2-chloro-N’-formylacetimidohydrazide | 89378-75-6

• 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: 2-chloro-N’-formylacetimidohydrazide
• 英文别名: N-formyl-2-chloroacetamidrazone；N-[(1-amino-2-chloroethylidene)amino]formamide
• CAS: 89378-75-6
• 化学式: C₃H₆ClN₃O
• mdl: MFCD19227955
• 分子量: 135.553
• InChiKey: WNPORCRRSCZMSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-N’-formylacetimidohydrazide 、 [(1R,2S,3S)-3-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-2-(4-fluoro-phenyl)-cyclopentyl]-ethyl-amine 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Cyclopentane-based human NK1 antagonists. Part 2: Development of potent, orally active, water-soluble derivatives

  摘要：

  The synthesis and optimization of a cyclopentane-based hNK1 antagonist scaffold 3, having four chiral centers, will be discussed in the context of its enhanced water-solubility properties relative to the marketed anti-emetic hNK1 antagonist EMEND (R) (Aprepitant). Sub-nanomolar hNK1 binding was achieved and oral activity comparable to Aprepitant in two in vivo models will be described. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.044
• 作为产物：
  描述：

  氯乙腈 、 甲酰肼 在 sodium methylate 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 1.75h， 以43%的产率得到2-chloro-N’-formylacetimidohydrazide
  参考文献：
  名称：

  WO2007/34277

  摘要：

  公开号：

文献信息

• [EN] 8-AZABICYCLO[3.2.1]OCTANE ETHER DERIVATIVES AND THEIR USE AS NEUROKININ RECEPTOR ANTAGONISTS<br/>[FR] DERIVES D'ETHER 8-AZABICYCLO[3.2.1]OCTANE ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DE RECEPTEUR DE NEUROKININE
  申请人：MERCK SHARP & DOHME

  公开号：WO2004031185A1

  公开（公告）日：2004-04-15

  The present invention relates compounds of the formula (I) : wherein X represents hydrogen, C1-4alkyl optionally substituted by a hydroxy, methoxy or benzyloxy group, or CO2(C1-2alkyl); Z is -CR9R10CH2- or -CH2CR9R10-; and R1, R2, R3, R4, R5 and R6 are as defined herein. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migaine, emesis or postherpetic neuralgia.

  本发明涉及以下式(I)的化合物：其中X代表氢，C1-4烷基，可选择地被羟基，甲氧基或苄氧基取代，或CO2(C1-2烷基)；Z为-CR9R10CH2-或-CH2CR9R10-；而R1、R2、R3、R4、R5和R6如本文所定义。这些化合物在治疗或预防抑郁症、焦虑、疼痛、炎症、偏头痛、呕吐或带状疱疹后神经痛方面具有特殊用途。
• 4,4-Disubstituted Piperidine High-Affinity NK₁ Antagonists:  Structure−Activity Relationships and <i>in Vivo</i> Activity
  作者：Graeme I. Stevenson、Ian Huscroft、Angus M. MacLeod、Christopher J. Swain、Margaret A. Cascieri、Gary G. Chicchi、Michael I. Graham、Timothy Harrison、Fintan J. Kelleher、Marc Kurtz、Tamara Ladduwahetty、Kevin J. Merchant、Joseph M. Metzger、D. E. MacIntyre、Sharon Sadowski、Balbinder Sohal、Andrew P. Owens

  DOI：10.1021/jm980376b

  日期：1998.11.1

  high-affinity NK1 antagonists based on the 4,4-disubstituted piperidine ring system. Further structure-activity studies have now established that for high NK1 affinity the benzyl ether side chain must be 3,5-disubstituted and highly lipophilic, the optimal side chain being the 3, 5-bis(trifluoromethyl)benzyl ether, 12 (hNK1 IC50 = 0.95 nM). Additional studies have shown that this class of NK1 antagonist tolerates

  这些实验室的先前报道的研究描述了基于4,4-二取代哌啶环系统的一系列新型高亲和力NK1拮抗剂的设计。进一步的结构活性研究现已确定，对于高NK1亲和力，苄基醚侧链必须为3,5-二取代且高度亲脂性，最佳侧链为3,5-双（三氟甲基）苄基醚12（hNK1 IC50 = 0.95 nM）。进一步的研究表明，这类NK1拮抗剂可耐受哌啶氮上更广泛的取代基，包括酰基（38）（hNK1 IC50 = 5.3 nM）和磺酰基（39）（hNK1 IC50 = 5.7 nM）衍生物。经过初步的药代动力学分析，在树脂毒素诱导的血管渗漏模型中选择了两种化合物（32和43）用于体内研究，
• Structure–activity relationships and CoMFA of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic properties
  作者：Ronald Palin、John K. Clark、Louise Evans、Andrea K. Houghton、Philip S. Jones、Alan Prosser、Grant Wishart、Kazuya Yoshiizumi

