发现4-取代甲氧基苯甲酰基-芳基噻唑作为新型抗癌剂：合成、生物学评价及构效关系
Discovery of 4-substituted methoxybenzoyl-aryl-thiazole as novel anticancer agents: synthesis, biological evaluation, and structure-activity relationships.
作者信息
Lu Yan, Li Chien-Ming, Wang Zhao, Ross Charles R, Chen Jianjun, Dalton James T, Li Wei, Miller Duane D
机构信息
Department of Pharmaceutical Sciences, University of Tennessee, Health Science Center, Memphis, Tennessee 38163, USA.
出版信息
J Med Chem. 2009 Mar 26;52(6):1701-11. doi: 10.1021/jm801449a.
Abstract
A series of 4-substituted methoxybenzoyl-aryl-thiazoles (SMART) have been discovered and synthesized as a result of structural modifications of the lead compound 2-arylthiazolidine-4-carboxylic acid amides (ATCAA). The antiproliferative activity of the SMART agents against melanoma and prostate cancer cells was improved from muM to low nM range compared with the ATCAA series. The structure-activity relationship was discussed from modifications of "A", "B", and "C" rings and the linker. Preliminary mechanism of action studies indicated that these compounds exert their anticancer activity through inhibition of tubulin polymerization.
摘要
通过对先导化合物2-芳基噻唑烷-4-羧酸酰胺（ATCAA）进行结构修饰，发现并合成了一系列4-取代甲氧基苯甲酰基-芳基噻唑（SMART）。与ATCAA系列相比，SMART药物对黑色素瘤和前列腺癌细胞的抗增殖活性从微摩尔范围提高到了低纳摩尔范围。从“A”、“B”和“C”环以及连接子的修饰方面讨论了构效关系。初步的作用机制研究表明，这些化合物通过抑制微管蛋白聚合发挥其抗癌活性。
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2
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Anticancer Res. 2007 Mar-Apr;27(2):883-8.
3
Expression and function of lysophosphatidic acid LPA1 receptor in prostate cancer cells.溶血磷脂酸LPA1受体在前列腺癌细胞中的表达及功能
Endocrinology. 2006 Oct;147(10):4883-92. doi: 10.1210/en.2005-1635. Epub 2006 Jun 29.
4
SAR studies of 2-arylthiazolidine-4-carboxylic acid amides: a novel class of cytotoxic agents for prostate cancer.2-芳基噻唑烷-4-羧酸酰胺的构效关系研究：一类新型的前列腺癌细胞毒性药物。
Bioorg Med Chem Lett. 2005 Sep 15;15(18):4010-3. doi: 10.1016/j.bmcl.2005.06.032.
5
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6
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7
Guanosine phosphate binding protein coupled receptors in prostate cancer: a review.前列腺癌中的鸟苷酸磷酸结合蛋白偶联受体：综述
J Urol. 2002 Mar;167(3):1458-63.
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