3-[(Z)-[(5Z)-5-benzylidene-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]-N-[4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]benzamide

• 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-[(Z)-[(5Z)-5-benzylidene-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]-N-[4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]benzamide
• 化学式: C₃₉H₃₈N₄O₅
• 分子量: 642.7
• InChiKey: RTIZZWMBGKGLFO-YWQXDYITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  48
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  6

文献信息

• [EN] PIPERAZINE-2,5-DIONE DERIVATIVES AS MODULATORS OF MULTIDRUG RESISTANCE<br/>[FR] DERIVES DE LA PIPERAZINE-2,5-DIONE EMPLOYES COMME MODULATEURS DE LA RESISTANCE MULTIPLE AUX ANTICANCEREUX
  申请人：XENOVA LIMITED

  公开号：WO1996020180A1

  公开（公告）日：1996-07-04

  (EN) A piperazinedione of general formula (I), wherein R1 is selected from hydrogen; a group of formula -COR3 -(NH)t-COR3 wherein t is 0 or 1 and R3 is selected from (i): (A) wherein v is 0 or 1 when t is 1 and v is 1 when t is 0; and wherein n is 0, 1, 2, or 3 at least one of n and m being other than 0, and either (ii): (B) wherein p is 1 or 2 and Z is C2-C6 alkenyl or a phenyl group optionally substituted by C1-C6 alkoxy; and (iii): (C) wherein R9 is C1-C6 alkyl, pyrimidinyl or a phenyl group optionally substituted by C1-C6 alkoxy; and (F) and R2 is hydrogen or a group of formula -COR3 as defined above, provided that one or R1 and R2 is hydrogen and the other is not hydrogen; and the pharmaceutically acceptable salts thereof have activity as modulators of multidrug resistance.(FR) L'invention concerne une pipérazinedione de formule générale (I). Dans cette formule, R1 est choisi parmi l'hydrogène et les groupes -COR3, -(NH)t-COR3 où t est égal à 0 ou 1. R3 représente (i) le groupe (A) dans lequel v est égal à 0 ou 1 quand t est égal à 1, v est égal à 1 quand t est égal à 0 et n est égal à 0, 1, 2 ou 3, à condition qu'au moins m ou n soit autre que 0; ou (ii) le groupe (B) dans lequel p est égal à 1 ou 2 et Z est un groupe C2-C6 alcényle ou phényle, éventuellement substitué par un groupe C1-C6alcoxy; ou (iii) le groupe (C) dans lequel R9 est un groupe C1-C6alkyle, pyrimidinyle ou phényle, éventuellement substitué par un C1-C6alcoxy; ou encore le groupe (F). R2 est un hydrogène ou un groupe de la formule -COR3 comme défini ci-dessus, à condition que R1 ou R3 soit un hydrogène et que l'autre de ces deux groupes ne soit pas un hydrogène. L'invention concerne également les sels de ces composés acceptables sur le plan pharmaceutique. Ces composés et leurs sels ont une activité de modulateurs de la résistance multiple aux anticancéreux.

  一种通式（I）的哌嗪二酮，其中R1选自氢; 公式-COR3-（NH）t-COR3，其中t为0或1，R3选自（i）：（A）其中当t为1时v为0或1，当t为0时v为1; 其中n为0、1、2或3，n和m中至少有一个不为0，或（ii）：（B）其中p为1或2，Z为C2-C6烯基或苯基，可选地被C1-C6烷氧基取代; 和（iii）：（C）其中R9为C1-C6烷基，嘧啶基或可选地被C1-C6烷氧基取代的苯基; 和（F），R2为氢或上述定义的公式-COR3的基团，前提是R1和R2中的一个为氢，另一个不为氢; 其药学上可接受的盐具有多药耐受性调节剂的活性。
• Treatment of rhinosinusitis with P-glycoprotein inhibitors
  申请人：Massachusetts Eye and Ear Infirmary

  公开号：US10653745B2

  公开（公告）日：2020-05-19

  Provided herein are, inter alia, methods for treating rhinosinusitis with P-glycoprotein inhibitors. A subject having rhinosinusitis is identified and then treated by administration to the subject an effective amount of a P-gp inhibitor. The subject having rhinosinusitis can be identified by one of skill in the art based on known methods, e.g., based on detection of the presence of symptoms, by endoscopy, or by computed tomography. The efficacy of the treatment can be monitored by methods known in the art, e.g., by monitoring symptoms, by endoscopy or computed tomography. The P-glycoprotein inhibitor can be delivered to the subject's nasal passage and sinuses by an inhalation device, by flushing, by spraying, or by an eluting implant surgically placed in the subject's nasal passage or sinuses. The P-glycoprotein inhibitor can also be administered in combination with one or both of a corticosteroid and an antibiotic.

  本文特别提供了用P-糖蛋白抑制剂治疗鼻炎的方法。首先确定患有鼻炎的受试者，然后通过向受试者施用有效量的 P-gp 抑制剂对其进行治疗。本领域技术人员可根据已知的方法，例如根据症状的存在、内窥镜检查或计算机断层扫描，确定患有鼻炎的受试者。治疗的疗效可以通过本领域已知的方法进行监测，例如通过监测症状、内窥镜检查或计算机断层扫描。P-糖蛋白抑制剂可通过吸入装置、冲洗、喷洒或通过手术将洗脱植入物置于受试者的鼻腔或鼻窦中，将其输送到受试者的鼻腔和鼻窦。P 糖蛋白抑制剂还可以与皮质类固醇和抗生素中的一种或两种结合使用。
• PIPERAZINE-2,5-DIONE DERIVATIVES AS MODULATORS OF MULTIDRUG RESISTANCE
  申请人：XENOVA LIMITED

  公开号：EP0799210B1

  公开（公告）日：2001-08-22
• TREATMENT OF RHINOSINUSITIS WITH P-GLYCOPROTEIN INHIBITORS
  申请人：Massachusetts Eye & Ear Infirmary

  公开号：EP2938339B1

  公开（公告）日：2020-08-19
• Treatment of Rhinosinusitis with P-glycoprotein Inhibitors
  申请人：MASSACHUSETTS EYE & EAR INFIRMARY

  公开号：US20160193286A1

  公开（公告）日：2016-07-07

  Provided herein are, inter alia, methods for treating rhinosinusitis with P-glycoprotein inhibitors. A subject having rhinosinusitis is identified and then treated by administration to the subject an effective amount of a P-gp inhibitor. The subject having rhinosinusitis can be identified by one of skill in the art based on known methods, e.g., based on detection of the presence of symptoms, by endoscopy, or by computed tomography. The efficacy of the treatment can be monitored by methods known in the art, e.g., by monitoring symptoms, by endoscopy or computed tomography. The P-glycoprotein inhibitor can be delivered to the subject's nasal passage and sinuses by an inhalation device, by flushing, by spraying, or by an eluting implant surgically placed in the subject's nasal passage or sinuses. The P-glycoprotein inhibitor can also be administered in combination with a corticosteroid.