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1
Identification of the GPR55 antagonist binding site using a novel set of high-potency GPR55 selective ligands.利用一组新型高活性 GPR55 选择性配体鉴定 GPR55 拮抗剂结合位点。
Biochemistry. 2013 Dec 31;52(52):9456-69. doi: 10.1021/bi4008885. Epub 2013 Dec 17.
2
The orphan receptor GPR55 drives skin carcinogenesis and is upregulated in human squamous cell carcinomas.孤儿受体 GPR55 驱动皮肤癌发生，并且在人类鳞状细胞癌中上调。
Oncogene. 2013 May 16;32(20):2534-42. doi: 10.1038/onc.2012.278. Epub 2012 Jul 2.
3
Minireview: recent developments in the physiology and pathology of the lysophosphatidylinositol-sensitive receptor GPR55.小型综述：溶血磷脂酰肌醇敏感受体GPR55的生理学和病理学最新进展
Mol Endocrinol. 2011 Nov;25(11):1835-48. doi: 10.1210/me.2011-1197. Epub 2011 Sep 29.
4
Pharmacology of GPR55 in yeast and identification of GSK494581A as a mixed-activity glycine transporter subtype 1 inhibitor and GPR55 agonist.GPR55 在酵母中的药理学及 GSK494581A 作为混合活性甘氨酸转运体亚型 1 抑制剂和 GPR55 激动剂的鉴定。
J Pharmacol Exp Ther. 2011 Apr;337(1):236-46. doi: 10.1124/jpet.110.172650. Epub 2011 Jan 13.
5
The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation.假定的大麻素受体 GPR55 在癌细胞增殖中定义了一个新的自分泌环。
Oncogene. 2011 Jan 13;30(2):142-52. doi: 10.1038/onc.2010.417. Epub 2010 Sep 13.
6
The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK.孤儿 G 蛋白偶联受体 GPR55 通过 ERK 促进癌细胞增殖。
Oncogene. 2011 Jan 13;30(2):245-52. doi: 10.1038/onc.2010.402. Epub 2010 Sep 6.
7
A role for L-alpha-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells.溶血磷脂酰肌醇和 GPR55 在调控人乳腺癌细胞迁移、定向和极化中的作用。
Br J Pharmacol. 2010 Jun;160(3):762-71. doi: 10.1111/j.1476-5381.2010.00743.x.
8
Pharmacological characterization of GPR55, a putative cannabinoid receptor.GPR55 的药理学特征，一种假定的大麻素受体。
Pharmacol Ther. 2010 Jun;126(3):301-13. doi: 10.1016/j.pharmthera.2010.02.004. Epub 2010 Mar 16.
9
Design, synthesis, and 3D-QSAR analysis of novel 1,3,4-oxadiazol-2(3H)-ones as protoporphyrinogen oxidase inhibitors.新型 1,3,4-噁二唑-2(3H)-酮作为原卟啉原氧化酶抑制剂的设计、合成与 3D-QSAR 分析。
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10
Discovery of 4-morpholino-6-aryl-1H-pyrazolo[3,4-d]pyrimidines as highly potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR): optimization of the 6-aryl substituent.发现 4-吗啉基-6-芳基-1H-吡唑并[3,4-d]嘧啶作为高度有效的和选择性的哺乳动物雷帕霉素靶蛋白(mTOR)的 ATP 竞争性抑制剂：6-芳基取代基的优化。
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GPR55拮抗剂的设计、合成与分析：哌啶取代的1,3,4-恶二唑-2-酮

Design, synthesis, and analysis of antagonists of GPR55: Piperidine-substituted 1,3,4-oxadiazol-2-ones.

作者信息

Meza-Aviña Maria Elena, Lingerfelt Mary A, Console-Bram Linda M, Gamage Thomas F, Sharir Haleli, Gettys Kristen E, Hurst Dow P, Kotsikorou Evangelia, Shore Derek M, Caron Marc G, Rao Narasinga, Barak Larry S, Abood Mary E, Reggio Patricia H, Croatt Mitchell P

机构信息

Department of Chemistry and Biochemistry, Natural Products and Drug Discovery Center, University of North Carolina at Greensboro, Greensboro, North Carolina 27402, United States.

Center for Substance Abuse Research, Temple University, Philadelphia, Pennsylvania 19140, United States.

出版信息

Bioorg Med Chem Lett. 2016 Apr 1;26(7):1827-1830. doi: 10.1016/j.bmcl.2016.02.030. Epub 2016 Feb 16.

DOI:10.1016/j.bmcl.2016.02.030
PMID:26916440
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4836065/
Abstract

A series of 1,3,4-oxadiazol-2-ones was synthesized and tested for activity as antagonists at GPR55 in cellular beta-arrestin redistribution assays. The synthesis was designed to be modular in nature so that a sufficient number of analogues could be rapidly accessed to explore initial structure-activity relationships. The design of analogues was guided by the docking of potential compounds into a model of the inactive form of GPR55. The results of the assays were used to learn more about the binding pocket of GPR55. With this oxadiazolone scaffold, it was determined that modification of the aryl group adjacent to the oxadiazolone ring was often detrimental and that the distal cyclopropane was beneficial for activity. These results will guide further exploration of this receptor.

摘要

合成了一系列1,3,4-恶二唑-2-酮，并在细胞β-抑制蛋白再分布试验中测试了其作为GPR55拮抗剂的活性。合成设计本质上是模块化的，以便能够快速获得足够数量的类似物，以探索初步的构效关系。类似物的设计以潜在化合物对接至GPR55无活性形式模型为指导。试验结果用于更深入了解GPR55的结合口袋。使用这种恶二唑酮支架，确定恶二唑酮环相邻芳基的修饰通常是有害的，而远端环丙烷对活性有益。这些结果将指导对该受体的进一步探索。