- Novel O-acylated amidoximes and substituted 1,2,4-oxadiazoles synthesised from (+)-ketopinic acid possessing potent virus-inhibiting activity against phylogenetically distinct influenza A viruses
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This article describes the synthesis and antiviral activity evaluation of new substituted 1,2,4-oxadiazoles containing a bicyclic substituent at position 5 of the heterocycle and O-acylated amidoximes as precursors for their synthesis. New compounds were
- Chernyshov, Vladimir V.,Yarovaya, Olga I.,Esaulkova, Iana L.,Sinegubova, Ekaterina,Borisevich, Sophia S.,Popadyuk, Irina I.,Zarubaev, Vladimir V.,Salakhutdinov, Nariman F.
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- CARBOXY DERIVATIVES WITH ANTIINFLAMMATORY PROPERTIES
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The invention relates to compounds of formula (I) and to their use in treating or preventing an inflammatory disease or a disease associated with an undesirable immune response: (I) wherein, RA1, RA2, RC and RD are as defined herein.
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Page/Page column 77; 89
(2021/07/02)
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- Catalyst-free, one-pot strategy to access 3-substituted-5-amino-1,2,4-thiadiazoles in water
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A protocol has been devised for the synthesis of 3-substituted 5-amino-1,2,4-thiadiazoles utilizing isothiocyanates, amidoximes and water as an eco-friendly solvent. The strategy involves consecutive C?N and S?N bonds formation in a one-pot reaction under
- Nagaraju, Chaithra,Ashok, Swarup Hassan,Narayana, Yatheesh,Nagarakere, Sandhya C.,Kempegowda, Mantelingu,Kanchugarkoppal, Rangappa S.
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p. 3610 - 3619
(2021/10/14)
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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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- 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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- 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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- 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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- Synthesis and Evaluation of Antibacterial Activity of 1,2,4-Oxadiazole-Containing Biphenylcarboxylic Acids
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Abstract: A one-pot method for the synthesis of biphenylcarboxylic acids containing 1,2,4-oxadiazole ring in the NaOH–DMSO system was developed. The results of in vitro experiments showed that the synthesized compounds exhibit antibacterial activity against susceptible strains of E. coli and S. aureus.
- Baikov, S. V.,Presnukhina, S. I.,Shetnev, A. A.,Tarasenko, M. V.
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p. 1611 - 1619
(2020/10/15)
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- 1,2,4-Oxadiazole ring–containing pyridylpyrazole-4-carboxamides: Synthesis and evaluation as novel insecticides of the anthranilic diamide family
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Herein, we describe the preparation of pyridylpyrazole-4-carboxamides containing a 1,2,4-oxadiazole ring as novel anthranilic diamide derivatives and compare their insecticidal activities to that of chlorantraniliprole, a well-established potent insectici
- Khallaf, Abdalla,Liu, Hui,Wang, Ping,Zhu, Hongjun,Zhuo, Shuping
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supporting information
(2020/02/18)
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- Discovery of 1,2,4-oxadiazole derivatives as a novel class of noncompetitive inhibitors of 3-hydroxykynurenine transaminase (HKT) from Aedes aegypti
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The mosquito Aedes aegypti is the vector of arboviruses such as Zika, Chikungunya, dengue and yellow fever. These infectious diseases have a major impact on public health. The unavailability of effective vaccines or drugs to prevent or treat most of these
- Guido, Rafael V. C.,Leal, Laylla L. L.,Maciel, Larissa G.,Oliveira, Andrew A.,Rom?o, Tatiany P.,Silva-Filha, Maria Helena N. L.,Soares, Thereza A.,dos Anjos, Janaína V.
