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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...

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Autores principales: Sadeghian-Rizi, Sedighe, Khodarahmi, Ghadamali, Sakhteman, Amirhossein, Jahanian-Najafabadi, Ali, Rostami, Mahboubeh, Mirzaei, Mahmoud, Hassanzadeh, Farshid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2018
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).
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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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