(S)-[2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethyl]-carbamic acid tert-butyl ester | 217172-22-0

• 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: (S)-[2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-(tert-butylamino)-1-oxo-3-(4-phenylmethoxyphenyl)propan-2-yl]carbamate
• CAS: 217172-22-0
• 化学式: C₂₅H₃₄N₂O₄
• 分子量: 426.556
• InChiKey: XRUCFRPFQQLUGK-NRFANRHFSA-N

物化性质

• 沸点：
  616.2±55.0 °C(Predicted)
• 密度：
  1.091±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-[2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethyl]-carbamic acid tert-butyl ester 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-4-Methyl-2-methylamino-pentanoic acid [(S)-2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethyl]-amide
  参考文献：
  名称：

  Structure-activity relationship of N-methyl-N-aralkyl-peptidylamines as novel N-type calcium channel blockers

  摘要：

  Selective N-type voltage sensitive calcium channel (VSCC) blockers have shown efficacy in several animal models of stroke and pain. In the process of searching for small molecule N-type calcium channel blockers, we have identified a series of N-methyl-N-aralkyl-peptidylamines with potent functional activity at N-type VSCCs. The most active compound discovered in this series is PD 173212 (11, IC50 = 36 nM in the IMR-32 assays). SAR and pharmacological evaluation of this series are described, (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00359-5
• 作为产物：
  描述：

  Boc-O-苄基-L-酪氨酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 叔丁胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以22.1 g (92%)的产率得到(S)-[2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Heteroaryl alkyl alpha substituted peptidylamine calcium channel blockers

  摘要：

  本发明提供了阻断钙通道的化合物，其具有下面所示的化学式I。本发明还提供了利用化合物I的方法，用于治疗中风、脑缺血、头部创伤、哮喘、肌萎缩性侧索硬化或癫痫，并提供含有化合物I的药物组合物。

  公开号：

  US06166052A1

文献信息

• Substituted peptidylamine calcium channel blockers
  申请人：Warner-Lambert Company

  公开号：US06117841A1

  公开（公告）日：2000-09-12

  The present invention provides compounds that block calcium channels having the Formula I shown below. ##STR1## The present invention also provides methods of using the compounds of Formula I to treat stroke, cerebral ischemia, head trauma, or epilepsy and to pharmaceutical compositions that contain the compounds of Formula I.

  本发明提供了阻断钙通道的化合物，其具有下面所示的化学式I。本发明还提供了利用化合物I治疗中风、脑缺血、头部创伤或癫痫的方法，以及含有化合物I的药物组合物。
• Reduced dipeptide analogues as calcium channel antagonists
  申请人：Warner-Lambert Company

  公开号：US06316440B1

  公开（公告）日：2001-11-13

  The present invention provides novel N-type calcium channel blockers, compositions comprising them, and methods of their use. The compounds of the invention are useful in the treatment of stroke, cerebral ischemia, pain, epilepsy, and head trauma. The novel compounds provided by this invention have Formula (1), wherein R1 is H or methyl; R2 is H, azepanylcarbonyl, C1-C7 alkyl, —(CH2)n-phenyl, wherein the phenyl is unsubstituted or substituted with C1-C4 alkyl, C1-C4 alkoxy, or halo; R3 is C1-C5 alkyl; X is —NR4R5 or —OR7; R4 and R5 are independently H, C1-C5 alkyl; or R4 and R5 together with the nitrogen to which they are both bound form formulae (a); (b); (c); (d) or (e); R6 is —(CH2)n-phenyl, wherein the phenyl is unsubstituted or substituted with C1-C4 alkyl, C1-C4 alkoxy, or halo; A and B are independently —CO— or —CH2—, provided that A and B are not both —CO—; R7 is C1-C5 alkyl; Z is —CH2—, —O—, —S—, or —N(R8)—; R8 is H or C1-C6 alkyl; and n is 1 or 2.

  本发明提供了新型N-型钙通道阻滞剂，包含它们的组合物，以及它们的使用方法。本发明的化合物在中风、脑缺血、疼痛、癫痫和头部创伤的治疗中是有用的。本发明提供的新型化合物具有式（1），其中R1为H或甲基；R2为H，氮杂环己酰基，C1-C7烷基，—（CH2）n-苯基，其中苯基未取代或取代为C1-C4烷基，C1-C4烷氧基或卤素；R3为C1-C5烷基；X为—NR4R5或—OR7；R4和R5独立地为H，C1-C5烷基；或R4和R5与它们共价结合的氮原子一起形成式（a）、（b）、（c）、（d）或（e）；R6为—（CH2）n-苯基，其中苯基未取代或取代为C1-C4烷基，C1-C4烷氧基或卤素；A和B独立地为—CO—或—CH2—，但A和B不能同时为—CO—；R7为C1-C5烷基；Z为—CH2—，—O—，—S—或—N(R8)—；R8为H或C1-C6烷基；n为1或2。
• [EN] SUBSTITUTED PEPTIDYLAMINE CALCIUM CHANNEL BLOCKERS<br/>[FR] INHIBITEURS DES CANAUX DE CALCIUM DE PEPTIDYLAMINE SUBSTITUEE
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1998054123A1

