methyl 2,4-dichloro-5-(1H-pyrazol-1-yl)benzoate | 1143025-64-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 2,4-dichloro-5-(1H-pyrazol-1-yl)benzoate
• 英文别名: methyl 2,4-dichloro-5-pyrazol-1-ylbenzoate
• CAS: 1143025-64-2
• 化学式: C₁₁H₈Cl₂N₂O₂
• 分子量: 271.103
• InChiKey: PZUNAMGIINAUGV-UHFFFAOYSA-N

物化性质

• 沸点：
  382.1±42.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2,4-dichloro-5-(1H-pyrazol-1-yl)benzoate 在 ammonium hydroxide 、 氨 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 18.16h， 生成
  参考文献：
  名称：

  Identification, Optimization, and Pharmacology of Acylurea GHS-R1a Inverse Agonists

  摘要：

  Ghrelin plays a major physiological role in the control of food intake, and inverse agonists of the ghrelin receptor (GHS-R1a) are widely considered to offer utility as antiobesity agents by lowering the set-point for hunger between meals. We identified an acylurea series of ghrelin modulators from high throughput screening and optimized binding affinity through structure activity relationship studies. Furthermore, we identified specific substructural changes, which switched partial agonist activity to inverse agonist activity, and optimized physicochemical and DMPK properties to afford the non-CNS penetrant inverse agonist 22 (AZ-GHS-22) and the CNS penetrant inverse agonist 38 (AZ-GHS-38). Free feeding efficacy experiments showed that CNS exposure was necessary to obtain reduced food intake in mice, and it was demonstrated using GHS-R1a null and wild-type mice that this effect operates through a mechanism involving GHS-R1a.

  DOI：

  10.1021/jm500610n
• 作为产物：
  描述：

  2,4-二氯-5-肼基苯甲酸 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 74.0h， 生成 methyl 2,4-dichloro-5-(1H-pyrazol-1-yl)benzoate
  参考文献：
  名称：

  Identification, Optimization, and Pharmacology of Acylurea GHS-R1a Inverse Agonists

  摘要：

  Ghrelin plays a major physiological role in the control of food intake, and inverse agonists of the ghrelin receptor (GHS-R1a) are widely considered to offer utility as antiobesity agents by lowering the set-point for hunger between meals. We identified an acylurea series of ghrelin modulators from high throughput screening and optimized binding affinity through structure activity relationship studies. Furthermore, we identified specific substructural changes, which switched partial agonist activity to inverse agonist activity, and optimized physicochemical and DMPK properties to afford the non-CNS penetrant inverse agonist 22 (AZ-GHS-22) and the CNS penetrant inverse agonist 38 (AZ-GHS-38). Free feeding efficacy experiments showed that CNS exposure was necessary to obtain reduced food intake in mice, and it was demonstrated using GHS-R1a null and wild-type mice that this effect operates through a mechanism involving GHS-R1a.

  DOI：

  10.1021/jm500610n
• 作为试剂：
  描述：

  1,1,3,3-四甲氧基丙烷 、 methyl 2,4-dichloro-5-hydrazinylbenzoate 在 methyl 2,4-dichloro-5-(1H-pyrazol-1-yl)benzoate 、 crude product 、 silica 、 乙酸乙酯 、 2-甲基戊烷 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以to afford crude methyl 2,4-dichloro-5-(1H-pyrazol-1-yl)benzoate (3.84 g, 57%)的产率得到methyl 2,4-dichloro-5-(1H-pyrazol-1-yl)benzoate
  参考文献：
  名称：

  BENZOTHIAZOLES AS GHRELIN RECEPTOR MODULATORS

  摘要：

  化合物I的公式或其药用可接受盐，其中R1、R2、R3、R4和m的描述如规范所述，用于治疗肥胖和/或糖尿病。

  公开号：

  US20130203730A1

文献信息

• [EN] BENZOTHIAZOLES AS GHRELIN RECEPTOR MODULATORS<br/>[FR] AGENTS THÉRAPEUTIQUES - 802
  申请人：ASTRAZENECA AB

  公开号：WO2009047558A1

  公开（公告）日：2009-04-16

  A compound of formula (I) or a pharmaceutically acceptable salt thereof in which R1, R2 , R3, R4 and m are as described in the specification for use in the treatment of obesity and/or diabetes.

  化合物的分子式（I）或其药用盐，其中R1、R2、R3、R4和m如说明书中所述，用于治疗肥胖和/或糖尿病。
• THERAPEUTIC AGENTS
  申请人：ALLEN Jack McQueen

  公开号：US20120115845A1

  公开（公告）日：2012-05-10

  A compound of formula I or a pharmaceutically acceptable salt thereof in which R 1 , R 2 , R 3 , R 4 and m are as described in the specification for use in the treatment of obesity and/or diabetes.

  公式I的化合物或其药学上可接受的盐，其中R1、R2、R3、R4和m如说明书所述，用于治疗肥胖症和/或糖尿病。
• Therapeutic Agents - 802
  申请人：ALLEN Jack McQueen

  公开号：US20090186870A1

  公开（公告）日：2009-07-23

  A compound of formula I or a pharmaceutically acceptable salt thereof in which R 1 , R 2 , R 3 , R 4 and m are as described in the specification for use in the treatment of obesity and/or diabetes.

  化合物I的公式或其药学上可接受的盐，其中R1、R2、R3、R4和m如规范所述，用于治疗肥胖和/或糖尿病。
• BENZOTHIAZOLES AS GHRELIN RECEPTOR MODULATORS
  申请人：Astrazeneca AB

  公开号：EP2607357A1

  公开（公告）日：2013-06-26

  A compound of formula I or a pharmaceutically acceptable salt thereof in which R1, R2, R3, R4 and m are as described in the specification for use in the treatment of obesity and/or diabetes.

  式 I 的化合物 或其药学上可接受的盐，其中 R1、R2、R3、R4 和 m 如说明书所述，用于治疗肥胖症和/或糖尿病。
• Identification, Optimization, and Pharmacology of Acylurea GHS-R1a Inverse Agonists
  作者：William McCoull、Peter Barton、Alastair J. H. Brown、Suzanne S. Bowker、Jennifer Cameron、David S. Clarke、Robert D. M. Davies、Alexander G. Dossetter、Anne Ertan、Mark Fenwick、Clive Green、Jane L. Holmes、Nathaniel Martin、David Masters、Jane E. Moore、Nicholas J. Newcombe、Claire Newton、Helen Pointon、Graeme R. Robb、Christopher Sheldon、Stephen Stokes、David Morgan

  DOI：10.1021/jm500610n

  日期：2014.7.24

  Ghrelin plays a major physiological role in the control of food intake, and inverse agonists of the ghrelin receptor (GHS-R1a) are widely considered to offer utility as antiobesity agents by lowering the set-point for hunger between meals. We identified an acylurea series of ghrelin modulators from high throughput screening and optimized binding affinity through structure activity relationship studies. Furthermore, we identified specific substructural changes, which switched partial agonist activity to inverse agonist activity, and optimized physicochemical and DMPK properties to afford the non-CNS penetrant inverse agonist 22 (AZ-GHS-22) and the CNS penetrant inverse agonist 38 (AZ-GHS-38). Free feeding efficacy experiments showed that CNS exposure was necessary to obtain reduced food intake in mice, and it was demonstrated using GHS-R1a null and wild-type mice that this effect operates through a mechanism involving GHS-R1a.