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(1S,3aS,3bS,9aR,9bS,11aS)-1-Benzylcarbamoyl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,7,8,9,9a,9b,10,11,11a-tetradecahydro-cyclopenta[i]phenanthridine-5-carboxylic acid tert-butyl ester | 1027970-78-0

中文名称
——
中文别名
——
英文名称
(1S,3aS,3bS,9aR,9bS,11aS)-1-Benzylcarbamoyl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,7,8,9,9a,9b,10,11,11a-tetradecahydro-cyclopenta[i]phenanthridine-5-carboxylic acid tert-butyl ester
英文别名
tert-butyl (1S,3aS,3bS,9aR,9bS,11aS)-1-(benzylcarbamoyl)-9a,11a-dimethyl-7-oxo-2,3,3a,3b,4,8,9,9b,10,11-decahydro-1H-cyclopenta[i]phenanthridine-5-carboxylate
(1S,3aS,3bS,9aR,9bS,11aS)-1-Benzylcarbamoyl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,7,8,9,9a,9b,10,11,11a-tetradecahydro-cyclopenta[i]phenanthridine-5-carboxylic acid tert-butyl ester化学式
CAS
1027970-78-0
化学式
C31H42N2O4
mdl
——
分子量
506.685
InChiKey
PMLIHAGFAPXDKB-FXBVBRSJSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

计算性质

  • 辛醇/水分配系数(LogP):
    5.2
  • 重原子数:
    37
  • 可旋转键数:
    5
  • 环数:
    5.0
  • sp3杂化的碳原子比例:
    0.65
  • 拓扑面积:
    75.7
  • 氢给体数:
    1
  • 氢受体数:
    4

上下游信息

  • 上游原料
    中文名称 英文名称 CAS号 化学式 分子量

反应信息

  • 作为反应物:
    描述:
    (1S,3aS,3bS,9aR,9bS,11aS)-1-Benzylcarbamoyl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,7,8,9,9a,9b,10,11,11a-tetradecahydro-cyclopenta[i]phenanthridine-5-carboxylic acid tert-butyl ester三氟乙酸 作用下, 生成 (1S,3aS,3bS,9aR,9bS,11aS)-9a,11a-Dimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid benzylamide
    参考文献:
    名称:
    6-氮杂类固醇:人1型和2型类固醇5α-还原酶的有效双重抑制剂。
    摘要:
    DOI:
    10.1021/jm00078a022
  • 作为产物:
    参考文献:
    名称:
    Mce3R Stress-Resistance Pathway Is Vulnerable to Small-Molecule Targeting That Improves Tuberculosis Drug Activities
    摘要:
    One-third of the world's population carries Mycobacterium tuberculosis (Mtb), the infectious agent that causes tuberculosis (TB), and every 17 s someone dies of TB. After infection, Mtb can live dormant for decades in a granuloma structure arising from the host immune response, and cholesterol is important for this persistence of Mtb. Current treatments require long-duration drug regimens with many associated toxicities, which are compounded by the high doses required. We phenotypically screened 35 6-azasteroid analogues against Mtb and found that, at low micromolar concentrations, a subset of the analogues sensitized Mtb to multiple TB drugs. Two analogues were selected for further study to characterize the bactericidal activity of bedaquiline and isoniazid under normoxic and low-oxygen conditions. These two 6-azasteroids showed strong synergy with bedaquiline (fractional inhibitory concentration index = 0.21, bedaquiline minimal inhibitory concentration = 16 nM at 1 mu M 6-azasteroid). The rate at which spontaneous resistance to one of the 6-azasteroids arose in the presence of bedaquiline was approximately 10-9, and the 6-azasteroid-resistant mutants retained their isoniazid and bedaquiline sensitivity. Genes in the cholesterol-regulated Mce3R regulon were required for 6-azasteroid activity, whereas genes in the cholesterol catabolism pathway were not. Expression of a subset of Mce3R genes was down-regulated upon 6-azasteroid treatment. The Mce3R regulon is implicated in stress resistance and is absent in saprophytic mycobacteria. This regulon encodes a cholesterol-regulated stress-resistance pathway that we conclude is important for pathogenesis and contributes to drug tolerance, and this pathway is vulnerable to small-molecule targeting in live mycobacteria.
    DOI:
    10.1021/acsinfecdis.9b00099
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文献信息

  • 6-Azasteroids: potent dual inhibitors of human type 1 and 2 steroid 5.alpha.-reductase
    作者:Stephen V. Frye、Curt D. Haffner、Patrick R. Maloney、Robert A. Mook、G. F. Dorsey、Roger N. Hiner、Kenneth W. Batchelor、H. Neal Bramson、J. Darren Stuart
    DOI:10.1021/jm00078a022
    日期:1993.12
  • Mce3R Stress-Resistance Pathway Is Vulnerable to Small-Molecule Targeting That Improves Tuberculosis Drug Activities
    作者:Xinxin Yang、Tianao Yuan、Rui Ma、Kieran I. Chacko、Melissa Smith、Gintaras Deikus、Robert Sebra、Andrew Kasarskis、Harm van Bakel、Scott G. Franzblau、Nicole S. Sampson
    DOI:10.1021/acsinfecdis.9b00099
    日期:2019.7.12
    One-third of the world's population carries Mycobacterium tuberculosis (Mtb), the infectious agent that causes tuberculosis (TB), and every 17 s someone dies of TB. After infection, Mtb can live dormant for decades in a granuloma structure arising from the host immune response, and cholesterol is important for this persistence of Mtb. Current treatments require long-duration drug regimens with many associated toxicities, which are compounded by the high doses required. We phenotypically screened 35 6-azasteroid analogues against Mtb and found that, at low micromolar concentrations, a subset of the analogues sensitized Mtb to multiple TB drugs. Two analogues were selected for further study to characterize the bactericidal activity of bedaquiline and isoniazid under normoxic and low-oxygen conditions. These two 6-azasteroids showed strong synergy with bedaquiline (fractional inhibitory concentration index = 0.21, bedaquiline minimal inhibitory concentration = 16 nM at 1 mu M 6-azasteroid). The rate at which spontaneous resistance to one of the 6-azasteroids arose in the presence of bedaquiline was approximately 10-9, and the 6-azasteroid-resistant mutants retained their isoniazid and bedaquiline sensitivity. Genes in the cholesterol-regulated Mce3R regulon were required for 6-azasteroid activity, whereas genes in the cholesterol catabolism pathway were not. Expression of a subset of Mce3R genes was down-regulated upon 6-azasteroid treatment. The Mce3R regulon is implicated in stress resistance and is absent in saprophytic mycobacteria. This regulon encodes a cholesterol-regulated stress-resistance pathway that we conclude is important for pathogenesis and contributes to drug tolerance, and this pathway is vulnerable to small-molecule targeting in live mycobacteria.
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