cas 5033-28-3, 4-CHLORO-N'-HYDROXYBENZENECARBOXIMIDAMIDE

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Design and synthesis of new triarylimidazole derivatives as dual inhibitors of BRAFV600E/p38α with potential antiproliferative activity
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.
(2021/12/30)

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
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.
(2021/12/16)

Synthesis, spectroscopic characterization and DNA/HSA binding studies of (phenyl/naphthyl)ethenyl-substituted 1,3,4-oxadiazolyl-1,2,4-oxadiazoles
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.
p. 471 - 484
(2021/01/11)

Cobalt-Catalyzed, Directed Intermolecular C-H Bond Functionalization for Multiheteroatom Heterocycle Synthesis: The Case of Benzotriazine
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
supporting information
p. 5652 - 5657
(2021/08/01)

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
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.
p. 1067 - 1078
(2021/05/28)

INHIBITOR COMPOUNDS
The disclosure relates to heterocyclic compounds and methods for their preparation. The disclosure provides compounds that may have beneficial therapeutic activity in the treatment of a disease or condition mediated by excessive or otherwise undesirable Des1 and/or fibrotic activity.
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Page/Page column 63; 213

(2021/01/29)

Novel 1,2,4-oxadiazole derivatives as selective butyrylcholinesterase inhibitors: Design, synthesis, and biological evaluation
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
p. 907 - 921
(2021/06/09)

Novel 1,2,4-oxadiazole-chalcone/oxime hybrids as potential antibacterial DNA gyrase inhibitors: Design, synthesis, ADMET prediction and molecular docking study
New antibacterial drugs are urgently needed to tackle the rapid rise in multi-drug resistant bacteria. DNA gyrase is a validated target for the development of new antibacterial drugs. Thus, in the present investigation, a novel series of 1,2,4-oxadiazole-
Ibrahim, Tarek S.,Almalki, Ahmad J.,Moustafa, Amr H.,Allam, Rasha M.,Abuo-Rahma, Gamal El-Din A.,El Subbagh, Hussein I.,Mohamed, Mamdouh F.A.
(2021/04/15)

Design, synthesis, and biological evaluation of 1,2,4-oxadiazole-containing pyrazolo[3,4-b]pyridinones as a new series of AMPKɑ1β1γ1 activators
Adenosine monophosphate-activated protein kinase (AMPK) plays a key role in maintaining whole-body homeostasis and has been regarded as a therapeutic target for the treatment of diabetic nephropathy (DN). Herein, a series of 1,2,4-oxadiazole-containing py
Xiao, Zhihong,Peng, Yajun,Zheng, Bifeng,Chang, Qi,Guo, Yating,Chen, Zhuo,Li, Qianbin,Hu, Gaoyun
(2021/03/16)

One-pot synthesis of 1,2,4-oxadiazoles from chalcogen amino acid derivatives under microwave irradiation
A series of sulfur- and selenium-bearing, amino acid-derived 1,2,4-oxadiazoles were obtained by a simple procedure. The method consists of EDC-promoted coupling of chalcogen amino acid derivatives with arylamidoximes in acetone, followed by solvent removal and microwave irradiation in water medium. Influence of amidoxime substituents, of the chalcogen atom and of the amino acid side chain is discussed. The results showed this to be a fast, easy and effective method to obtain these compounds, with good functional-group tolerance, potentially favouring future applications in organic synthesis.
Wolf, Lucas,Mayer, Jo?o C.P.,Quoos, Natália,Sauer, André C.,Schwab, Ricardo S.,Rodrigues, Oscar E.D.,Dornelles, Luciano
supporting information

(2021/06/06)

Catalyst-free, one-pot strategy to access 3-substituted-5-amino-1,2,4-thiadiazoles in water
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.
p. 3610 - 3619
(2021/10/14)

Imidazole hydrochloride promoted synthesis of 3,5-disubstituted-1,2,4-oxadiazoles
Imidazole hydrochloride as an additive promotes the reaction of amidoximes and DMA derivatives to generated 3,5-disubstituted-1,2,4-oxadiazoles in low to excellent yields without the use of coupling reagents, oxidants, strong acids or bases and other additives.
Wang, Xuetong,Wang, Yin,Liu, Xiaoling,He, Tingshu,Li, Lingli,Wu, Huili,Zhou, Shangjun,Li, Dan,Liao, Siwei,Xu, Ping,Huang, Xing,Yuan, Jianyong
supporting information

(2021/10/14)

