3'-dephenyl-10-(methoxycarbonyl)-3'-(2-methylpropyl)-docetaxel | 178250-30-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 3'-dephenyl-10-(methoxycarbonyl)-3'-(2-methylpropyl)-docetaxel
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,9-dihydroxy-15-[(2R,3S)-2-hydroxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoyl]oxy-12-methoxycarbonyloxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 178250-30-1
• 化学式: C₄₃H₅₉NO₁₆
• 分子量: 845.939
• InChiKey: NKEJLJZYGXPVTQ-BCCFMUKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  60
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  240
• 氢给体数：
  4
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  二十二碳六烯酸 、 3'-dephenyl-10-(methoxycarbonyl)-3'-(2-methylpropyl)-docetaxel 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以90%的产率得到3'-dephenyl-10-(methoxycarbonyl)-3'-(2-methylpropyl)-2'-docosahexaenoyl-docetaxel
  参考文献：
  名称：

  [EN] TAXOID-FATTY ACID CONJUGATES AND PHARMACEUTICAL COMPOSITIONS THEREOF
  [FR] CONJUGUES TAXOIDE/ACIDE GRAS ET PREPARATIONS LES CONTENANT

  摘要：

  公开号：

  WO2005041881A3
• 作为产物：
  描述：

  10-methoxycarbonyl-7-triethylsilylbaccatin III 在 palladium on activated charcoal 吡啶 、 氢氟酸 、 氢气 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙酸乙酯 、 乙腈 为溶剂， -15.0~30.0 ℃ 、101.33 kPa 条件下， 反应 29.0h， 生成 3'-dephenyl-10-(methoxycarbonyl)-3'-(2-methylpropyl)-docetaxel
  参考文献：
  名称：

  Syntheses and Structure−Activity Relationships of the Second-Generation Antitumor Taxoids:  Exceptional Activity against Drug-Resistant Cancer Cells

  摘要：

  A series of new 3'-(2-methyl-1-propenyl) and 3'-(2-methylpropyl) taxoids with modifications at C-10 was synthesized by means of the beta-lactam synthon method using 10-modified 7-(triethylsilyl)-10-deacetylbaccatin III derivatives. The new taxoids thus synthesized show excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A549), colon (HT-29), and breast (MCF-7) cancer cell lines. All but one of these new taxoids possess better activity than paclitaxel and docetaxel in the same assay, i.e., the IC50 values of almost all the taxoids are in the subnanomolar level. It is found that a variety of modifications at C-10 is tolerated for the activity against normal cancer cell lines, but the activity against a drug-resistant human breast cancer cell line expressing MDR phenotype (MCF7-R) is highly dependent on the structure of the C-10 modifier. A number of the new taxoids exhibit remarkable activity (IC50 = 2.1-9.1 nM) against MCF7-R. Among these, three new taxoids, SB-T-1213 (4a), SB-T-1214 (4b), and SB-T-1102 (5a), are found to be exceptionally potent, possessing 2 orders of magnitude better activity than paclitaxel and docetaxel. The observed exceptional activity of these taxoids may well be ascribed to an effective inhibition of P-glycoprotein binding by the modified C-10 moieties. The new taxoid SB-T-1213 (4a) shows an excellent activity (T/C = 0% at 12.4 and 7.7 mg/kg/dose, log(10) cell kill = 2.3 and 2.0, respectively) against B16 melanoma in B6D2F(1) mice via intravenous administration.

  DOI：

  10.1021/jm9604080

文献信息

• Syntheses and Structure−Activity Relationships of the Second-Generation Antitumor Taxoids:  Exceptional Activity against Drug-Resistant Cancer Cells
  作者：Iwao Ojima、John C. Slater、Evelyne Michaud、Scott D. Kuduk、Pierre-Yves Bounaud、Patricia Vrignaud、Marie-Christine Bissery、Jean M. Veith、Paula Pera、Ralph J. Bernacki

  DOI：10.1021/jm9604080

  日期：1996.1.1

  A series of new 3'-(2-methyl-1-propenyl) and 3'-(2-methylpropyl) taxoids with modifications at C-10 was synthesized by means of the beta-lactam synthon method using 10-modified 7-(triethylsilyl)-10-deacetylbaccatin III derivatives. The new taxoids thus synthesized show excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A549), colon (HT-29), and breast (MCF-7) cancer cell lines. All but one of these new taxoids possess better activity than paclitaxel and docetaxel in the same assay, i.e., the IC50 values of almost all the taxoids are in the subnanomolar level. It is found that a variety of modifications at C-10 is tolerated for the activity against normal cancer cell lines, but the activity against a drug-resistant human breast cancer cell line expressing MDR phenotype (MCF7-R) is highly dependent on the structure of the C-10 modifier. A number of the new taxoids exhibit remarkable activity (IC50 = 2.1-9.1 nM) against MCF7-R. Among these, three new taxoids, SB-T-1213 (4a), SB-T-1214 (4b), and SB-T-1102 (5a), are found to be exceptionally potent, possessing 2 orders of magnitude better activity than paclitaxel and docetaxel. The observed exceptional activity of these taxoids may well be ascribed to an effective inhibition of P-glycoprotein binding by the modified C-10 moieties. The new taxoid SB-T-1213 (4a) shows an excellent activity (T/C = 0% at 12.4 and 7.7 mg/kg/dose, log(10) cell kill = 2.3 and 2.0, respectively) against B16 melanoma in B6D2F(1) mice via intravenous administration.
• [EN] TAXOID-FATTY ACID CONJUGATES AND PHARMACEUTICAL COMPOSITIONS THEREOF<br/>[FR] CONJUGUES TAXOIDE/ACIDE GRAS ET PREPARATIONS LES CONTENANT
  申请人：YORK THE RES FOUNDATION OF STA

  公开号：WO2005041881A3

  公开（公告）日：2005-12-08