(2R,3R,4S,5R,6E)-3,5-(methylethylidene)-3,4,5-trihydroxy-2-methoxy-8,8-dimethyl-N-[(3S,6R)-hexahydro-2-oxo-6-hydroxy-2H-azepin-3-yl]non-6-enamide | 270902-75-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,3R,4S,5R,6E)-3,5-(methylethylidene)-3,4,5-trihydroxy-2-methoxy-8,8-dimethyl-N-[(3S,6R)-hexahydro-2-oxo-6-hydroxy-2H-azepin-3-yl]non-6-enamide
• 英文别名: (2R)-2-[(4R,5S,6R)-6-[(E)-3,3-dimethylbut-1-enyl]-5-hydroxy-2,2-dimethyl-1,3-dioxan-4-yl]-N-[(3S,6R)-6-hydroxy-2-oxoazepan-3-yl]-2-methoxyacetamide
• CAS: 270902-75-5
• 化学式: C₂₁H₃₆N₂O₇
• 分子量: 428.526
• InChiKey: VIMKKTWWSHJRTI-FBLUROHSSA-N

物化性质

• 沸点：
  661.8±55.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5R,6E)-3,5-(methylethylidene)-3,4,5-trihydroxy-2-methoxy-8,8-dimethyl-N-[(3S,6R)-hexahydro-2-oxo-6-hydroxy-2H-azepin-3-yl]non-6-enamide 在 4-二甲氨基吡啶 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (2R,3R,4S,5R,6E)-3,4,5-trihydroxy-2-methoxy-8,8-dimethyl-N-[(3S,6R)-hexahydro-2-oxo-6-(trans-1-oxo-3-phenylpropenoxy)-2H-azepin-3-yl]non-6-enamide
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Ester-Modified Analogues of Bengamide B

  摘要：

  Bengamide B, a novel sponge-derived marine natural product with broad spectrum antitumor activity, was not suitable for further preclinical development because of its difficult synthesis and very poor water solubility. Bengamide B produced a 31% T/C at its solubility-limited maximum intravenous dose of 33 micromol/kg in MDA-MB-435 breast carcinoma implanted subcutaneously as a xenograft in nude mice. Compound 8a, a bengamide B analogue with three structural changes (t-Bu alkene substituent, unsubstituted lactam nitrogen, and inverted lactam 5'-myristoyloxy group), was as potent as bengamide B in vitro and more efficacious than bengamide B in vivo. A series of ester-modified analogues based on 8a were synthesized and tested in vitro and in vivo (MDA-MB-435). The cyclohexyl- and phenethyl-substituted esters, 8c and 8g, respectively, had in vitro and in vivo activities similar to that of 8a and enhanced water solubility (ca. 1 mg/mL). Consequently, 8c and 8g were tested in the MDA-MB-435 xenograft model at 100 micromol/kg and produced 29% and 57% tumor regression, respectively.

  DOI：

  10.1021/jm010188c
• 作为产物：
  描述：

  (6E)-6,7,8,9-tetradeoxy-8,8-dimethyl-2-O-methyl-3,5-O-(1-methylethylidene)-gulo-non-6-enonic acid lactone 在 四丁基氟化铵 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 3.0h， 生成 (2R,3R,4S,5R,6E)-3,5-(methylethylidene)-3,4,5-trihydroxy-2-methoxy-8,8-dimethyl-N-[(3S,6R)-hexahydro-2-oxo-6-hydroxy-2H-azepin-3-yl]non-6-enamide
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Ester-Modified Analogues of Bengamide B

  摘要：

  Bengamide B, a novel sponge-derived marine natural product with broad spectrum antitumor activity, was not suitable for further preclinical development because of its difficult synthesis and very poor water solubility. Bengamide B produced a 31% T/C at its solubility-limited maximum intravenous dose of 33 micromol/kg in MDA-MB-435 breast carcinoma implanted subcutaneously as a xenograft in nude mice. Compound 8a, a bengamide B analogue with three structural changes (t-Bu alkene substituent, unsubstituted lactam nitrogen, and inverted lactam 5'-myristoyloxy group), was as potent as bengamide B in vitro and more efficacious than bengamide B in vivo. A series of ester-modified analogues based on 8a were synthesized and tested in vitro and in vivo (MDA-MB-435). The cyclohexyl- and phenethyl-substituted esters, 8c and 8g, respectively, had in vitro and in vivo activities similar to that of 8a and enhanced water solubility (ca. 1 mg/mL). Consequently, 8c and 8g were tested in the MDA-MB-435 xenograft model at 100 micromol/kg and produced 29% and 57% tumor regression, respectively.

  DOI：

  10.1021/jm010188c

文献信息

• CERTAIN SUBSTITUTED CAPROLACTAMS, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR USE IN TREATING TUMORS
  申请人：Novartis AG

  公开号：EP1131297B1

  公开（公告）日：2004-04-14
• Synthesis and Antitumor Activity of Ester-Modified Analogues of Bengamide B
  作者：Frederick R. Kinder,、Richard W. Versace、Kenneth W. Bair、John M. Bontempo、David Cesarz、Steven Chen、Phillip Crews、Ania M. Czuchta、Christopher T. Jagoe、Yin Mou、Raphael Nemzek、Penny E. Phillips、Long D. Tran、RunMing Wang、Susan Weltchek、Sonya Zabludoff

  DOI：10.1021/jm010188c

  日期：2001.10.1

  Bengamide B, a novel sponge-derived marine natural product with broad spectrum antitumor activity, was not suitable for further preclinical development because of its difficult synthesis and very poor water solubility. Bengamide B produced a 31% T/C at its solubility-limited maximum intravenous dose of 33 micromol/kg in MDA-MB-435 breast carcinoma implanted subcutaneously as a xenograft in nude mice. Compound 8a, a bengamide B analogue with three structural changes (t-Bu alkene substituent, unsubstituted lactam nitrogen, and inverted lactam 5'-myristoyloxy group), was as potent as bengamide B in vitro and more efficacious than bengamide B in vivo. A series of ester-modified analogues based on 8a were synthesized and tested in vitro and in vivo (MDA-MB-435). The cyclohexyl- and phenethyl-substituted esters, 8c and 8g, respectively, had in vitro and in vivo activities similar to that of 8a and enhanced water solubility (ca. 1 mg/mL). Consequently, 8c and 8g were tested in the MDA-MB-435 xenograft model at 100 micromol/kg and produced 29% and 57% tumor regression, respectively.