(1R,3S,7S,10R,11S,12S,16S)-10-allyl-7,11-dihydroxy-8,8,12,16-tetramethyl-3-(2-methylbenzothiazol-5-yl)-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (1R,3S,7S,10R,11S,12S,16S)-10-allyl-7,11-dihydroxy-8,8,12,16-tetramethyl-3-(2-methylbenzothiazol-5-yl)-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
• 英文别名: (1R,3S(Z),7S,10R,11S,12S,16S)-7.11-dihydroxy-3-(2-methyl-benzothiazol-5-yl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,17-dioxabicyclo[14.1.0]heptadecane-5.9-dione；(1R,3S,7S,10R,11S,12S,16S)-7,11-dihydroxy-3-(2-methyl-benzothiazol-5-yl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione；(1R,3S,7S,10R,11S,12S,16S)-7,11-dihydroxy-8,8,12,16-tetramethyl-3-(2-methyl-1,3-benzothiazol-5-yl)-10-prop-2-enyl-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
• 化学式: C₃₀H₄₁NO₆S
• 分子量: 543.725
• InChiKey: BFZKMNSQCNVFGM-FSECONRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  38
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (4S)-4-(2-methyl-3-oxohept-6-en-2-yl)-2,2-dimethyl[1,3]dioxane 在 2,6-二甲基吡啶 、 sodium chlorite 、 sodium dihydrogenphosphate 、 六氟合硅酸 、 2-甲基-2-丁烯 、 草酰氯 、 2,4,6-三氯苯甲酰氯 、 camphor-10-sulfonic acid 、 四丁基氟化铵 、 二甲基二环氧乙烷 、 对甲苯磺酸 、 氟化氢吡啶 、 二甲基亚砜 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 丙酮 、 乙腈 、 叔丁醇 为溶剂， 反应 20.75h， 生成 (1R,3S,7S,10R,11S,12S,16S)-10-allyl-7,11-dihydroxy-8,8,12,16-tetramethyl-3-(2-methylbenzothiazol-5-yl)-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
  参考文献：
  名称：

  ZK-EPO的总合成和抗肿瘤活性：临床开发中的第一个完全合成的埃博霉素。

  摘要：

  DOI：

  10.1002/anie.200602785

文献信息

• 6-Alkenyl-, 6-alkinyl- and 6-epoxy-epothilone derivatives, process for their production, and their use in pharmaceutical preparations
  申请人：Klar Ulrich

  公开号：US20050113429A1

  公开（公告）日：2005-05-26

  This invention describes the new 6-alkenyl- and 6-alkinyl-epothilone derivatives of general formula (I) in which R 1a , R 1b , R 2b , R 3a , R 3b , R 4 , R 5 , R 6 , R 7 , A, Y, D, E, G, Y and Z have the meanings that are indicated in the description. The new compounds interact with tubulin by stabilizing microtubuli that are formed. They are able to influence the cell-splitting in a phase-specific manner and thus find use in treating diseases or conditions associated with the need for cell growth, division and/or proliferation. Thus the compounds are suitable for treating malignant tumors, for example, ovarian, stomach, colon, adeno-, breast, lung, head and neck carcinomas, malignant melanoma, acute lymphocytic and myelocytic leukemia. In addition, they are suitable for anti-angiogenesis therapy as well as for treatment of chronic inflammatory diseases (such as psoriasis, arthritis). Methods of use and preparation of the compounds are also described.

  该发明描述了通式(I)中的新6-烯基-和6-炔基-epothilone衍生物，其中R1a、R1b、R2b、R3a、R3b、R4、R5、R6、R7、A、Y、D、E、G、Y和Z具有说明中指示的含义。这些新化合物通过稳定形成的微管蛋白质与微管结合。它们能够以特定阶段的方式影响细胞分裂，因此可用于治疗与细胞生长、分裂和/或增殖需求相关的疾病或状况。因此，这些化合物适用于治疗恶性肿瘤，例如卵巢、胃、结肠、腺癌、乳腺、肺、头颈癌、恶性黑色素瘤、急性淋巴细胞和骨髓性白血病。此外，它们也适用于抗血管生成治疗以及慢性炎症性疾病的治疗（如牛皮癣、关节炎）。还描述了这些化合物的使用方法和制备方法。
• 6-Alkenyl -, 6-alkinyl- and 6-epoxy-epothilone derivatives, process for their production, and their use in pharmaceutical preparations
  申请人：Klar Ulrich

  公开号：US20060046997A1

  公开（公告）日：2006-03-02

  This invention describes the new 6-alkenyl- and 6-alkinyl-epothilone derivatives of general formula (I) in which R 1a , R 1b , R 2a , R 3a , R 3b , R 4 , R 5 , R 6 , R 7 , A, Y, D, E, G, Y and Z have the meanings that are indicated in the description. The new compounds interact with tubulin by stabilizing microtubuli that are formed. They are able to influence the cell-splitting in a phase-specific manner and thus find use in treating diseases or conditions associated with the need for cell growth, division and/or proliferation. Thus the compounds are suitable for treating malignant tumors, for example, ovarian, stomach, colon, adeno-, breast, lung, head and neck carcinomas, malignant melanoma, acute lymphocytic and myelocytic leukemia. In addition, they are suitable for anti-angiogenesis therapy as well as for treatment of chronic inflammatory diseases (such as psoriasis, arthritis). Methods of use and preparation of the compounds are also described.

  该发明描述了新的6-烯基和6-炔基-依托酮衍生物，其一般式为（I），其中R1a、R1b、R2a、R3a、R3b、R4、R5、R6、R7、A、Y、D、E、G、Y和Z的含义如描述中所示。这些新化合物通过稳定形成的微管蛋白质与微管相互作用。它们能够以特定于阶段的方式影响细胞分裂，因此可用于治疗与细胞生长、分裂和/或增殖需求相关的疾病或症状。因此，这些化合物适用于治疗恶性肿瘤，例如卵巢、胃、结肠、腺癌、乳腺癌、肺癌、头颈癌、恶性黑色素瘤、急性淋巴细胞白血病和骨髓性白血病。此外，它们也适用于抗血管生成治疗以及慢性炎症性疾病（如牛皮癣、关节炎）的治疗。该文还描述了这些化合物的使用方法和制备方法。
• Composition comprising an epothilone and methods for producing a composition comprising an epothilone
  申请人：Reer Olaf

  公开号：US20060194762A1

  公开（公告）日：2006-08-31

  The present invention concerns methods for the production of pharmaceutical formulations of Epothilones suitable for being administered parenterally, such as intravenously.

  本发明涉及生产适合肠外给药，如静脉注射的埃博霉素药物制剂的方法。
• 6-ALKENYL-, 6-ALKINYL- AND 6-EPOXY-EPOTHILONE DERIVATIVES, PROCESS FOR THEIR PRODUCTION, AND THEIR USE IN PHARMACEUTICAL PREPARATIONS
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP1173441B1

  公开（公告）日：2009-08-26
• Composition Comprising An Epothilone And Methods For Producing A Composition Comprising An Epothilone
  申请人：Reer Olaf

  公开号：US20120095066A1

  公开（公告）日：2012-04-19

  The present invention concerns methods for the production of pharmaceutical formulations of Epothilones suitable for being administered parenterally, such as intravenously.