Phenyl {N-{4-[4-(2-{4-(8-Chloro(5,6-dihydrobenzo[f]pyridino[2,3-b][7]annulen-11-ylidene))piperidyl}ethoxy)phenyl]but-3-ynyl}phenoxycarbonylaminooxy}formate | 299461-36-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并环庚烷吡啶
• 英文名称: Phenyl {N-{4-[4-(2-{4-(8-Chloro(5,6-dihydrobenzo[f]pyridino[2,3-b][7]annulen-11-ylidene))piperidyl}ethoxy)phenyl]but-3-ynyl}phenoxycarbonylaminooxy}formate
• 英文别名: [4-[4-[2-[4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidin-1-yl]ethoxy]phenyl]but-3-ynyl-phenoxycarbonylamino] phenyl carbonate
• CAS: 299461-36-2
• 化学式: C₄₅H₄₀ClN₃O₆
• 分子量: 754.282
• InChiKey: XZOZEAXFMPEJDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  55
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  90.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Phenyl {N-{4-[4-(2-{4-(8-Chloro(5,6-dihydrobenzo[f]pyridino[2,3-b][7]annulen-11-ylidene))piperidyl}ethoxy)phenyl]but-3-ynyl}phenoxycarbonylaminooxy}formate 在 氨 作用下， 以 甲醇 为溶剂， 生成 1-(4-{4-[2-(4-{13-Chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene}piperidin-1-yl)ethoxy]phenyl}but-3-yn-1-yl)-1-hydroxyurea
  参考文献：
  名称：

  Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity

  摘要：

  A series of compounds possessing both H, histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H-1-binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observed in vivo, as was increased CYP3A4 inhibition compared to their respective single-function drugs. Selected analogs in the series were shown to be orally active in guinea pig models. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.060
• 作为产物：
  描述：

  4-[4-(2-Bromoethoxy)phenyl]but-3-yn-1-ol 在 偶氮二甲酸二异丙酯 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 Phenyl {N-{4-[4-(2-{4-(8-Chloro(5,6-dihydrobenzo[f]pyridino[2,3-b][7]annulen-11-ylidene))piperidyl}ethoxy)phenyl]but-3-ynyl}phenoxycarbonylaminooxy}formate
  参考文献：
  名称：

  Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity

  摘要：

  A series of compounds possessing both H, histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H-1-binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observed in vivo, as was increased CYP3A4 inhibition compared to their respective single-function drugs. Selected analogs in the series were shown to be orally active in guinea pig models. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.060

文献信息

• Compounds and methods for treatment of asthma, allergy and inflammatory disorders
  申请人：UCB, S.A.

  公开号：US06451801B1

  公开（公告）日：2002-09-17

  The present invention provides 1,4 substituted piperazines, 1,4 substituted piperidines, and 1-substituted, 4-alkylidenyl peperidines compounds. The compounds of the invention are dual acting molecules having both leukotriene inhibition properties as well as antihistaminergic properties. The compounds of the invention are useful for treating conditions in which there is likely to be a histamine and/or leukotriene component. These conditions include preferable asthma, seasonal and perennial allergic rhinitis, sinusitus, conjunctivitis, food allergy, scombroid poisoning, psoriasis, urticaria, pruritus, eczema, rheumatoid arthritis, inflammatory bowel disease, chronic obstructive pulmonary disease, thrombotic disease and otitis media. Also provided are methods of treating asthma and rhinitis by administering an effective asthma and rhinitis-relieving amount of the compounds to a subject in need thereof.

  本发明提供了1,4取代哌嗪、1,4取代哌啶和1-取代、4-烷基亚乙基哌啶化合物。本发明的化合物是双重作用分子，具有白三烯抑制和抗组胺作用。本发明的化合物可用于治疗可能存在组胺和/或白三烯成分的疾病。这些疾病包括哮喘、季节性和全年过敏性鼻炎、鼻窦炎、结膜炎、食物过敏、鲭鱼中毒、牛皮癣、荨麻疹、瘙痒、湿疹、类风湿性关节炎、炎症性肠病、慢性阻塞性肺疾病、血栓性疾病和中耳炎。还提供了通过向需要治疗哮喘和鼻炎的受试者施用有效的哮喘和鼻炎缓解量的化合物的方法。
• Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity
  作者：Timothy A. Lewis、Michelle A. Young、Mark P. Arrington、Lynn Bayless、Xiong Cai、Philippe Collart、Joseph B. Eckman、James L. Ellis、Doina G. Ene、Lyn Libertine、Jean-Marie Nicolas、Ralph T. Scannell、Bruce F. Wels、Karen Wenberg、Donna M. Wypij

  DOI：10.1016/j.bmcl.2004.08.060

  日期：2004.11

  A series of compounds possessing both H, histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H-1-binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observed in vivo, as was increased CYP3A4 inhibition compared to their respective single-function drugs. Selected analogs in the series were shown to be orally active in guinea pig models. (C) 2004 Elsevier Ltd. All rights reserved.