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- Synthesis of Some Azamacrocycles Bearing 1,2,4-Oxadiazole and 1,2,3-Triazole Moieties
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Abstract: A tetraazacrown ether,4,9-di(prop-2-yn-1-yl)-1,4,9,12-tetraazacyclohexadecane-2,11-dione, bearingpropargyl groups on two nitrogens was synthesized starting from1,4,9,12-tetraazacyclohexadecane-2,11-dione and subjected to 1,3-cycloadditionreactio
- ?zer, B.,Dürüst, Y.
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p. 698 - 705
(2020/06/01)
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- Synthesis and Anticancer Activity of Novel Actinonin Derivatives as HsPDF Inhibitors
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Human mitochondrial peptide deformylase (HsPDF) is responsible for removing the formyl group from N-terminal formylmethionines of newly synthesized mitochondrial proteins and plays important roles in maintaining mitochondria function. It is overexpressed
- Hu, Liu,Cai, Xing,Dong, Suzhen,Zhen, Yongjia,Hu, Jidi,Wang, Shenjun,Jiang, Jingwen,Huang, Jiawu,Han, Yuqiao,Qian, Yu,Yuan, Yanqiu,Hu, Wenhao
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p. 6959 - 6978
(2020/08/14)
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- NOVEL TRIAZOLONE DERIVATIVES OR SALTS THEREOF AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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The present technology provides triazolone derivatives or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and the use thereof. The triazolone derivatives or their pharmaceutically acceptable salts exhibit selective inhibitory activity on VAP-1 and therefore can be usefully applied, e.g., for the treatment and prophylaxis of nonalcoholic hepatosteatosis (NASH).
- -
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Paragraph 0211-0212
(2019/10/15)
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- NOVEL ARYL OR HETEROARYL TRIAZOLONE DERIVATIVES OR SALTS THEREOF, OR PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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The present technology provides aryl or heteroaryl triazolone derivatives or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and the use thereof. The aryl or heteroaryl triazolone derivatives or their pharmaceutically acceptable salts exhibit selective inhibitory activity on VAP-1 and therefore can be usefully applied, e.g., for the treatment and prophylaxis of nonalcoholic hepatosteatosis (NASH).
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-
Paragraph 0332-0334; 0341-0343
(2019/10/15)
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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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- Efficient Synthesis of Functionalized Indene Derivatives via Rh(III)-Catalyzed Cascade Reaction between Oxadiazoles and Allylic Alcohols
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A highly efficient rhodium(III)-catalyzed synthesis of novel functionalized indene derivatives has been achieved via C?H activation/intramolecular aldol condensation. This cascade reaction is an atom economical protocol which could be further applied to build more complex compounds. (Figure presented.).
- Zhang, Jing,Sun, Jun-Shu,Xia, Ying-Qi,Dong, Lin
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supporting information
p. 2037 - 2041
(2019/03/28)
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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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- Compounds for organic electroluminescent devices
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The present invention relates to boron compounds for use in electronic devices, especially organic electroluminescent devices, and to a process for preparing these compounds and to electronic devices, especially organic electroluminescent devices, comprising these compounds.
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Page/Page column 38
(2018/08/12)
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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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- Pharmacophore requirements for HIV-1 reverse transcriptase inhibitors that selectively “Freeze” the pre-translocated complex during the polymerization catalytic cycle
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Reverse transcriptase (RT) is responsible for replicating the HIV-1 genome and is a validated therapeutic target for the treatment of HIV infections. During each cycle of the RT-catalyzed DNA polymerization process, inorganic pyrophosphate is released as the by-product of nucleotide incorporation. Small molecules were identified that act as bioisosteres of pyrophosphate and can selectively freeze the catalytic cycle of HIV-1 RT at the pre-translocated stage of the DNA- or RNA-template-primer-enzyme complex.
- Lacbay, Cyrus M.,Menni, Michael,Bernatchez, Jean A.,G?tte, Matthias,Tsantrizos, Youla S.
