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Synthesis and characterization of some novel diaryl urea derivatives bearing quinoxalindione moiety
Diaryl urea derivatives have exhibited a broad spectrum of biochemical effects and pharmaceutical applications. Several diaryl urea derivatives such as sorafenib, regorafenib, linifanib, and tivozanib and lenvatinib are in clinical trial or clinical use. Therefore, development of small molecules wit...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772085/ https://www.ncbi.nlm.nih.gov/pubmed/29387115 http://dx.doi.org/10.4103/1735-5362.220971 |
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author | Sadeghian-Rizi, Sedighe Khodarahmi, Ghadamali Sakhteman, Amirhossein Jahanian-Najafabadi, Ali Rostami, Mahboubeh Mirzaei, Mahmoud Hassanzadeh, Farshid |
author_facet | Sadeghian-Rizi, Sedighe Khodarahmi, Ghadamali Sakhteman, Amirhossein Jahanian-Najafabadi, Ali Rostami, Mahboubeh Mirzaei, Mahmoud Hassanzadeh, Farshid |
author_sort | Sadeghian-Rizi, Sedighe |
collection | PubMed |
description | Diaryl urea derivatives have exhibited a broad spectrum of biochemical effects and pharmaceutical applications. Several diaryl urea derivatives such as sorafenib, regorafenib, linifanib, and tivozanib and lenvatinib are in clinical trial or clinical use. Therefore, development of small molecules within the diaryl urea scaffold with the ability of binding to variety of enzymes and receptors in the biological system are an interesting topic for researchers. Sorafenib as a diaryl urea derivative is a well-known anticancer agent. Corresponding to available information about biological activities of quinoxaline moieties, based on sorafenib scaffold, several structures were designed by replacement of pyridyl carboxamide group of sorafenib with quinoxalindione moiety. A total of 14 novel compounds in 7 synthetic steps were synthesized. Briefly, the amino group of p-aminophenol was first protected followed by O-arylation of 4-acetamidophenol with 5-chloro-2-nitroaniline to provide 5-(4-acetamidophenoxy)-2-nitroaniline. Reduction of the nitro group of 5-(4-acetamidophenoxy)-2-nitroaniline and cyclization of diamine N-(4-(3,4-diaminophenoxy) phenyl) acetamides with oxalic acid afforded compound N-(4-((2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-6-yl)oxy)phenyl) acetamides which on deacetylation gave compounds 6-(4-aminophenoxy) quinoxaline-2,3 (1H, 4H)-diones. Then resultant compounds, 6-(4-aminophenoxy) quinoxaline-2,3 (1H, 4H)-diones were reacted by appropriate isocyanates/ carbamates to give the target compounds 1-(4-((2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-6-yl)oxy)phenyl)-3-phenylureas. The structures of compounds confirmed by proton nuclear magnetic resonance ((1)H NMR), mass spectrum and Fourier transform infrared (FT-IR). |
format | Online Article Text |
id | pubmed-5772085 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-57720852018-02-01 Synthesis and characterization of some novel diaryl urea derivatives bearing quinoxalindione moiety Sadeghian-Rizi, Sedighe Khodarahmi, Ghadamali Sakhteman, Amirhossein Jahanian-Najafabadi, Ali Rostami, Mahboubeh Mirzaei, Mahmoud Hassanzadeh, Farshid Res Pharm Sci Original Article Diaryl urea derivatives have exhibited a broad spectrum of biochemical effects and pharmaceutical applications. Several diaryl urea derivatives such as sorafenib, regorafenib, linifanib, and tivozanib and lenvatinib are in clinical trial or clinical use. Therefore, development of small molecules within the diaryl urea scaffold with the ability of binding to variety of enzymes and receptors in the biological system are an interesting topic for researchers. Sorafenib as a diaryl urea derivative is a well-known anticancer agent. Corresponding to available information about biological activities of quinoxaline moieties, based on sorafenib scaffold, several structures were designed by replacement of pyridyl carboxamide group of sorafenib with quinoxalindione moiety. A total of 14 novel compounds in 7 synthetic steps were synthesized. Briefly, the amino group of p-aminophenol was first protected followed by O-arylation of 4-acetamidophenol with 5-chloro-2-nitroaniline to provide 5-(4-acetamidophenoxy)-2-nitroaniline. Reduction of the nitro group of 5-(4-acetamidophenoxy)-2-nitroaniline and cyclization of diamine N-(4-(3,4-diaminophenoxy) phenyl) acetamides with oxalic acid afforded compound N-(4-((2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-6-yl)oxy)phenyl) acetamides which on deacetylation gave compounds 6-(4-aminophenoxy) quinoxaline-2,3 (1H, 4H)-diones. Then resultant compounds, 6-(4-aminophenoxy) quinoxaline-2,3 (1H, 4H)-diones were reacted by appropriate isocyanates/ carbamates to give the target compounds 1-(4-((2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-6-yl)oxy)phenyl)-3-phenylureas. The structures of compounds confirmed by proton nuclear magnetic resonance ((1)H NMR), mass spectrum and Fourier transform infrared (FT-IR). Medknow Publications & Media Pvt Ltd 2018-02 /pmc/articles/PMC5772085/ /pubmed/29387115 http://dx.doi.org/10.4103/1735-5362.220971 Text en Copyright: © 2017 Research in Pharmaceutical Sciences http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Sadeghian-Rizi, Sedighe Khodarahmi, Ghadamali Sakhteman, Amirhossein Jahanian-Najafabadi, Ali Rostami, Mahboubeh Mirzaei, Mahmoud Hassanzadeh, Farshid Synthesis and characterization of some novel diaryl urea derivatives bearing quinoxalindione moiety |
title | Synthesis and characterization of some novel diaryl urea derivatives bearing quinoxalindione moiety |
title_full | Synthesis and characterization of some novel diaryl urea derivatives bearing quinoxalindione moiety |
title_fullStr | Synthesis and characterization of some novel diaryl urea derivatives bearing quinoxalindione moiety |
title_full_unstemmed | Synthesis and characterization of some novel diaryl urea derivatives bearing quinoxalindione moiety |
title_short | Synthesis and characterization of some novel diaryl urea derivatives bearing quinoxalindione moiety |
title_sort | synthesis and characterization of some novel diaryl urea derivatives bearing quinoxalindione moiety |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772085/ https://www.ncbi.nlm.nih.gov/pubmed/29387115 http://dx.doi.org/10.4103/1735-5362.220971 |
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