4-{[(2,3-Dihydrobenzo[1,4]dioxin-5-carbonyl)amino]methyl}piperidine-1-carboxylic acid tert-butyl ester | 261767-14-0

• 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: 4-{[(2,3-Dihydrobenzo[1,4]dioxin-5-carbonyl)amino]methyl}piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-Butyl 4-((2,3-dihydrobenzo[b][1,4]dioxine-5-carboxamido)methyl)piperidine-1-carboxylate；tert-butyl 4-[(2,3-dihydro-1,4-benzodioxine-5-carbonylamino)methyl]piperidine-1-carboxylate
• CAS: 261767-14-0
• 化学式: C₂₀H₂₈N₂O₅
• 分子量: 376.453
• InChiKey: OHIDTOHABVCDBC-UHFFFAOYSA-N

物化性质

• 沸点：
  502.0±50.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-{[(2,3-Dihydrobenzo[1,4]dioxin-5-carbonyl)amino]methyl}piperidine-1-carboxylic acid tert-butyl ester 在 TEA 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 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
  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：

  2,3-二氢-1,4-苯并二恶烷-5-羰酰氯 、 1-叔丁氧羰基-4-氨甲基哌啶 在 TEA 作用下， 以 二氯甲烷 为溶剂， 生成 4-{[(2,3-Dihydrobenzo[1,4]dioxin-5-carbonyl)amino]methyl}piperidine-1-carboxylic acid tert-butyl ester
  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

• [EN] DIHYDROBENZODIOXINE CARBOXAMIDE AND KETONE DERIVATIVES AS 5-HT4 RECEPTOR ANTAGONISTS<br/>[FR] DIHYDROBENZODIOXINE CARBOXAMIDE ET DERIVES DE CETONE UTILISES COMME ANTAGONISTES DU RECEPTEUR 5-HT4
  申请人：HOFFMANN LA ROCHE

  公开号：WO2000015636A1

  公开（公告）日：2000-03-23

  This invention relates to certain 5-HT4 receptor antagonist compounds represented by Formula (I), wherein Z is represented by formula (A) or (B), wherein R?1, R2, R3, R4 and R5¿ and the other substituents are as defined in the specification; and the individual isomers, racemic or non-racemic mixtures of isomers, and pharmaceutically acceptable salts or hydrates thereof. The invention further relates to pharmaceutical compositions containing such compounds and for their use as therapeutic agents.

  本发明涉及由公式(I)所代表的某些5-HT4受体拮抗剂化合物，其中Z由公式(A)或(B)所代表，其中R?1，R2，R3，R4和R5¿和其他取代基在说明书中定义；以及其单个异构体，混合物（包括混合物的外消旋体或非外消旋体混合物）和其药学上可接受的盐或水合物。本发明还涉及含有这种化合物的药物组合物及其作为治疗剂的用途。
• US6172062
  申请人：——

  公开号：——

  公开（公告）日：——
• DIHYDROBENZODIOXINE CARBOXAMIDE AND KETONE DERIVATIVES AS 5-HT4 RECEPTOR ANTAGONISTS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1112270A1

  公开（公告）日：2001-07-04
• 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.