- Functional characterization of protein variants encoded by nonsynonymous single nucleotide polymorphisms in MARC1 and MARC2 in healthy Caucasians
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Human molybdenum-containing enzyme mitochondrial amidoxime reducing component (mARC), cytochrome b5 type B, and NADH cytochrome b5 reductase form an N-reductive enzyme system that is capable of reducing N-hydroxylated compounds. Genetic variations are known, but their functional relevance is unclear. Our study aimed to investigate the incidence of nonsynonymous single nucleotide polymorphisms (SNPs) in the mARC genes in healthy Caucasian volunteers, to determine saturation of the protein variants with molybdenum cofactor (Moco), and to characterize the kinetic behavior of the protein variants by in vitro biotransformation studies. Genotype frequencies of six SNPs in the mARC genes (c. 493A>G, c. 560T>A, c. 736T>A, and c. 739G>C in MARC1; c. 730G>A and c. 735T>G in MARC2) were determined by pyrosequencing in a cohort of 340 healthy Caucasians. Protein variants were expressed in Escherichia coli. Saturation with Moco was determined by measurement of molybdenum by inductively coupled mass spectrometry. Steady state assays were performed with benzamidoxime. The six variants were of low frequency in this Caucasian population. Only one homozygous variant (c.493A; MARC1) was detected. All protein variants were able to bind Moco. Steady state assays showed statistically significant decreases of catalytic efficiency values for the mARC-2 wild type compared with the mARC-1 wild type (P 0.05) and for two mARC-2 variants compared with the mARC-2 wild type (G244S, P 0.05; C245W, P 0.05). After simultaneous substitution of more than two amino acids in the mARC-1 protein, N-reductive activity was decreased 5-fold. One homozygous variant of MARC1 was detected in our sample. The encoded protein variant (A165T) showed no different kinetic parameters in the N-reduction of benzamidoxime. Copyright
- Ott, Gudrun,Reichmann, Debora,Boerger, Cornelia,Cascorbi, Ingolf,Bittner, Florian,Mendel, Ralf-Rainer,Kunze, Thomas,Clement, Bernd,Havemeyer, Antje
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Read Online
- Analysis of highly potent amidine containing inhibitors of serine proteases and their N-hydroxylated prodrugs (amidoximes)
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The development of serine protease inhibitors often results in the discovery of new lead compounds containing strong basic amidine functions that usually suffer from poor absorption from the intestine. In order to improve oral bioavailability of these dru
- Kotthaus, Joscha,Steinmetzer, Torsten,Van De Locht, Andreas,Clement, Bernd
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Read Online
- Design and synthesis of new triarylimidazole derivatives as dual inhibitors of BRAFV600E/p38α with potential antiproliferative activity
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Recent studies have shown that combining kinase inhibitors has additive and synergistic effects. BRAFV600E and p38α have been extensively studied as potential therapeutic targets for a variety of diseases. In keeping with our interest in developing multi-targeted anticancer agents, a series of novel triaryl-imidazole-based analogues containing 3-aryl-1,2,4-oxadiazoles moiety (4a-h, Scaffold B) and their reaction intermediates aryl carboximidamides moiety (3a-h, Scaffold A) have been rationally designed, synthesized, and evaluated in vitro for their antiproliferative activity as dual p38α/BRAFV600E inhibitors. The results revealed that the presence of the carboximidamide moiety is required for activity, and the best activity correlates with the Ar = 1,2-benzodioxole (3e) ≥ 4-CH3O-C6H5-(3c) > 2-naphthyl (3h) > 4-Cl-C6H5 (3b). Ring closure of carboximidamide to 1,2,4-oxadiazole significantly reduces the activity. The results of docking study into p38α revealed higher binding affinities for compounds 3c, 3e, and 3h compared to the co-crystallized ligand, SB2. However, the docking study of compounds 3c and 3e into BRAFV600E revealed slightly lower affinities than vemurafenib.
- Abdelhamid, Antar A.,Gomaa, Hesham A. M.,Gouda, Ahmed M.,Kamal, Islam,Marzouk, Adel A.,Moustafa, Amr H.,Youssif, Bahaa G. M.
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- Novel 1,2,4-oxadiazole derivatives as selective butyrylcholinesterase inhibitors: Design, synthesis, and biological evaluation
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Alzheimer’s disease (AD) is a progressive mental disorder that brings a huge economic burden to the healthcare systems. During this illness, acetylcholine levels in the cholinergic systems gradually diminish, which results in severe memory loss and cognitive impairments. Moreover, Butyrylcholinesterase (BuChE) enzyme participates in cholinergic neurotransmission regulation by playing a prominent role in the latter phase of AD. In this study, based on donepezil, which is an effective acetylcholinesterase (AChE) inhibitor, a series of 1,2,4-oxadiazole compounds were designed, synthesized and their inhibitory activities towards AChE and BuChE enzymes were evaluated. Some structures exhibited a higher selectivity rate towards BuChE in comparison to donepezil. Notably, compound 6n with an IC50 value of 5.07 μM and an SI ratio greater than 19.72 showed the highest potency and selectivity towards BuChE enzyme. The docking result revealed that compound 6n properly fitted the active site pocket of BuChE enzyme, and formed desirable lipophilic interactions and hydrogen bonds. Moreover, according to in silico ADME studies, these compounds have proper potential for being developed as new oral anti-Alzheimer’s agents.
- Akbarzadeh, Tahmineh,Hariri, Roshanak,Nazari, Maryam,Rezaee, Elham,Tabatabai, Sayyed Abbas
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p. 907 - 921
(2021/06/09)
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- 2-(1,2,4-Oxadiazol-5-yl)anilines Based on Amidoximes and Isatoic Anhydrides: Synthesis and Structure Features
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Abstract: An efficient one-pot method was developed for the synthesis of 2-(1,2,4-oxadiazol-5-yl)anilines via the reaction of amidoximes with isatoic anhydrides in a NaOH–DMSO medium at ambient temperature. The method allows to obtain structurally diverse
- Baykov, S. V.,Kotlyarova, V. D.,Shetnev, A. A.,Tarasenko, M. V.