Design, synthesis and biological activities of piperidine-spirooxadiazole derivatives as α7 nicotinic receptor antagonists
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
(2020/09/03)

Optimization of the synthesis of het/aryl-amidoximes using an efficient green chemistry
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.
p. 1217 - 1231
(2020/03/19)

Synthesis and Evaluation of Antibacterial Activity of 1,2,4-Oxadiazole-Containing Biphenylcarboxylic Acids
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.
p. 1611 - 1619
(2020/10/15)

Synthesis of 2,4-Disubstituted Imidazoles via Nucleophilic Catalysis
A convergent, microwave-assisted protocol for the synthesis of disubstituted NH-imidazoles via nucleophilic catalysis is described. The substituted imidazoles are accessed via the intramolecular addition of a variety of amidoxime substrates to activated a
Camp, Jason E.,Dunsford, Jay J.,Gill, Duncan M.,Ngwerume, Simbarashe,Saunders, Alexandra R.,Shabalin, Dmitrii A.
supporting information
p. 797 - 800
(2020/05/19)

Synthesis and evaluation of new 1,2,4-oxadiazole based trans- acrylic acid derivatives as potential PPAR-alpha/gamma dual agonist
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
(2020/04/29)

1,2,4-Oxadiazole ring–containing pyridylpyrazole-4-carboxamides: Synthesis and evaluation as novel insecticides of the anthranilic diamide family
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
supporting information

(2020/02/18)

Discovery of 1,2,4-oxadiazole derivatives as a novel class of noncompetitive inhibitors of 3-hydroxykynurenine transaminase (HKT) from Aedes aegypti
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.
(2020/01/03)

Synthesis of Some Azamacrocycles Bearing 1,2,4-Oxadiazole and 1,2,3-Triazole Moieties
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.
p. 698 - 705
(2020/06/01)

KCNT1 INHIBITORS AND METHODS OF USE
The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.
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Paragraph 000277; 000453

(2020/11/23)

Synthesis and Biological Evaluation of Sigma-1 (σ1) Receptor Ligands Based on Phenyl-1,2,4-oxadiazole Derivatives
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
(2019/02/26)

A Straightforward and High-Yielding Synthesis of 1,2,4-Oxadiazoles from Chiral N-Protected α-Amino Acids and Amidoximes in Acetone-Water: An Eco-Friendly Approach
A straightforward and high-yielding methodology for the synthesis of a high structural diversity of 1,2,4-oxadiazoles from different chiral N-protected α-amino acids and amidoximes under microwave (MW) irradiation is described herein. This greener approac
Sauer, André C.,Wolf, Lucas,Quoos, Natália,Rodrigues, Mariele B.,Braga, Ant?nio L.,Rodrigues, Oscar E. D.,Dornelles, Luciano
(2019/02/05)

Efficient Synthesis of Functionalized Indene Derivatives via Rh(III)-Catalyzed Cascade Reaction between Oxadiazoles and Allylic Alcohols
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
supporting information
p. 2037 - 2041
(2019/03/28)

A cascade process for directly converting nitriles (RCN) to cyanamides (RNHCN) via SO2F2-activated Tiemann rearrangement
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
supporting information
p. 7684 - 7688
(2019/08/30)

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
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
p. 1376 - 1394
(2018/09/13)

Function-oriented synthesis of marine phidianidine derivatives as potential PTP1B inhibitors with specific selectivity
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
(2018/04/02)

Design and Synthesis of Marine Phidianidine Derivatives as Potential Immunosuppressive Agents
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
p. 11298 - 11308
(2019/01/04)

An efficient synthesis and antimicrobial evaluation of 5-alkenyl- and 5-styryl-1,2,4-oxadiazoles
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.
supporting information
p. 458 - 470
(2019/03/07)

1, 2, 4-oxadiazole incorporated ketoprofen analogues in search of safer non-steroidal anti-inflammatory agents: Design, syntheses, biological evaluation and molecular docking Studies
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
p. 590 - 601
(2018/06/06)

Pharmacophore requirements for HIV-1 reverse transcriptase inhibitors that selectively “Freeze” the pre-translocated complex during the polymerization catalytic cycle
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.
p. 1713 - 1726
(2018/02/27)

TiO2-Nanoparticles Catalyzed Synthesis of New Trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles and Trifluoromethyl-1,2,4-oxadiazoles
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
p. 1702 - 1708
(2018/05/30)

Focused microwave irradiation-assisted synthesis of N-cyclohexyl-1,2,4-oxadiazole derivatives with antitumor activity
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
p. 2522 - 2532
(2018/10/15)