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p. 1713 - 1726
(2018/02/27)
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- TiO2-Nanoparticles Catalyzed Synthesis of New Trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles and Trifluoromethyl-1,2,4-oxadiazoles
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Synthesis of a new series of trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles and trifluoromethyl-1,2,4-oxadiazoles have been described by utilizing the reactions between amidoximes and trifluoroacetimidoyl chlorides. Trifluoromethyl-4,5-dihydro-1,2,4-oxadia
- Darehkordi, Ali,Ramezani, Mahin,Rahmani, Fariba
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p. 1702 - 1708
(2018/05/30)
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- Focused microwave irradiation-assisted synthesis of N-cyclohexyl-1,2,4-oxadiazole derivatives with antitumor activity
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A facile synthesis of 3,5-disubstituted 1,2,4-oxadiazole derivatives under focused microwave irradiation (FMWI) is reported. Arylamidoximes 1a–i and dicyclohexylcarbodiimide (DCC) were carried out in DMF under FMWI to obtain 1,2,4-oxadiazoles 2a–i in 61–8
- de Oliveira, Valentina Nascimento Melo,dos Santos, Franciane Gon?alves,Ferreira, Vanessa Pinheiro Gon?alves,Araújo, Héverton Mendes,do ó Pessoa, Cláudia,Nicolete, Roberto,de Oliveira, Ronaldo Nascimento
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p. 2522 - 2532
(2018/10/15)
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- Structure-activity and structure-property relationships of novel Nrf2 activators with a 1,2,4-oxadiazole core and their therapeutic effects on acetaminophen (APAP)-induced acute liver injury
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The antioxidant function induced by Nrf2 protects the liver from damage. We found a novel Nrf2 activator named compound 25 via structural modification of compound 1 we previously reported. In vitro, compound 25 induced Nrf2 transport into the nucleus and protected hepatocyte L02 cells from APAP-induced cytotoxicity via activating the Nrf2-ARE signaling pathway. In vivo, 25 exhibited therapeutic effects in a mouse model of acute liver injury induced by acetaminophen (APAP) by up-regulating Nrf2-dependent antioxidases and down-regulating liver injury markers in serum. Together, these results indicated that 25 is a potent Nrf2/ARE activator both in vitro and in vivo. The drug-like properties of compound 25 further revealed its potential for development as a therapeutic drug against acute liver injury.
- Xu, Li-Li,Wu, Yu-Feng,Wang, Lei,Li, Cui-Cui,Li, Li,Di, Bin,You, Qi-Dong,Jiang, Zheng-Yu
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p. 1376 - 1394
(2018/09/13)
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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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- Reactions of pentafluoropyridine with amidoximes
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Abstract: In this paper, site reactivity of amidoximes with pentafluoropyridine under basic conditions in dry CH3CN was investigated. The aromatic nucleophilic substitution of pentafluoropyridine with amidoximes occurs in the 4-position of the
- Ranjbar-Karimi, Reza,Karbakhsh-Ravari, Asma,Poorfreidoni, Alireza
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p. 2397 - 2405
(2017/10/30)
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- Oxadiazole compound, as well as preparation method and application thereof
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The invention discloses oxadiazole compound, as well as a preparation method and application thereof, and relates to the field of pesticides. The novel oxadiazole compound, the preparation method thereof and the application of the oxadiazole compound to t
- -
-
Paragraph 0075; 0076
(2017/08/27)
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- Iron(III) Chloride/l-Proline as an Efficient Catalyst for the Synthesis of 3-Substituted 1,2,4-Oxadiazoles from Amidoximes and Triethyl Orthoformate
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A general, facile, and efficient method is presented for the synthesis of 3-substituted 1,2,4-oxadiazoles from amidoximes and triethyl orthoformate. The procedure employs an iron(III) chloride/l-proline catalytic system and the 3-substituted 1,2,4-oxadiaz
- Kaboudin, Babak,Kazemi, Foad,Pirouz, Maryam,Khoshkhoo, Aysan Baharian,Kato, Jun-Ya,Yokomatsu, Tsutomu
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p. 3597 - 3602
(2016/10/18)
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- Base-mediated one-pot synthesis of 1,2,4-oxadiazoles from nitriles, aldehydes and hydroxylamine hydrochloride without addition of extra oxidant