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p. 768 - 778
(2021/06/26)
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- Novel chalcone/aryl carboximidamide hybrids as potent anti-inflammatory via inhibition of prostaglandin E2 and inducible NO synthase activities: design, synthesis, molecular docking studies and ADMET prediction
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Two series of chalcone/aryl carboximidamide hybrids 4a–f and 6a–f were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their in?vivo anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds 4c, 4d, 6c and 6d were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, 4c, 4d, 6c and 6d showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, 4c, 6a and 6e displayed good COX2 inhibitory activity while 4c, 6a and 6c exhibited the highest 5LOX inhibitory activity. Compounds 4c, 4d, 6c and 6d fit nicely into the pocket of iNOS protein (PDB ID: 1r35) via the important amino acid residues. Prediction of physicochemical parameters exhibited that 4c, 4d, 6c and 6d had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides 4c, 4d, 6c and 6d, in particular 4d and 6d, could be used as promising lead candidates as potent anti-inflammatory agents.
- Ibrahim, Tarek S.,Moustafa, Amr H.,Almalki, Ahmad J.,Allam, Rasha M.,Althagafi, Abdulhamid,Md, Shadab,Mohamed, Mamdouh F. A.
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p. 1067 - 1078
(2021/05/28)
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- Synthesis, spectroscopic characterization and DNA/HSA binding studies of (phenyl/naphthyl)ethenyl-substituted 1,3,4-oxadiazolyl-1,2,4-oxadiazoles
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Two new series of conjugated arylethenyl-1,3,4-oxadiazolyl-1,2,4-oxadiazoles were obtained and spectroscopically characterized in terms of UV-Vis absorption, fluorescence and interaction with CT-DNA and Human Serum Albumin (HSA) biomolecules. Phenyl- and 1-naphthyl-bearing examples were analysed, and the spectroscopic properties of its substitution series were compared, showing extensive conjugation in all compounds and absorption differences due to both the aryl-ethenyl subunit and substituted phenyl/phenylene at the 1,2,4-oxadiazole side. Strong binding interactions of the obtained compounds with CT-DNA and moderate HSA-association capability were observed spectroscopically, and further docking studies were performed. This journal is
- Mayer, Joao C. P.,Acunha, Thiago V.,Rodrigues, Oscar E. D.,Back, Davi F.,Chaves, Otavio A.,Dornelles, Luciano,Iglesias, Bernardo A.
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p. 471 - 484
(2021/01/11)
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- Cobalt-Catalyzed, Directed Intermolecular C-H Bond Functionalization for Multiheteroatom Heterocycle Synthesis: The Case of Benzotriazine
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Transition-metal-catalyzed, directed intermolecular C-H bond functionalization is synthetically useful but heavily underexplored in multiheteroatom heterocycle synthesis. Herein we report a cobalt catalytic method for the formation of a three-nitrogen-bearing benzotriazine scaffold via the coupling of arylhydrazine and oxadiazolone. This synthetic protocol features a low-cost base metal catalyst, a maximum number of heteroatoms built into a heterocycle, a distinct synthetic logic for benzotriazines, a superior step economy, and a broad substrate scope.
- Wu, Weiping,Fan, Shuaixin,Li, Tielei,Fang, Lili,Chu, Benfa,Zhu, Jin
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supporting information
p. 5652 - 5657
(2021/08/01)
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- Development of Potent 3-Br-isoxazoline-Based Antimalarial and Antileishmanial Compounds
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Starting from the structure of previously reported 3-Br-isoxazoline-based covalent inhibitors of P. falciparum glyceraldehyde 3-phosphate dehydrogenase, and with the intent to improve their metabolic stability and antimalarial activity, we designed and synthesized a series of simplified analogues that are characterized by the insertion of the oxadiazole ring as a bioisosteric replacement for the metabolically labile ester/amide function. We then further replaced the oxadiazole ring with a series of five-membered heterocycles and finally combined the most promising structural features. All the new derivatives were tested in vitro for antimalarial as well as antileishmanial activity. We identified two very promising new lead compounds, endowed with submicromolar antileishmanial activity and nanomolar antiplasmodial activity, respectively, and a very high selectivity index with respect to mammalian cells.
- Galbiati, Andrea,Zana, Aureliano,Coser, Consuelo,Tamborini, Lucia,Basilico, Nicoletta,Parapini, Silvia,Taramelli, Donatella,Conti, Paola
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supporting information
p. 1726 - 1732
(2021/11/01)
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- SSAO INHIBITOR
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The present invention provides an SSAO inhibitor and an application thereof in preparing a drug for treating a disease related to SSAO. In particular, the present invention provides a compound shown in formula (IV) and a pharmaceutically acceptable salt thereof.
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Paragraph 0183-0185; 0190; 0191; 0192
(2020/04/02)
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- Efficient insecticidal aerosol and preparation method thereof
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The invention provides an efficient insecticidal aerosol, which comprises the following components in percentage by weight: 0.1-0.5wt% of a component A, i.e. a 1, 2, 4-diazole derivative shown as a formula I, 1-1.5wt% of a component B, i.e. a marigold ext
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Paragraph 0035; 0046-0050; 0058; 0069-0073; 0081; 0092-0096
(2020/10/30)
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- 2,3-diketone indole compound, preparation method and applications thereof
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The invention discloses a 2,3-diketone indole compound, a preparation method and applications thereof, wherein the compound has a structure represented by the following general formula (I) or (II). The invention further relates to a pharmaceutical composi
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Paragraph 0144-0146
(2020/02/10)
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- Insecticidal aerosol and preparation method thereof
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The invention provides an insecticidal aerosol. The insecticidal aerosol is prepared from the following components by weight percentage: 0.2-0.7% of a component A, namely a 1, 2, 4-diazole derivativeshown as formula I, 1.5-2% of a component B, namely a ma
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Paragraph 0033; 0045-0047; 0053; 0066-0068; 0074; 0087-0089
(2020/10/30)
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- Optimization of the synthesis of het/aryl-amidoximes using an efficient green chemistry
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This work focuses on optimizing an efficient green synthesis of arylamidoximes from appropriate nitrile and hydroxylamine hydrochloride in water and triethylamine (1.6 mol equivalent) as a base at room temperature for 6 h. This new green synthetic methodology is compared with previously known methods. The main advantages of this new process reported are good yield, easier work-up and short reaction times. Moreover, some of the synthesized arylamidoximes converted to 1,2,4-oxadiazole derivatives 13a,b and 14via the reaction with (4-acetylphenoxy)acetic acid 12.
- Albayati, Mustafa R.,Mohamed, Mamdouh F. A.,Moustafa, Amr H.
