- 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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- 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.
- Basilico, Nicoletta,Conti, Paola,Coser, Consuelo,Galbiati, Andrea,Parapini, Silvia,Tamborini, Lucia,Taramelli, Donatella,Zana, Aureliano
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p. 1726 - 1732
(2021/11/01)
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- Novel 1,2,4-oxadiazole-chalcone/oxime hybrids as potential antibacterial DNA gyrase inhibitors: Design, synthesis, ADMET prediction and molecular docking study
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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.
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- Imidazole hydrochloride promoted synthesis of 3,5-disubstituted-1,2,4-oxadiazoles
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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
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supporting information
(2021/10/14)
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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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- 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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- Design, synthesis and biological evaluation of triaryl compounds as novel 20S proteasome inhibitors
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Thirty novel triaryl compounds were designed and synthesized based on the known proteasome inhibitor PI-1840. Most of them showed significant inhibition against the β5c subunit of human 20S proteasome, and five of them exhibited IC50 values at the sub-micromolar level, which were comparable to or even more potent than PI-1840. The most active two (1c and 1d) showed IC50 values of 0.12 and 0.18 μM against the β5c subunit, respectively, while they displayed no obvious inhibition against the β2c, β1c and β5i subunits. Molecular docking provided informative clues for the subunit selectivity. The potent and subunit selective proteasome inhibitors identified herein represent new chemical templates for further molecular optimization.
- Yang, Yajun,Wang, Ke,Wu, Bo,Yang, Ying,Lai, Fangfang,Chen, Xiaoguang,Xiao, Zhiyan
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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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- Investigation around the Oxadiazole Core in the Discovery of a New Chemotype of Potent and Selective FXR Antagonists
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Recent findings have shown that Farnesoid X Receptor (FXR) antagonists might be useful in the treatment of cholestasis and related metabolic disorders. In this paper, we report the discovery of a new chemotype of FXR antagonists featured by a 3,5-disubsti
- Festa, Carmen,Finamore, Claudia,Marchianò, Silvia,Di Leva, Francesco Saverio,Carino, Adriana,Monti, Maria Chiara,Del Gaudio, Federica,Ceccacci, Sara,Limongelli, Vittorio,Zampella, Angela,Fiorucci, Stefano,De Marino, Simona
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supporting information
p. 504 - 510
(2019/01/26)
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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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- OXADIAZOLES AS FXR RECEPTOR ANTAGONISTS
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The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof: It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses, in particular to prevent and/or treat a disorder selected from the group consisting of gastrointestinal disorders, liver disorders, cardiovascular disorders, vascular disorders, pulmonary disorders, metabolic pathologies, infectious diseases, cancer, renal disorders, inflammatory disorders including immune-mediated, and neurological disorders.
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Page/Page column 24-25
(2019/12/15)
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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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- Synthesis of carboxyimidamide-substituted benzo[c][1,2,5]oxadiazoles and their analogs, and evaluation of biological activity against Leishmania donovani
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A facile synthesis route to carboxyimidamide-substituted benzoxadiazoles and related derivatives was developed. A total of 25 derivatives were synthesized. They were evaluated for antileishmanial activity by inhibition of Leishmania donovani axenic amastigote growth using a fluorescent viability microplate assay. The most promising derivative (14) demonstrated an antileishmanial EC50 of 4.0 μM, and it also showed activity in infected macrophages (EC50 5.92 μM) without signs of cytotoxicity.
