N-(1-benzyl-2-carbamoyl-2-hydroxyethyl)-2-[E-2-(naphth-2-yl)ethen-1-yl]benzamide | 561067-00-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: N-(1-benzyl-2-carbamoyl-2-hydroxyethyl)-2-[E-2-(naphth-2-yl)ethen-1-yl]benzamide
• 英文别名: N-(4-amino-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-2-[(E)-2-naphthalen-2-ylethenyl]benzamide
• CAS: 561067-00-3
• 化学式: C₂₉H₂₆N₂O₃
• 分子量: 450.537
• InChiKey: MZBUHNPNYPXYIE-BMRADRMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  92.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(1-benzyl-2-carbamoyl-2-hydroxyethyl)-2-[E-2-(naphth-2-yl)ethen-1-yl]benzamide 在 三氧化硫吡啶 、 二甲基亚砜 作用下， 生成 N-(1-benzyl-2-carbamoyl-2-oxoethyl)-2-[E-2-(naphth-2-yl)ethen-1-yl]benzamide
  参考文献：
  名称：

  Discovery of phenyl alanine derived ketoamides carrying benzoyl residues as novel calpain inhibitors

  摘要：

  Novel calpain inhibitors derived from phenyl alanine aldehydes or ketoamides carrying a benzoyl residue were prepared and evaluated for their biological potency. A brief structure-activity relationship elucidated the importance of ortho-substitutents in the benzoyl moiety. The most potent derivative, the ketoamide 19c, exhibited a K, of 6 nM and represents a novel class of reversible, highly potent and non-peptidic calpain inhibitors. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00176-2
• 作为产物：
  描述：

  2-溴苯甲酸乙酯 在 palladium diacetate 、 氢氧化钾 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 N-(1-benzyl-2-carbamoyl-2-hydroxyethyl)-2-[E-2-(naphth-2-yl)ethen-1-yl]benzamide
  参考文献：
  名称：

  Benzoylalanine-Derived Ketoamides Carrying Vinylbenzyl Amino Residues:  Discovery of Potent Water-Soluble Calpain Inhibitors with Oral Bioavailability

  摘要：

  Novel benzoylalanine-derived ketoamides were prepared and evaluated for calpain I inhibition. Derivatives carrying vinylbenzyl amino residues in the P-2-P-3 region inhibited calpain in nanomolar concentrations and thus represent a novel class of nonpeptidic calpain inhibitors. Selected examples exhibited an improved pharmacokinetic profile including improved water-solubility and metabolic stability. In particular, these calpain inhibitors showed oral bioavailability in rats as demonstrated by N-(1-benzyl-2-carbamoyl-2-oxoethyl)-2-[E-2-(4-diethylaminomethylphenyl)ethen-1-yl]benzamide (5d). The closely related derivative N-(1-carbamoyl-1-oxohex-1-yl)-2-[E-2-(4-dimethylaminomethylphenyl)-ethen-1-yl]benzamide (5b) was evaluated for neuroprotective efficacy after experimental traumatic brain injury in a fluid percussion model in rats. When administered after injury, 5b reduced the number of damaged neurons by 41%, and this result would be in line with the suggested neuroprotective efficacy of calpain inhibition.

  DOI：

  10.1021/jm0210717

文献信息

• [DE] KETOBENZAMIDE ALS CALPAIN-INHIBITOREN<br/>[EN] KETOBENZAMIDES AS CALPAIN INHIBITORS<br/>[FR] CETOBENZAMIDES S'UTILISANT COMME INHIBITEURS DE LA CALPAINE
  申请人：BASF AKTIENGESELLSCHAFT

  公开号：WO1998025883A1

  公开（公告）日：1998-06-18

  (DE) Es werden Ketobenzamide der Formel (I), worin R1, R2, R3, R4, X und n die in der Beschreibung angegebene Bedeutung haben, sowie deren Herstellung beschrieben. Die neuen Verbindungen eignen sich zur Bekämpfung von Krankheiten.(EN) The invention concerns ketobenzamides of formula (I) in which R1, R2, R3, R4, X and n have the meanings given in the description. The invention further concerns their preparation. The novel compounds are suitable for combating diseases.(FR) L'invention concerne des cétobenzamides de la formule (I) dans laquelle R1, R2, R3, R4, X et n ont la signification mentionnée dans la description, ainsi que leur préparation. Ces nouveaux composés s'utilisent pour lutter contre les maladies.

  该发明涉及一类化学式为(I)的苯甲酸酯类药物，其中：R1、R2、R3、R4、X和n分别具有描述中所定义的意义，该发明还涉及为此类化合物的制备。该新合成的化合物适于用于治疗疾病。
• KETOBENZAMIDE ALS CALPAIN-INHIBITOREN
  申请人：BASF AKTIENGESELLSCHAFT

  公开号：EP0944582A1

  公开（公告）日：1999-09-29