3α-N-tert-butylcarbamate-7α,12α-diacetoxy-5β-cholanoic acid | 1608486-48-1

• 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: 3α-N-tert-butylcarbamate-7α,12α-diacetoxy-5β-cholanoic acid
• CAS: 1608486-48-1
• 化学式: C₃₃H₅₃NO₈
• 分子量: 591.786
• InChiKey: ULCIHFFXYTUUTP-RBDYHKFXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.12
• 重原子数：
  42.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  128.23
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3α-N-tert-butylcarbamate-7α,12α-diacetoxy-5β-cholanoic acid 在 氯甲酸乙酯 、 三乙酰氧基硼氢化钠 、 三乙胺 、 pyridinium chlorochromate 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 23.75h， 生成 24-N-methyl-N-[(7-chloroquinoline-4-yl)amino]propylamino-3α-amino-7α,12α-diacetoxy-5β-cholane
  参考文献：
  名称：

  Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease andP. falciparumMalaria

  摘要：

  Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ) based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were synthesized. Introducing an amino group at the C(3) position of the cholate component markedly increased potency (IC50 values for such derivatives ranged from 0.81 to 2.27 mu M). Two additional subclasses were prepared: bis(steroidal)-4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided inhibitors with nanomolar-range potencies (e.g., the K-i of compound 67 is 0.10 mu M). During BoNT/A challenge using primary neurons, select derivatives protected SNAP-25 by up to 89%. Docking simulations were performed to rationalize the compounds' in vitro potencies. In addition to specific residue contacts, coordination of the enzyme's catalytic zinc and expulsion of the enzyme's catalytic water were a consistent theme. With respect to antimalarial activity, the compounds provided better IC90 activities against chloroquine resistant (CQR) malaria than CQ, and seven compounds were more active than mefloquine against CQR strain W2.

  DOI：

  10.1021/jm500033r
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 1.5h， 生成 3α-N-tert-butylcarbamate-7α,12α-diacetoxy-5β-cholanoic acid
  参考文献：
  名称：

  Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease andP. falciparumMalaria

  摘要：

  Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ) based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were synthesized. Introducing an amino group at the C(3) position of the cholate component markedly increased potency (IC50 values for such derivatives ranged from 0.81 to 2.27 mu M). Two additional subclasses were prepared: bis(steroidal)-4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided inhibitors with nanomolar-range potencies (e.g., the K-i of compound 67 is 0.10 mu M). During BoNT/A challenge using primary neurons, select derivatives protected SNAP-25 by up to 89%. Docking simulations were performed to rationalize the compounds' in vitro potencies. In addition to specific residue contacts, coordination of the enzyme's catalytic zinc and expulsion of the enzyme's catalytic water were a consistent theme. With respect to antimalarial activity, the compounds provided better IC90 activities against chloroquine resistant (CQR) malaria than CQ, and seven compounds were more active than mefloquine against CQR strain W2.

  DOI：

  10.1021/jm500033r