α-acetamido-α-bromo-N-benzylacetamide | 133873-18-4

• 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: α-acetamido-α-bromo-N-benzylacetamide
• 英文别名: α-acetamido-N-benzyl-α-bromoacetamide；2-acetamido-N-benzyl-2-bromoacetamide
• CAS: 133873-18-4
• 化学式: C₁₁H₁₃BrN₂O₂
• 分子量: 285.14
• InChiKey: NGBWVSSPZVFOFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  α-acetamido-α-bromo-N-benzylacetamide 在 盐酸 、 正丁基锂 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 9.25h， 生成 α-acetamido-N-benzyl-α-(imidazol-4-yl)acetamide
  参考文献：
  名称：

  Synthesis and anticonvulsant activities of .alpha.-heterocyclic .alpha.-acetamido-N-benzylacetamide derivatives

  摘要：

  Earlier studies showed that (R,S)-alpha-acetamido-N-benzylacetamides (2) containing a five- and six-membered aromatic or heteroaromatic group appended at the C(alpha) site displayed outstanding activity in the maximal electroshock-induced seizure (MES) test in mice. An expanded set of C(alpha)-heteroaromatic analogues of 2 have been prepared and evaluated. The observed findings extended the structure-activity relationships previously discerned for this novel class of anti-convulsants and have validated previous trends. The alpha-furan-2-yl (4), alpha-oxazol-2-yl (18), and alpha-thiazol-2-yl (19) alpha-acetamido-N-benzylacetamides afforded excellent protection against MES-induced seizures in mice. The ED50 and PI values for these adducts rivaled those reported for phenytoin. The outstanding properties provided by 4 led to an in-depth examination of the effect of structural modification at key sites within this compound on biological activity. The pharmacological data in this series indicated that stringent steric and electronic requirements existed for maximal activity and revealed the outstanding activity of (R)-(-)-alpha-acetamido-N-(4-fluorobenzyl)-alpha-(furan-2-yl)acetamide [(R)-30].

  DOI：

  10.1021/jm00074a016
• 作为产物：
  描述：

  α-acetamido-α-ethoxy-N-benzylacetamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 α-acetamido-α-bromo-N-benzylacetamide
  参考文献：
  名称：

  一系列功能化的α-杂原子取代的氨基酸的制备及其抗惊厥活性。

  摘要：

  （R，S）-2-乙酰氨基-N-苄基-2-甲基乙酰胺（2a）的抗惊厥活性已有报道。已经制备了2a的选择的被α-杂原子取代的衍生物（26个实例），其中α-甲基已被含氮（3a-q），氧（3r-u）和硫（3v-z）部分取代。在小鼠中通过最大电休克发作（MES）和水平筛选（tox）测试评估了功能化的氨基酸衍生物。活性最高的化合物是（R，S）-2-乙酰氨基-N-苄基-2-（甲氧基氨基）乙酰胺（31）和（R，S）-2-乙酰氨基-N-苄基-2-（甲氧基甲基氨基）乙酰胺（3n）。腹膜内给药后，31（6.2 mg / kg）和3n（6.7 mg / kg）的MES ED50值优于苯妥英（9.50 mg / kg）。

  DOI：

  10.1021/jm00112a020

文献信息

• Anticonvulsant Properties ofN‐Substituted α,α‐Diamino Acid Derivatives
  作者：Harold Kohn、Kailash N. Sawhney、David W. Robertson、J. David Leander

  DOI：10.1002/jps.2600830519

  日期：1994.5

  studies have demonstrated that functionalized α,α‐diamino acids ( 1 ) display excellent activity when evaluated in the maximal electroshock seizure (MES) test in mice. The synthesis and pharmacological evaluation of 14 select analogues within this series of compounds are detailed. Included in this survey were 10 N ‐acyl derivatives in which the basic C(α) N ‐group in 1 was replaced by a neutral N ‐substituent

  摘要最近的研究表明，在小鼠的最大电击惊厥（MES）测试中评估时，功能化的α，α-二氨基酸（1）具有出色的活性。详细介绍了该系列化合物中14种选择类似物的合成和药理学评估。本次调查包括10种N-酰基衍生物，其中1个碱性C（α）N-基团被一个中性N-取代基和四个二肽取代，其中两个氨基酸的融合点为α-碳位点。N酰化为1会导致抗惊厥活性降低。简要讨论了这些发现相对于1中C（α）取代抗腐剂活性的要求的重要性。
• Amino acid derivative anticonvulsant
  申请人：Research Corporation Technologies, Inc.

  公开号：US05654301A1

  公开（公告）日：1997-08-05

  The present invention relates to compounds of the formula ##STR1##

  本发明涉及以下结构的化合物 ##STR1##
• Synthesis and Anticonvulsant Activities of .alpha.-Acetamido-N-benzylacetamide Derivatives Containing an Electron-Deficient .alpha.-Heteroaromatic Substituent
  作者：Patrick Bardel、Antoinette Bolanos、Harold Kohn

  DOI：10.1021/jm00052a017

  日期：1994.12

  pyrazin-2-yl (12), pyrimid-2-yl (13)). Expedient syntheses for 12 and 13 were developed using a phase-transfer, nucleophilic aromatic substitution process. All three adducts exhibited potencies comparable to or greater than phenytoin in the MES test (mice, ip). These findings required us to modify in part the previously proposed structure-activity relationship for this class of anticonvulsants.

