9-β-dihydro-9,10-O-acetal taxane | 272129-21-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 9-β-dihydro-9,10-O-acetal taxane
• 英文别名: [(2R,4S,6S,7R,10R,13S,14R,15S,16S,18S)-13-acetyloxy-16-hydroxy-18-[(2R,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-pyridin-2-ylpropanoyl]oxy-7,19,20,20-tetramethyl-4-(morpholin-4-ylmethyl)-3,5,11-trioxapentacyclo[14.3.1.02,6.07,14.010,13]icos-1(19)-en-15-yl] benzoate
• CAS: 272129-21-2
• 化学式: C₄₈H₆₃N₃O₁₄
• 分子量: 906.04
• InChiKey: FPXXOTBTDWZLCK-CFGKGYHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  65
• 可旋转键数：
  15
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  211
• 氢给体数：
  3
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  9-β-dihydro-9,10-O-acetal taxane 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 反应 1.0h， 以92%的产率得到(1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-acetoxy-2-benzoyloxy-5,20-epoxy-1-hydroxy-9,10-[(1S)-2-(morpholino-N-oxide)ethylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl)propionate
  参考文献：
  名称：

  New highly active taxoids from 9β-Dihydrobaccatin-9,10-acetals. Part 4

  摘要：

  It was shown that a new taxane analogue 3, which exhibited both in vitro antitumor activity and in vivo efficacy by both iv and po administration, was prone to be metabolized by human liver microsomes. We identified a major metabolite, M-1. generated by human liver microsomes as 20a, a hydroxylated compound at the pyridine ring of 3. To improve the metabolic stability of 3, we designed and synthesized new taxane analogues based on the structure of M-1. and obtained some compounds that maintained excellent antitumor activity and were scarcely metabolized by human liver microsomes. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00454-1
• 作为产物：
  描述：

  (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-(acetoxy)-2-(benzoyloxy)-5,20-epoxy-1,9,10,13-tetrahydroxytax-11-ene 在 四氧化锇 、 N-甲基吲哚酮 、 camphor-10-sulfonic acid 、 四丁基氟化铵 、 sodium cyanoborohydride 、 溶剂黄146 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 丙酮 为溶剂， 生成 9-β-dihydro-9,10-O-acetal taxane
  参考文献：
  名称：

  New highly active taxoids from 9β-dihydrobaccatin-9,10-acetals. Part 3

  摘要：

  We synthesized novel water-soluble and orally active taxane analogues, 7-deoxy-9beta-dihydro-9,10-O-acetal taxanes. Cytotoxicities of the synthetic compounds were greater than those of paclitaxel and docetaxel, especially against resistant cancer cell lines expressing P-glycoprotein. In addition, some compounds showed potent antitumor effects against B16 melanoma BL6 in vivo by both iv and po administration. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00891-0

文献信息

• New highly active taxoids from 9β-Dihydrobaccatin-9,10-acetals. Part 4
  作者：Yasuyuki Takeda、Kouichi Uoto、Jun Chiba、Takao Horiuchi、Michio Iwahana、Ryo Atsumi、Chiho Ono、Hirofumi Terasawa、Tsunehiko Soga

  DOI：10.1016/s0968-0896(03)00454-1

  日期：2003.10

  It was shown that a new taxane analogue 3, which exhibited both in vitro antitumor activity and in vivo efficacy by both iv and po administration, was prone to be metabolized by human liver microsomes. We identified a major metabolite, M-1. generated by human liver microsomes as 20a, a hydroxylated compound at the pyridine ring of 3. To improve the metabolic stability of 3, we designed and synthesized new taxane analogues based on the structure of M-1. and obtained some compounds that maintained excellent antitumor activity and were scarcely metabolized by human liver microsomes. (C) 2003 Elsevier Ltd. All rights reserved.
• New highly active taxoids from 9β-dihydrobaccatin-9,10-acetals. Part 3
  作者：Yasuyuki Takeda、Toshiharu Yoshino、Kouichi Uoto、Jun Chiba、Takashi Ishiyama、Michio Iwahana、Takeshi Jimbo、Noriko Tanaka、Hirofumi Terasawa、Tsunehiko Soga

  DOI：10.1016/s0960-894x(02)00891-0

  日期：2003.1

  We synthesized novel water-soluble and orally active taxane analogues, 7-deoxy-9beta-dihydro-9,10-O-acetal taxanes. Cytotoxicities of the synthetic compounds were greater than those of paclitaxel and docetaxel, especially against resistant cancer cell lines expressing P-glycoprotein. In addition, some compounds showed potent antitumor effects against B16 melanoma BL6 in vivo by both iv and po administration. (C) 2002 Elsevier Science Ltd. All rights reserved.