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A simple base-mediated one-pot synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from nitriles, aldehydes and hydroxylamine hydrochloride has been developed, in which the aldehydes act as both substrates and oxidants. The reactions include three sequential
- Wang, Wei,Xu, Hao,Xu, Yuanqing,Ding, Tao,Zhang, Wenkai,Ren, Yanrong,Chang, Haibo
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p. 9814 - 9822
(2016/10/31)
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- Conjugation of N-acylhydrazone and 1,2,4-oxadiazole leads to the identification of active antimalarial agents
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Malaria, caused by several Plasmodium species, is the major life-threatening parasitic infection worldwide. Due to the parasite resistance to quinoline based drugs, the search for antimalarial agents is necessary. Here, we report the structural design, sy
- dos Santos Filho, José Maurício,de Queiroz e Silva, Diogo Manoel Alves,Macedo, Taís Soares,Teixeira, Helena Mariana Pitangueira,Moreira, Diogo Rodrigo Magalhaes,Challal, Soura,Wolfender, Jean-Luc,Queiroz, Emerson Ferreira,Soares, Milena Botelho Pereira
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p. 5693 - 5701
(2016/11/09)
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- Nitrobenzofurazan derivatives of N′-hydroxyamidines as potent inhibitors of indoleamine-2,3-dioxygenase 1
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Tryptophan metabolism through the kynurenine pathway is considered as a crucial mechanism in immune tolerance. Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in tryptophan catabolism in the immune system and it is also considered as an important therapeutic target for the treatment of cancer and other diseases that are linked with kynurenine pathway. In this study, a series of nitrobenzofurazan derivatives of N′-hydroxybenzimidamides (1) and N′-hydroxy-2-phenylacetimidamides (2) were synthesized and their inhibitory activities against human IDO1 enzyme were tested using in-vitro and cellular enzyme activity assay. The optimization leads to the identification of potent compounds, 1d, 2i and 2k (IC50 = 39-80 nM), which are either competitive or uncompetitive inhibitors of IDO1 enzyme. These compounds also showed IDO1 inhibition potencies in the nanomolar range (IC50 = 50-71 nM) in MDA-MB-231 cells with no/negligible amount of cytotoxicity. The stronger selectivity of the potent compounds for IDO1 enzyme over tryptophan 2,3-dioxygenase (TDO) enzyme (312-1593-fold) also makes them very attractive for further immunotherapeutic applications.
- Paul, Saurav,Roy, Ashalata,Deka, Suman Jyoti,Panda, Subhankar,Trivedi, Vishal,Manna, Debasis
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p. 364 - 375
(2016/06/13)
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- Structure-based design, synthesis and evaluation in vitro of arylnaphthyridinones, arylpyridopyrimidinones and their tetrahydro derivatives as inhibitors of the tankyrases
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Abstract The tankyrases are members of the PARP superfamily; they poly(ADP-ribosyl)ate their target proteins using NAD+ as a source of electrophilic ADP-ribosyl units. The three principal protein substrates of the tankyrases (TRF1, NuMA and axin) are involved in replication of cancer cells; thus inhibitors of the tankyrases may have anticancer activity. Using structure-based drug design and by analogy with known 3-arylisoquinolin-1-one and 2-arylquinazolin-4-one inhibitors, series of arylnaphthyridinones, arylpyridinopyrimidinones and their tetrahydro-derivatives were synthesised and evaluated in vitro. 7-Aryl-1,6-naphthyridin-5-ones, 3-aryl-2,6-naphthyridin-1-ones and 3-aryl-2,7-naphthyridin-1-ones were prepared by acid-catalysed cyclisation of the corresponding arylethynylpyridinenitriles or reaction of bromopyridinecarboxylic acids with β-diketones, followed by treatment with NH3. The 7-aryl-1,6-naphthyridin-5-ones were methylated at 1-N and reduced to 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones. Cu-catalysed reaction of benzamidines with bromopyridinecarboxylic acids furnished 2-arylpyrido[2,3-d]pyrimidin-4-ones. Condensation of benzamidines with methyl 1-benzyl-4-oxopiperidine-3-carboxylate and deprotection gave 2-aryl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ones, aza analogues of the known inhibitor XAV939. Introduction of the ring-N in the arylnaphthyridinones and the arylpyridopyrimidinones caused >1000-fold loss in activity, compared with their carbocyclic isoquinolinone and quinazolinone analogues. However, the 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones showed excellent inhibition of the tankyrases, with some examples having IC50 = 2 nM. One compound (7-(4-bromophenyl)-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-one) showed 70-fold selectivity for inhibition of tankyrase-2 versus tankyrase-1. The mode of binding was explored through crystal structures of inhibitors in complex with tankyrase-2.
