手性简化树脂毒素（sRTX）类似物作为瞬时受体电位香草素 1（TRPV1）配体的不对称合成及受体活性。
Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands.
机构信息
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
出版信息
Bioorg Med Chem Lett. 2014 Jan 1;24(1):382-5. doi: 10.1016/j.bmcl.2013.10.064. Epub 2013 Nov 6.
Abstract
The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R.
摘要
两种有效简化的 RTX 香草素手性异构体，化合物 2 和 3，采用高度对映选择性 PTC 烷基化合成，并作为 hTRPV1 配体进行了评估。分析表明，R-异构体在结合亲和力和功能活性方面是优势对映体。化合物 2R 的激动作用与 RTX 相当。3 的对映异构体的对接分析表明了其立体特异性活性的基础和 3R 的结合模式。
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2
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J Med Chem. 2012 Oct 11;55(19):8392-408. doi: 10.1021/jm300780p. Epub 2012 Sep 20.
3
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Bioorg Med Chem Lett. 2012 Jun 1;22(11):3656-60. doi: 10.1016/j.bmcl.2012.04.034. Epub 2012 Apr 13.
4
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5
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Chem Commun (Camb). 2009 Feb 21(7):782-4. doi: 10.1039/b821468a. Epub 2009 Jan 14.
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