Synthesis and Biological Evaluation of Novel 8-Morpholinoimidazo[1,2-a]pyrazine Derivatives Bearing Phenylpyridine/Phenylpyrimidine-Carboxamides

Herein we designed and synthesized three series of novel 8-morpholinoimidazo[1,2-a]pyrazine derivatives bearing phenylpyridine/phenylpyrimidine-carboxamides (compounds 12a–g, 13a–g and 14a–g). All the compounds were evaluated for their IC50 values against three cancer cell lines (A549, PC-3 and MCF-...

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Main Authors: Shan Xu, Chengyu Sun, Chen Chen, Pengwu Zheng, Yong Zhou, Hongying Zhou, Wufu Zhu
Format: Article
Language:English
Published: MDPI AG 2017-02-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/22/2/310
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spelling doaj-14361d87c26248bea07d9a49a912a4f02020-11-24T23:46:42ZengMDPI AGMolecules1420-30492017-02-0122231010.3390/molecules22020310molecules22020310Synthesis and Biological Evaluation of Novel 8-Morpholinoimidazo[1,2-a]pyrazine Derivatives Bearing Phenylpyridine/Phenylpyrimidine-CarboxamidesShan Xu0Chengyu Sun1Chen Chen2Pengwu Zheng3Yong Zhou4Hongying Zhou5Wufu Zhu6School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, ChinaSchool of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, ChinaSchool of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, ChinaSchool of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, ChinaDepartment of Pharmacy, The Affiliated Hospital of Chongqing Three Gorges Medical College, Chongqing 404000, ChinaDepartment of Pharmacy, The Affiliated Hospital of Chongqing Three Gorges Medical College, Chongqing 404000, ChinaSchool of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, ChinaHerein we designed and synthesized three series of novel 8-morpholinoimidazo[1,2-a]pyrazine derivatives bearing phenylpyridine/phenylpyrimidine-carboxamides (compounds 12a–g, 13a–g and 14a–g). All the compounds were evaluated for their IC50 values against three cancer cell lines (A549, PC-3 and MCF-7). Most of the target compounds exhibited moderate cytotoxicity against the three cancer cell lines. Two selected compounds 14b, 14c were further tested for their activity against PI3Kα kinase, and the results indicated that compound 14c showed inhibitory activity against PI3Kα kinase with an IC50 value of 1.25 μM. Structure-activity relationships (SARs) and pharmacological results indicated that the replacement of the thiopyranopyrimidine with an imidazopyrazine was beneficial for the activity and the position of aryl group has a significant influence to the activity of these compounds. The compounds 13a–g in which an aryl group substituted at the C-4 position of the pyridine ring were more active than 12a–g substituted at the C-5 position. Moreover, the cytotoxicity of compounds 14a–g bearing phenylpyrimidine-carboxamides was better than that of the compounds 12a–g, 13a–g bearing phenylpyridine-carboxamides. Furthermore, the substituents on the benzene ring also had a significant impact on the cytotoxicity and the pharmacological results showed that electron donating groups were beneficial to the cytotoxicity.http://www.mdpi.com/1420-3049/22/2/310imidazopyrazinephenylpyridine-carboxamidephenylpyrimidine-carboxamidePI3Kαsynthesis
collection DOAJ
language English
format Article
sources DOAJ
author Shan Xu
Chengyu Sun
Chen Chen
Pengwu Zheng
Yong Zhou
Hongying Zhou
Wufu Zhu
spellingShingle Shan Xu
Chengyu Sun
Chen Chen
Pengwu Zheng
Yong Zhou
Hongying Zhou
Wufu Zhu
Synthesis and Biological Evaluation of Novel 8-Morpholinoimidazo[1,2-a]pyrazine Derivatives Bearing Phenylpyridine/Phenylpyrimidine-Carboxamides
Molecules
imidazopyrazine
phenylpyridine-carboxamide
phenylpyrimidine-carboxamide
PI3Kα
synthesis
author_facet Shan Xu
Chengyu Sun
Chen Chen
Pengwu Zheng
Yong Zhou
Hongying Zhou
Wufu Zhu
author_sort Shan Xu
title Synthesis and Biological Evaluation of Novel 8-Morpholinoimidazo[1,2-a]pyrazine Derivatives Bearing Phenylpyridine/Phenylpyrimidine-Carboxamides
title_short Synthesis and Biological Evaluation of Novel 8-Morpholinoimidazo[1,2-a]pyrazine Derivatives Bearing Phenylpyridine/Phenylpyrimidine-Carboxamides
title_full Synthesis and Biological Evaluation of Novel 8-Morpholinoimidazo[1,2-a]pyrazine Derivatives Bearing Phenylpyridine/Phenylpyrimidine-Carboxamides
title_fullStr Synthesis and Biological Evaluation of Novel 8-Morpholinoimidazo[1,2-a]pyrazine Derivatives Bearing Phenylpyridine/Phenylpyrimidine-Carboxamides
title_full_unstemmed Synthesis and Biological Evaluation of Novel 8-Morpholinoimidazo[1,2-a]pyrazine Derivatives Bearing Phenylpyridine/Phenylpyrimidine-Carboxamides
title_sort synthesis and biological evaluation of novel 8-morpholinoimidazo[1,2-a]pyrazine derivatives bearing phenylpyridine/phenylpyrimidine-carboxamides
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2017-02-01
description Herein we designed and synthesized three series of novel 8-morpholinoimidazo[1,2-a]pyrazine derivatives bearing phenylpyridine/phenylpyrimidine-carboxamides (compounds 12a–g, 13a–g and 14a–g). All the compounds were evaluated for their IC50 values against three cancer cell lines (A549, PC-3 and MCF-7). Most of the target compounds exhibited moderate cytotoxicity against the three cancer cell lines. Two selected compounds 14b, 14c were further tested for their activity against PI3Kα kinase, and the results indicated that compound 14c showed inhibitory activity against PI3Kα kinase with an IC50 value of 1.25 μM. Structure-activity relationships (SARs) and pharmacological results indicated that the replacement of the thiopyranopyrimidine with an imidazopyrazine was beneficial for the activity and the position of aryl group has a significant influence to the activity of these compounds. The compounds 13a–g in which an aryl group substituted at the C-4 position of the pyridine ring were more active than 12a–g substituted at the C-5 position. Moreover, the cytotoxicity of compounds 14a–g bearing phenylpyrimidine-carboxamides was better than that of the compounds 12a–g, 13a–g bearing phenylpyridine-carboxamides. Furthermore, the substituents on the benzene ring also had a significant impact on the cytotoxicity and the pharmacological results showed that electron donating groups were beneficial to the cytotoxicity.
topic imidazopyrazine
phenylpyridine-carboxamide
phenylpyrimidine-carboxamide
PI3Kα
synthesis
url http://www.mdpi.com/1420-3049/22/2/310
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