Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated...

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Autores principales: Fang, Yuanying, Zhang, Shaokun, Li, Min, Xiong, Lijuan, Tu, Liangxing, Xie, Saisai, Jin, Yi, Liu, Yanhua, Yang, Zunhua, Liu, Ronghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830257/
https://www.ncbi.nlm.nih.gov/pubmed/31656107
http://dx.doi.org/10.1080/14756366.2019.1681988
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author Fang, Yuanying
Zhang, Shaokun
Li, Min
Xiong, Lijuan
Tu, Liangxing
Xie, Saisai
Jin, Yi
Liu, Yanhua
Yang, Zunhua
Liu, Ronghua
author_facet Fang, Yuanying
Zhang, Shaokun
Li, Min
Xiong, Lijuan
Tu, Liangxing
Xie, Saisai
Jin, Yi
Liu, Yanhua
Yang, Zunhua
Liu, Ronghua
author_sort Fang, Yuanying
collection PubMed
description GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC(50) values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC(0–2h) at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction).
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spelling pubmed-68302572019-11-13 Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists Fang, Yuanying Zhang, Shaokun Li, Min Xiong, Lijuan Tu, Liangxing Xie, Saisai Jin, Yi Liu, Yanhua Yang, Zunhua Liu, Ronghua J Enzyme Inhib Med Chem Research Paper GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC(50) values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC(0–2h) at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction). Taylor & Francis 2019-10-28 /pmc/articles/PMC6830257/ /pubmed/31656107 http://dx.doi.org/10.1080/14756366.2019.1681988 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Fang, Yuanying
Zhang, Shaokun
Li, Min
Xiong, Lijuan
Tu, Liangxing
Xie, Saisai
Jin, Yi
Liu, Yanhua
Yang, Zunhua
Liu, Ronghua
Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists
title Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists
title_full Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists
title_fullStr Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists
title_full_unstemmed Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists
title_short Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists
title_sort optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent gpr 119 agonists
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830257/
https://www.ncbi.nlm.nih.gov/pubmed/31656107
http://dx.doi.org/10.1080/14756366.2019.1681988
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