Chemical Biology and Drug Design p. 599 - 607 (2016)
Update date:2022-07-29
Topics:
Li, Wei
Zhang, Li
Xu, Lili
Yuan, Congmin
Du, Peng
Chen, Jiaojiao
Zhen, Xuechu
Fu, Wei
(?)-Stepholidine is an active ingredient of the Chinese herb Stephania and naturally occurring tetrahydroprotoberberine alkaloid with mixed dopamine receptor D1 agonistic and dopamine receptor D2 antagonistic activities. In this work, a series of novel hexahydrobenzo[4,5]azepino [2,1-a]isoquinolines were designed and synthesized as ring-expanded analogues of (?)-Stepholidine. Initial pharmacological assays demonstrated that a benzazepine replacement was associated with significant increase in selectivity and functional reversal at dopamine receptor D1. Compound-(?)-15e (Ki?=?5.32?±?0.01?nm) is more potent than (?)-Stepholidine (Ki?=?13?nm) and was identified as a selective dopamine receptor D1 antagonist (IC50?=?0.14?μm). Moreover, molecular modeling suggested that (?)-15e might exert its dopamine receptor D1 antagonistic activities through interacting with the transmembrane helix 7 of dopamine receptor D1.
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Doi:10.1007/s11178-008-3003-6
(2008)Doi:10.1021/jo9702709
(1997)Doi:10.1007/BF00757487
(1988)Doi:10.1016/S0040-4020(01)82226-2
(1965)Doi:10.1021/jo00060a048
(1993)Doi:10.1016/S0040-4039(00)84559-1
(1986)