Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties
Pyrazino[2,1-a]isoquinolin analogues were reported as potent activators of Nrf2/ARE signaling both in vitro and in vivo by our group. In this study, we simplified the ring system to investigate the functions of various parts of the pyrazino[2,1-a]isoquinolin scaffold. We proved that the tetrahydrois...
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MDPI AG
2017-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/22/9/1541 |
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doaj-4a2ae929ceb04f9392af4cd3a7015f4a2020-11-24T20:47:19ZengMDPI AGMolecules1420-30492017-09-01229154110.3390/molecules22091541molecules22091541Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical PropertiesHongbin Dai0Qiong Jiao1Tian Liu2Qidong You3Zhengyu Jiang4Jiangsu Hengrui Medicine Company, Kunlunshan Road, Lianyungang Eco & Tech Development Zone, Lianyungang 222047, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, ChinaPyrazino[2,1-a]isoquinolin analogues were reported as potent activators of Nrf2/ARE signaling both in vitro and in vivo by our group. In this study, we simplified the ring system to investigate the functions of various parts of the pyrazino[2,1-a]isoquinolin scaffold. We proved that the tetrahydroisoquinoline was not essential for activity and the pyrido[1,2-a]pyrazin analogues 3b and 3g retained the cellular Nrf2/ARE activation activity. Besides, this simplification significantly enhanced water solubility and membrane permeability, indicating that these compounds are more favourable for the further development of therapeutic agents around Nrf2 activation.https://www.mdpi.com/1420-3049/22/9/1541Nrf2 activatorpyrido[1,2-a]pyrazin analoguesoxidative stressphysicochemical properties |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Hongbin Dai Qiong Jiao Tian Liu Qidong You Zhengyu Jiang |
| spellingShingle |
Hongbin Dai Qiong Jiao Tian Liu Qidong You Zhengyu Jiang Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties Molecules Nrf2 activator pyrido[1,2-a]pyrazin analogues oxidative stress physicochemical properties |
| author_facet |
Hongbin Dai Qiong Jiao Tian Liu Qidong You Zhengyu Jiang |
| author_sort |
Hongbin Dai |
| title |
Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties |
| title_short |
Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties |
| title_full |
Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties |
| title_fullStr |
Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties |
| title_full_unstemmed |
Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties |
| title_sort |
development of novel nrf2/are inducers bearing pyrazino[2,1-a]isoquinolin scaffold with potent in vitro efficacy and enhanced physicochemical properties |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2017-09-01 |
| description |
Pyrazino[2,1-a]isoquinolin analogues were reported as potent activators of Nrf2/ARE signaling both in vitro and in vivo by our group. In this study, we simplified the ring system to investigate the functions of various parts of the pyrazino[2,1-a]isoquinolin scaffold. We proved that the tetrahydroisoquinoline was not essential for activity and the pyrido[1,2-a]pyrazin analogues 3b and 3g retained the cellular Nrf2/ARE activation activity. Besides, this simplification significantly enhanced water solubility and membrane permeability, indicating that these compounds are more favourable for the further development of therapeutic agents around Nrf2 activation. |
| topic |
Nrf2 activator pyrido[1,2-a]pyrazin analogues oxidative stress physicochemical properties |
| url |
https://www.mdpi.com/1420-3049/22/9/1541 |
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