17α-ethynyl-7α-cyano-4-estren-3-one-17β-ol | 107782-59-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 17α-ethynyl-7α-cyano-4-estren-3-one-17β-ol
• 英文别名: (7R,8R,9S,10R,13S,14S,17R)-17-ethynyl-17-hydroxy-13-methyl-3-oxo-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-7-carbonitrile
• CAS: 107782-59-2
• 化学式: C₂₁H₂₅NO₂
• 分子量: 323.435
• InChiKey: JLJYGCVYHWUKFA-HNWQHMRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  61.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  三正丁基氢锡 、 17α-ethynyl-7α-cyano-4-estren-3-one-17β-ol 在 三乙基硼 、 碘 作用下， 以 四氢呋喃 、 正己烷 、 氯仿 为溶剂， 生成 (17α,20Z)-17β-hydroxy-7α-cyano-21-iodo-19-norpregna-4,20-dien-3-one 、 (17α,20E)-17β-hydroxy-7α-cyano-21-tri-n-butylstannyl-19-norpregna-4,20-dien-3-one
  参考文献：
  名称：

  Synthesis of the 7α-cyano-(17α,20E/Z)-[125I]iodovinyl-19-nortestosterones: potential radioligands for androgen and progesterone receptors

  摘要：

  We report the preparation of the 7alpha-cyano derivative of the isomeric (17alpha,20E/Z)-[I-125]iodovinyl-19-nortestosterones (IVNT) together with their binding affinity for the androgen receptor (AR) and their biodistribution in two different animal models. The cyano group was introduced at the 7alpha-position by hydrocyanation of 4,6-estradien-17beta-ol-3-one with diethylaluminum cyanide. Selective protection of the A-ring enone system as the dienol ether followed by ethynylation and deprotection under base and acid hydrolysis condition gave 7alpha-cyano-17alpha-ethynyl-19-nortestosterone. The stannyl derivatives were prepared by addition of tri-n-butylstannyl hydride and converted stereospecifically to the corresponding [I-125]iodovinyl analog using [I-125]NaI and H2O2. The [I-125]iodovinylsteroids were intravenously administered to male rats and estrogen-primed immature female rats and tissue uptake was measured up to 6 h post-injection. Co-administration of NLP-004 or ORG-2058, highly selective ligands for the progesterone receptor, to the female rats did not affect uterus uptake of the I-125-ligands. However co-injection of testosterone to DES-primed male rats induced a marked increase in prostate uptake of the 20Z-isomer of 7alpha-cyano-[I-125]-IVNT. The relative binding affinity (RBA) of either 7alpha-cyano-(17alpha,20E/Z)-IVNT isomer for the AR is low (RBA = 4 and 3, respectively, versus 100 for 5alpha-dihydrotestosterone (DHT)), suggesting the absence of a possible role of the AR in the localization process. These findings contrast previously reported data for the analogous 7alpha-methyl-[I-125]-IVNT where co-administration of testosterone was shown to result in a 50% drop in prostate uptake. These data indicate that the addition of an electron withdrawing 7alpha-cyano group to I-123-labeled nortestosterone derivatives does not improve their potential to serve as SPECT agents for the imaging of AR densities in the prostate. (C) 2003 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2003.08.011
• 作为产物：
  描述：

  17α-ethynyl-7α-cyano-3-methoxy-3,5-estradien-17β-ol 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以90%的产率得到17α-ethynyl-7α-cyano-4-estren-3-one-17β-ol
  参考文献：
  名称：

  Synthesis of the 7α-cyano-(17α,20E/Z)-[125I]iodovinyl-19-nortestosterones: potential radioligands for androgen and progesterone receptors

  摘要：

  We report the preparation of the 7alpha-cyano derivative of the isomeric (17alpha,20E/Z)-[I-125]iodovinyl-19-nortestosterones (IVNT) together with their binding affinity for the androgen receptor (AR) and their biodistribution in two different animal models. The cyano group was introduced at the 7alpha-position by hydrocyanation of 4,6-estradien-17beta-ol-3-one with diethylaluminum cyanide. Selective protection of the A-ring enone system as the dienol ether followed by ethynylation and deprotection under base and acid hydrolysis condition gave 7alpha-cyano-17alpha-ethynyl-19-nortestosterone. The stannyl derivatives were prepared by addition of tri-n-butylstannyl hydride and converted stereospecifically to the corresponding [I-125]iodovinyl analog using [I-125]NaI and H2O2. The [I-125]iodovinylsteroids were intravenously administered to male rats and estrogen-primed immature female rats and tissue uptake was measured up to 6 h post-injection. Co-administration of NLP-004 or ORG-2058, highly selective ligands for the progesterone receptor, to the female rats did not affect uterus uptake of the I-125-ligands. However co-injection of testosterone to DES-primed male rats induced a marked increase in prostate uptake of the 20Z-isomer of 7alpha-cyano-[I-125]-IVNT. The relative binding affinity (RBA) of either 7alpha-cyano-(17alpha,20E/Z)-IVNT isomer for the AR is low (RBA = 4 and 3, respectively, versus 100 for 5alpha-dihydrotestosterone (DHT)), suggesting the absence of a possible role of the AR in the localization process. These findings contrast previously reported data for the analogous 7alpha-methyl-[I-125]-IVNT where co-administration of testosterone was shown to result in a 50% drop in prostate uptake. These data indicate that the addition of an electron withdrawing 7alpha-cyano group to I-123-labeled nortestosterone derivatives does not improve their potential to serve as SPECT agents for the imaging of AR densities in the prostate. (C) 2003 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2003.08.011