Ferrocenylethenyl-substituted 1,3,4-oxadiazolyl-1,2,4-oxadiazoles: Synthesis, characterization and DNA-binding assays
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
p. 1 - 11
(2017/04/24)

Oxadiazole compound, as well as preparation method and application thereof
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
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(2017/08/27)

Indazole-oxadiazole derivative, medicinal composition containing derivative, and application of derivative in tumor prevention
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; 0105; 0106

(2017/07/25)

Palladium-Catalyzed, Silver-Assisted Direct C-5–H Arylation of 3-Substituted 1,2,4-Oxadiazoles under Microwave Irradiation
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
supporting information
p. 772 - 778
(2017/03/11)

Room-temperature synthesis of pharmaceutically important carboxylic acids bearing the 1,2,4-oxadiazole moiety
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.
supporting information
p. 3672 - 3677
(2017/08/23)

Design, synthesis, and bioactivities of novel oxadiazole-substituted pyrazole oximes
A series of novel pyrazole oxime derivatives containing a substituted oxadiazole group were designed and synthesized. The bioassay results indicated that some title compounds displayed good acaricidal and insecticidal activities against Tetranychus cinnabarinus, Aphis medicaginis, Oriental armyworm, and Nilaparvata lugens. Especially, compounds 7a, 7b, and 7c had 80%, 90%, and 90% insecticidal activities against A. medicaginis at 20 μg/mL, respectively. Interestingly, some of the designed compounds displayed wonderful fungicidal activities in vivo against cucumber Pseudoperonospora cubensis. Furthermore, compounds 7a (EC50= 4.97 μg/mL) and 7h (EC50= 0.51 μg/mL) showed excellent fungicidal activity against P. cubensis comparable or better than that of the control Pyraclostrobin (EC50= 4.59 μg/mL).
Dai, Hong,Chen, Jia,Li, Gang,Ge, Shushan,Shi, Yujun,Fang, Yuan,Ling, Yong
supporting information
p. 950 - 953
(2017/02/10)

Cobalt(III)-Catalyzed Oxadiazole-Directed C-H Activation for the Synthesis of 1-Aminoisoquinolines
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
supporting information
p. 2885 - 2888
(2017/06/07)

From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II)
The sphingosine kinase (SK) inhibitor, SKI-II, has been employed extensively in biological investigations of the role of SK1 and SK2 in disease and has demonstrated impressive anticancer activity in vitro and in vivo. However, interpretations of results u
Aurelio, Luigi,Scullino, Carmen V.,Pitman, Melissa R.,Sexton, Anna,Oliver, Victoria,Davies, Lorena,Rebello, Richard J.,Furic, Luc,Creek, Darren J.,Pitson, Stuart M.,Flynn, Bernard L.
p. 965 - 984
(2016/02/23)

Nitrobenzofurazan derivatives of N′-hydroxyamidines as potent inhibitors of indoleamine-2,3-dioxygenase 1
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
p. 364 - 375
(2016/06/13)

Oxadiazolone-Enabled Synthesis of Primary Azaaromatic Amines
Despite their tremendous synthetic and pharmaceutical utility, primary azaaromatic amines remain elusive for access based on a generally applicable C-H functionalization strategy. An oxadiazolone-enabled approach is reported for convenient entry into N-unsubstituted 1-aminoisoquinolines through Co(III)-catalyzed redox-neutral, step-, atom-, and purification-economic C-H functionalization with alkynes. A 15N labeling experiment reveals the effectiveness of both oxadiazolone N atoms as directing sites. The installed primary amine can be harnessed as a synthetically useful handle for attachment of divergent appendages.
Yu, Xiaolong,Chen, Kehao,Yang, Fan,Zha, Shanke,Zhu, Jin
supporting information
p. 5412 - 5415
(2016/11/06)