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supporting information
p. 1217 - 1231
(2020/03/19)
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- Synthesis and evaluation of new 1,2,4-oxadiazole based trans- acrylic acid derivatives as potential PPAR-alpha/gamma dual agonist
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Diabetes is a ubiquitously a metabolic disorder and life-threatening disease. Peroxisome proliferator-activated receptors (PPARs) belong to the class of nuclear receptors which acts as transcription factors to regulate lipid and glucose metabolism. PPAR alpha/gamma dual agonists tend to corroborate the functions of both thiazolidinediones and fibrates and they hold substantial promise for ameliorating the type 2 diabetic treatments and providing potential therapeutic diabetic interventions. New 1,2,4-oxadiazole based trans- acrylic acid derivatives compounds possessing aryl/methylene linker in between pharmacophore head and lipophilic tail for dual PPAR-alpha/gamma agonists are studied. AutoDock Vina used for potential PPAR alpha/gamma dual agonists and 6 compounds 9a, 9g, 9 m, 9n, 9o, and 9r were identified comparable to PPAR gamma agonist Pioglitazone on the basis of their affinity scores and further their in-silico toxicity and in-silico ADME properties. The selected compounds showed better-calculated lipophilicity (iLogP) was found to be 0.92 to 3.19. Compound 9n and 9a were found to be most potent on both PPAR alpha and gamma receptors with EC50 of 0.07 ± 0.0006 μM, 0.06 ± 0.0005 μM and 0.781 ± 0.008 μM, 3.29 μM ± 0.03 respectively as better to pioglitazone having EC50 of 32.38 ± 0.2 and 38.03 ± 0.13 for both receptors. The in-vivo evaluation found to reduce the plasma glucose level and total cholesterol level significantly in diabetic rats compared to pioglitazone at 5 mg/kg/day dose for 7 days of treatment. Thus, trans- acrylic acid derivatives can be further developed as oral therapeutic agents for diabetic interventions as PPAR alpha/gamma dual agonists.
- Bhat, Sana,Bhat, Zahid Rafiq,Gupta, Jeena,Kaur, Jaskiran,Kaur, Paranjeet,Khatik, Gopal L.,Khurana, Navneet,Kumar, Rajan,Kumar, Rakesh,Tikoo, Kulbhushan
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- Entry into (E)-3-(1,2,4-oxadiazol-5-yl)acrylic acids via a one-pot ring-opening/ring-closing/retro-Diels-Alder reaction sequence
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A simple and convenient one-pot method is reported for the synthesis of (E)-3-(3-aryl(heteroaryl, alkyl)-1,2,4-oxadiazole-5-yl)acrylic acids utilizing readily accessible or commercially available substituted benzamidoximes and inexpensive exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic anhydride. The method is based on the reaction of amidoximes with the anhydride in a basic medium at RT followed by an acid-catalyzed retro-Diels-Alder reaction. The observed stereoselective heterocyclization/retro-Diels-Alder cascade process is suitable for the synthesis of a wide range of substituted (E)-1,2,4-oxadiazole-5-ylacrylic acids featuring electron donating and electron withdrawing groups on the aryl moiety, as well as heteroaryl or alkyl substituents at position 3 of the 1,2,4-oxadiazole ring (42–79%; 15 examples).
- Presnukhina, Sofia,Tarasenko, Marina,Baykov, Sergey,Smirnov, Sergey N.,Boyarskiy, Vadim P.,Shetnev, Anton,Korsakov, Mikhail K.
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supporting information
(2019/12/27)
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- SO2F2-Mediated one-pot cascade process for transformation of aldehydes (RCHO) to cyanamides (RNHCN)
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A simple, mild and practical cascade process for the direct conversion of aldehydes to cyanamides was developed featuring a wide substrate scope and great functional group tolerability. This method allows for transformations of readily available, inexpensive, and abundant aldehydes to highly valuable cyanamides in a pot, atom, and step-economical manner with a green nitrogen source. This protocol will serve as a robust tool for the installation of the cyanamide moiety in various complicated molecules.
- Ding, Chengrong,Ge, Shuting,Wei, Junjie,Zhang, Guofu,Zhao, Yiyong
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p. 17288 - 17292
(2020/05/18)
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- Design, synthesis and biological activities of piperidine-spirooxadiazole derivatives as α7 nicotinic receptor antagonists
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α: 7 nicotinic acetylcholine receptors (nAChRs) expressed in the nervous and immune systems have been suggested to play important roles in the control of inflammation. However, the lack of antagonist tools specifically inhibiting α7 nAChR impedes the validation of the channel as therapeutic target. To discover a selective α7 antagonist, we started a pharmacophore-based virtual screening and identified a piperidine-spirooxadiazole derivative T761–0184 that acts as a α7 antagonist. A series of novel piperidine-spirooxadiazole derivatives were subsequently synthesized and evaluated using two-electrode voltage clamp (TEVC) assay in Xenopus oocytes. Lead compounds from two series inhibited α7 with their IC50 values ranging from 3.3 μM to 13.7 μM. Compound B10 exhibited α7 selectivity over other α4β2 and α3β4 nAChR subtypes. The analysis of structure-activity relationship (SAR) provides valuable insights for further development of selective α7 nAChR antagonists.
- Zhang, Han,He, Xiaomeng,Wang, Xintong,Yu, Bo,Zhao, Siqi,Jiao, Peili,Jin, Hongwei,Liu, Zhenming,Wang, KeWei,Zhang, Liangren,Zhang, Lihe
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- Synthesis and anticancer evaluation of new lipophilic 1,2,4 and 1,3,4-oxadiazoles
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A series of1,2,4- and 1,3,4-oxadiazole derivatives were synthesized and evaluated for their anticancer activity. Halogenated 1,2,4-oxadiazoles were obtained from benzonitrile and coupled either lipophilic amines or with aminoalcohols. Lipophilic 1,3,4-oxadiazole derivatives were obtained through the Mannich reactions between 5-(aryl)-1,3,4-oxadiazole-2-thiol and alkylated or acylated amines. The in vitro cytotoxic effects were evaluated against 4T1– mammary carcinoma and CT26 – colon cancer cells. The best results were obtained for the 1,3,4-oxadiazole coupled to alkylated piperazine with 10–14 carbon chain moiety, with IC50 values ranging from 1.6 to 3.55μΜ for the 4T1 cell line, and from 1.6 to 3.9 μM for the CT26.WT cell line, and selectivity index up to 19. The most potent compounds were investigated with AnnexinV and PI staining as indicative of apoptosis induction.
