17β-hydroxy-7α-cyanoestr-4-en-3-one | 54502-58-8

• 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: 17β-hydroxy-7α-cyanoestr-4-en-3-one
• 英文别名: 7α-cyano-19-nortestosterone；(7R,8R,9S,10R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-7-carbonitrile
• CAS: 54502-58-8
• 化学式: C₁₉H₂₅NO₂
• 分子量: 299.413
• InChiKey: UBVKOBJIILIRDN-PWGQXJFJSA-N

物化性质

• 沸点：
  508.4±50.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 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：

  17β-hydroxy-7α-cyanoestr-4-en-3-one 在 吡啶 、 盐酸 、 氢氧化钾 、 N-溴代丁二酰亚胺(NBS) 、 乙酸酐 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成 (7R,8R,9S,13S,14S,17S)-3,17-Dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-7-carbonitrile
  参考文献：
  名称：

  Synthesis of nitrile derivatives of estrogens

  摘要：

  The first time synthesis of 7alpha- and 11beta-nitrile estradiol is described. Reaction of 7alpha-cyano- 19-nortestosterone with copper(II) bromide in acetonitrile at room temperature results in aromatization of the A-ring. Treatment of 11beta-cyano-19-nortestosterone-17-one under similar condition does not induce A-ring aromatization but rather results in bromination at the 2beta-position. However A-ring aromatized products are obtained when the latter compound is treated with Ac2O-Py-AcOCI, NBS and HCl. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00634-0
• 作为产物：
  描述：

  6-去氢诺龙 、 二乙基氰化铝 以 四氢呋喃 为溶剂， 反应 3.0h， 以75%的产率得到17β-hydroxy-7α-cyanoestr-4-en-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

文献信息

• Synthesis of 7α-(Fluoromethyl)dihydrotestosterone and 7α-(Fluoromethyl)nortestosterone, Structurally Paired Androgens Designed To Probe the Role of Sex Hormone Binding Globulin in Imaging Androgen Receptors in Prostate Tumors by Positron Emission Tomography
  作者：Ephraim E. Parent、Kathryn E. Carlson、John A. Katzenellenbogen

  DOI：10.1021/jo070328b

  日期：2007.7.1

  Although prostate cancer growth is regulated by androgens through the androgen receptor (AR), in vitro assays of AR levels in prostate tumors have limited prognostic value. This might be improved by direct measurement of tumor AR in vivo using positron emission tomography (PET) imaging with fluorine-18-labeled androgens. Most AR PET imaging agents have been designed to limit steroid binding to serum proteins, but there is evidence that binding to sex hormone binding globulin (SHBG) might enhance tumor uptake. To probe the role of SHBG in prostate tumor uptake of PET imaging agents, we have synthesized two fluoro steroids, 7 alpha-(fluoromethyl)dihydrotestosterone (7 alpha-FM-DHT) and 7 alpha-(fluoromethyl)nortestosterone (7 alpha-FM-norT), by a route amenable to their labeling with [F-18]fluoride ion. Both compounds have high affinity for AR, but 7 alpha-FM-norT has much lower affinity for SHBG. Thus, these two fluoro steroids are well matched in terms of their site of fluorine labeling, similarity of structure, and equivalent AR binding affinitybut contrasting SHBG bindingand therefore can be used as agents for evaluating the role of SHBG binding in the target tissue uptake of AR PET imaging agents in humans.