新型取代（Z）-5-((N-苄基-1H-吲哚-3-基)亚甲基)咪唑烷-2,4-二酮和 5-((N-苄基-1H-吲哚-3-基)亚甲基)嘧啶-2,4,6(1H,3H,5H)-三酮作为有效的放射增敏剂。
Novel substituted (Z)-5-((N-benzyl-1H-indol-3-yl)methylene)imidazolidine-2,4-diones and 5-((N-benzyl-1H-indol-3-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones as potent radio-sensitizing agents.
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
出版信息
Bioorg Med Chem Lett. 2010 Jan 15;20(2):600-2. doi: 10.1016/j.bmcl.2009.11.082. Epub 2009 Nov 22.
Abstract
A series of (Z)-5-((N-benzyl-1H-indol-3-yl)methylene)imidazolidine-2,4-dione (9a-9m) and 5-((N-benzyl-1H-indol-3-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (10a-10i) derivatives that incorporate a variety of aromatic substituents in both the indole and N-benzyl moieties have been synthesized. These analogs were evaluated for their radiosensitization activity against the HT-29 cell line. Three analogs, 10a, 10b, and 10c were identified as the most potent radiosensitizing agents.
摘要
一系列（Z）-5-((N-苄基-1H-吲哚-3-基)亚甲基)咪唑烷-2,4-二酮（9a-9m）和 5-((N-苄基-1H-吲哚-3-基)亚甲基)嘧啶-2,4,6(1H,3H,5H)-三酮（10a-10i）衍生物，其中吲哚和 N-苄基部分都包含了各种芳香取代基。这些类似物被评估了对 HT-29 细胞系的放射增敏活性。三种类似物，10a、10b 和 10c，被确定为最有效的放射增敏剂。
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1
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J Surg Oncol. 2009 Aug 1;100(2):149-58. doi: 10.1002/jso.21318.
2
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CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20.
3
Long-term results of salvage radiotherapy for the treatment of recurrent cervical carcinoma after prior surgery.挽救性放疗用于治疗既往手术后复发性宫颈癌的长期疗效。
Radiother Oncol. 2008 Nov;89(2):197-204. doi: 10.1016/j.radonc.2008.01.004. Epub 2008 Jan 30.
4
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5
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6
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7
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8
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Int J Hyperthermia. 2005 Dec;21(8):681-7. doi: 10.1080/02656730500307298.
9
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Surg Oncol. 2004 Aug-Nov;13(2-3):93-101. doi: 10.1016/j.suronc.2004.08.012.
10
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