2-Amino-4-aryl thiazole: A promising scaffold identified as a potent 5-LOX inhibitor
Human 5-lipoxygenase (5-LOX) is an important enzyme in the biosynthesis of leukotrienes and is a target for asthma and allergy treatment. Zileuton is the only drug currently marketed that targets this enzyme (IC50 ～ 1 μM). So, the development of novel lead compounds is highly desirable. A series of 2-aryl indole, thiazolopyrazole acid, oxadiazolobenzothiophene, 1,4-disubstituted-1,2,3-triazole, 2-amino-4-aryl thiazole and 4,4′-(1,4-phenylene)bis(1,3-thiazole) derivatives when tested against this enzyme resulted in the identification of a potent compound (1d), p-fluoro substituted 2-amino-4-aryl thiazole, with an IC50 of ～10 μM. Another lead compound identified is (4a), a thiazolopyrazole acid derivative (IC50 ～ 40 μM). All the compounds exhibit poor DPPH radical scavenging activity which suggests that their action occurs not due to the disruption of the redox cycle of iron present in the enzyme (unlike zileuton) but through competitive inhibition, since the Vmax remains constant but the Km increases with an increase in inhibitor concentration. Molecular docking of 1d and 4a to the active site of 5-LOX also supports the experimental data, and suggests that their possible mechanism of action is through competitive inhibition. The current study identifies a promising lead molecule which could be improved further to match the activity of the commercial drug.
Sinha, Shweta,Sravanthi,Yuvaraj,Manju,Doble, Mukesh
p. 19271 - 19279
(2016/03/01)

Novel benzimidazole-oxadiazole hybrid molecules as promising antimicrobial agents
In the present study, we describe the design and expeditious synthesis of novel 2-aryl-5-(3-aryl-[1,2,4]-oxadiazol-5-yl)-1-methyl-1H-benzo[d]imidazole hybrid molecules as promising antimicrobial agents. The core moiety 2-aryl-ethyl-1H-benzo[d]imidazole-5-
Shruthi,Poojary, Boja,Kumar, Vasantha,Hussain, Mumtaz Mohammed,Rai, Vaishali M.,Pai, Vinitha R.,Bhat, Mahima,Revannasiddappa
p. 8303 - 8316
(2016/02/09)

Molecular properties prediction and synthesis of new oxadiazole derivatives possessing 3-fluoro-4-methoxyphenyl moiety as potent anti-inflammatory and analgesic agents
A new series of 1,2,4- and 1,3,4-oxadiazole derivatives possessing 3-fluoro-4-methoxyphenyl moiety were efficiently synthesized and characterized by spectroscopic methods and elemental analysis. All the compounds were evaluated in vivo for their anti-infl
Dinesha,Viveka, Shivapura,Khandige, Prasanna S.,Nagaraja, Gundibasappa K.
p. 435 - 443
(2016/02/16)

An efficient one-pot synthesis of 3-aryl-5-(dialkoxymethyl)-1,2,4-oxadiazoles under solvent-free conditions
An efficient and simple synthesis of 3-aryl-5-(dialkoxymethyl)-1,2,4-oxadiazoles is described. The in situ prepared amidoximes from the reaction between nitriles and hydroxylamine are condensed with alkyl 2,2-dialkoxyacetates under solvent-free conditions
Adib, Mehdi,Saeedi, Sara,Soheilizad, Mehdi,Bayanati, Maryam,Tajbakhsh, Mahmood,Amanlou, Massoud
p. 314 - 317
(2016/07/06)

Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1,2,4-oxadiazoles as potential anticonvulsant agents
A number of acridone-based oxadiazoles 11a–n have been synthesized and evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizures in mice. Also, their neurotoxicity was evaluated by the rotarod test. Most of the compounds exhibited better anticonvulsant activity and higher safety respect to the standard drug, phenobarbital. Among the tested derivatives, compounds 11l with ED50value of 2.08?mg/kg was the most potent compound in the PTZ test. The anticonvulsant effect of compound 11l was blocked by flumazenil, suggesting the involvement of benzodiazepine (BZD) receptors in the anticonvulsant activity of prototype compound 11l. Also, docking study of compound 11l in the BZD-binding site of GABAAreceptor confirms possible binding of compound 11l with BZD receptors.
Mohammadi-Khanaposhtani, Maryam,Shabani, Mohammad,Faizi, Mehrdad,Aghaei, Iraj,Jahani, Reza,Sharafi, Zainab,Shamsaei Zafarghandi, Narges,Mahdavi, Mohammad,Akbarzadeh, Tahmineh,Emami, Saeed,Shafiee, Abbas,Foroumadi, Alireza
p. 91 - 98
(2016/10/04)

Iron(III) Chloride/l-Proline as an Efficient Catalyst for the Synthesis of 3-Substituted 1,2,4-Oxadiazoles from Amidoximes and Triethyl Orthoformate
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
p. 3597 - 3602
(2016/10/18)

Base-mediated one-pot synthesis of 1,2,4-oxadiazoles from nitriles, aldehydes and hydroxylamine hydrochloride without addition of extra oxidant
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
p. 9814 - 9822
(2016/10/31)