Biphenyl-4-carboxylic Acid [4-(2-diethylamino-ethoxy)-3-(1-hydroxy-ethyl)-phenyl]-amide | 394248-82-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Biphenyl-4-carboxylic Acid [4-(2-diethylamino-ethoxy)-3-(1-hydroxy-ethyl)-phenyl]-amide
• 英文别名: N-[4-[2-(diethylamino)ethoxy]-3-(1-hydroxyethyl)phenyl]-4-phenylbenzamide
• CAS: 394248-82-9
• 化学式: C₂₇H₃₂N₂O₃
• 分子量: 432.563
• InChiKey: OOYODHLEJJEKDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Biphenyl-4-carboxylic Acid [4-(2-diethylamino-ethoxy)-3-(1-hydroxy-ethyl)-phenyl]-amide 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 Biphenyl-4-carboxylic acid [4-(2-diethylamino-ethoxy)-3-ethyl-phenyl]-amide
  参考文献：
  名称：

  SAR of biphenyl carboxamide ligands of the human melanin-concentrating hormone receptor 1 (MCH R1): Discovery of antagonist SB-568849

  摘要：

  We report here the discovery of a class of MCH R1 ligands based on a biphenyl carboxamide template. A docked-in model is presented indicating key interactions in the putative binding site of the receptor. Parallel high throughput synthetic techniques were utilised to allow rapid exploration of the structure-activity relationship around this template, leading to compound SB-568849 which possessed good receptor affinity and selectivity. This compound proved to be an antagonist with stability in vivo, an acceptable brain-blood ratio and oral bioavailability. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.056
• 作为产物：
  描述：

  联苯-4-甲酰氯 在 sodium tetrahydroborate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 Biphenyl-4-carboxylic Acid [4-(2-diethylamino-ethoxy)-3-(1-hydroxy-ethyl)-phenyl]-amide
  参考文献：
  名称：

  SAR of biphenyl carboxamide ligands of the human melanin-concentrating hormone receptor 1 (MCH R1): Discovery of antagonist SB-568849

  摘要：

  We report here the discovery of a class of MCH R1 ligands based on a biphenyl carboxamide template. A docked-in model is presented indicating key interactions in the putative binding site of the receptor. Parallel high throughput synthetic techniques were utilised to allow rapid exploration of the structure-activity relationship around this template, leading to compound SB-568849 which possessed good receptor affinity and selectivity. This compound proved to be an antagonist with stability in vivo, an acceptable brain-blood ratio and oral bioavailability. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.056

文献信息

• Carboxamide compounds and their use as antagonists of a human 11cby receptor
  申请人：——

  公开号：US20040063686A1

  公开（公告）日：2004-04-01

  Compounds of formula (I) in which: each A is independently hydrogen, C1-6alkyl optionally substituted by hydroxyl, C1-6alkoxy, C1-6alkenyl or C1-6acyl group or a halogen atom or hydroxyl, CN or CF3 group; R3 is hydrogen, methyl or ethyl; R4 is an optionally substituted aromatic carbocyclic or heterocyclic ring; Z is an O or S atom, or an NH or CH2 group, or a single bond, at the 3 or 4 position of R4 relative to the carbonyl group; R5 is an optionally substituted aromatic carbocyclic or heterocyclic ring, or an optionally substituted, saturated or unsaturated, carbocyclic or heterocyclic ring; and Q is (a) Where X, Y, R1 and R2 are as defined in claim 1; are antagonists of a human 11CBy receptor. 1

  公式（I）的化合物，其中： 每个A独立地为氢、C1-6烷基，可选地被羟基、C1-6烷氧基、C1-6烯基或C1-6酰基或卤素原子或羟基、CN或CF3基取代； R3为氢、甲基或乙基； R4为可选地取代的芳香族碳环或杂环，Z为O或S原子，或NH或CH2基，或单键，在相对于羰基的R4的3或4位置； R5为可选地取代的芳香族碳环或杂环，或可选地取代的饱和或不饱和的碳环或杂环； Q为（a），其中X、Y、R1和R2如权利要求1所定义；是人类11CBy受体的拮抗剂。
• SAR of biphenyl carboxamide ligands of the human melanin-concentrating hormone receptor 1 (MCH R1): Discovery of antagonist SB-568849
  作者：David R. Witty、John H. Bateson、Guillaume J. Hervieu、Phillip Jeffrey、Christopher N. Johnson、Alison I. Muir、Peter J. O’Hanlon、Geoffrey Stemp、Alex J. Stevens、Kevin M. Thewlis、Shelagh Wilson、Kim Y. Winborn

  DOI：10.1016/j.bmcl.2006.06.056

  日期：2006.9

  We report here the discovery of a class of MCH R1 ligands based on a biphenyl carboxamide template. A docked-in model is presented indicating key interactions in the putative binding site of the receptor. Parallel high throughput synthetic techniques were utilised to allow rapid exploration of the structure-activity relationship around this template, leading to compound SB-568849 which possessed good receptor affinity and selectivity. This compound proved to be an antagonist with stability in vivo, an acceptable brain-blood ratio and oral bioavailability. (c) 2006 Elsevier Ltd. All rights reserved.