2,3-Dihydrobenzo[1,4]dioxine-5-carboxylic acid{1-[3-(piperazine-1-sulfonyl)-propyl]piperidin-4-ylmethyl}amide | 767274-66-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 2,3-Dihydrobenzo[1,4]dioxine-5-carboxylic acid{1-[3-(piperazine-1-sulfonyl)-propyl]piperidin-4-ylmethyl}amide
• 英文别名: N-[[1-(3-piperazin-1-ylsulfonylpropyl)piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide
• CAS: 767274-66-8
• 化学式: C₂₂H₃₄N₄O₅S
• 分子量: 466.602
• InChiKey: SOTGMDWAHFUQPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 2,3-Dihydrobenzo[1,4]dioxine-5-carboxylic acid{1-[3-(piperazine-1-sulfonyl)-propyl]piperidin-4-ylmethyl}amide 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 生成 2,3-dihydrobenzo[1,4]-dioxine-5-carboxylic acid {1-[3-(4-methylpiperazine-1-sulfonyl)propyl]piperidin-4-ylmethyl}amide
  参考文献：
  名称：

  Identification of a 5-HT4 receptor antagonist clinical candidate through side-chain modification

  摘要：

  Replacement of the N-butyl side-chain of lead 5-HT4 receptor antagonist 2 with propanesulfonylpiperidinyl, morpholinyl, and piperazinyl groups led to higher affinity analogs 4-6. In vitro drug metabolism screens and cassette pharmacokinetic studies in the dog led to identification of the N-methylpiperazinyl analog (6b), which displayed pharmacokinetic, selectivity, and safety parameters sufficient for advancement to the clinic for the treatment of urinary incontinence. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.039
• 作为产物：
  描述：

  4-[3-(4-{[(2,3-Dihydro-benzo[1,4]dioxine-5-carbonyl)-amino]-methyl}-piperidin-1-yl)-propane-1-sulfonyl]-piperazine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 2,3-Dihydrobenzo[1,4]dioxine-5-carboxylic acid{1-[3-(piperazine-1-sulfonyl)-propyl]piperidin-4-ylmethyl}amide
  参考文献：
  名称：

  Identification of a 5-HT4 receptor antagonist clinical candidate through side-chain modification

  摘要：

  Replacement of the N-butyl side-chain of lead 5-HT4 receptor antagonist 2 with propanesulfonylpiperidinyl, morpholinyl, and piperazinyl groups led to higher affinity analogs 4-6. In vitro drug metabolism screens and cassette pharmacokinetic studies in the dog led to identification of the N-methylpiperazinyl analog (6b), which displayed pharmacokinetic, selectivity, and safety parameters sufficient for advancement to the clinic for the treatment of urinary incontinence. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.039

文献信息

• US6172062B1
  申请人：——

  公开号：US6172062B1

  公开（公告）日：2001-01-09
• Identification of a 5-HT4 receptor antagonist clinical candidate through side-chain modification
  作者：Robin D. Clark、Alam Jahangir、Muzaffar Alam、Cynthia Rocha、Lin Lin、Bodil Bjorner、Khanh Nguyen、Carole Grady、Timothy J. Williams、George Stepan、Hai Ming Tang、Anthony P.D.W. Ford

  DOI：10.1016/j.bmcl.2005.01.039

  日期：2005.3

  Replacement of the N-butyl side-chain of lead 5-HT4 receptor antagonist 2 with propanesulfonylpiperidinyl, morpholinyl, and piperazinyl groups led to higher affinity analogs 4-6. In vitro drug metabolism screens and cassette pharmacokinetic studies in the dog led to identification of the N-methylpiperazinyl analog (6b), which displayed pharmacokinetic, selectivity, and safety parameters sufficient for advancement to the clinic for the treatment of urinary incontinence. (c) 2005 Elsevier Ltd. All rights reserved.