- Kumpan, Katerina,Nathubhai, Amit,Zhang, Chenlu,Wood, Pauline J.,Lloyd, Matthew D.,Thompson, Andrew S.,Haikarainen, Teemu,Lehti?, Lari,Threadgill, Michael D.
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supporting information
p. 3013 - 3032
(2015/08/03)
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- Microwave-assisted synthesis, molecular docking and antiproliferative activity of (3/5-aryl-1,2,4-oxadiazole-5/3-yl)(3,4,5-trimethoxyphenyl)methanone oxime derivatives
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A series of (3/5-aryl-1,2,4-oxadiazole-5/3-yl)(3,4,5-trimethoxyphenyl)methanone oxime derivatives were synthesized via a rapid and facile microwave-assisted synthesis method of building a 1,2,4-oxadiazole skeleton using mandelic acid as the starting material. Twenty-four target compounds were evaluated for their in vitro antiproliferative activities against three human cancer cell lines (SGC-7901, A549 and HT-1080). Among them, 16b exhibited the highest potency against different tumour cell lines, especially the A549 cell line (IC50 = 87 nM). Structure-activity relationship (SAR) studies revealed that the aryl substituent at the C-5 position on the 1,2,4-oxadiazole ring is superior to that at the C-3 position. An oxime as a connector can obviously increase the potency, contrary to that in SMART derivatives. Moreover, 16b significantly induced a cell cycle arrest in the G2/M phase and caused microtubule destabilization. Molecular docking studies provided a theoretical binding mode of 16b at the colchicine site in the tubulin dimer. Our work laid the foundation for further structure-guided design of novel tubulin polymerization inhibitors.
- Guan, Qi,Feng, Dongjie,Bai, Zhaoshi,Cui, Yuanhang,Zuo, Daiying,Zhai, Min'An,Jiang, Xuewei,Zhou, Wenbo,Bao, Kai,Wu, Yingliang,Zhang, Weige
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supporting information
p. 1484 - 1493
(2015/08/18)
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- Design, synthesis, biological evaluation, and docking study of acetylcholinesterase inhibitors: New acridone-1,2,4-oxadiazole-1,2,3-triazole hybrids
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In this study, novel acridone-1,2,4-oxadiazole-1,2,3-triazole hybrids were designed, synthesized, and evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activity. Among various synthesized compounds, 10-((1-((3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)acridin-9(10H)-one 10b showed the most potent anti-acetylcholinesterase activity (IC50 = 11.55 μm) being as potent as rivastigmine. Also docking outcomes were in good agreement with in vitro results confirming the dual binding inhibitory activity of compound 10b. A novel series of acridone-1,2,4-oxadiazole-1,2,3-triazole hybrids were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities.
