24-N-[(7-chloroquinoline-4-yl)amino]ethylamino-3α-N′-tertbutylcarbamate-7α,12α-diacetoxy-5β-cholane | 1608486-56-1

• 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: 24-N-[(7-chloroquinoline-4-yl)amino]ethylamino-3α-N′-tertbutylcarbamate-7α,12α-diacetoxy-5β-cholane
• 英文别名: [(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-12-acetyloxy-17-[(2R)-5-[2-[(7-chloroquinolin-4-yl)amino]ethylamino]pentan-2-yl]-10,13-dimethyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-7-yl] acetate
• CAS: 1608486-56-1
• 化学式: C₄₄H₆₅ClN₄O₆
• 分子量: 781.476
• InChiKey: RYPBRHIRRGNRHT-GXCGCXEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.1
• 重原子数：
  55
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  24-N-[(7-chloroquinoline-4-yl)amino]ethylamino-3α-N′-tertbutylcarbamate-7α,12α-diacetoxy-5β-cholane 在 哌啶 、 sodium cyanoborohydride 、 三氟乙酸 、 zinc(II) chloride 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 56.0h， 生成 24-N-[(7-chloroquinoline-4-yl)amino]ethylamino-3α-N′,N′-dimethylamino-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：

  4-(2-氨基乙基)氨基-7-氯喹啉 、 (3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3-((tert-butoxycarbonyl)amino)-10,13-dimethyl-17-((R)-5-oxopentan-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthrene-7,12-diyl diacetate 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以168 mg的产率得到N,N-di-(3α-N″-tert-butylcarbamate-7α,12α-diacetoxy-5β-cholan-24-yl)-N′-(7′-chloroquinoline-4′-yl)-1,3-ethanediamine
  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

文献信息

• Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and<i>P. falciparum</i>Malaria
  作者：Milica Videnović、Dejan M. Opsenica、James C. Burnett、Laura Gomba、Jonathan E. Nuss、Života Selaković、Jelena Konstantinović、Maja Krstić、Sandra Šegan、Mario Zlatović、Richard J. Sciotti、Sina Bavari、Bogdan A. Šolaja

  DOI：10.1021/jm500033r

  日期：2014.5.22

  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.