17-demethoxy-17-(2,3-dihydroxypropylamino)geldanamycin | 169521-73-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 17-demethoxy-17-(2,3-dihydroxypropylamino)geldanamycin
• 英文别名: 17Aag metabolite M5；[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-(2,3-dihydroxypropylamino)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate
• CAS: 169521-73-7
• 化学式: C₃₁H₄₅N₃O₁₀
• 分子量: 619.712
• InChiKey: BDPJPPWISVHITL-AXONLCQGSA-N

物化性质

• 沸点：
  888.2±65.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  207
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  17-demethoxy-17-(2,3-dihydroxypropylamino)geldanamycin 在 吡啶 、 盐酸羟胺 、 potassium carbonate 作用下， 反应 24.0h， 以59%的产率得到17-demethoxy-17-(2,3-dihydroxypropylamino)geldanamycin-18-oxime
  参考文献：
  名称：

  WO2008/34895

  摘要：

  公开号：
• 作为产物：
  描述：

  3-氨基-1,2-丙二醇 、 格尔德霉素 以 四氢呋喃 为溶剂， 反应 64.0h， 生成 17-demethoxy-17-(2,3-dihydroxypropylamino)geldanamycin
  参考文献：
  名称：

  [EN] ANALOGS OF BENZOQUINONE-CONTAINING ANSAMYCINS FOR THE TREATMENT OF CANCER
  [FR] ANALOGUES D'ANSAMYCINES CONTENANT DE LA BENZOQUINONE POUR LE TRAITEMENT DU CANCER

  摘要：

  本发明提供了含苯醌的ansamycins的类似物及其用于治疗和调节与过度增殖相关的疾病，如癌症（公式（I）和（IV））。本发明提供了含苯醌的ansamycins的类似物，其中苯醌被还原为氢醌，并通过与适当酸反应而被困，最好是增加所得（17）-氨基氢醌ansamycin类似物的溶解性和空气稳定性的酸。

  公开号：

  WO2005063714A1

文献信息

• Inhibition of the oncogene product p185erbB-2 in vitro and in vivo by geldanamycin and dihydrogeldanamycin derivatives
  作者：R. C. Schnur、M. L. Corman、R. J. Gallaschun、B. A. Cooper、M. F. Dee、J. L. Doty、M. L. Muzzi、J. D. Moyer、C. I. DiOrio

  DOI：10.1021/jm00019a010

  日期：1995.9

  The erbB-2 oncogene encodes a transmembrane protein tyrosine kinase which plays a pivotal role in signal transduction and has been implicated when overexpressed in breast, ovarian, and gastric cancers. Naturally occurring benzoquinoid ansamycin antibiotics herbimycin A, geldanamycin (GDM), and dihydrogeldanamycin were found to potently deplete p185, the erbB-2 oncoprotein, in human breast cancer SKBR-3 cells in culture. Chemistry efforts to modify selectively the quinoid moiety of GDM afforded derivatives with greater potency in vitro and in vivo. Analogs demonstrated inhibition of p185 phosphotyrosine in cell culture and in vivo after systemic drug administration to nu/nu nude mice bearing Fisher rat embryo cells transfected with human erbB-2 (FRE/erbB-2). Specifically, dosed intraperitoneally at 100 mg/kg, 17-(allylamino)-17-demethoxygeldanamycin and other 17-amino analogs were effective at reducing p185 phosphotyrosine in subcutaneous flank FRE/erbB-2 tumors. Modifications to the 17-19-positions of the quinone ring revealed a broad structure-activity relationship in vitro.
• [EN] ANALOGS OF BENZOQUINONE-CONTAINING ANSAMYCINS FOR THE TREATMENT OF CANCER<br/>[FR] ANALOGUES D'ANSAMYCINES CONTENANT DE LA BENZOQUINONE POUR LE TRAITEMENT DU CANCER
  申请人：INFINITY PHARMACEUTICALS INC

  公开号：WO2005063714A1

  公开（公告）日：2005-07-14

  The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer ( formula (I) and (IV). The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting (17)-­ammonium hydroquinone ansamycin analog.

  本发明提供了含苯醌的ansamycins的类似物及其用于治疗和调节与过度增殖相关的疾病，如癌症（公式（I）和（IV））。本发明提供了含苯醌的ansamycins的类似物，其中苯醌被还原为氢醌，并通过与适当酸反应而被困，最好是增加所得（17）-氨基氢醌ansamycin类似物的溶解性和空气稳定性的酸。
• WO2008/34895
  申请人：——

  公开号：——

  公开（公告）日：——