- Caneschi, Wiliam,Enes, Karine Braga,Carvalho de Mendon?a, Camille,de Souza Fernandes, Fábio,Miguel, Fabio Balbino,da Silva Martins, Jefferson,Le Hyaric, Mireille,Pinho, Roberto Rosas,Duarte, Lucas Mattos,Leal de Oliveira, Marcone Augusto,Dos Santos, Hélio F.,Paz Lopes, Miriam Teresa,Dittz, Dalton,Silva, Heveline,Costa Couri, Mara Rubia
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- Synthesis and Biological Evaluation of Sigma-1 (σ1) Receptor Ligands Based on Phenyl-1,2,4-oxadiazole Derivatives
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In this study, a series of phenyl-1,2,4-oxadiazole derivatives were synthesized and evaluated for anti-allodynic activity. Structure–activity relationship studies identified 1-{4-[3-(2,4-dichlorophenyl)-1,2,4-oxadiazol-5-yl]butyl}piperidine (39) with excellent affinity for the σ1 receptor and selectivity for the σ2 receptor, with poor activity to other central nervous system neurotransmitter receptors and transporters associated with pain. Compound 39 exhibited dose-dependent efficacy in suppressing the formalin-induced flinching and attenuating mechanical allodynia in chronic constriction injury-induced neuropathic rats. These results suggest that compound 39 exerts potent antihyperalgesic activity and could be considered as a promising candidate for treating neuropathic pain.
- Cao, Xudong,Yao, Zhongyuan,Dou, Fei,Zhang, Yifang,Qiu, Yinli,Zhao, Song,Xu, Xiangqing,Liu, Xin,Liu, Bi-Feng,Chen, Yin,Zhang, Guisen
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- A cascade process for directly converting nitriles (RCN) to cyanamides (RNHCN) via SO2F2-activated Tiemann rearrangement
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A simple, mild and practical process for the direct conversion of nitriles to cyanamides was newly discovered and exhibited a wide substrate scope as well as great functional group-tolerability (36 examples). In this efficient strategy, the in situ generated amidoximes obtained from the reaction of nitriles with hydroxylamine subsequently underwent Tiemann rearrangement, producing the corresponding cyanamides with great isolated yields under SO2F2. Additionally, the control experiments reportedly shed light on the tentative mechanism involved in the formation and elimination of the key intermediate: a sulfonyl ester.
- Zhang, Guofu,Zhao, Yiyong,Ding, Chengrong
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supporting information
p. 7684 - 7688
(2019/08/30)
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- Continued exploration of 1,2,4-oxadiazole periphery for carbonic anhydrase-targeting primary arene sulfonamides: Discovery of subnanomolar inhibitors of membrane-bound hCA IX isoform that selectively kill cancer cells in hypoxic environment
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An expanded set of diversely substituted 1,2,4-oxadiazole-containing primary aromatic sulfonamides was synthesized and tested for inhibition of human carbonic anhydrase I, II, IX and XII isoforms. The initial biochemical profiling revealed a significantly
- Krasavin, Mikhail,Shetnev, Anton,Sharonova, Tatyana,Baykov, Sergey,Kalinin, Stanislav,Nocentini, Alessio,Sharoyko, Vladimir,Poli, Giulio,Tuccinardi, Tiziano,Presnukhina, Sofia,Tennikova, Tatiana B.,Supuran, Claudiu T.
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- Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis
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In order to discover novel hypoxia-inducible factor 1 (HIF-1) inhibitors for the cancer metastasis treatment, 68 new aryl carboxamide compounds were synthesized and evaluated for their inhibitory effect by dual luciferase-reporter assay. Based on five rounds of investigation on structure-activity relationships step by step, compound 30m was discovered as the most active inhibitor (IC50 = 0.32 μM) with no obvious cytotoxicity (CC50 > 50 μM). It effectively attenuated hypoxia-induced HIF-1α protein accumulation and reduced transcription of vascular epidermal growth factor in a dose-dependent manner, which was further demonstrated by its inhibitory potency on capillary-like tube formation, angiogenesis of zebrafish as well as cellular migration and invasion. Importantly, compound 30m exhibited antimetastatic potency in breast cancer lung metastasis in the mice model, indicating its promising therapeutic potential for prevention and treatment of tumor metastasis. These results definitely merit attention for further rational design of more efficient HIF-1 inhibitors in the future.
- Liu, Mingming,Liang, Yuru,Zhu, Zhongzhen,Wang, Jin,Cheng, Xingxing,Cheng, Jiayi,Xu, Binpeng,Li, Rong,Liu, Xinhua,Wang, Yang
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supporting information
p. 9299 - 9314
(2019/10/16)
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- Rifamycin derivatives active against pathogenic rapidly-growing mycobacteria
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Infections due to rapidly growing mycobacteria (RGM), and in particular the RGM species Mycobacterium abscessus (Mab), are very difficult to treat and reports on novel therapeutic options are scarce. A hallmark of all pathogenic RGM species is their resis
- Combrink, Keith D.,Ramos, Andrea Ramirez,Spring, Stephanie,Schmidl, Sebastian,Elizondo, Kira,Morin, Petronilo,De Jesus, Bryant,Maurer, Florian P.
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supporting information
p. 2112 - 2115
(2019/07/09)
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- Convenient entry to N-pyridinylureas with pharmaceutically privileged oxadiazole substituents via the acid-catalyzed C[sbnd]H activation of N-oxides
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Pyridine-N-oxides bearing a pharmacophoric oxadiazole moiety could be C[sbnd]H functionalized via the acid-catalyzed reaction with dialkylcyanamides, providing access to hitherto undescribed pyridine-2-yl substituted ureas, which have potential as “lead-l
- Geyl, Kirill,Baykov, Sergey,Tarasenko, Marina,Zelenkov, Lev E.,Matveevskaya, Vladislava,Boyarskiy, Vadim P.