  DOI：10.1016/j.bmc.2008.01.005

  日期：2008.3.15

  The N-3 position of a series of 3-phenoxypropyl piperidine benzimidazol-2-one analogues was optimised using the predictive power of a CoMFA model. The model was used to prioritise compounds for synthesis culminating in the triazole (+)-24. (+)-24 was found to be a high affinity, potent NOP agonist and demonstrated both antinociceptive and antiallodynic effects when administered iv to rodents.

  使用CoMFA模型的预测能力，优化了一系列3-苯氧基丙基哌啶苯并咪唑-2-一类似物的N-3位置。该模型用于对化合物进行优先排序，最终合成出三唑（+）-24。（+）-24被发现是一种高亲和力，强效的NOP激动剂，并在静脉内施用给啮齿动物后表现出抗伤害感受和抗痛觉过敏的作用。
• <i>N</i>-Heteroaryl-2-phenyl-3-(benzyloxy)piperidines:  A Novel Class of Potent Orally Active Human NK₁ Antagonists
  作者：T. Ladduwahetty、R. Baker、M. A. Cascieri、M. S. Chambers、K. Haworth、L. E. Keown、D. E. MacIntyre、J. M. Metzger、S. Owen、W. Rycroft、S. Sadowski、E. M. Seward、S. L. Shepheard、C. J. Swain、F. D. Tattersall、A. P. Watt、D. W. Williamson、R. J. Hargreaves

  DOI：10.1021/jm9506534

  日期：1996.1.1

  The preparation of a series of N-heteroarylpiperidine ether-based human NK1 antagonists is described. Two of the compounds 3-[-(2S,3S)-3-(((3,5-bis(trifluoromethyl)phenyl)methyl)oxy)- 2-phenylpiperidino}methyl]-1,2,4-triazole (11) and 5-[ inverted question mark(2S,3S)-3-(((3,5-bis(trifluoromethyl)-phenyl)methyl)oxy)-2- phenylpiperidino}methyl]-3-oxo-1,2,4-triazolone (12)), in particular, are orally

  描述了一系列基于N-杂芳基哌啶醚的人NK1拮抗剂的制备。化合物3-[-（2S，3S）-3-（（（（3,5-双（三氟甲基）苯基）甲基）氧基）-2-苯基哌啶子基}甲基] -1,2,4-三唑中的两种（11 ）和5- [倒问号（2S，3S）-3-（（（（3,5-双（三氟甲基）-苯基）甲基）氧基）-2-苯基哌啶基}甲基] -3-氧-1,2，尤其是4-triazolone（12））具有口服生物利用度，并且与铅（羧酰胺基甲基）哌啶醚1相比，在体内和体外显示出显着的效力改善。大鼠肝脏微粒体研究了从中选择的多种化合物系列显示三唑酮杂环比其他杂环稳定得多。此外，11和12均已在许多可预测P物质拮抗剂临床应用的试验中进行了分析。
• Cyclopentane-based human NK1 antagonists. Part 1: Discovery and initial SAR
  作者：Paul E. Finke、Laura C. Meurer、Dorothy A. Levorse、Sander G. Mills、Malcolm MacCoss、Sharon Sadowski、Margaret A. Cascieri、Kwei-Lan Tsao、Gary G. Chicchi、Joseph M. Metzger、D. Euan MacIntyre

  DOI：10.1016/j.bmcl.2006.06.035

  日期：2006.9

  An initial investigation of the novel cyclopentane scaffold 6 afforded low nanomolar human NK1 antagonists having enhanced water solubility properties compared to morpholine 1. A synthesis of this cyclopentane scaffold, having three contiguous chiral centers, and the unexpected determination that the 1,2-trans-2,3-trans-ring stereochemistry, as opposed to the cis-ether/phenyl configuration of the known structures 1-5, is optimal for this class of antagonist are described. (c) 2006 Elsevier Ltd. All rights reserved.