TY - JOUR
T1 - Design, Synthesis, and Biological Activity Studies of Istradefylline Derivatives Based on Adenine as A2A Receptor Antagonists
AU - Wang, Yiyun
AU - Xu, Haojie
AU - Wang, Hongyi
AU - Zheng, Zhonghui
AU - Meng, Zihui
AU - Xu, Zhibin
AU - Li, Jiarong
AU - Xue, Min
N1 - Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society.
PY - 2021/2/16
Y1 - 2021/2/16
N2 - Due to its double bond, istradefylline rapidly isomerizes to Z-istradefylline when exposed to normal daylight in dilute solution. To solve the poor photostability of the istradefylline solution, a series of istradefylline derivatives (in total 17 compounds, including II-1 and II-2 series) were designed and synthesized, and their biological activity in inhibiting cAMP was evaluated. The IC50 values of compounds II-1-3, II-2-1, II-2-2, II-2-3, II-2-4, and II-2-6 were 7.71, 6.52, 6.16, 7.23, 7.96, and 9.68 μg/mL, respectively, which had the same order of activity as that of istradefylline (IC50 value was 1.94 μg/mL). The preliminary structure-activity relationship suggested that the 6-amino in adenine played an important role in binding an A2A receptor. The results of photostability experiments showed that the photostability of the target compounds of II-1 and II-2 series was improved when compared with that of istradefylline.
AB - Due to its double bond, istradefylline rapidly isomerizes to Z-istradefylline when exposed to normal daylight in dilute solution. To solve the poor photostability of the istradefylline solution, a series of istradefylline derivatives (in total 17 compounds, including II-1 and II-2 series) were designed and synthesized, and their biological activity in inhibiting cAMP was evaluated. The IC50 values of compounds II-1-3, II-2-1, II-2-2, II-2-3, II-2-4, and II-2-6 were 7.71, 6.52, 6.16, 7.23, 7.96, and 9.68 μg/mL, respectively, which had the same order of activity as that of istradefylline (IC50 value was 1.94 μg/mL). The preliminary structure-activity relationship suggested that the 6-amino in adenine played an important role in binding an A2A receptor. The results of photostability experiments showed that the photostability of the target compounds of II-1 and II-2 series was improved when compared with that of istradefylline.
UR - http://www.scopus.com/inward/record.url?scp=85100989647&partnerID=8YFLogxK
U2 - 10.1021/acsomega.0c05741
DO - 10.1021/acsomega.0c05741
M3 - Article
AN - SCOPUS:85100989647
SN - 2470-1343
VL - 6
SP - 4386
EP - 4394
JO - ACS Omega
JF - ACS Omega
IS - 6
ER -