  最近的研究表明，Cα-取代的α-乙酰氨基-N-苄基乙酰胺在小鼠中表现出出色的抗惊厥活性。对这一系列化合物的结构活性关系的分析表明，将小的，富电子的芳族和杂芳族基团放置在Cα位会导致针对MES引起的癫痫发作的明显保护。在此说明中，报告了合成方案，用于制备三种新型的非天然存在的电子缺陷的Cα-氮杂芳族α-乙酰氨基-N-苄基乙酰胺（即，吡啶-2-基（11），吡嗪-2-基（12），嘧啶-2-基（13））。使用相转移亲核芳香族取代过程开发了12和13的便捷合成方法。在MES测试中，所有三种加合物均显示出与苯妥英相当或更高的效力（小鼠，ip）。
• Uses for amino acid anticonvulsants
  申请人：——

  公开号：US20020086828A1

  公开（公告）日：2002-07-04

  The present invention is directed to the use of compounds of the formula: 1 for treating pain, in particular neuropathic pain, bipolar disease and migraine headaches.

  本发明涉及使用式1化合物治疗疼痛，特别是神经病性疼痛、双相情感障碍和偏头痛。
• New uses for amino acid anticonvulsants for treatment of migraine
  申请人：Research Corporation Technologies, Inc

  公开号：EP1486205A1

  公开（公告）日：2004-12-15

  The present invention describes the use of a compound of the following formula (I) for the manufacture of a medicament effective in the treatment or prevention of migraine headaches of a mammal:    wherein Ris hydrogen or lower alkyl, lower alkenyl, lower alkynyl, aryl, aryl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower alkyl heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, each optionally substituted with at least one electron withdrawing or electron donating group; R1is hydrogen or lower alkyl, lower alkenyl, lower alkynyl, aryl lower alkyl, aryl, heterocyclic lower alkyl, heterocyclic, lower alkyl heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, each optionally substituted with an electron donating or an electron withdrawing group; R2 and R3are independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl lower alkyl, aryl, halogen, heterocyclic, heterocyclic lower alkyl, lower alkyl heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, or Z-Y; R2 and R3 are optionally substituted with at least one electron withdrawing or electron donating group; Zis O, S, S(O)a, NR4 or PR4; Yis hydrogen, lower alkyl, aryl, aryl lower alkyl, lower alkenyl, lower alkynyl, heterocyclic, heterocyclic lower alkyl, and Y is optionally substituted with an electron donating or electron withdrawing group, or ZYtaken together is NR4NR5R7, NR4OR5, ONR4R7, OPR4R5, PR4OR5, SNR4R7, NR4SR7, SPR4R5, PR4SR7, NR4PR5R6, PR4NR5R7, NR4C(=O)R5, S(C=O)R5, NR4C(=O)OR5, or S(C=O)OR5, R4, R5 and R6are independently hydrogen or lower alkyl, aryl, aryl lower alkyl, lower alkenyl, or lower alkynyl, each optionally substituted with an electron withdrawing or an electron donating group; R7is COOR8, COR8, hydrogen or lower alkyl, aryl, aryl lower alkyl, lower alkenyl or lower alkynyl, each optionally substituted with an electron withdrawing or electron donating group; R8is hydrogen, lower alkyl or aryl lower alkyl, the aryl or alkyl group is optionally substituted with an electron withdrawing or an electron donating group; nis 1-4; and ais 1-3.

  本发明描述了下式（I）化合物在制造有效治疗或预防哺乳动物偏头痛的药物中的用途： 其中 Ris氢或低级烷基、低级烯基、低级炔基、芳基、芳基低级烷基、杂环基、杂环低级烷基、低级烷基杂环基、低级环烷基、低级环烷基低级烷基，各自任选被至少一个取电子或供电子基团取代； R1 为氢或低级烷基、低级烯基、低级炔基、低级芳烷基、芳基、杂环低级烷基、杂环、低级烷基杂环、低级环烷基、低级环烷基低级烷基，各自可选地被一个电子捐赠基团或一个电子撤回基团取代； R2 和 R3 独立地为氢、低级烷基、低级烯基、低级炔基、低级芳烷基、芳基、卤素、杂环、杂环低级烷基、低级烷基杂环、低级环烷基、低级环烷基低级烷基或 Z-Y； R2 和 R3 可任选被至少一个析电子或供电子基团取代； Z 是 O、S、S(O)a、NR4 或 PR4； Y 是氢、低级烷基、芳基、芳基低级烷基、低级烯基、低级炔基、杂环、杂环低级烷基，且 Y 可选择被一个电子捐赠基团或电子撤回基团取代，或 ZY合起来是 NR4NR5R7、NR4OR5、ONR4R7、OPR4R5、PR4OR5、SNR4R7、NR4SR7、SPR4R5、PR4SR7、NR4PR5R6、PR4NR5R7、NR4C(=O)R5、S(C=O)R5、NR4C(=O)OR5 或 S(C=O)OR5、 R4、R5 和 R6 独立地为氢或低级烷基、芳基、芳基低级烷基、低级烯基或低级炔基，各自可选地被一个取电子基团或一个供电子基团取代； R7 是 COOR8、COR8、氢或低级烷基、芳基、芳基低级烷基、低级烯基或低级炔基，各自任选被一个取电子或捐电子基团取代； R8 是氢、低级烷基或芳基低级烷基，芳基或烷基可任选被一个取电子或捐电子基团取代； n 是 1-4；和 ais 1-3。