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supporting information
(2019/09/12)
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- Electrocyclic Ring-Opening of 1,2,4-Oxadiazole[4,5-a]piridinium Chloride: a New Route to 1,2,4-Oxadiazole Dienamino Compounds
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1,2,4-Oxadiazole[4,5-a]piridinium chloride adds nucleophiles to undergo electrocyclic ring opening affording 1,2,4-oxadiazole dienamino derivatives. These pyridinium salts represent a special class of Zincke salts that are prone to rearrange when treated
- Carella, Stefano,Memeo, Misal Giuseppe,Quadrelli, Paolo
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p. 1209 - 1221
(2019/10/19)
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- Design, synthesis and biological evaluation of novel 2,3-indolinedione derivatives against mantle cell lymphoma
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2,3-Indolinedione derivatives have been identified as a novel class of promising agents for cancer treatment. In this study, eighteen 2,3-indolinedione derivatives were designed and synthesized, and their anticancer activities against mantle cell lymphoma (MCL) cells were evaluated. Most of them exhibited significant antiproliferative activity against the tested cell lines, and compound K5 was the most potent (MCL cellular IC50 = 0.4–0.7 μM). Further, compound K5 could induce cell apoptosis and cell cycle arrest in G2/M phase. Additionally, the results of drug-likeness analysis demonstrated that these novel 2,3-indolinedione derivatives could have potential as novel treatment strategies for MCL.
- Yu, Shengping,Liu, Yang,Zhang, Zhen,Zhang, Jingya,Zhao, Guisen
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p. 3319 - 3327
(2019/06/21)
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- Development of the 99mTc-Hydroxamamide Complex as a Probe Targeting Carbonic Anhydrase IX
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Carbonic anhydrase IX (CA-IX) is regarded as a favorable target for in vivo imaging because of its specific expression in hypoxic regions of tumors. Hypoxia assists tumor propagation and growth and is resistant to chemotherapy and radiotherapy. Here, we designed and synthesized [99mTc]hydroxamamide ([99mTc]Ham) and [99mTc]methyl-substituted-hydroxamamide ([99mTc]MHam) complexes including a bivalent CA-IX ligand, sulfonamide (SA), and ureidosulfonamide (UR). In a cell binding assay, [99mTc]Ham complexes with bivalent SA ([99mTc]SAB2A and [99mTc]SAB2B) and UR ([99mTc]URB2A and [99mTc]URB2B) showed significantly greater uptake into CA-IX high-expressing (HT-29) cells than that into CA-IX low-expressing cells. Since the binding affinity of [99mTc]URB2A and [99mTc]URB2B for CA-IX was significantly higher than that of [99mTc]SAB2A and [99mTc]SAB2B, we additionally synthesized [99mTc]MURB2 (a [99mTc]MHam complex with bivalent UR) and evaluated the CA-IX-specific binding affinity of [99mTc]URB2A, [99mTc]URB2B, and [99mTc]MURB2. Their uptake into HT-29 cells was reduced by the addition of a CA inhibitor, acetazolamide, suggesting their CA-IX-specific binding affinity. A biodistribution study in HT-29 tumor-bearing mice was carried out using [99mTc]URB2A and [99mTc]MURB2 with the highest specificity for HT-29 cells. [99mTc]URB2A showed moderate tumor uptake and reduction by coinjection with acetazolamide; however, the tumor/blood ratio was insufficient for in vivo imaging. These results provided key information for the design of novel Ham-based imaging probes targeting CA-IX.
- Iikuni, Shimpei,Tanimura, Keiichi,Watanabe, Hiroyuki,Shimizu, Yoichi,Saji, Hideo,Ono, Masahiro
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p. 1489 - 1497
(2019/04/25)
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- With eliminating free radical effect of the benzopyran-containing cosmetic auxiliary material and its preparation method (by machine translation)
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The invention has disclosed a kind of scavenging free radical effect of the benzopyran-containing cosmetic auxiliary material and its preparation method, which belongs to the functional organic molecular synthesis of technical field. Technical proposal of the invention points are: the benzopyran-containing cosmetic supplementary product has the structure The invention through a new method for synthesizing a novel structure of the benzofuran compound, and to carry out the oxidation resistant research, and carry on the skin of the human body the spot pastes experiment, display under certain concentration does not have harmful effects on human body skin, and then hope that can be applied to the cosmetics, as auxiliary antioxidant additive. (by machine translation)
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Paragraph 0022-0036
(2019/07/04)
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- Efficient synthesis of novel 1-hydroxy-2,4,5-trisubstituted imidazole derivatives via a one-pot, four-component reaction between hydroxylamine, benzonitriles, arylglyoxals and cyclic 1,3-dicarbonyl compounds
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A simple, and efficient procedure for the synthesis of novel 2,5-diaryl-1-hydroxy-1H-imidazol-4-yl derivatives via a one-pot, four-component reaction between hydroxylamine, benzonitriles, arylglyoxals and cyclic 1,3-dicarbonyl compounds (Melrum’s acid or dimedone) in ethanol under reflux conditions without using bases and catalysts is reported. All the products were obtained in good yields and their structures were established from their spectroscopic data.
- Alizadeh-Bami, Farzaneh,Salehzadeh, Mina,Mehrabi, Hossein,Ranjbar-Karimi, Reza
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supporting information
p. 55 - 63
(2019/11/11)
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- One-pot synthesis of 3,5-diaryl substituted-1,2,4-oxadiazoles using gem -dibromomethylarenes
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1,2,4-Oxadiazole is one of the most promising heterocyclic ring systems in medicinal chemistry. In the present paper, we report the method for an efficient one-pot synthesis of 3,5-diaryl substituted 1,2,4-oxadiazoles using a two-component reaction of gem-dibromomethylarenes with amidoximes in good yields. In this method, gem-dibromomethylarenes are used as benzoic acid equivalents for the efficient synthesis of aryl-substituted 1,2,4-oxadiazoles. It is anticipated that this methodology will have versatile applications in the practical syntheses of various molecules of both medicinal and material chemistry importance.
- Vinaya, Kambappa,Chandrashekara, Ganganahalli K.,Shivaramu, Prasanna D.
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p. 690 - 696
(2019/09/06)
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- 1, 2, 4-oxadiazole incorporated ketoprofen analogues in search of safer non-steroidal anti-inflammatory agents: Design, syntheses, biological evaluation and molecular docking Studies
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Background: Improving the gastrointestinal safety profile of Non-Steroidal Anti- Inflammatory Drugs (NSAIDs) is an important goal. An important strategy to develop NSAIDs with minimal Gastrointestinal (GI) toxicity is to target the COX-2 isoform with a se
- Ranjan, Chanda,Kumar, Jagdish,Sharma, Kalicharan,Akhter, Mymoona,Siddiqui, Anees A.,Chawla, Gita
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p. 590 - 601
(2018/06/06)
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- Facile room-temperature assembly of the 1,2,4-oxadiazole core from readily available amidoximes and carboxylic acids
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A one-pot ambient-temperature procedure for the synthesis of 3,5-disubstituted-1,2,4-oxadiazoles from amidoximes and carboxylic acids under superbase-promoted conditions is reported.