- Mohammadi-Khanaposhtani, Maryam,Mahdavi, Mohammad,Saeedi, Mina,Sabourian, Reyhaneh,Safavi, Maliheh,Khanavi, Mahnaz,Foroumadi, Alireza,Shafiee, Abbas,Akbarzadeh, Tahmineh
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p. 1425 - 1432
(2016/02/05)
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- Design and discovery of 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide inhibitors of HIV-1 integrase
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Raltegravir (RAL) is a first clinically approved integrase (IN) inhibitor for the treatment of HIV but rapid mutation of the virus has led to chemo-resistant strains. Therefore, there is a medical need to develop new IN inhibitors to overcome drug resista
- Zhang, Daoguang,Debnath, Bikash,Yu, Shenghui,Sanchez, Tino Wilson,Christ, Frauke,Liu, Yang,Debyser, Zeger,Neamati, Nouri,Zhao, Guisen
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p. 5446 - 5453
(2014/12/11)
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- An Efficient Synthesis of 2-Substituted Quinazolin-4(3 H)-ones Catalyzed by Iron(III) Chloride
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A simple and highly efficient synthesis of 2-substituted quinazolin-4(3H)-ones by the iron(III) chloride catalyzed reaction of isatoic anhydride with various amidoxime derivatives was developed. Several aryl and alkyl amidoximes were screened to demonstra
- Mekala, Ramamohan,Akula, Raghunadh,Kamaraju, Raghavendra Rao,Bannoth, Chandrasekhar Kothapalli,Regati, Sridhar,Sarva, Jayaprakash
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supporting information
p. 821 - 826
(2014/04/03)
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- Synthesis and characterization of 1,2,4-oxadiazole-based deep-blue and blue color emitting polymers
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Two donor-acceptor-donor monomers such as 3,5-bis(4-bromophenyl)-1,2,4- oxadiazole (BOB) and 3,5-bis(5-bromothiophen-2-yl)-1,2,4-oxadiazole (TOT) incorporating electron transporting and hole blocking 1,2,4-oxadiazloe moiety were copolymerized with light emitting fluorene derivative via Suzuki polycondensation toafford two new polymers, PFBOB and PFTOT, respectively. The optical studies for polymers PFBOB andPFTOT revealed that the band gaps are 3.10 eV and 2.72 eV, respectively, and polymer PFBOB exhibited a deep-blue emission while polymer PFTOT showed blue emission in chloroform and as thin film. The photoluminescence quantum efficiencies (Φf) of polymers PFBOB and PFTOT in chloroform calculated against highly blue emitting 9,10-diphenylanthracene (DPA, Φf = 0.90) were 1.00 and 0.44, respectively.
- Agneeswari, Rajalingam,Tamilavan, Vellaiappillai,Hyun, Myung Ho
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p. 513 - 517
(2014/03/21)
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- One-pot synthesis of highly substituted polyheteroaromatic compounds by rhodium(III)-catalyzed multiple C-H activation and annulation
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A new method for the synthesis of highly substituted naphthyridine-based polyheteroaromatic compounds in high yields proceeds through rhodium(III)-catalyzed multiple C-H bond cleavage and C-C and C-N bond formation in a one-pot process. Such highly substituted polyheteroaromatic compounds have attracted much attention because of their unique π-conjugation, which make them suitable materials for organic semiconductors and luminescent materials. Furthermore, a possible mechanism, which involves multiple chelation-assisted ortho C-H activation, alkyne insertion, and reductive elimination, is proposed for this transformation.
