4-(1-benzo[1,3]dioxol-5-ylmethyl-piperidin-4-ylamino)-6-methoxy-chromen-2-one | 638191-48-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 4-(1-benzo[1,3]dioxol-5-ylmethyl-piperidin-4-ylamino)-6-methoxy-chromen-2-one
• 英文别名: 4-[[1-(1,3-benzodioxol-5-ylmethyl)piperidin-4-yl]amino]-6-methoxychromen-2-one
• CAS: 638191-48-7
• 化学式: C₂₃H₂₄N₂O₅
• 分子量: 408.454
• InChiKey: IQNDRUCHCWJNAN-UHFFFAOYSA-N

物化性质

• 沸点：
  601.9±55.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(1-benzo[1,3]dioxol-5-ylmethyl-piperidin-4-ylamino)-6-methoxy-chromen-2-one 在 Selectfluor 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 4-(1-benzo{1,3}dioxol-5-ylmethyl-piperidin-4-ylamino)-3-fluoro-6-methoxychromene-2-one
  参考文献：
  名称：

  [EN] ANTAGONISTS OF MELANIN CONCENTRATING HORMONE RECEPTOR
  [FR] ANTAGONISTES DU RECEPTEUR DE L'HORMONE DE MELANO-CONCENTRATION

  摘要：

  公开号：

  WO2003106452A3
• 作为产物：
  描述：

  4-羟基-6-甲氧基香豆素 在 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 4-(1-benzo[1,3]dioxol-5-ylmethyl-piperidin-4-ylamino)-6-methoxy-chromen-2-one
  参考文献：
  名称：

  Discovery and Characterization of Aminopiperidinecoumarin Melanin Concentrating Hormone Receptor 1 Antagonists

  摘要：

  4-(1-Benzo[1,3]dioxol-5-ylmethylpiperidine-4-ylmethyl)-6-chlorochromen-2-one (7) is a potent, orally bioavailable melanin concentrating hormone receptor 1 (MCHr1) antagonist that causes dose-dependent weight loss in diet-induced obese mice. Further evaluation of 7 in an anesthetized dog model of cardiovascular safety revealed adverse hemodynamic effects at a plasma concentration comparable to the minimally effective therapeutic concentration. These results highlight the need for scrutiny of the cardiovascular safety profile of MCHr1 antagonists.

  DOI：

  10.1021/jm050598r

文献信息

• Antagonists of melanin concentrating hormone receptor
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20040106645A1

  公开（公告）日：2004-06-03

  This invention provides compounds that are antagonists of melanin concentrating hormone receptor-1 (MCH-R1). The compounds are represented by formula I: 1 where m is zero or one, n is zero to two, Y is oxygen or —N(R 9 )—, R 1 , R 2 , R 3 , R 4 , R 5 , R 9 and Ring A are defined in the specification. Coumarin and quinolone compounds where R 1 and R 2 together form a fused benzo ring are preferred. The invention also provides compounds of formula VI where the coumarin moiety is replaced by a quinazolinone ring. The compounds are useful for treating MCH-R1-related disorders, particularly overweight conditions including obesity.

  这项发明提供了一些与黑色素浓集激素受体-1 (MCH-R1) 相对抗的化合物。这些化合物由公式 I 表示：其中 m 为零或一，n 为零至二，Y 为氧或 —N(R9)—，R1、R2、R3、R4、R5、R9 和环 A 在说明书中有定义。偏好使用 R1 和 R2 结合形成融合苯环的香豆素和喹啉类化合物。该发明还提供了公式 VI 的化合物，其中香豆素基团被喹嗪酮环替换。这些化合物可用于治疗与 MCH-R1 相关的疾病，特别是超重症，包括肥胖症。
• ANTAGONISTS OF MELANIN CONCENTRATING HORMONE RECEPTOR
  申请人：ABBOTT LABORATORIES

  公开号：EP1534703A2

  公开（公告）日：2005-06-01
• US6921821B2
  申请人：——

  公开号：US6921821B2

  公开（公告）日：2005-07-26
• Discovery and Characterization of Aminopiperidinecoumarin Melanin Concentrating Hormone Receptor 1 Antagonists
  作者：Philip R. Kym、Rajesh Iyengar、Andrew J. Souers、John K. Lynch、Andrew S. Judd、Ju Gao、Jennifer Freeman、Mathew Mulhern、Gang Zhao、Anil Vasudevan、Dariusz Wodka、Christopher Blackburn、Jim Brown、Jennifer Lee Che、Courtney Cullis、Su Jen Lai、Matthew J. LaMarche、Tom Marsilje、Jon Roses、Todd Sells、Brad Geddes、Elizabeth Govek、Michael Patane、Dennis Fry、Brian D. Dayton、Sevan Brodjian、Doug Falls、Michael Brune、Eugene Bush、Robin Shapiro、Victoria Knourek-Segel、Thomas Fey、Cathleen McDowell、Glenn A. Reinhart、Lee C. Preusser、Kennan Marsh、Lisa Hernandez、Hing L. Sham、Christine A. Collins

  DOI：10.1021/jm050598r

  日期：2005.9.1

  4-(1-Benzo[1,3]dioxol-5-ylmethylpiperidine-4-ylmethyl)-6-chlorochromen-2-one (7) is a potent, orally bioavailable melanin concentrating hormone receptor 1 (MCHr1) antagonist that causes dose-dependent weight loss in diet-induced obese mice. Further evaluation of 7 in an anesthetized dog model of cardiovascular safety revealed adverse hemodynamic effects at a plasma concentration comparable to the minimally effective therapeutic concentration. These results highlight the need for scrutiny of the cardiovascular safety profile of MCHr1 antagonists.
• [EN] ANTAGONISTS OF MELANIN CONCENTRATING HORMONE RECEPTOR<br/>[FR] ANTAGONISTES DU RECEPTEUR DE L'HORMONE DE MELANO-CONCENTRATION
  申请人：——

  公开号：WO2003106452A3

  公开（公告）日：2004-04-08