3β-acetoxy-androsta-5,16-dien-17-carboxylic acid chloride | 37911-30-1

• 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: 3β-acetoxy-androsta-5,16-dien-17-carboxylic acid chloride
• CAS: 37911-30-1
• 化学式: C₂₂H₂₉ClO₃
• 分子量: 376.923
• InChiKey: FEEGSWPRWIBWLH-CSOYKPOESA-N

物化性质

• 沸点：
  465.5±45.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.18
• 重原子数：
  26.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  43.37
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3β-acetoxy-androsta-5,16-dien-17-carboxylic acid chloride 以 ammonium hydroxide 为溶剂， 以2.345 g的产率得到3β-acetoxy-androsta-5,16-dien-17-carboxamide
  参考文献：
  名称：

  Novel P45017α inhibitors: 17-(2′-oxazolyl)- and 17-(2′-thiazolyl)-androstene derivatives

  摘要：

  Twelve 17-(2'-oxazolyl)- and 17-(2'-thiazolyl)-androsta-5,16-diene derivatives were designed and synthesized from 3beta-acetoxy-pregna-5,16-dien-20-one (1b) as inhibitors of 17alpha-hydroxylase-C-17,C-20-lyase (P450(17alpha)). Potent inhibitors of this enzyme could be of value as treatment of prostate cancer. Two substituents (methyl and phenyl) were introduced either at their 4'- or 5'-position in order to investigate their structure-activity relationship. Due to the 16,17-double bond, 17-thiazoles were generally obtained in low yield. The pharmacological results showed that the compounds containing 17-(2'-oxazolyl) (14c) and 17-(2'-thiazolyl) (8c) (41.5%) demonstrated reasonable inhibition against P45017a. Their 3-acetate (13c and 7c) were less potent than their 3-OH counterparts. The introduction of a phenyl or methyl group generally decreased inhibitory activity. Surprisingly, 17-(5'-methyl-2'-thiazolyl) (12a) was the most potent compound in this series and was almost as potent as L-39, which has good antitumor activity. (C) 2003 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(03)00082-5
• 作为产物：
  描述：

  Δ^5,16-Androstadien-3β-ol-17-saeure 在 吡啶 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 3β-acetoxy-androsta-5,16-dien-17-carboxylic acid chloride
  参考文献：
  名称：

  An efficient approach to novel 17-5′-(1′,2′,4′)-oxadiazolyl androstenes via the cyclodehydration of cytotoxic O-steroidacylamidoximes, and an evaluation of their inhibitory action on 17α-hydroxylase/C17,20-lyase

  摘要：

  Novel 17-exo-oxadiazoles in the androst-5-ene series were efficiently synthesized in a two-step sequence via the corresponding O-acylamidoxime intermediates (obtained from steroidal 17-carboxylic acids and amidoximes in the presence of coupling reagent), which then underwent tetrabutylammonium fluoride-induced cyclocondensation under mild reaction conditions. The synthesized compounds were subjected to in vitro pharmacological studies to investigate their inhibitory effect on rat testicular C-17,C-20-lyase and their antiproliferative action on four malignant human adherent cell lines (HeLa, MCF7, A2780 and A431). One of the oxadiazolyl derivatives proved to exert significant enzyme-inhibitory action (IC50 = 0.60 mu M), while some of the isolated O-acylated amidoxime intermediates displayed high cytotoxic activities on all examined cell lines, with IC50 values in the range 0.22-3.94 mu M. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.038

文献信息

• New steroidal oxazolines, benzoxazoles and benzimidazoles related to abiraterone and galeterone
  作者：Alexandra S. Latysheva、Vladimir A. Zolottsev、Alexander V. Veselovsky、Kirill A. Scherbakov、Galina E. Morozevich、Vadim S. Pokrovsky、Roman A. Novikov、Vladimir P. Timofeev、Yaroslav V. Tkachev、Alexander Y. Misharin

  DOI：10.1016/j.steroids.2019.108534

  日期：2020.1

  Seven new oxazoline, benzoxazole and benzimidazole derivatives were synthesized from 3 beta-acetoxyandrosta-5,16-dien-17-carboxylic, 3 beta-acetoxyandrost-5-en-17 beta-carboxylic and 3 beta-acetoxypregn-5-en-21-oic acids. Docking to active site of human 17 alpha-hydroxylase/17,20-lyase revealed that all oxazolines, as well as benzoxazoles and benzimidazoles comprising Delta(16) could form stable complexes with enzyme, in which steroid moiety is positioned similarly to that of abiraterone and galeterone, and nitrogen atom coordinates heme iron, while 16,17-saturated benzoxazoles and benzimidazoles could only bind in a position where heterocycle is located nearly parallel to heme plane. Modeling of the interaction of new benzoxazole and benzimidazole derivatives with androgen receptor revealed the destabilization of helix 12, constituting activation function 2 (AF2) site, by mentioned compounds, similar to one induced by known antagonist galeterone. The synthesized compounds inhibited growth of prostate carcinoma LNCaP and PC-3 cells at 96 h incubation; the potency of 2'-(3-hydroxyandrosta-5,16-dien-17-yl)-4',5'-dihydro-1',3'-oxazole and 2'-(3 beta-hydroxyandrosta-5,16-dien-17-yl)-benzimidazole was superior and could inspire further investigations of these compounds as potential anti-cancer agents.