(+/-)-cis-1-amino-2-(phosphonomethyl)-1-cyclobutanecarboxylic acid

• 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: (+/-)-cis-1-amino-2-(phosphonomethyl)-1-cyclobutanecarboxylic acid
• 英文别名: (1S,2R)-1-amino-2-(phosphonomethyl)cyclobutane-1-carboxylic acid
• 化学式: C₆H₁₂NO₅P
• 分子量: 209.139
• InChiKey: AMWJBVSUSSJGCN-NJGYIYPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.64
• 重原子数：
  13.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  120.85
• 氢给体数：
  4.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  2-Dimethylaminomethyl-cyclobutanon-(1) 在 吡啶 、 盐酸 、 ammonium hydroxide 、 氯化铵 作用下， 以 甲醇 、 乙醚 、 苯 为溶剂， 生成 (+/-)-cis-1-amino-2-(phosphonomethyl)-1-cyclobutanecarboxylic acid
  参考文献：
  名称：

  2,3-Ethylene- and 2,3-trimethylene-bridged analogues of the group III metabotropic glutamate receptor ligand 2-amino-4-phosphonobutanoic acid

  摘要：

  The estrogen receptor alpha (ER alpha) is understood to play an important role in the progression of breast cancer. Therefore, pure antiestrogens with a preference for this receptor form are of interest as new agents for the treatment of this malignancy. Several chemical structures with selective binding affinity for ER alpha have been identified and might be useful for the synthesis of ER alpha-selective pure antiestrogens. In this study we applied the 2,5-diphenyifuran system which is closely related to the triphenylfurans described by others. Various side chains with amino and/or sulfur functions were linked to C3 to convert the furans to estrogen antagonists without residual estrogenic activity. The degree of alpha-selectivity which ranges from 2.5- to 236-fold is strongly influenced by the alkyl group at C4. Antiestrogenic potency was determined in MCF-7/2a breast cancer cells stably transfected with a luciferase gene under the control of an ERE. The 2,5-bis(4-hydroxyphenyl)furan with an ethyl substituent and a 6-[N-methyl-N-(3-pentylthiopropyi)amino]hexyl side chain exerted the strongest antiestrogenic effect in this series with an IC50 value of 50 nM in cells stimulated with 1 nM estradiol. The RBA values of this derivative were 18% (ER alpha) and 3.4% (ER beta) of estradiol, respectively. It inhibited the growth of wild-type MCF-7 cells with an IC50 value of 22 nM. The data show that the 2,5-diphenylfuran system is appropriate for the development of pure antiestrogens with preference for ER alpha. (c) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.10.040