- Jayakumar, Jayachandran,Parthasarathy, Kanniyappan,Chen, Yi-Hsiang,Cheng, Chien-Hong,Lee, Tai-Hua,Chuang, Shih-Ching
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supporting information
p. 9889 - 9892,4
(2014/11/08)
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- An efficient approach to novel 17-5′-(1′,2′,4′)- oxadiazolyl androstenes via the cyclodehydration of cytotoxic O-steroidacylamidoximes, and an evaluation of their inhibitory action on 17α-hydroxylase/C17,20-lyase
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Novel 17-exo-oxadiazoles in the androst-5-ene series were efficiently synthesized in a two-step sequence via the corresponding O-acylamidoxime intermediates (obtained from steroidal 17-carboxylic acids and amidoximes in the presence of coupling reagent), which then underwent tetrabutylammonium fluoride-induced cyclocondensation under mild reaction conditions. The synthesized compounds were subjected to in vitro pharmacological studies to investigate their inhibitory effect on rat testicular C17,20-lyase and their antiproliferative action on four malignant human adherent cell lines (HeLa, MCF7, A2780 and A431). One of the oxadiazolyl derivatives proved to exert significant enzyme-inhibitory action (IC50 = 0.60 μM), while some of the isolated O-acylated amidoxime intermediates displayed high cytotoxic activities on all examined cell lines, with IC50 values in the range 0.22-3.94 μM.
- Kovács, Dóra,W?lfling, János,Szabó, Nikoletta,Szécsi, Mihály,Kovács, Ida,Zupkó, István,Frank, éva
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p. 649 - 660
(2013/12/04)
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- Synthesis, insecticidal activity, and structure-activity relationship (SAR) of anthranilic diamides analogs containing oxadiazole rings
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A series of anthranilic diamides analogs (3-11, 16-24) containing 1,2,4- or 1,3,4-oxadiazole rings were synthesized and characterized by 1H NMR, MS and elemental analyses. The structure of 3-bromo-N-(2-(3-(4-bromophenyl)-1, 2,4-oxadiazol-5-yl)-
- Li, Yuhao,Zhu, Hongjun,Chen, Kai,Liu, Rui,Khallaf, Abdalla,Zhang, Xiangning,Ni, Jueping
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supporting information
p. 3979 - 3988
(2013/07/05)
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- Design, synthesis and SAR of piperidyl-oxadiazoles as 11β- hydroxysteroid dehydrogenase 1 inhibitors
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The potential roles of 11β-HSD1 inhibitors in metabolic syndrome, T2D and obesity were well established and currently several classes of 11β-HSD1 inhibitors have been developed as promising agents against metabolic diseases. To find potent compounds with good pharmacokinetics, we used the bioisosterism approach, and designed the compound 2 and 3 bearing an 1,2,4-oxadiazole ring to replace the amide group in compound 1. Guided by docking study, we then transformed compound 3 into a potent lead compound 4a by changing sulfonamide group to amide. To elaborate this series of piperidyl-oxadiazole derivatives as human 11β-HSD1 inhibitors, we explored the structure-activity relationship of several parts of the lead compound. Based on their potency toward human 11β-HSD1 two compounds 4h and 4q were advanced to pharmacokinetic study. It was found that 4h and 4q are potent and selective human 11β-HSD1 inhibitors with better pharmacokinetic properties than those of the original piperidine-3-carboxamide compound 1, and suitable for further in vivo preclinical study in primate model.
- Xia, Guangxin,You, Xiaodi,Liu, Lin,Liu, Haiyan,Wang, Jianfa,Shi, Yufang,Li, Ping,Xiong, Bing,Liu, Xuejun,Shen, Jingkang
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- Condensation of Vilsmeier salts, derived from tetraalkylureas, with amidoximes: a novel approach to access N,N-dialkyl-1,2,4-oxadiazol-5-amines
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A novel approach, consendation of vilsmeier salts and amidoximes, to access N,N-dialkyl-1,2,4-oxadiazol-5-amines has been developed. By this approach, a broad range of N,N-dialkyl-1,2,4-oxadiazol-5-amines, including aromatic, heteroaromatic and alphatic s
- Su, Dongshan,Duan, Haifeng,Wei, Zhonglin,Cao, Jungang,Liang, Dapeng,Lin, Yingjie
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supporting information
p. 6959 - 6963
(2019/04/10)
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- Synthesis of polymers containing 1,2,4-oxadiazole as an electron-acceptor moiety in their main chain and their solar cell applications
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To explore the aptitude of 1,2,4-oxadiazole-based electron-acceptor unit in polymer solar cell applications, we prepared four new polymers (P1-P4) containing 1,2,4-oxadiazole moiety in their main chain and applied them to solar cell applications. Thermal,
- Agneeswari, Rajalingam,Tamilavan, Vellaiappillai,Song, Myungkwan,Kang, Jae-Wook,Jin, Sung-Ho,Hyun, Myung Ho
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p. 2131 - 2141
(2013/05/21)
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- METABOTROPIC GLUTAMATE RECEPTORS 5 MODULATORS AND METHODS OF USE THEREOF
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Compounds that modulate GluR5 activity and methods of using the same are disclosed.
