2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-17-carboxylate | 1223423-85-5

• 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: 2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-17-carboxylate
• 英文别名: methyl 3β-hydroxyandrosta-5,7-diene-17β-carboxylate；methyl (3S,9S,10R,13S,14R,17S)-3-hydroxy-10,13-dimethyl-2,3,4,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthrene-17-carboxylate
• CAS: 1223423-85-5
• 化学式: C₂₁H₃₀O₃
• 分子量: 330.467
• InChiKey: GWGLLVKDTWYKLO-TWLHIMTCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3β-acetoxyetienic acid 在 4-二甲氨基吡啶 、 1,3-二溴-5,5-二甲基海因 、 偶氮二异丁腈 、 硫酸 、 水 、 溴 、 三乙胺 、 sodium hydroxide 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 26.41h， 生成 2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-17-carboxylate
  参考文献：
  名称：

  发现新型 3-羟基雄雄-5,7-二烯-17-羧酸衍生物作为抗炎性肠病 (IBD) 药物

  摘要：

  设计、合成了一系列基于3-羟基雄激素-5,7-二烯-17-羧酸核心结构的甾体化合物，并对其抗炎功效进行了生物评价。其中，化合物5c 、 6f和6q有效抑制脂多糖（LPS）刺激的RAW 264.7巨噬细胞中一氧化氮（NO）的产生。它们在 mRNA 水平上抑制诱导型 NO 合酶 (iNOS) 和前列腺素合酶 2 (COX-2) 的表达。化合物6q以浓度依赖性方式对iNOS和COX-2表达具有抑制作用。此外，发现6q可以有效降低白细胞介素 6 (IL-6) 的 mRNA 和蛋白质水平。从机制上讲， 6q可以通过抑制 Akt/PI3K 通路有效下调 NF-κB 信号传导。此外， 6q在葡聚糖硫酸钠 (DSS) 诱导的小鼠结肠炎模型中表现出较高的体内抗炎活性。总而言之，这些数据表明6q是一种新型且有前途的抗炎性肠病 (IBD) 药物，值得进一步研究。

  DOI：

  10.1016/j.ejmech.2021.113468

文献信息

• A new steroidal 5,7-diene derivative, 3β-hydroxyandrosta-5,7-diene-17β-carboxylic acid, shows potent anti-proliferative activity
  作者：Tae-Kang Kim、Jianjun Chen、Wei Li、Jordan Zjawiony、Duane Miller、Zorica Janjetovic、Robert C. Tuckey、Andrzej Slominski

  DOI：10.1016/j.steroids.2009.12.004

  日期：2010.3

  The new steroidal 5,7-diene, 3 beta-hydroxyandrosta-5,7-diene-17 beta-carboxylic acid (17-COOH-7DA), was synthesized from 21-acetoxypregnenolone, with the oxidative cleavage of the side chain being dependent on the presence of oxygen. In human epidermal (HaCaT) keratinocytes, 17-COOH-7DA inhibited proliferation in a close-dependent manner, starting at a dose as low as 10(-11) M. This inhibition was accompanied by decreased expression of epidermal growth factor receptor, bcl2 and cyclin E2 mRNAs and by increased expression of involucrin mRNA. Inhibition of proliferation was associated with slowing of the cell cycle in G1/G0 phases but not with cell death. 17-COOH-7DA was significantly more potent than pregnenolone, 17-COOH-pregnenolone, 17-COOCH(3)-7DA and calcitriol. 17-COOH-7DA also inhibited proliferation of normal human epidermal melanocytes and human and hamster melanoma lines, however, with lower potency than for keratinocytes. In normal human dermal fibroblasts 17-COOH-7DA stimulated proliferation in serum-free media but inhibited it in the presence of 5% serum. 17-COOH-7DA inhibited cell colony formation of human and hamster melanoma cells, and induced monocyte-like differentiation of human HL60 leukemia cells. Thus, the new steroidal 5,7-diene, 17-COOH-7DA, can serve as an inhibitor of proliferation of normal keratinocytes and normal and malignant melanocytes, as a condition-dependent regulator of fibroblast proliferation and a stimulator of leukemia cell differentiation. (C) 2009 Elsevier Inc. All rights reserved.