- Sharonova, Tatyana,Pankrat'eva, Vitalina,Savko, Polyna,Baykov, Sergey,Shetnev, Anton
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supporting information
p. 2824 - 2827
(2018/06/13)
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- An efficient synthesis and antimicrobial evaluation of 5-alkenyl- and 5-styryl-1,2,4-oxadiazoles
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The cyclodehydration of O-acylamidoximes at room temperature in the superbase system KOH/DMSO represents a simple and efficient way to 5-alkenyl- and 5-styryl-1,2,4-oxadiazoles. This method is suitable for the preparation of 5-(4-vinylphenyl)-1,2,4-oxadia
- Tarasenko, Marina,Sidneva, Vera,Belova, Alexandra,Romanycheva, Anna,Sharonova, Tatyana,Baykov, Sergey,Shetnev, Anton,Kofanov, Eugeniy,Kuznetsov, Mikhail A.
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supporting information
p. 458 - 470
(2019/03/07)
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- Function-oriented synthesis of marine phidianidine derivatives as potential PTP1B inhibitors with specific selectivity
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Phidianidines A and B are two novel marine indole alkaloids bearing an uncommon 1,2,4-oxadiazole ring and exhibiting various biological activities. Our previous research showed that the synthesized phidianidine analogs had the potential to inhibit the activity of protein tyrosine phosphatase 1B (PTP1B), a validated target for Type II diabetes, which indicates that these analogs are worth further structural modification. Therefore, in this paper, a series of phidianidine derivatives were designed and rapidly synthesized with a function-oriented synthesis (FOS) strategy. Their inhibitory effects on PTP1B and T-cell protein tyrosine phosphatase (TCPTP) were evaluated, and several compounds displayed significant inhibitory potency and specific selectivity over PTP1B. The structure-activity relationship (SAR) and molecular docking analyses are also described.
- Liu, Jin,Chen, Yu,Li, Jing-Ya,Luo, Cheng,Li, Jia,Chen, Kai-Xian,Li, Xu-Wen,Guo, Yue-Wei
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- Design and Synthesis of Marine Phidianidine Derivatives as Potential Immunosuppressive Agents
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A series of novel marine phidianidine derivatives were designed, synthesized, and evaluated for their immunosuppressive activities during our search of potential immunosuppressive agents with high efficacy and low toxicity from marine sources. These compounds were tested for their inhibitory activity on Con A-induced T cell and lipopolysaccharide-induced B cell proliferation. Compounds 14a and 18c, displaying the most promising inhibitory effects and low toxicities, were further found to possess immune-regulatory activities upon cross-linking of T cell receptor (TCR) and B cell receptor (BCR) on purified T and B cells, respectively.
- Liu, Jin,Li, Heng,Chen, Kai-Xian,Zuo, Jian-Ping,Guo, Yue-Wei,Tang, Wei,Li, Xu-Wen
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p. 11298 - 11308
(2019/01/04)
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- Design, synthesis, and biological evaluation of novel oxadiazole- and thiazole-based histamine H3R ligands
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Histamine H3 receptor (H3R) is largely expressed in the CNS and modulation of the H3R function can affect histamine synthesis and liberation, and modulate the release of many other neurotransmitters. Targeting H3R with antagonists/inverse agonists may have therapeutic applications in neurodegenerative disorders, gastrointestinal and inflammatory diseases. This prompted us to design and synthesize azole-based H3R ligands, i.e. having oxadiazole- or thiazole-based core structures. While ligands of oxadiazole scaffold were almost inactive, thiazole-based ligands were very potent and several exhibited binding affinities in a nanomolar concentration range. Ligands combining 4-cyanophenyl moiety as arbitrary region, para-xylene or piperidine carbamoyl linkers, and/or pyrrolidine or piperidine basic heads were found to be the most active within this series of thiazole-based H3R ligands. The most active ligands were in silico screened for ADMET properties and drug-likeness. They fulfilled Lipinski's and Veber's rules and exhibited potential activities for oral administration, blood–brain barrier penetration, low hepatotoxicity, combined with an overall good toxicity profile.
- Khanfar, Mohammad A.,Reiner, David,Hagenow, Stefanie,Stark, Holger
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supporting information
p. 4034 - 4046
(2018/06/30)
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- Exploration of diphenylalkyloxadiazoles as novel cardiac myosin activator
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To explore novel cardiac myosin activator, a series of diphenylalkyl substituted 1,3,4-oxadiazoles and 1,2,4-oxadiazoles have been prepared and tested for cardiac myosin ATPase activation in vitro. In all cases, three carbon spacer between the oxadiazole core and one of the phenyl ring was considered crucial. In case of 1,3,4-oxadiazole, zero to two carbon spacer between oxadiazole core and other phenyl ring are favorable. Phenyl ring can be replaced by cyclohexyl moiety. In case of 1,2,4-oxadiazole, zero or one carbon spacer between the oxadiazole and other phenyl ring are favorable. Introduction of hydrogen bonding donor (NH) group at the 2nd position of the 1,3,4-oxadiazole enhances the activity. Substitutions on either of the phenyl rings or change of phenyl ring to other heterocycle are not tolerated for both the oxadiazoles. The prepared oxadiazoles showed selective activation for cardiac muscle over smooth and skeleton muscles.
- Manickam, Manoj,Boggu, Pulla Reddy,Pillaiyar, Thanigaimalai,Sharma, Niti,Jalani, Hitesh B.,Venkateswararao, Eeda,Jung, Sang-Hun
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supporting information
p. 2369 - 2374
(2018/06/25)
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- Survey Reactivity of Some Substituted Quinazolinones with Pentafluoro(chloro)pyridine
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A new series of 4-hetroaryl substituted quinazolines were designed and synthesized by the reaction of pentafluoro(chloro)pyridine and 2-substituted quinazolinone. The aromatic nucleophilic substitution of pentafluoro(chloro)pyridine with quinazolinone occurs at the 4-position of pyridine ring by the oxygen site (O-centered nucleophile) of quinazolinone. The structures of all the compounds were confirmed by IR, 1H NMR, 19F NMR, and 13C NMR spectroscopy as well as elemental analysis.
