3,5-Dibenzylidene-1-[4-(2-piperidin-1-ylethoxy)benzoyl]piperidin-4-one | 933824-13-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,5-Dibenzylidene-1-[4-(2-piperidin-1-ylethoxy)benzoyl]piperidin-4-one
• 英文别名: 3,5-dibenzylidene-1-[4-(2-piperidin-1-ylethoxy)benzoyl]piperidin-4-one
• CAS: 933824-13-6
• 化学式: C₃₃H₃₄N₂O₃
• 分子量: 506.645
• InChiKey: ICTAHJUWCPFEBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,5-Dibenzylidene-1-[4-(2-piperidin-1-ylethoxy)benzoyl]piperidin-4-one 在 盐酸 作用下， 以 异丙醇 为溶剂， 生成 1-[4-{2-(1-Piperidinyl)ethoxy}phenylcarbonyl]-3,5-bis(phenylmethylene)-4-piperidone hydrochloride hemihydrate
  参考文献：
  名称：

  1-[4-(2-Aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidines: A novel series of highly potent revertants of P-glycoprotein associated multidrug resistance

  摘要：

  The 1-[4-(2-aminoethoxy) phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidines 5-8 are a novel cluster of highly potent P-glycoprotein dependent multidrug resistance (MDR) revertants. Using a concentration of 4 mu g/mL, these compounds possess 11-43 times the potency of verapamil in reversing MDR in murine L-5178 lymphoma cells transfected with the human MDR1 gene. Structure-activity relationships reveal that the attachment of the N-aroyl group to various 3,5-bis(benzylidene)-4-piperidones is essential for MDR reversal to occur. In terms of potencies, the 1-piperidinyl group is the preferred terminal amine while the 4-methyl and 4-chloro substituents are the optimal groups for placement in the benzylidene aryl rings. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.034
• 作为产物：
  描述：

  对羟基苯甲酸甲酯 在 氯化亚砜 、 potassium carbonate 、 sodium hydroxide 作用下， 生成 3,5-Dibenzylidene-1-[4-(2-piperidin-1-ylethoxy)benzoyl]piperidin-4-one
  参考文献：
  名称：

  3,5-Bis(benzylidene)-4-piperidones and related N-acyl analogs: A novel cluster of antimalarials targeting the liver stage of Plasmodium falciparum

  摘要：

  Drug resistance is a major challenge in antimalarial chemotherapy. In addition, a complete cure of malaria requires intervention at various stages in the development of the parasite within the host. There are only a few antimalarials that target the liver stage of the Plasmodium species which is an essential part of the life cycle of the malarial parasite. We report a series of antimalarial 3,5-bis(benzylidene)-4-piperidones and related N-acyl analogs 1-5, a number of which exhibit potent in vitro growth-inhibiting properties towards drug-sensitive D6 and drug-resistant C235 strains of Plasmodium falciparum as well as inhibiting the liver stage development of the malarial life cycle. The compounds 2b (IC50: 165 ng/mL), 3b (IC50: 186 ng/mL), 5c (IC50: 159 ng/mL) and 5d (IC50: 93.5 ng/mL) emerged as lead molecules that inhibit liver stage Plasmodium berghei and are significantly more potent than chloroquine (IC50: >2000 ng/mL) and mefloquine (IC50: >2000 ng/mL) in this screen. All the compounds that showed potent inhibitory activity against the P. berghei liver stage were nontoxic to human HepG2 liver cells (IC50: >2000 ng/mL). The compounds 5a and 5b exhibit comparable metabolic stability as chloroquine and mefloquine in human plasma and the most potent compound 5d demonstrated suitable permeability characteristics using the MDCK monolayer. These results emphasize the value of 3,5-bis(benzylidene)-4-piperidones as novel antimalarials for further drug development. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.065

文献信息

• 3,5-Bis(benzylidene)-4-piperidones and related N-acyl analogs: A novel cluster of antimalarials targeting the liver stage of Plasmodium falciparum
  作者：Umashankar Das、Ravi S.P. Singh、Jane Alcorn、Mark R. Hickman、Richard J. Sciotti、Susan E. Leed、Patricia J. Lee、Norma Roncal、Jonathan R. Dimmock

  DOI：10.1016/j.bmc.2013.09.065

  日期：2013.12

  Drug resistance is a major challenge in antimalarial chemotherapy. In addition, a complete cure of malaria requires intervention at various stages in the development of the parasite within the host. There are only a few antimalarials that target the liver stage of the Plasmodium species which is an essential part of the life cycle of the malarial parasite. We report a series of antimalarial 3,5-bis(benzylidene)-4-piperidones and related N-acyl analogs 1-5, a number of which exhibit potent in vitro growth-inhibiting properties towards drug-sensitive D6 and drug-resistant C235 strains of Plasmodium falciparum as well as inhibiting the liver stage development of the malarial life cycle. The compounds 2b (IC50: 165 ng/mL), 3b (IC50: 186 ng/mL), 5c (IC50: 159 ng/mL) and 5d (IC50: 93.5 ng/mL) emerged as lead molecules that inhibit liver stage Plasmodium berghei and are significantly more potent than chloroquine (IC50: >2000 ng/mL) and mefloquine (IC50: >2000 ng/mL) in this screen. All the compounds that showed potent inhibitory activity against the P. berghei liver stage were nontoxic to human HepG2 liver cells (IC50: >2000 ng/mL). The compounds 5a and 5b exhibit comparable metabolic stability as chloroquine and mefloquine in human plasma and the most potent compound 5d demonstrated suitable permeability characteristics using the MDCK monolayer. These results emphasize the value of 3,5-bis(benzylidene)-4-piperidones as novel antimalarials for further drug development. (C) 2013 Elsevier Ltd. All rights reserved.
• 1-[4-(2-Aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidines: A novel series of highly potent revertants of P-glycoprotein associated multidrug resistance
  作者：Umashankar Das、Joseph Molnár、Zoltán Baráth、Zsuzsanna Bata、Jonathan R. Dimmock

  DOI：10.1016/j.bmcl.2008.05.034

  日期：2008.6

  The 1-[4-(2-aminoethoxy) phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidines 5-8 are a novel cluster of highly potent P-glycoprotein dependent multidrug resistance (MDR) revertants. Using a concentration of 4 mu g/mL, these compounds possess 11-43 times the potency of verapamil in reversing MDR in murine L-5178 lymphoma cells transfected with the human MDR1 gene. Structure-activity relationships reveal that the attachment of the N-aroyl group to various 3,5-bis(benzylidene)-4-piperidones is essential for MDR reversal to occur. In terms of potencies, the 1-piperidinyl group is the preferred terminal amine while the 4-methyl and 4-chloro substituents are the optimal groups for placement in the benzylidene aryl rings. (C) 2008 Elsevier Ltd. All rights reserved.