2-((((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)methyl)thio)benzo[d]thiazole | 1508307-47-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-((((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)methyl)thio)benzo[d]thiazole
• 英文别名: 2-((((3R,5S)-7,7-Dimethyl-1,6-Dioxaspiro[2.5]Octan-5-yl)Methyl)Thio)Benzo[D]Thiazole；2-[[(3R,7S)-5,5-dimethyl-1,6-dioxaspiro[2.5]octan-7-yl]methylsulfanyl]-1,3-benzothiazole
• CAS: 1508307-47-8
• 化学式: C₁₆H₁₉NO₂S₂
• 分子量: 321.464
• InChiKey: AEZCNZQFGDWCIO-MEDUHNTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  88.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-((((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)methyl)thio)benzo[d]thiazole 在 ammonium molybdate tetrahydrate 、 四丁基氟化铵 、 水 、 双氧水 、 sodium hexamethyldisilazane 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 aq. phosphate buffer 、 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 、 苯 为溶剂， 反应 24.09h， 生成 (S,Z)-5-(((1s,4s)-4-((2E,4E)-5-((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)-3-methylpenta-2,4-dien-1-yl)cyclohexyl)-amino)-5-oxopent-3-en-2-yl methylcarbamate
  参考文献：
  名称：

  Optimization of Antitumor Modulators of Pre-mRNA Splicing

  摘要：

  The spliceosome regulates pre-mRNA splicing, which is a critical process in normal mammalian cells. Recently, recurrent mutations in numerous spliceosomal proteins have been associated with a number of cancers. Previously, natural product antitumor agents have been shown to interact with one of the proteins that is subject to recurrent mutations (SF3B1). We report the optimization of a class of tumor-selective spliceosome modulators that demonstrate significant in vivo antitumor activity. This optimization culminated in the discovery of sudemycin D6, which shows potent cytotoxic activity in the melanoma line SK-MEL-2 (IC50 = 39 nM) and other tumor cell lines, including JeKo-1 (IC50 = 22 nM), He La (IC50 = SO nM), and SK-N-AS (IC50 = 81 nM). We also report improved processes for the synthesis of these compounds. Our work supports the idea that sudemycin D6 is worthy of further investigation as a novel preclinical anticancer agent with application in the treatment of numerous human cancers.

  DOI：

  10.1021/jm401370h
• 作为产物：
  描述：

  butyl (3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octane-5-carboxylate 在 titanium(IV) isopropylate 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 25.25h， 生成 2-((((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)methyl)thio)benzo[d]thiazole
  参考文献：
  名称：

  Optimization of Antitumor Modulators of Pre-mRNA Splicing

  摘要：

  The spliceosome regulates pre-mRNA splicing, which is a critical process in normal mammalian cells. Recently, recurrent mutations in numerous spliceosomal proteins have been associated with a number of cancers. Previously, natural product antitumor agents have been shown to interact with one of the proteins that is subject to recurrent mutations (SF3B1). We report the optimization of a class of tumor-selective spliceosome modulators that demonstrate significant in vivo antitumor activity. This optimization culminated in the discovery of sudemycin D6, which shows potent cytotoxic activity in the melanoma line SK-MEL-2 (IC50 = 39 nM) and other tumor cell lines, including JeKo-1 (IC50 = 22 nM), He La (IC50 = SO nM), and SK-N-AS (IC50 = 81 nM). We also report improved processes for the synthesis of these compounds. Our work supports the idea that sudemycin D6 is worthy of further investigation as a novel preclinical anticancer agent with application in the treatment of numerous human cancers.

  DOI：

  10.1021/jm401370h

文献信息

• ANTICANCER COMPOUNDS
  申请人：ST. JUDE CHILDREN'S RESEARCH HOSPITAL

  公开号：US20160009728A1

  公开（公告）日：2016-01-14

  In one aspect, the invention relates to compounds having anticancer activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with uncontrolled cellular proliferation using the compounds and compositions. This abstract is intended to be used as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本发明涉及具有抗癌活性的化合物；制备这些化合物的合成方法；包含这些化合物的制药组合物；以及使用这些化合物和组合物治疗与细胞不受控制增殖相关的疾病的方法。本摘要旨在作为在特定领域搜索的扫描工具使用，不旨在限制本发明。
• US9682993B2
  申请人：——

  公开号：US9682993B2

  公开（公告）日：2017-06-20
• [EN] ANTICANCER COMPOUNDS<br/>[FR] COMPOSÉS ANTI-CANCER
  申请人：ST JUDE CHILDRENS RES HOSPITAL

  公开号：WO2014089571A1

  公开（公告）日：2014-06-12

  In one aspect, the invention relates to compounds having anticancer activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with uncontrolled cellular proliferation using the compounds and compositions. This abstract is intended to be used as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• Optimization of Antitumor Modulators of Pre-mRNA Splicing
  作者：Chandraiah Lagisetti、Gustavo Palacios、Tinopiwa Goronga、Burgess Freeman、William Caufield、Thomas R. Webb

  DOI：10.1021/jm401370h

  日期：2013.12.27

  The spliceosome regulates pre-mRNA splicing, which is a critical process in normal mammalian cells. Recently, recurrent mutations in numerous spliceosomal proteins have been associated with a number of cancers. Previously, natural product antitumor agents have been shown to interact with one of the proteins that is subject to recurrent mutations (SF3B1). We report the optimization of a class of tumor-selective spliceosome modulators that demonstrate significant in vivo antitumor activity. This optimization culminated in the discovery of sudemycin D6, which shows potent cytotoxic activity in the melanoma line SK-MEL-2 (IC50 = 39 nM) and other tumor cell lines, including JeKo-1 (IC50 = 22 nM), He La (IC50 = SO nM), and SK-N-AS (IC50 = 81 nM). We also report improved processes for the synthesis of these compounds. Our work supports the idea that sudemycin D6 is worthy of further investigation as a novel preclinical anticancer agent with application in the treatment of numerous human cancers.