[(R)-1-[(R)-5-cyclopropylmethyl-2-oxo-1-(2,2,2-trifluoro-ethyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester | 1023710-76-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(R)-1-[(R)-5-cyclopropylmethyl-2-oxo-1-(2,2,2-trifluoro-ethyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl (R)-1-((R)-5-(cyclopropylmethyl)-2-oxo-1-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-3-(4-fluorophenyl)-1-oxopropan-2-ylcarbamate；tert-butyl N-[(2R)-1-[[(3R)-1-(cyclopropylmethyl)-4-oxo-5-(2,2,2-trifluoroethyl)-2,3-dihydro-1,5-benzodiazepin-3-yl]amino]-3-(4-fluorophenyl)-1-oxopropan-2-yl]carbamate
• CAS: 1023710-76-0
• 化学式: C₂₉H₃₄F₄N₄O₄
• 分子量: 578.607
• InChiKey: IHGLQJAFQRVZAT-FGZHOGPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  91
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-[叔丁氧羰基]-3-[(2-硝基苯基)氨基]-D-丙氨酸 在 palladium 10% on activated carbon 氢气 、 四丁基碘化铵 、 双(三甲基硅烷基)氨基钾 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 147.5h， 生成 [(R)-1-[(R)-5-cyclopropylmethyl-2-oxo-1-(2,2,2-trifluoro-ethyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  WO2008/106077

  摘要：

  公开号：

文献信息

• Substituted Benzodiazepinones, Benzoxazepinones and Benzothiazepinones as Sodium Channel Blockers
  申请人：Hoyt Scott B.

  公开号：US20100144715A1

  公开（公告）日：2010-06-10

  The present invention is directed to substituted benzodiazepinones, benzoxazepinones and benzothiazepinones compounds that are sodium channel blockers useful for the treatment of chronic and neuropathic pain. The compounds of the present invention are also useful for the treatment of other conditions, including disorders of the CNS such as anxiety, depression, epilepsy, manic depression and bipolar disorder. This invention also provides pharmaceutical compositions comprising a compound of the present invention, either alone, or in combination with one or more therapeutically active compounds, and a pharmaceutically acceptable carrier. This invention further comprises methods for the treatment of acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain and disorders of the CNS including, but not limited to, epilepsy, manic depression, depression, anxiety and bipolar disorder comprising administering the compounds and pharmaceutical compositions of the present invention.

  本发明涉及替代苯二氮平酮、苯并噁唑酮和苯并噻唑酮化合物，它们是钠通道阻滞剂，可用于治疗慢性和神经病理性疼痛。本发明的化合物也可用于治疗其他疾病，包括中枢神经系统紊乱，如焦虑、抑郁、癫痫、躁郁症和双相障碍。本发明还提供了含有本发明化合物的药物组合物，可以单独使用或与一个或多个治疗活性化合物组合使用，并与药学上可接受的载体一起使用。本发明还包括治疗急性疼痛、慢性疼痛、内脏疼痛、炎症性疼痛、神经病理性疼痛和中枢神经系统紊乱的方法，包括但不限于癫痫、躁郁症、抑郁症、焦虑症和双相障碍，通过给予本发明的化合物和药物组合物进行治疗。
• 3-Amino-1,5-benzodiazepinones: Potent, state-dependent sodium channel blockers with anti-epileptic activity
  作者：Scott B. Hoyt、Clare London、Matthew J. Wyvratt、Michael H. Fisher、Doreen E. Cashen、John P. Felix、Maria L. Garcia、Xiaohua Li、Kathryn A. Lyons、D. Euan MacIntyre、William J. Martin、Birgit T. Priest、McHardy M. Smith、Vivien A. Warren、Brande S. Williams、Gregory J. Kaczorowski、William H. Parsons

  DOI：10.1016/j.bmcl.2008.01.123

  日期：2008.3

  A series of 3-amino-1,5-benzodiazepinones were synthesized and evaluated as potential sodium channel blockers in a functional, membrane potential-based assay. One member of this series displayed subnanomolar, state-dependent sodium channel block, and was orally efficacious in a mouse model of epilepsy. (C) 2008 Elsevier Ltd. All rights reserved.
• [EN] SUBSTITUTED BENZODIAZEPINONES, BENZOXAZEPINONES AND BENZOTHIAZEPINONES AS SODIUM CHANNEL BLOCKERS<br/>[FR] BENZODIAZÉPINONES, BENZOXAZÉPINONES ET BENZOTHIAZÉPINONES SUBSTITUÉES EN TANT QUE BLOQUEURS DE CANAUX SODIQUES
  申请人：MERCK & CO INC

  公开号：WO2008106077A1

  公开（公告）日：2008-09-04

  [EN] The present invention is directed to substituted benzodiazepinones, benzoxazepinones and benzothiazepinones compounds that are sodium channel blockers useful for the treatment of chronic and neuropathic pain. The compounds of the present invention are also useful for the treatment of other conditions, including disorders of the CNS such as anxiety, depression, epilepsy, manic depression and bipolar disorder. This invention also provides pharmaceutical compositions comprising a compound of the present invention, either alone, or in combination with one or more therapeutically active compounds, and a pharmaceutically acceptable carrier. This invention further comprises methods for the treatment of acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain and disorders of the CNS including, but not limited to, epilepsy, manic depression, depression, anxiety and bipolar disorder comprising administering the compounds and pharmaceutical compositions of the present invention.
  [FR] L'invention concerne des composés de benzodiazépinones, benzoxazépinones et benzothiazépinones substitués qui sont des bloqueurs de canaux sodiques utiles pour le traitement d'une douleur chronique et neuropathique. Les composés de la présente invention sont également utiles pour le traitement d'autres états, y compris des troubles du CNS comme l'anxiété, la dépression, l'épilepsie, une dépression chronique et un trouble bipolaire. L'invention fournit également des compositions pharmaceutiques comprenant un composé de la présente invention, seul ou en combinaison avec un ou plusieurs composés thérapeutiquement actifs, et un support pharmaceutiquement acceptable. L'invention concerne en outre des procédés pour le traitement de la douleur aigue, de la douleur chronique, de la douleur viscérale, de la douleur inflammatoire, de la douleur neuropathique et de trouble du CNS y compris, mais sans s'y limiter, l'épilepsie, une dépression chronique, une dépression, une anxiété et un trouble bipolaire, comprenant l'administration des composés et compositions pharmaceutiques de la présente invention.
• WO2008/106077
  申请人：——

  公开号：——

  公开（公告）日：——