  公开（公告）日：1998-12-03

  (EN) The present invention provides compounds that block calcium channels having Formula (I). The present invention also provides methods of using the compounds of Formula (I) to treat stroke, cerebral ischemia, head trauma, or epilepsy and to pharmaceutical compositions that contain the compounds of Formula (I).(FR) L'invention concerne des composés inhibiteurs des canaux de calcium et représentés par la formule (I). Elle concerne également des procédés servant à mettre en application ces composés afin de traiter les attaques, l'ischémie cérébrale, le traumatisme crânien ou l'épilepsie, ainsi que des compositions pharmaceutiques contenant ces composés.

  (中) 本发明提供了具有公式（I）的阻断钙通道的化合物。本发明还提供了使用公式（I）的化合物治疗中风、脑缺血、头部创伤或癫痫的方法，以及含有公式（I）的制药组合物。
• Reduced dipeptide analogues as calcium channel antagonitsts
  申请人：——

  公开号：US20020028801A1

  公开（公告）日：2002-03-07

  The present invention provides novel N-type calcium channel blockers, compositions comprising them, and methods of their use. The compounds of the invention are useful in the treatment of stroke, cerebral ischemia, pain, epilepsy, and head trauma. The novel compounds provided by this invention have the Formula I: 1 wherein R 1 is H or methyl, R 2 is H, azepanylcarbonyl, C 1 -C 7 alkyl, —(CH 2 ) n -phenyl, wherein the phenyl is unsubstituted or substituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or halo, R 3 is C 1 -C 5 alkyl, X is —NR 4 R 5 or —OR 7 , R 4 and R 5 are independently H, C 1 -C 5 alkyl, or R 4 and R 5 together with the nitrogen to which they are both bound form: 2 R 6 is —(CH 2 ) n -phenyl, wherein the phenyl is unsubstituted or substituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or halo, A and B are independently —CO— or —CH 2 —, provided that A and B are not both —CO—, R 7 is C 1 -C 5 alkyl, Z is —CH 2 —, —O—, —S—, or —N(R 8 )—, R 8 is H or C 1 -C 6 alkyl, and n is 1 or 2.

  本发明提供了新型N型钙通道阻滞剂，包括它们的组成和使用方法。该发明的化合物在中风、脑缺血、疼痛、癫痫和头部创伤的治疗中是有用的。本发明提供的新型化合物具有式I:1，其中R1为H或甲基，R2为H、氮杂七元环羧酰基、C1-C7烷基、-(CH2)n-苯基，其中苯基未取代或取代有C1-C4烷基、C1-C4甲氧基或卤素，R3为C1-C5烷基，X为-NR4R5或-OR7，R4和R5独立地为H、C1-C5烷基或R4和R5与它们都结合的氮原子一起形成2，R6为-(CH2)n-苯基，其中苯基未取代或取代有C1-C4烷基、C1-C4甲氧基或卤素，A和B独立地为-CO-或-CH2-，但A和B不能同时为-CO-，R7为C1-C5烷基，Z为-CH2-、-O-、-S-或-N(R8)-，R8为H或C1-C6烷基，n为1或2。
• Tyrosine-derived compounds as calcium channel antagonists
  申请人：Warner-Lambert Company

  公开号：US06323243B1

  公开（公告）日：2001-11-27

  The present invention provides compounds that block calcium channels and have the Formula I: and pharmaceutically acceptable salts, esters, and pro-drugs thereof, wherein R1 and R2 are independently H, phenylcyclopentylcarbonyl, C1-C7 alkyl, cyclohexylmethyl, benzyl, C1-C5 alkylbenzyl, or C1-C5 alkoxybenzyl, A is —C(O)— or —CH2—; R3 is H or —CH3; R4 is C1-C4 alkyl or piperidin-1-ylethyl; R5 is phenyl-(CH2)n—, C1-C4 alkylphenyl-(CH2)n—, or halophenyl-(CH2)n—; and n is 1 or 2. The present invention also provides pharmaceutical compositions containing the compounds of Formula I and methods of using them to treat stroke, cerebral ischemia, head trauma, and epilepsy.

  本发明提供了阻断钙通道的化合物，其具有公式I：以及其药学上可接受的盐，酯和前药，其中R1和R2独立地是H，苯基环戊基甲酰基，C1-C7烷基，环己基甲基，苄基，C1-C5烷基苄基或C1-C5烷氧基苄基，A是—C（O）—或—CH2—; R3是H或—CH3; R4是C1-C4烷基或哌啶-1-乙基; R5是苯基-(CH2)n—，C1-C4烷基苯基-(CH2)n—或卤代苯基-(CH2)n—; n为1或2。本发明还提供了含有公式I化合物的药物组合物以及使用它们治疗中风，脑缺血，头部创伤和癫痫的方法。