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Molecules 2017, 22(2), 310;

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

School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
Department of Pharmacy, The Affiliated Hospital of Chongqing Three Gorges Medical College, Chongqing 404000, China
Authors to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 29 December 2016 / Revised: 13 February 2017 / Accepted: 15 February 2017 / Published: 17 February 2017
(This article belongs to the Section Medicinal Chemistry)
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Herein we designed and synthesized three series of novel 8-morpholinoimidazo[1,2-a]pyrazine derivatives bearing phenylpyridine/phenylpyrimidine-carboxamides (compounds 12ag, 13ag and 14ag). 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 13ag in which an aryl group substituted at the C-4 position of the pyridine ring were more active than 12ag substituted at the C-5 position. Moreover, the cytotoxicity of compounds 14ag bearing phenylpyrimidine-carboxamides was better than that of the compounds 12ag, 13ag 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. View Full-Text
Keywords: imidazopyrazine; phenylpyridine-carboxamide; phenylpyrimidine-carboxamide; PI3Kα; synthesis imidazopyrazine; phenylpyridine-carboxamide; phenylpyrimidine-carboxamide; PI3Kα; synthesis

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Xu, S.; Sun, C.; Chen, C.; Zheng, P.; Zhou, Y.; Zhou, H.; Zhu, W. Synthesis and Biological Evaluation of Novel 8-Morpholinoimidazo[1,2-a]pyrazine Derivatives Bearing Phenylpyridine/Phenylpyrimidine-Carboxamides. Molecules 2017, 22, 310.

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