methanesulfonic acid 2-[2-(2,2-dimethyl-4-oxo-3,4-dihydro-2H-benzo[e][1,3]oxazin-6-ylmethoxy)ethoxy]ethyl ester | 636595-61-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: methanesulfonic acid 2-[2-(2,2-dimethyl-4-oxo-3,4-dihydro-2H-benzo[e][1,3]oxazin-6-ylmethoxy)ethoxy]ethyl ester
• 英文别名: methanesulfonic acid 2-[2-(2,2-dimethyl-4-oxo-3,4-dihydro-2H-benzo[e][1,3]oxazin-6-ylmethoxy)-ethoxy]-ethyl ester；2-[2-[(2,2-dimethyl-4-oxo-3H-1,3-benzoxazin-6-yl)methoxy]ethoxy]ethyl methanesulfonate
• CAS: 636595-61-4
• 化学式: C₁₆H₂₃NO₇S
• 分子量: 373.427
• InChiKey: LBEBXCLNQYLHIQ-UHFFFAOYSA-N

物化性质

• 沸点：
  611.6±55.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methanesulfonic acid 2-[2-(2,2-dimethyl-4-oxo-3,4-dihydro-2H-benzo[e][1,3]oxazin-6-ylmethoxy)ethoxy]ethyl ester 在 sodium hydride 、 对甲苯磺酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 57.0h， 生成 5-(2-{2-[3-(4-cyano-3-trifluoromethyl-phenyl)-5,5-dimethyl-2,4-dioxo-imidazolidin-1-yl]-ethoxy}-ethoxymethyl)-2-hydroxy-benzamide
  参考文献：
  名称：

  Rational Design and Synthesis of Androgen Receptor-Targeted Nonsteroidal Anti-Androgen Ligands for the Tumor-Specific Delivery of a Doxorubicin−Formaldehyde Conjugate

  摘要：

  The synthesis and preliminary evaluation of a doxorubicin-formaldehyde conjugate tethered to the nonsteroidal antiandrogen, cyanonilutamide (RU 56279), for the treatment of prostate cancer are reported. The relative ability of the targeting group to bind to the human androgen receptor was studied as a function of tether. The tether served to attach the antiandrogen to the doxorubicin-formaldehyde conjugate via an N-Mannich base of a salicylamide derivative. The salicylamide was selected to serve as a trigger release mechanism to separate the doxorubicin-formaldehyde conjugate from the targeting group after it has bound to the androgen receptor. The remaining part of the tether consisted of a linear group that spanned from the 5-position of the salicylamide to the X-position of cyanonilutamide. The structures explored for the linear region of the tether were derivatives of di(ethylene glycol), tri(ethylene glycol), N,N'-disubstituted-piperazine, and 2-butyne-1,4-diol. Relative binding affinity of the tethers bound to the targeting group for human androgen receptor were measured using a 3 H-Mibolerone competition assay and varied from 18% of nilutamide binding for the butynediol-based linear region to less than 1% for one of the piperazine derivatives. The complete targeted drug with the butynediol-based linear region has a relative binding affinity of 10%. This relative binding affinity is encouraging in light of the cocrystal structure of human androgen receptor ligand binding domain bound to the steroid Metribolone which predicts very limited space for a tether connecting the antiandrogen on the inside to the cytotoxin on the outside.

  DOI：

  10.1021/jm0303305
• 作为产物：
  描述：

  柳胺苄心定 在 吡啶 、 decaborane 、 碳酸氢钠 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 9.61h， 生成 methanesulfonic acid 2-[2-(2,2-dimethyl-4-oxo-3,4-dihydro-2H-benzo[e][1,3]oxazin-6-ylmethoxy)ethoxy]ethyl ester
  参考文献：
  名称：

  [EN] TARGETED DRUG-FORMALDEHYDE CONJUGATES AND METHODS OF MAKING AND USING THE SAME
  [FR] CONJUGUES CIBLES MEDICAMENT-FORMALDEHYDE ET PROCEDES DE FABRICATION ASSOCIES

  摘要：

  公开号：

  WO2005034856A3

文献信息

• Rational Design and Synthesis of Androgen Receptor-Targeted Nonsteroidal Anti-Androgen Ligands for the Tumor-Specific Delivery of a Doxorubicin−Formaldehyde Conjugate
  作者：Peter S. Cogan、Tad H. Koch

  DOI：10.1021/jm0303305

  日期：2003.11.1

  The synthesis and preliminary evaluation of a doxorubicin-formaldehyde conjugate tethered to the nonsteroidal antiandrogen, cyanonilutamide (RU 56279), for the treatment of prostate cancer are reported. The relative ability of the targeting group to bind to the human androgen receptor was studied as a function of tether. The tether served to attach the antiandrogen to the doxorubicin-formaldehyde conjugate via an N-Mannich base of a salicylamide derivative. The salicylamide was selected to serve as a trigger release mechanism to separate the doxorubicin-formaldehyde conjugate from the targeting group after it has bound to the androgen receptor. The remaining part of the tether consisted of a linear group that spanned from the 5-position of the salicylamide to the X-position of cyanonilutamide. The structures explored for the linear region of the tether were derivatives of di(ethylene glycol), tri(ethylene glycol), N,N'-disubstituted-piperazine, and 2-butyne-1,4-diol. Relative binding affinity of the tethers bound to the targeting group for human androgen receptor were measured using a 3 H-Mibolerone competition assay and varied from 18% of nilutamide binding for the butynediol-based linear region to less than 1% for one of the piperazine derivatives. The complete targeted drug with the butynediol-based linear region has a relative binding affinity of 10%. This relative binding affinity is encouraging in light of the cocrystal structure of human androgen receptor ligand binding domain bound to the steroid Metribolone which predicts very limited space for a tether connecting the antiandrogen on the inside to the cytotoxin on the outside.
• [EN] TARGETED DRUG-FORMALDEHYDE CONJUGATES AND METHODS OF MAKING AND USING THE SAME<br/>[FR] CONJUGUES CIBLES MEDICAMENT-FORMALDEHYDE ET PROCEDES DE FABRICATION ASSOCIES
  申请人：UNIV COLORADO

  公开号：WO2005034856A3

  公开（公告）日：2005-08-11