- Ranjbar-Karimi, Reza,Davodian, Tayebeh,Mehrabi, Hossein
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p. 475 - 480
(2017/12/28)
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- METHOD FOR PRODUCING 1,2,4-OXADIAZOLE DERIVATIVE
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The invention provides a production method of a 1,2,4-oxadiazole derivative represented by formula (A), which comprises reacting a compound represented by formula (B) and a compound represented by formula (C) in the presence of a basic compound: wherein Ar is an aromatic group or an aromatic group having substituent(s); W, X, Y and Z are each independently —S—, —N═, —CH═ or —CR═, and one selected from W, X, Y and Z is —S—; and R is an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 3 carbon atoms, a haloalkyl group having 1 to 3 carbon atoms, a haloalkoxy group having 1 to 3 carbon atoms or a halogen atom.
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Paragraph 0147
(2018/03/01)
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- A convenient one-pot synthesis of: N -substituted amidoximes and their application toward 1,2,4-oxadiazol-5-ones
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The first direct one-pot approach for the synthesis of N-substituted amidoximes from secondary amides or the intermediate amides has been developed. Through the Ph3P-I2-mediated dehydrative condensation, a variety of N-aryl and N-alkyl amidoximes (R1(CNOH)NHR2, where R1 or R2 = aryl, alkyl, or benzyl) were readily afforded under mild conditions and short reaction times. The synthetic application of the obtained amidoximes has also been demonstrated through the formation of 1,2,4-oxadiazolones via base-mediated carbonylative cyclization with 1,1′-carbonyldiimidazole.
- Phakhodee, Wong,Duangkamol, Chuthamat,Wiriya, Nitaya,Pattarawarapan, Mookda
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p. 38281 - 38288
(2018/12/02)
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- Development of Pyridazinone Chemotypes Targeting the PDEδ Prenyl Binding Site
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The K-Ras GTPase is a major target in anticancer drug discovery. However, direct interference with signaling by K-Ras has not led to clinically useful drugs yet. Correct localization and signaling by farnesylated K-Ras is regulated by the prenyl binding protein PDEδ. Interfering with binding of PDEδ to K-Ras by means of small molecules provides a novel opportunity to suppress oncogenic signaling. Here we describe the identification and structure-guided development of novel K-Ras–PDEδ inhibitor chemotypes based on pyrrolopyridazinones and pyrazolopyridazinones that bind to the farnesyl binding pocket of PDEδ with low nanomolar affinity. We delineate the structure–property relationship and in vivo pharmacokinetic (PK) and toxicokinetic (Tox) studies for pyrazolopyridazinone-based K-Ras–PDEδ inhibitors. These findings may inspire novel drug discovery efforts aimed at the development of drugs targeting oncogenic Ras.
- Murarka, Sandip,Martín-Gago, Pablo,Schultz-Fademrecht, Carsten,Al Saabi, Alaa,Baumann, Matthias,Fansa, Eyad K.,Ismail, Shehab,Nussbaumer, Peter,Wittinghofer, Alfred,Waldmann, Herbert
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supporting information
p. 6083 - 6093
(2017/05/05)
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- Environmental-protection preparation method for high yielding of 1,2,4-oxadiazole compounds containing alpha,beta-unsaturated ketones
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The invention provides an environmental-protection preparation method for high yielding of 1,2,4-oxadiazole compounds containing alpha,beta-unsaturated ketones; with 2,3-dichlorophenol as a raw material, an intermediate 5 is obtained through methylation and protection of phenolic hydroxyl groups, Friedel-Crafts acylation, methyl protecting group removal, nucleophilic substitution, ester hydrolysis, aldol condensation and dehydration reaction and then undergoes cyclization reaction with substituted amine oxime to obtain the target products 6r, 6s and 6u. The method has the advantages of mild reaction conditions, has no use of first-class reagents and other reagents harmful on the environment and operating personnel, fewer by-products, stable and controllable reactions, simple postprocessing, high yield and purity, and easy industrialized production.
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Paragraph 0078; 0079; 0080
(2017/08/30)
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- Synthesis method of benzamidine hydrochloride
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The invention discloses a synthesis method of benzamidine hydrochloride, and belongs to the field of chemical synthesis. Benzonitrile and hydroxylamine hydrochloride carry out addition reactions under the effect of an acid-binding agent and a phase transfer agent to obtain benzamidoxime; obtained benzamidoxime carries out reduction reactions at first and then is acidified to obtain a coarse product of benzamidine hydrochloride; then the coarse product is heated and dissolved in a solvent, active carbon is added into the solution to carry out color removal, then the solution is filtered, and the filtrate is dried to obtain pure benzamidine hydrochloride. The preparation method has the advantages of simpleness, green, environmental friendliness, and suitability for industrial production.
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Paragraph 0022; 0023; 0024; 0027; 0028; 0029
(2017/12/09)
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- A Potent, Selective, and Orally Bioavailable HCV NS5A Inhibitor for Treatment of Hepatitis C Virus: (S)-1-((R)-2-(Cyclopropanecarboxamido)-2-phenylacetyl)-N-(4-phenylthiazol-2-yl)pyrrolidine-2-carboxamide
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Starting from the initial lead 4-phenylthiazole 18, a modest HCV inhibitor (EC50 = 9440 nM), a series of structurally related thiazole derivatives has been identified as a novel chemical class of potent and selective HCV NS5A inhibitors. The introduction of a carboxamide group between the thiazole and pyrrolidine ring (42) of compound 18 resulted in a dramatic increase in activity (EC50 = 0.92 nM). However, 42 showed only moderate pharmacokinetic properties and limited oral bioavalability of 18.7% in rats. Further optimization of the substituents at the 4-position of the thiazole ring and pyrrolidine nitrogen of the lead compound 42 led to the identification of compound 57, a highly potent and selective NS5A inhibitor of HCV (EC50 = 4.6 nM), with greater therapeutic index (CC50/EC50 > 10000). Pharmacokinetic studies revealed that compound 57 had a superior oral exposure and desired bioavailability of 45% after oral administration in rats.
