16α-bromoandrost-4-en-17-one | 135144-23-9

• 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: 16α-bromoandrost-4-en-17-one
• 英文别名: 16α-bromoandrosta-4-en-17-one；(8R,9S,10R,13S,14S,16R)-16-bromo-10,13-dimethyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one
• CAS: 135144-23-9
• 化学式: C₁₉H₂₇BrO
• 分子量: 351.327
• InChiKey: GSOJBPSBUAABDR-NBBHSKLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  16α-bromoandrost-4-en-17-one 在 吡啶 、 sodium hydroxide 作用下， 反应 4.0h， 以63%的产率得到16α-hydroxyandrosta-4-en-17-one
  参考文献：
  名称：

  Aromatization of androstenedione and 16α-hydroxyandrostenedione in human placental microsomes

  摘要：

  Inhibition of aromatase activity in human placental microsomes with androstenedione (AD) (1a) and its 19-oxygenated derivatives 1b and 1c, their 16a-hydroxy compounds 2 and 3, and 3-deoxyandrost-4-ene compounds 5 and 6 was studied using [1 beta-(3)H]AD as a substrate and compared to that with [1 beta-(3)H]16 alpha-hydroxyandrostenedione (16-OHAD). AD series of steroids, compounds 1, inhibited competitively [1 beta-(3)H]AD aromatization whereas other 16a-hydroxy steroids 2, 3, S, and 6 inhibited AD aromatization in a non-competitive manner. On the other hand, all of 16-OHAD series, compounds 2, blocked the [1 beta-(3)H]16-OHAD aromatization in a competitive manner whereas the AD series steroids 1 as well as the 3-deoxy-16 alpha-hydroxy-17-one steroids 5 and 3-deoxy-16 alpha,17 beta-diol steroids 6 inhibited 16-OHAD aromatization non-competitively. 3-Carbonyl and 16 alpha-hydroxy functions of 16-OHAD play a critical role of selection of the 16-OHAD binding site. The results suggest that the AD derivatives 1 are kinetically aromatized at a different site from the 16-OHAD derivatives 2. Physical and/or chemical environments around the aromatase protein in the microsomal membrane may play a significant role in the expression of the substrate specificity, and the present results do not exclude the idea that the placental microsomes have a single binding site. (C) 2008 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2008.06.001
• 作为产物：
  描述：

  雄甾-4-烯-17-酮 以7%的产率得到
  参考文献：
  名称：

  NUMAZAWA, MITSUTERU;MUTSUMI, AYAKO;HOSHI, KUMIKO;OSHIBE, MARIKO;ISHIKAWA,+, J. MED. CHEM., 34,(1991) N, C. 2496-2504

  摘要：

  DOI：

文献信息

• Synthesis and biochemical studies of 16- or 19-substituted androst-4-enes as aromatase inhibitors
  作者：Mitsuteru Numazawa、Ayako Mutsumi、Kumiko Hoshi、Mariko Oshibe、Etsushi Ishikawa、Hiroki Kigawa

  DOI：10.1021/jm00112a028

  日期：1991.8

  Androst-4-en-17-one derivatives [19-acetoxide 4, 16-bromides 14 and 15, 19,19-difluoride 18, and (19R,S)-19-acetylenic alcohol 25] and androst-4-en-17-beta-ol derivatives 3, 5, 10, 12, and 19 were synthesized and tested for their ability to inhibit aromatase in human placental microsomes. All the 17-oxo steroids, except compound 25 and 17,19-diol 3 of this series, were effective competitive inhibitors with apparent K(i)'s ranging from 170 to 455 nM. 19,19-Difluoro steroid 18 and 19-acetylenic alcohol 25, a weak competitive inhibitor (K(i) = 7.75-mu-M), caused a time-dependent, pseudo-first-order inactivation of aromatase activity with k(inact)'s of 0.0213 and 0.1053 min-1 for compounds 18 and 25, respectively. NADPH and oxygen were required for the time-dependent inactivation, and the substrate, androst-4-ene-3,17-dione, prevented it, but a nucleophile, L-cysteine, did not in each case. The results strongly suggest that aromatase would attack the 19-carbon of steroids 18 and 25.
• NUMAZAWA, MITSUTERU;MUTSUMI, AYAKO;HOSHI, KUMIKO;OSHIBE, MARIKO;ISHIKAWA,+, J. MED. CHEM., 34,(1991) N, C. 2496-2504
  作者：NUMAZAWA, MITSUTERU、MUTSUMI, AYAKO、HOSHI, KUMIKO、OSHIBE, MARIKO、ISHIKAWA,+

  DOI：——

  日期：——
• Aromatization of androstenedione and 16α-hydroxyandrostenedione in human placental microsomes
  作者：Mitsuteru Numazawa、Yoko Watari、Sachiko Komatsu、Kouwa Yamashita、Masao Nagaoka

  DOI：10.1016/j.steroids.2008.06.001

  日期：2008.11

  Inhibition of aromatase activity in human placental microsomes with androstenedione (AD) (1a) and its 19-oxygenated derivatives 1b and 1c, their 16a-hydroxy compounds 2 and 3, and 3-deoxyandrost-4-ene compounds 5 and 6 was studied using [1 beta-(3)H]AD as a substrate and compared to that with [1 beta-(3)H]16 alpha-hydroxyandrostenedione (16-OHAD). AD series of steroids, compounds 1, inhibited competitively [1 beta-(3)H]AD aromatization whereas other 16a-hydroxy steroids 2, 3, S, and 6 inhibited AD aromatization in a non-competitive manner. On the other hand, all of 16-OHAD series, compounds 2, blocked the [1 beta-(3)H]16-OHAD aromatization in a competitive manner whereas the AD series steroids 1 as well as the 3-deoxy-16 alpha-hydroxy-17-one steroids 5 and 3-deoxy-16 alpha,17 beta-diol steroids 6 inhibited 16-OHAD aromatization non-competitively. 3-Carbonyl and 16 alpha-hydroxy functions of 16-OHAD play a critical role of selection of the 16-OHAD binding site. The results suggest that the AD derivatives 1 are kinetically aromatized at a different site from the 16-OHAD derivatives 2. Physical and/or chemical environments around the aromatase protein in the microsomal membrane may play a significant role in the expression of the substrate specificity, and the present results do not exclude the idea that the placental microsomes have a single binding site. (C) 2008 Elsevier Inc. All rights reserved.