4-(4-methoxy-2-(S)-methylsulfinylphenyl)-N-Cbz-piperidine | 255050-46-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(4-methoxy-2-(S)-methylsulfinylphenyl)-N-Cbz-piperidine
• 英文别名: benzyl 4-[4-methoxy-2-[(S)-methylsulfinyl]phenyl]piperidine-1-carboxylate
• CAS: 255050-46-5
• 化学式: C₂₁H₂₅NO₄S
• 分子量: 387.5
• InChiKey: URUMSDSLSUEBFK-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  75
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-methoxy-2-(S)-methylsulfinylphenyl)-N-Cbz-piperidine 在 氢氧化钾 作用下， 以 乙醇 、 水 为溶剂， 反应 18.0h， 以47%的产率得到4-(4-methoxy-2-(S)-methylsulfinylphenyl)piperidine
  参考文献：
  名称：

  Design, Synthesis, and SAR of Tachykinin Antagonists:  Modulation of Balance in NK₁/NK₂ Receptor Antagonist Activity

  摘要：

  Through optimization of compounds based on the dual NK1/NK2 antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK1 and NK2 potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK1 potency and thus afforded NK1 preferential antagonists. Alterations of the piperidine region could then increase NK2 potency to restore dual NK1/NK2 selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK1/NK2 antagonists, and the third is an NK1 preferential antagonist. In this paper, the factors affecting the balance of NK1 and NK2 selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.

  DOI：

  10.1021/jm020094i
• 作为产物：
  描述：

  2-溴-5-甲氧基苯酚 在 三乙烯二胺 、 titanium(IV) isopropylate 、 三乙基硅烷 、 叔丁基过氧化氢 、 氢氧化钾 、 正丁基锂 、 D-(-)-酒石酸二乙酯 、 potassium carbonate 、 三氟乙酸 、 N,N-二乙基苯胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 224.5h， 生成 4-(4-methoxy-2-(S)-methylsulfinylphenyl)-N-Cbz-piperidine
  参考文献：
  名称：

  Design, Synthesis, and SAR of Tachykinin Antagonists:  Modulation of Balance in NK₁/NK₂ Receptor Antagonist Activity

  摘要：

  Through optimization of compounds based on the dual NK1/NK2 antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK1 and NK2 potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK1 potency and thus afforded NK1 preferential antagonists. Alterations of the piperidine region could then increase NK2 potency to restore dual NK1/NK2 selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK1/NK2 antagonists, and the third is an NK1 preferential antagonist. In this paper, the factors affecting the balance of NK1 and NK2 selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.

  DOI：

  10.1021/jm020094i

文献信息

• A New Approach to Rapid Parallel Development of Four Neurokinin Antagonists. Part 4. Synthesis of ZD2249 Methoxy Sulfoxide
  作者：Sharon A. Bowden、J. Nigel Burke、Fiona Gray、Steven McKown、Jonathan D. Moseley、William O. Moss、Paul M. Murray、Matthew J. Welham、Maureen J. Young

  DOI：10.1021/op030039z

  日期：2004.1.1

  The manufacture of ZD2249 methoxy sulfoxide (1) using a new project approach is described. Research department processes were scaled up to 100 L if process safety and robustness were not compromised; other factors were treated according to the new approach. Using this strategy, we were able to manufacture a key intermediate on sufficient scale to support delivery of 1 kg quantities of bulk drug within

  描述了使用新的项目方法制造 ZD2249 甲氧基亚砜 (1)。如果过程安全性和稳健性不受影响，研究部门的过程可扩大到 100 L；其他因素按照新方法处理。使用这种策略，我们能够在实验室工作开始后的 6 个月内制造出足够规模的关键中间体，以支持交付 1 公斤的原料药。
• Design, Synthesis, and SAR of Tachykinin Antagonists:  Modulation of Balance in NK₁/NK₂ Receptor Antagonist Activity
  作者：Jeffrey S. Albert、David Aharony、Donald Andisik、Herbert Barthlow、Peter R. Bernstein、Russell A. Bialecki、Robert Dedinas、Bruce T. Dembofsky、Daniel Hill、Karin Kirkland、Gerard M. Koether、Benedict J. Kosmider、Cyrus Ohnmacht、William Palmer、William Potts、William Rumsey、Lihong Shen、Ashok Shenvi、Scott Sherwood、Paul J. Warwick、Keith Russell

  DOI：10.1021/jm020094i

  日期：2002.8.1

  Through optimization of compounds based on the dual NK1/NK2 antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK1 and NK2 potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK1 potency and thus afforded NK1 preferential antagonists. Alterations of the piperidine region could then increase NK2 potency to restore dual NK1/NK2 selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK1/NK2 antagonists, and the third is an NK1 preferential antagonist. In this paper, the factors affecting the balance of NK1 and NK2 selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.