16562-14-4Relevant academic research and scientific papers
Asymmetric total synthesis of tetrahydroprotoberberine derivatives and evaluation of their binding affinities at dopamine receptors
Lee, David Y.W.,Liu, Jing,Zhang, Shuzhen,Huang, Peng,Liu-Chen, Lee-Yuan
, p. 1437 - 1440 (2017/03/08)
Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. L-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites L-ICP, L-CD, and L-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors. The synthesis of these bioactive metabolites will allow further in vivo study of their potential in treating cocaine addiction.
Optical isomerism levorotatory Japanese Stephania root pyridine alkali and its derivatives of the process for the preparation of
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, (2017/01/05)
Provided is a compound as shown in general formula (I), wherein the definitions for the various substituents are as stated in the specification. Also provided are a method for preparing the compound, use of the compound in the preparation of L-stepholidine (L-SPD) compound, and intermediates in the preparation method.
Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity
Gadhiya, Satishkumar,Madapa, Sudharshan,Kurtzman, Thomas,Alberts, Ian L.,Ramsey, Steven,Pillarsetty, Nagavara-Kishore,Kalidindi, Teja,Harding, Wayne W.
, p. 2060 - 2071 (2016/04/20)
Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (±)-stepholidine that (a) contain various alkoxy substituents at the C10 position and, (b) were de-rigidified with respect to (±)-stepholidine, were synthesized and evaluated for affinity at dopamine and σ receptors in order to evaluate effects on D3 and σ2 receptor affinity and selectivity. Small n-alkoxy groups are best tolerated by D3 and σ2 receptors. Among all compounds tested, C10 methoxy and ethoxy analogues (10 and 11 respectively) displayed the highest affinity for σ2 receptors as well as σ2 versus σ1 selectivity and also showed the highest D3 receptor affinity. De-rigidification of stepholidine resulted in decreased affinity at all receptors evaluated; thus the tetracyclic THPB framework is advantageous for affinity at dopamine and σ receptors. Docking of the C10 analogues at the D3 receptor, suggest that an ionic interaction between the protonated nitrogen atom and Asp110, a H-bond interaction between the C2 phenol and Ser192, a H-bond interaction between the C10 phenol and Cys181 as well as hydrophobic interactions of the aryl rings to Phe106 and Phe345, are critical for high affinity of the compounds.
Preparation method for stepholidine and derivatives thereof
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Paragraph 0371; 0393; 0394; 0395, (2016/10/07)
The invention provides a preparation method for stopholidine and derivatives thereof. Specifically, the method comprises the following steps: with a chemical compound as shown in a formula A as an intermediate, carrying out B-N cyclization/sodium borohydride reduction reaction and cyclization reaction so as to obtain a skeleton of a stepholidine compound, wherein definitions of all groups are described in the specification. The method provided by the invention has the advantages of simple operation of related reactions, high yield, cheap reagents, and facilitation to enlargement of the preparation method for methylphenethylamine compounds as shown in a general formula I, and specifically for o-bromobenzeneacetic acid compounds corresponding to 9,10-substituted modes, so the method is applicable to large-scale preparation for optically pure stepholidine or the derivatives thereof.
Asymmetric total synthesis and identification of tetrahydroprotoberberine derivatives as new antipsychotic agents possessing a dopamine D1, D2 and serotonin 5-HT1A multi-action profile
Sun, Haifeng,Zhu, Liyuan,Yang, Huicui,Qian, Wangke,Guo, Lin,Zhou, Shengbin,Gao, Bo,Li, Zeng,Zhou, Yu,Jiang, Hualiang,Chen, Kaixian,Zhen, Xuechu,Liu, Hong
supporting information, p. 856 - 868 (2013/03/13)
An effective and rapid method for the microwave-assisted preparation of the key intermediate for the total synthesis of tetrahydroprotoberberines (THPBs) including l-stepholidine (l-SPD) was developed. Thirty-one THPB derivatives with diverse substituents on A and D ring were synthesized, and their binding affinity to dopamine D1, D2 and serotonin 5-HT 1A and 5-HT2A receptors were determined. Compounds 18k and 18m were identified as partial agonists at the D1 receptor with Ki values of 50 and 6.3 nM, while both compounds act as D2 receptor antagonists (Ki = 305 and 145 nM, respectively) and 5-HT1A receptor full agonists (Ki = 149 and 908 nM, respectively). These two THPBs compounds exerted antipsychotic actions in animal models. Further electrophysiological studies employing single-unit recording in intact animals demonstrated that 18k-excited dopaminergic (DA) neurons are associated with its 5-HT1A receptor agonistic activity. These results suggest that these two compounds targeted to multiple neurotransmitter receptors may present novel lead drugs with new pharmacological profiles for the treatment of schizophrenia.
Total synthesis of (S)-(-)-stepholidine using (S)-tert-butanesulfinylimine
Cheng, Jianjun,Fu, Liqiang,Ling, Chenyu,Yang, Yushe
, p. 2581 - 2592 (2011/04/24)
A new synthetic strategy of (S)-(-)-stepholidine, a promising antipsychotic drug candidate, is described. Nucleophilic addition of a laterally lithiated nitrile to a (S)-tert-butanesulfinylimine was used as the key step, which was complished in 94 % de and the main isomer was isolated in 52% yield. (S)-(-)-Stepholidine was prepared after another 5 steps, with an overall yield of 18.3% and > 98% ee. The Japan Institute of Heterocyclic Chemistry.
Enantioselective total synthesis of (-)-(S)-stepholidine
Cheng, Jian-Jun,Yang, Yu-She
experimental part, p. 9225 - 9228 (2010/03/01)
(Chemical Equation Presented) Enantioselective total synthesis of (-)-(S)-stepholidine, a drug candidate for the treatment of schizophrenia and/or drug abuse, is described. Asymmetric transfer hydrogenation of imines with use of Noyori's catalyst was used
