4-imidazolylacetyl chloride | 27146-05-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-imidazolylacetyl chloride
• 英文别名: (1(3)H-imidazol-4-yl)-acetyl chloride；2-(1H-imidazol-5-yl)acetyl chloride
• CAS: 27146-05-0
• 化学式: C₅H₅ClN₂O
• mdl: MFCD19228011
• 分子量: 144.56
• InChiKey: UPRKJRUZQSYJHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [(1R,2S,3S)-3-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-2-(4-fluoro-phenyl)-cyclopentyl]-methyl-amine 、 4-imidazolylacetyl chloride 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到N-[(1R,2S,3S)-3-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-2-(4-fluoro-phenyl)-cyclopentyl]-2-(1H-imidazol-4-yl)-N-methyl-acetamide
  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

文献信息

• HYDRAZINE DERIVATIVES
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1089964B1

  公开（公告）日：2003-10-29
• US6239151B1
  申请人：——

  公开号：US6239151B1

  公开（公告）日：2001-05-29
• [EN] HYDRAZINE DERIVATIVES<br/>[FR] DERIVES D'HYDRAZINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2000000465A1

  公开（公告）日：2000-01-06

  The invention provides hydrazine derivatives of formula (I) wherein R1 is lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl, aryl or aryl-lower alkyl; R2 is an acyl group derived from an α-, β-, η- or δ-(amino, hydroxy or thiol) carboxylic acid in which the amino, hydroxy or thiol group is optionally lower alkylated or the amino group is optionally acylated, sulphonylated or amidated and in which any functional group present in a side-chain is optionally protected, or a group of the formula Het(CH¿2?)mCO; R?3¿ is hydrogen, lower alkyl, halo-lower alkyl, cyano-lower alkyl, amino-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, lower cycloalkyl-lower alkyl, aryl-lower alkyl, heterocyclyl-lower alkyl, heterocyclylcarbonyl-lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl-lower alkenyl, aryl or heterocyclyl; R4 is lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl or a grouping of the formula X-aryl, X-heteroaryl or (CH¿2?)n-CH=CR?5R6; R5 and R6¿ together are lower alkylene in which one CH¿2? group is optionally replaced by a hetero atom; Het is heterocyclyl; X is a spacer group; m is 0, 1, 2, 3 or 4; and n is 1 or 2; and their pharmaceutically acceptable salts inhibit the release of tumour necrosis factor alpha (TNF-α) from cells. They can be used as medicaments, especially in the treatment of inflammatory and autoimmune diseases, osteoarthritis, respiratory diseases, tumours, cachexia, cardiovascular diseases, fever, haemorrhage and sepsis.
• Cyclopentane-based human NK1 antagonists. Part 2: Development of potent, orally active, water-soluble derivatives
  作者：Laura C. Meurer、Paul E. Finke、Karen A. Owens、Nancy N. Tsou、Richard G. Ball、Sander G. Mills、Malcolm MacCoss、Sharon Sadowski、Margaret A. Cascieri、Kwei-Lan Tsao、Gary G. Chicchi、Linda A. Egger、Silvi Luell、Joseph M. Metzger、D. Euan MacIntyre、Nadia M.J. Rupniak、Angela R. Williams、Richard J. Hargreaves

  DOI：10.1016/j.bmcl.2006.06.044

  日期：2006.9

  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.