(3-methyl-3-oxetanyl)methyl 6-bromohexanoate | 127947-01-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (3-methyl-3-oxetanyl)methyl 6-bromohexanoate
• 英文别名: (3-methyloxetan-3-yl)methyl 6-bromohexanoate
• CAS: 127947-01-7
• 化学式: C₁₁H₁₉BrO₃
• 分子量: 279.174
• InChiKey: ZDOPDEQSRPWVCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3-methyl-3-oxetanyl)methyl 6-bromohexanoate 在 锂硼氢 、 三氟化硼乙醚 、 caesium carbonate 、 sodium sulfate 、 sodium iodide 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 丙酮 为溶剂， 反应 41.0h， 生成
  参考文献：
  名称：

  Design, synthesis, cytocidal activity and estrogen receptor α affinity of doxorubicin conjugates at 16α-position of estrogen for site-specific treatment of estrogen receptor positive breast cancer

  摘要：

  Doxorubicin (DOX) is an important medicine for the treatment of breast cancer, which is the most frequently diagnosed and the most lethal cancer in women worldwide. However, the clinical use of DOX is impeded by serious toxic effects such as cardiomyopathy and congestive heart failure. Covalently linking DOX to estrogen to selectively deliver the drug to estrogen receptor-positive (Er) cancer tissues is one of the strategies under investigation for improving the efficacy and decreasing the cardiac toxicity of DOX. However, conjugation of drug performed until now was at 3- or 17-position of estrogen, which is not ideal since the hydroxyl groups at this position are important for receptor binding affinity. In this study, we designed, prepared and evaluated in vitro the first estrogen-doxorubicin conjugates at 16 alpha-position of estradiol termed E-DOXs (8a-d). DOX was conjugated using a 3-9 carbon atoms alkylamide linking arm. E-DOXs were prepared from estrone using a seven-step procedure to afford the desired conjugates in low to moderate yields. The antiproliferative activities of the E-DOX 8a conjugate through a 3-carbon spacer chain on ER+ MCF7 and HT-29 are in the micromolar range while inactive on M21 and the ER- MDA-MB-231 cells (>50 mu M). Compound 8a exhibits a selectivity ratio (ER+/ER- cell lines) of >3.5. Compounds 8b-8d bearing alkylamide linking arms ranging from 5 to 9 carbon atoms were inactive at the concentrations tested (>50 mu M). Interestingly, compounds 8a-8c exhibited affinity for the estrogen receptor alpha (ER alpha) in the nanomolar range (72-100 nM) whereas compound 8d exhibited no affinity at concentrations up to 215 nM. These results indicate that a short alkylamide spacer is required to maintain both antiproliferative activity toward ER+ MCF7 and affinity for the ER alpha of the E-DOX conjugates. Compound 8a is potentially a promising conjugate to target ER. breast cancer and might be useful also for the design of more potent E-DOX conjugates. (C) 2012 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2012.06.004
• 作为产物：
  描述：

  3-甲基-3-羟甲基氧杂环丁烷 、 6-溴己酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 反应 85.0h， 生成 (3-methyl-3-oxetanyl)methyl 6-bromohexanoate
  参考文献：
  名称：

  Studies related to in vivo CH activation: Synthesis and influence of 8,8- and 11,11-dimethyl oleic and 11,11-dimethyl linoleic acids on Δ12-desaturation of C. sorokiniana

  摘要：

  The synthesis of three acids was achieved using the Wittig reaction in order to study their in vivo influence on the Delta 12-desaturase of Chlorella sorokiniana. It was shown that the introduction of two methyls near the double bond prevent the desaturation of these exogenous acids while they seem to be accurately incorporated. This functionality could be of interest for the design of new thiaoleic acids as probes of the different oxidation processes. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(98)01166-1

文献信息

• Synthesis of 15-Deoxy-12-hydroxy-10-(trifluoromethyl)-Δ⁷-PGA₁ Methyl Ester
  作者：Marcus A. Tius、Huaping Hu、Joel K. Kawakami、Jakob Busch-Petersen

  DOI：10.1021/jo980621z

  日期：1998.8.1

  Cross-conjugated alkylidene prostaglandins have been shown to be potent cytostatic agents that exert their action through a unique and unusual mechanism. Compounds in this class also inhibit viral replication and have a role in osteogenesis and adipogenesis; consequently, they are of considerable current interest as pharmaceutical lead compounds. The purpose of our research was to define an efficent

  交叉缀合的亚烷基前列腺素已被证明是有效的细胞抑制剂，可通过独特而不同寻常的机制发挥作用。这类化合物还抑制病毒复制，并在成骨和脂肪形成中起作用。因此，它们作为药物先导化合物在当前具有相当大的意义。我们研究的目的是为标题中提及的C-10三氟甲基前列腺素的组装定义一种有效的方案。根据该系列中已知的结构-活性关系，预测该化合物显示出强大的抗肿瘤活性。描述了一种新颖的策略，用于通过离子电环过程组装在C-12处具有氧官能团的Delta（7）-不饱和前列腺素的碳骨架。合成的关键步骤是通过电环开环反应制备二烯酮14b和26a的离子电环化，从而形成官能化的碳骨架。发现目标化合物在体外对两种低M范围的人肿瘤细胞系具有细胞毒性，从而证实了我们的预测。
• Jones, Raymond C. F.; Schofield, Julie, Journal of the Chemical Society. Perkin transactions I, 1990, # 2, p. 375 - 383
  作者：Jones, Raymond C. F.、Schofield, Julie

  DOI：——

  日期：——