- Kang, Iou-Jiun,Hsu, Sheng-Ju,Yang, Hui-Yun,Yeh, Teng-Kuang,Lee, Chung-Chi,Lee, Yen-Chun,Tian, Ya-Wen,Song, Jen-Shin,Hsu, Tsu-An,Chao, Yu-Sheng,Yueh, Andrew,Chern, Jyh-Haur
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p. 228 - 247
(2017/04/26)
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- Room-temperature synthesis of pharmaceutically important carboxylic acids bearing the 1,2,4-oxadiazole moiety
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An efficient and mild one-pot protocol has been developed for the synthesis of 1,2,4-oxadiazoles via the reaction of amidoximes with dicarboxylic acid anhydrides in a NaOH/DMSO medium. The method allows the synthesis of diversely substituted carboxylic acids bearing the 1,2,4-oxadiazole motif, – a popular building block for pharmaceutical research, in moderate to excellent yields. The reaction scope includes aromatic and heteroaromatic amidoximes as well as five-, six- and seven-membered anhydrides. The advantages of this procedure are proven gram-scalability and the use of inexpensive starting materials, which from a process chemistry point of view are essential for future industrial applications.
- Tarasenko, Marina,Duderin, Nikolay,Sharonova, Tatyana,Baykov, Sergey,Shetnev, Anton,Smirnov, Alexey V.
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supporting information
p. 3672 - 3677
(2017/08/23)
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- Synthesis, characterisation and photophysical studies of oxadiazolyl coumarin: A new class of blue light emitting fluorescent dyes
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A library of novel 1, 2, 4-oxadiazole linked coumarin dyes have been synthesised via condensation of corresponding acid 6 and N’-hydroxybenzimidamide 8. This new class of organic compounds were examined for their fluorescent properties and found to emit blue light in the visible region of the spectrum with very high Stoke's shift values. Most of these compounds demonstrated high quantum yields and fluorescence life time in nano-second range which makes them quite lucrative to be used as new fluorescent probes. The highest quantum yield of 0.68 was shown by compound 9j which also shows high Stoke's shift value. The electronic structure of these coumarin-based donor–π–acceptor (D–π–A)-type organic dyes have been examined by Density Functional Theory (DFT). TGA analysis of few of the compounds show that they are stable up to temperature range of 0–245?°C. The synthesised compounds were characterised by NMR and mass spectrometry and the structure of two of these compounds have been confirmed by X-ray crystallography.
- Matta, Akanksha,Bahadur, Vijay,Taniike, Toshiaki,Van der Eycken, Johan,Singh, Brajendra K.
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p. 250 - 260
(2017/02/05)
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- Cobalt(III)-Catalyzed Oxadiazole-Directed C-H Activation for the Synthesis of 1-Aminoisoquinolines
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Aromatic heterocycles have been identified as effective directing groups (DGs) in C-H functionalization but can be retained as undesired bulky substituents in the final products. Herein, we report a Co(III)-catalyzed 1-aminoisoquinoline synthesis strategy based on oxadiazole-directed aromatic C-H coupling with alkynes and a subsequent redox-neutral C-N cyclization reaction. This labile N-O bond-based protocol has allowed the toleration of a broad range of functional groups.
- Yang, Fan,Yu, Jiaojiao,Liu, Yun,Zhu, Jin
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supporting information
p. 2885 - 2888
(2017/06/07)
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- Rhodium-catalyzed synthesis of 1-(acylamino)isoquinolines through direct annulative coupling of 3-aryl-1,2,4-oxadiazoles with alkynes
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A Rh(III)-catalyzed direct annulative coupling of 3-aryl-1,2,4-oxadiazoles with alkynes through coordination-assisted CH activation is developed, providing a facile route to 1-(acylamino)isoquinolines. The oxadiazole ring acts as a directing group as well as an internal oxidant.
- Nishii, Yuji,Bachon, Anne-Katrin,Moon, Sanghun,Bolm, Carsten,Miura, Masahiro
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supporting information
p. 1347 - 1349
(2017/08/14)
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- Indazole-oxadiazole derivative, medicinal composition containing derivative, and application of derivative in tumor prevention
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The invention discloses an indazole-oxadiazole derivative with the structure represented by general formula a shown in the description, or a pharmaceutically acceptable salt or solvate thereof. In the formula, X is O or N, Y is N, Z is N or O, and all groups are as defined in the description. The invention also discloses a medicinal composition adopting the derivative as an active component, and a use of the derivative. Compounds synthesized in the invention have an HIF-1 inhibition effect, and most of the compounds have a substantial HIF-1 inhibition effect, have strong in-vivo and in-vitro anti-HIF-1 effect on human colorectal carcinoma cell strains (HCT116) and other tumor cell strains, and can be used for treating tumor diseases.
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Paragraph 0099; 0100; 0109; 0110
(2017/07/25)
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- Palladium-Catalyzed, Silver-Assisted Direct C-5–H Arylation of 3-Substituted 1,2,4-Oxadiazoles under Microwave Irradiation
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A direct C-5–H arylation of 3-substituted 1,2,4-oxadiazoles with aryl iodides in the presence of a palladium catalyst and silver acetate is reported. This method provides a rapid, reliable way to obtain versatile 3,5-diaryl-1,2,4-oxadiazole derivatives, which are common moieties of many biologically active molecules. The synthetic applications of this novel method have been demonstrated in the concise syntheses of Ataluren and a potent RET inhibitor Yhhu251. (Figure presented.).
- Li, Shan,Wan, Penghui,Ai, Jing,Sheng, Rong,Hu, Yongzhou,Hu, Youhong
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supporting information
p. 772 - 778
(2017/03/11)
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- Ferrocenylethenyl-substituted 1,3,4-oxadiazolyl-1,2,4-oxadiazoles: Synthesis, characterization and DNA-binding assays
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This article describes the synthesis, characterization and DNA-binding assays of a series of oxadiazoles derived from (E)-3-ferrocenylacrylic acid. The compounds were obtained in satisfactory yields and characterized by NMR and high resolution mass spectrometry analysis. Additionally, the X-Ray characterization of compound 8a was investigated. A series of ferrocenylethenyl-substituted 1,3,4-oxadiazolyl-1,2,4-oxadiazoles was prepared and studied by UV-visible and electrochemical techniques. The characteristic signals of the redox-active ferrocene/ferrocenium couple were monitored, which allowed verification of the influence of electron-withdrawing oxadiazole heterocycles and their dependence on the 1,2,4-oxadiazole substituent. Also, DNA-binding experiments were performed by UV-vis and emission titrations with ct-DNA.
- Mayer, Jo?o C.P.,Sauer, André C.,Iglesias, Bernardo A.,Acunha, Thiago V.,Back, Davi F.,Rodrigues, Oscar E.D.,Dornelles, Luciano
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