative Heck reaction of allyl alcohols with heteroaryl boronic acids under air was described. The ready availability of starting materials and the mild reaction conditions made this protocol a safe and operationally convenient strategy for the efficient synthesis of β-heteroaryl carbonyl compounds.
Iridium-Catalyzed Enantioselective Allylic Substitution of Aliphatic Esters with Silyl Ketene Acetals as the Ester Enolates
Jiang, Xingyu,Hartwig, John F.
, p. 8887 - 8891 (2017/07/17)
Enantioselective allylic substitution with enolates derived from aliphatic esters under mild conditions remains challenging. Herein we report iridium-catalyzed enantioselective allylation reactions of silyl ketene acetals, the silicon enolates of esters, to form products containing a quaternary carbon atom at the nucleophile moiety and a tertiary carbon atom at the electrophile moiety. Under relatively neutral conditions, the allylated aliphatic esters were obtained with excellent regioselectivity and enantioselectivity. These products were readily converted into primary alcohols, carboxylic acids, amides, isocyanates, and carbamates, as well as tetrahydrofuran and γ-butyrolactone derivatives, without erosion of enantiomeric purity.
Preparation of Boc-protected cinnamyl-type alcohols: A comparison of the Suzuki-Miyaura coupling, cross-metathesis, and Horner-Wadsworth-Emmons approaches and their merit in parallel synthesis
Stambasky, Jan,Malkov, Andrei V.,Kocovsky, Pavel
experimental part, p. 705 - 732 (2009/04/03)
Three synthetic strategies for the construction of tert-butyl (E)-3-arylprop-2-en-1-ol carbonates are described. Complementary approaches employing Suzuki-Miyaura coupling and cross-metathesis reaction gave moderate yields of the title compounds in one-step, both methods are suitable for high-throughput and parallel chemistry. A detailed investigation into the Suzuki-Miyaura coupling reaction is provided along with the studies on the synthesis of pinacolyl 1-(tert-butyloxycarbonyl)propenol-3-ylboronate, the key building block. Conventional synthesis of the title compounds via the Horner-Wadsworth-Emmons reaction as a key step in a three-step-one-purification protocol was optimized and the results are compared with those of the latter reactions.
Palladium-Catalyzed Cyclocarbonylation of 3-(Heteroaryl)allyl Acetates1
Iwasaki, Masakazu,Kobayashi, Yoshihiro,Li, Ji-Ping,Matsuzaka, Hiroyuki,Ishii, Youichi,Hidai, Masanobu
, p. 1922 - 1927 (2007/10/02)
Acetoxybenzofurans, acetoxybenzothiophenes, acetoxyindoles, and acetoxycarbazoles were obtained in high yields by cyclocarbonylation of 3-furyl-, 3-thienyl-, 3-pyrrolyl-, and 3-indolylallyl acetates, respectively, in the presence of Ac2O, NEt3, and a catalytic amount of PdCl2(PPh3)2 at 130 - 170 deg C under 50 - 70 atm of CO. 3-(3-Furyl)allyl and 3-(3-thienyl)allyl acetates cyclized selectively at the 2-position of the heterocyclic nucleus to give 7-acetoxybenzofuran and 7-acetoxybenzothiophene, respectively.The synthetic utility of the reaction was demonstrated by the synthesis of canabifuran from isothymol.
