3β-hydroxy-22-benzylamino-22-oxo-23,24-bisnor-chol-5-ene | 78542-22-0

• 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-hydroxy-22-benzylamino-22-oxo-23,24-bisnor-chol-5-ene
• 英文别名: 3β-hydroxy-22,23-dinor-5-cholenic acid N-benzylamine；(3I(2),20S)-3-Hydroxy-N-(phenylmethyl)pregn-5-ene-20-carboxamide；(2S)-N-benzyl-2-[(3S,8S,9S,10R,13S,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]propanamide
• CAS: 78542-22-0
• 化学式: C₂₉H₄₁NO₂
• 分子量: 435.65
• InChiKey: WHMFPFFXEXERAN-WLSCSYPLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.88
• 重原子数：
  32.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  49.33
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  3β-acetoxy-23,24-dinorchol-5-en-22-oyl chloride 在 氢氧化钾 作用下， 以 苯 为溶剂， 反应 16.0h， 生成 3β-hydroxy-22-benzylamino-22-oxo-23,24-bisnor-chol-5-ene
  参考文献：
  名称：

  抑制胆固醇侧链裂解。3.带有芳基取代的侧链的22-氮杂胆固醇类似物。

  摘要：

  22-氮杂胆固醇类似物2a的有效抑制活性，其中（3-甲基丁基）氨基侧链已被（苯乙基）氨基侧链取代，对胆固醇向孕烯醇酮的转化促进了两个系列的合成和酶学研究带有（芳烷基）氨基和（芳烷基）氨基侧链的22-氮杂胆固醇类似物的制备。胺（2）和酰胺（3）的强抑制活性都表明碱性氮不是抑制活性的必要条件。然而，其中羰基和氮的位置互换的酰胺类似物（4）是较差的抑制剂。芳香族环上的吸电子基团降低了苯乙酰胺基系列的抑制活性，而供电子基团的抑制作用则有所增加。

  DOI：

  10.1021/jm00141a003

文献信息

• Preparation of transition-state analogues of sterol 24-methyl transferase as potential anti-parasitics
  作者：Silvia Orenes Lorente、Carmen Jimenez Jimenez、Ludovic Gros、Vanessa Yardley、Kate de Luca-Fradley、Simon L. Croft、Julio A. Urbina、Luis M. Ruiz-Perez、Dolores Gonzalez Pacanowska、Ian H. Gilbert

  DOI：10.1016/j.bmc.2005.06.012

  日期：2005.9

  There is an urgent need for new drugs to treat leishmaniasis and Chagas disease. One important drug target in these organisms is sterol biosynthesis. In these organisms the main endogenous sterols are ergosta- and stigmata-like compounds in contrast to the situation in mammals, which have cholesterol as the sole sterol. In this paper we discuss the design, synthesis and evaluation of potential transition state analogues of the enzyme Delta(24(25))-methyltransferase (24-SMT). This enzyme is essential for the biosynthesis of ergosterol, but not required for the biosynthesis of cholesterol. A series of compounds were successfully synthesised in which mimics of the S-adenosyl methionine co-factor were attached to the sterol nucleus. Compounds were evaluated against recombinant Leishmania major 24-SMT and the parasites L. donovani and Trypanosoma cruzi in vitro, causative organisms of leishmaniasis and Chagas disease, respectively. Some of the-compounds showed inhibition of the recombinant Leishmania major 24-SMT and induced growth inhibition of the parasites. Some compounds also showed anti-parasitic activity against L. donovani and T cruzi, but no inhibition of the enzyme. In addition, some of the compounds had anti-proliferative activity against the bloodstream forms of Trypanosoma brucei rhodesiense, which causes African trypanosomiasis. (c) 2005 Published by Elsevier Ltd.
• Regulation of liver X receptor target genes by 22-functionalized oxysterols. Synthesis, in silico and in vitro evaluations
  作者：Elvar Örn Viktorsson、Mari Gabrielsen、Nugalya Kumarachandran、Ingebrigt Sylte、Pål Rongved、Ove Alexander Høgmoen Åstrand、Eili Tranheim Kase

  DOI：10.1016/j.steroids.2016.12.003

  日期：2017.2

  The endogenous oxysterol 22(R)-hydroxycholesterol (22RHC, 1) is an LXR agonist which upregulates genes of critical involvement in human cholesterol- and lipid metabolism. In contrast, its synthetic epimer 22(S)-hydroxycholesterol (22SHC, 8) has shown specific antagonistic effects in recent studies, avoiding unwanted side effects provided by potent LXR agonists. In terms of LXR modulation, the aim of this study was to compare 22SHC (8), 22RHC (1) and synthesized ligands with keto- and amide functionality in the 22nd position of the cholesterol scaffold. 22SHC (8) and 22RHC (1) performed as expected while 22-ketocholesterol (22KC, 10) revealed an attractive in vitro profile for further investigation in terms of anti-atherosclerotic properties as selective upregulation of the ATP-binding cassette transporter ABCA1 was observed. A new synthesized amide derivate, Fernholtz cyclohexylamide (13) was shown to reduce lipogenesis in a dose-responsive manner and abolish the effect of the potent LXR agonist T0901317 when administered simultaneously. (C) 2016 Elsevier Inc. All rights reserved.