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Page/Page column 81
(2012/12/13)
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- Synthesis and anti-protozoal activity of novel dihydropyrrolo[3,4-d][1,2,3] triazoles
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1,2,4-Oxadiazole and 1,2,3-triazole containing heterocyclic compounds continue to gain interest in synthesis of chemical entities and exhibit various biological activities as anti-protozoal and anti-cancer agents. By using the principle of bioisosterism,
- Dürüst, Yaar,Karaku, Hamza,Kaiser, Marcel,Tasdemir, Deniz
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scheme or table
p. 296 - 304
(2012/03/27)
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- Design and synthesis of 3,5-disubstituted boron-containing 1,2,4-oxadiazoles as potential combretastatin A-4 (CA-4) analogs
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We have designed and synthesized a small library of 3,5-disubstituted-1,2, 4-oxadiazole containing combretastatin A-4 (CA-4) analogs. Our objective is to increase the efficacy of the CA-4 as an anti-tubulin and antimitotic agent by substituting the cis-al
- Das, Bhaskar C.,Tang, Xiang-Ying,Rogler, Patrick,Evans, Todd
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supporting information; experimental part
p. 3947 - 3950
(2012/08/14)
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- Optimization of anti-Trypanosoma cruzi oxadiazoles leads to identification of compounds with efficacy in infected mice
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We recently showed that oxadiazoles have anti-Trypanosoma cruzi activity at micromolar concentrations. These compounds are easy to synthesize and show a number of clear and interpretable structure-activity relationships (SAR), features that make them attr
- Dos Santos Filho, Jose Mauricio,Moreira, Diogo Rodrigo M.,De Simone, Carlos Alberto,Ferreira, Rafaela Salgado,McKerrow, James H.,Meira, Cassio Santana,Guimaraes, Elisalva Teixeira,Soares, Milena Botelho Pereira
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p. 6423 - 6433,11
(2012/12/11)
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- Synthesis of amidoximes using an efficient and rapid ultrasound method
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This is a report on an efficient and rapid synthesis of amidoximes using ultrasound irradiation with appropriate nitrile and hydroxylamine hydrochloride in water/ethanol. This new synthetic methodology is compared with previously known methods. The main a
- Barros, Carlos Jonnatan Pimentel,De Freitas, Jucleiton J. Rufino,De Oliveira, Ronaldo N.,De Freitas Filho, Jo?o R.
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experimental part
p. 721 - 722
(2012/05/20)
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- PROLINE DERIVATIVES
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Compounds of formula (I): wherein A, B, C, D, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, m, n, p, q, r, t, u, and v are defined herein. Also disclosed is a method for treating hepatitis C virus infection with these compounds.
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Page/Page column 43-44
(2011/06/24)
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- Organic reactions in water: An efficient method for the synthesis of 1,2,4-oxadiazoles in water
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A simple and efficient process has been developed for the synthesis of 1,2,4-oxadiazoles in good yields through the reaction of amidoximes with anhydrides under catalyst-free conditions in water.
- Kaboudin, Babak,Malekzadeh, Leila
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supporting information; experimental part
p. 6424 - 6426
(2011/12/22)
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