5,6,7-Trimethoxy-1H-indole-2-carboxylic acid [4-benzylamino-1-(2-chloro-ethyl)-naphthalen-2-yl]-amide | 855299-67-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5,6,7-Trimethoxy-1H-indole-2-carboxylic acid [4-benzylamino-1-(2-chloro-ethyl)-naphthalen-2-yl]-amide
• 英文别名: N-[4-(benzylamino)-1-(2-chloroethyl)naphthalen-2-yl]-5,6,7-trimethoxy-1H-indole-2-carboxamide
• CAS: 855299-67-1
• 化学式: C₃₁H₃₀ClN₃O₄
• 分子量: 544.05
• InChiKey: PJHZHMYLPFMGOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  84.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5,6,7-Trimethoxy-1H-indole-2-carboxylic acid [4-benzylamino-1-(2-chloro-ethyl)-naphthalen-2-yl]-amide 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 以74%的产率得到centanamycin
  参考文献：
  名称：

  A Novel Class of in Vivo Active Anticancer Agents:  Achiral seco-Amino- and seco-Hydroxycyclopropylbenz[e]indolone (seco-CBI) Analogues of the Duocarmycins and CC-1065

  摘要：

  One achiral seco-hydroxycyclopropylbenz[e]indolone (seco-CBI) (12) and seven achiral seco-amino-CBI (11a-g) analogues of CC-1065 and the duocarmycins were designed, synthesized and evaluated for their DNA-binding and anticancer properties. These compounds contain a core 2-chloroethylnaphthalene structure and they do not have a stereocenter. From thermal cleavage gel analyses, compounds 11a-g and 12 demonstrated similar covalent sequence specificity to adozelesin 3 and the racemic seco-CBI-TMI 4 for binding to the 5'-AAAAA(865)-3' site. Continuous exposure of human (K562) and murine (B16, L1210 and P815) cancer cell lines to the compounds demonstrated their significant cytotoxicity, with IC50 values in the sub-micromolar range. Generally, a good leaving group on the ethyl moiety and a free amino or hydroxyl group on the naphthyl moiety are essential for activity. According to NCI's cytotoxicity screen, compounds 11a and 12 were active against human cancer cell lines derived from lung, colon, melanoma, renal system, and breast. At the respective doses of 15 and 20 mg/kg (administered via an ip route), compounds 11a and 12 inhibited the growth of murine B16-F0 melanoma in C57BL/6 mice, with minimal toxicity, and 11a gave a significant anticancer effect. The in vivo anticancer activity of compound 11a was confirmed in a human tumor xenograft study (advanced stage SC-OVCAR-3 ovarian cancer growing in scid mice). Finally, compound 11a was not toxic to murine bone marrow cell growth in culture at a dose that was toxic for the previously reported compound 4.

  DOI：

  10.1021/jm050179u
• 作为产物：
  描述：

  2-[4-benzylamino-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethanol 在 三乙胺 、 lithium chloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.0h， 生成 5,6,7-Trimethoxy-1H-indole-2-carboxylic acid [4-benzylamino-1-(2-chloro-ethyl)-naphthalen-2-yl]-amide
  参考文献：
  名称：

  A Novel Class of in Vivo Active Anticancer Agents:  Achiral seco-Amino- and seco-Hydroxycyclopropylbenz[e]indolone (seco-CBI) Analogues of the Duocarmycins and CC-1065

  摘要：

  One achiral seco-hydroxycyclopropylbenz[e]indolone (seco-CBI) (12) and seven achiral seco-amino-CBI (11a-g) analogues of CC-1065 and the duocarmycins were designed, synthesized and evaluated for their DNA-binding and anticancer properties. These compounds contain a core 2-chloroethylnaphthalene structure and they do not have a stereocenter. From thermal cleavage gel analyses, compounds 11a-g and 12 demonstrated similar covalent sequence specificity to adozelesin 3 and the racemic seco-CBI-TMI 4 for binding to the 5'-AAAAA(865)-3' site. Continuous exposure of human (K562) and murine (B16, L1210 and P815) cancer cell lines to the compounds demonstrated their significant cytotoxicity, with IC50 values in the sub-micromolar range. Generally, a good leaving group on the ethyl moiety and a free amino or hydroxyl group on the naphthyl moiety are essential for activity. According to NCI's cytotoxicity screen, compounds 11a and 12 were active against human cancer cell lines derived from lung, colon, melanoma, renal system, and breast. At the respective doses of 15 and 20 mg/kg (administered via an ip route), compounds 11a and 12 inhibited the growth of murine B16-F0 melanoma in C57BL/6 mice, with minimal toxicity, and 11a gave a significant anticancer effect. The in vivo anticancer activity of compound 11a was confirmed in a human tumor xenograft study (advanced stage SC-OVCAR-3 ovarian cancer growing in scid mice). Finally, compound 11a was not toxic to murine bone marrow cell growth in culture at a dose that was toxic for the previously reported compound 4.

  DOI：

  10.1021/jm050179u

文献信息

• A Novel Class of in Vivo Active Anticancer Agents:  Achiral <i>seco</i>-Amino- and <i>seco</i>-Hydroxycyclopropylbenz[<i>e</i>]indolone (<i>seco</i>-CBI) Analogues of the Duocarmycins and CC-1065
  作者：Atsushi Sato、LuAnne McNulty、Kari Cox、Susan Kim、Adrienne Scott、Kristen Daniell、Kaitlin Summerville、Carly Price、Stephen Hudson、Konstantinos Kiakos、John A. Hartley、Tetsuji Asao、Moses Lee

  DOI：10.1021/jm050179u

  日期：2005.6.1

  One achiral seco-hydroxycyclopropylbenz[e]indolone (seco-CBI) (12) and seven achiral seco-amino-CBI (11a-g) analogues of CC-1065 and the duocarmycins were designed, synthesized and evaluated for their DNA-binding and anticancer properties. These compounds contain a core 2-chloroethylnaphthalene structure and they do not have a stereocenter. From thermal cleavage gel analyses, compounds 11a-g and 12 demonstrated similar covalent sequence specificity to adozelesin 3 and the racemic seco-CBI-TMI 4 for binding to the 5'-AAAAA(865)-3' site. Continuous exposure of human (K562) and murine (B16, L1210 and P815) cancer cell lines to the compounds demonstrated their significant cytotoxicity, with IC50 values in the sub-micromolar range. Generally, a good leaving group on the ethyl moiety and a free amino or hydroxyl group on the naphthyl moiety are essential for activity. According to NCI's cytotoxicity screen, compounds 11a and 12 were active against human cancer cell lines derived from lung, colon, melanoma, renal system, and breast. At the respective doses of 15 and 20 mg/kg (administered via an ip route), compounds 11a and 12 inhibited the growth of murine B16-F0 melanoma in C57BL/6 mice, with minimal toxicity, and 11a gave a significant anticancer effect. The in vivo anticancer activity of compound 11a was confirmed in a human tumor xenograft study (advanced stage SC-OVCAR-3 ovarian cancer growing in scid mice). Finally, compound 11a was not toxic to murine bone marrow cell growth in culture at a dose that was toxic for the previously reported compound 4.