- Keurulainen, Leena,Heiskari, Mikko,Nenonen, Satu,Nasereddin, Abedelmajeed,Kopelyanskiy, Dmitry,Leino, Teppo O.,Yli-Kauhaluoma, Jari,Jaffe, Charles L.,Kiuru, Paula
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supporting information
p. 1673 - 1678
(2015/09/15)
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- One-pot synthesis of amidoxime via Pd-catalyzed cyanation and amidoximation
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A novel "one-pot" reaction was developed for the synthesis of aryl or heteroaryl-substituted amidoxime compounds containing various functional groups. Fluorescence titration experiments coupled with theoretical analysis revealed that the steric hindrance and electronic effects of substituents influence the binding ability of the amidoxime compounds to uranyl ions. This journal is
- Yang, Chu-Ting,Han, Jun,Liu, Jun,Gu, Mei,Li, Yi,Wen, Jun,Yu, Hai-Zhu,Hu, Sheng,Wang, Xiaolin
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supporting information
p. 2541 - 2545
(2015/04/14)
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- Synthesis, enzyme kinetics and computational evaluation of N-(β-d-glucopyranosyl) oxadiazolecarboxamides as glycogen phosphorylase inhibitors
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All possible isomers of N-β-d-glucopyranosyl aryl-substituted oxadiazolecarboxamides were synthesised. O-Peracetylated N-cyanocarbonyl-β- d-glucopyranosylamine was transformed into the corresponding N-glucosyl tetrazole-5-carboxamide, which upon acylation
- Polyak, Maria,Varga, Gergely,Szilagyi, Bence,Juhasz, Laszlo,Docsa, Tibor,Gergely, Pal,Begum, Jaida,Hayes, Joseph M.,Somsak, Laszlo
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p. 5738 - 5747
(2013/09/12)
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- COMPOSITIONS AND METHODS RELATING TO HEAT SHOCK TRANSCRIPTION FACTOR ACTIVATING COMPOUNDS AND TARGETS THEREOF
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The present invention relates to HSF activating compounds, methods for their discovery, and their research and therapeutic uses, as well as pharmaceutically acceptable salts, solvates, chelates, non-covalent complexes, prodrugs, mixtures (including both R
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Page/Page column 24
(2011/05/16)
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- Synthesis, characterization, and antimicrobial activities of clubbed [1,2,4]-oxadiazoles with fluorobenzimidazoles
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(Chemical Equation Presented) In this study, a novel series of substituted 4,6-difluoro-2-{2-[3-(substituted-phenyl)-[1,2,4]-oxadiazol-5-yl]-ethyl} -1H-benzo[d]imidazole derivatives were synthesized by condensation of 2,4-difluoro-6-nitrophenyl amine with 3-(substitutedphenyl-[1,2,4]-oxadiazol- 5yl) propionic acid by using 2,4,6-trichlorobenzoyl chloride in the presence of triethyl amine base. The compounds were evaluated for their preliminary in vitro antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Salmonella typhosa. The antibacterial data of the tested compounds indicated that most of the synthesized compounds showed moderate activity with reference standard Gentamycin.
- Jadhav, Ganesh R.,Shaikh, Mohammad U.,Kale, Rajesh P.,Ghawalkar, Anand R.,Gill, Charansingh H.
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experimental part
p. 980 - 987
(2009/12/05)
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- NOVEL ALKYNYL DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
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The present invention relates to novel compounds of formula (I) wherein W, n, X and W’ are defined in the description; invention compounds are modulators of metabotropic glutamate receptors - subtype 5 (“mGluR5”) which are useful for the treatment of central nervous system disorders as well as other disorders modulated by mGluR5 receptors.
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Page/Page column 116
(2008/06/13)
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- Antihyperglycemic Activity of Novel Naphthalenyl 3H-1,2,3,5-Oxathiadiazole 2-Oxides
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A series of naphthalenyl 3H-1,2,3,5-oxathiadiazole 2-oxides was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non-insulin dependent) diabetes mellitus.Substitution at the 1-,5-, or 8-positions of the naphthalene ring with a halogen was found to be beneficial to antihyperglycemic activity. 4--3H-1,2,3,5-oxathiadiazole 2-oxide (45), one of the most potent compounds in this series, was selected for further pharmacological evaluation.
- Ellingboe, John W.,Lombardo, Louis J.,Alessi, Thomas R.,Nguyen, Thomas T.,Guzzo, Frieda,et al.
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p. 2485 - 2493
(2007/10/02)
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