β-<3-Acetylamino-benzoyl>-propionsaeure | 14714-31-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: β-<3-Acetylamino-benzoyl>-propionsaeure
• 英文别名: 3-<3-Acetamino-benzoyl>-propionsaeure；3-(3-Acetamino-benzoyl)-propionsaeure；4-(3-Acetamidophenyl)-4-oxobutanoic acid
• CAS: 14714-31-9
• 化学式: C₁₂H₁₃NO₄
• 分子量: 235.24
• InChiKey: CNGYZSNFNVKILU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  83.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  β-<3-Acetylamino-benzoyl>-propionsaeure 在 aluminum (III) chloride 、 氯化亚砜 作用下， 以 硝基甲烷 为溶剂， 反应 1.5h， 生成 N-(5-氧代-5,6,7,8-四氢萘酚-2-基)乙酰胺
  参考文献：
  名称：

  Discovery, synthesis, and structure–activity relationship of 6-aminomethyl-7,8-dihydronaphthalenes as human melanin-concentrating hormone receptor 1 antagonists

  摘要：

  Human melanin-concentrating hormone receptor 1 (hMCHR1) antagonists are promising targets for obesity treatment. We identified the tetrahydronaphthalene derivative 1a with modest binding affinity for hMCHR1 by screening an in-house G protein-coupled receptor (GPCR) ligand library. We synthesized a series of 6-aminomethyl-5,6,7,8-tetrahydronaphthalenes and evaluated their activity as hMCHR1 antagonists. Modification of the biphenylcarbonylamino group revealed that the biphenyl moiety played a crucial role in the interaction of the antagonist with the receptor. The stereoselective effect of the chiral center on binding affinity generated the novel 6-aminomethyl-7,8-dihydronaphthalene scaffold without a chiral center. Optimization of the amino group led to the identification of a potent antagonist 2s (4'-fluoro-N[6-(1-pyrrolidinylmethyl)-7,8-dihydro-2-naphthalenyl][1,1'-biphenyl]-4-carboxamide), which significantly inhibited the nocturnal food intake in rats after oral administration. Pharmacokinetic analysis confirmed that 2s had good oral bioavailability and brain penetrance. This antagonist appears to be a viable lead compound that can be used to develop a promising therapy for obesity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.038
• 作为产物：
  描述：

  3-(3-硝基苯甲酰基)丙酸 在 吡啶 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 20.0 ℃ 、400.01 kPa 条件下， 反应 8.0h， 生成 β-<3-Acetylamino-benzoyl>-propionsaeure
  参考文献：
  名称：

  Discovery, synthesis, and structure–activity relationship of 6-aminomethyl-7,8-dihydronaphthalenes as human melanin-concentrating hormone receptor 1 antagonists

  摘要：

  Human melanin-concentrating hormone receptor 1 (hMCHR1) antagonists are promising targets for obesity treatment. We identified the tetrahydronaphthalene derivative 1a with modest binding affinity for hMCHR1 by screening an in-house G protein-coupled receptor (GPCR) ligand library. We synthesized a series of 6-aminomethyl-5,6,7,8-tetrahydronaphthalenes and evaluated their activity as hMCHR1 antagonists. Modification of the biphenylcarbonylamino group revealed that the biphenyl moiety played a crucial role in the interaction of the antagonist with the receptor. The stereoselective effect of the chiral center on binding affinity generated the novel 6-aminomethyl-7,8-dihydronaphthalene scaffold without a chiral center. Optimization of the amino group led to the identification of a potent antagonist 2s (4'-fluoro-N[6-(1-pyrrolidinylmethyl)-7,8-dihydro-2-naphthalenyl][1,1'-biphenyl]-4-carboxamide), which significantly inhibited the nocturnal food intake in rats after oral administration. Pharmacokinetic analysis confirmed that 2s had good oral bioavailability and brain penetrance. This antagonist appears to be a viable lead compound that can be used to develop a promising therapy for obesity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.038

文献信息

• Synthesis of Some Functionally Substituted Benzocyclanones¹
  作者：NORMAN L. ALLINGER、EDWARD S. JONES

  DOI：10.1021/jo01048a018

  日期：1962.1
• Discovery, synthesis, and structure–activity relationship of 6-aminomethyl-7,8-dihydronaphthalenes as human melanin-concentrating hormone receptor 1 antagonists
  作者：Makoto Kamata、Toshiro Yamashita、Toshihiro Imaeda、Toshio Tanaka、Jun Terauchi、Maki Miyamoto、Taiichi Ora、Michiko Tawada、Satoshi Endo、Shiro Takekawa、Asano Asami、Nobuhiro Suzuki、Yasutaka Nagisa、Yoshihide Nakano、Kaoru Watanabe、Hitomi Ogino、Koki Kato、Kaneyoshi Kato、Yuji Ishihara

  DOI：10.1016/j.bmc.2011.07.038

  日期：2011.9

  Human melanin-concentrating hormone receptor 1 (hMCHR1) antagonists are promising targets for obesity treatment. We identified the tetrahydronaphthalene derivative 1a with modest binding affinity for hMCHR1 by screening an in-house G protein-coupled receptor (GPCR) ligand library. We synthesized a series of 6-aminomethyl-5,6,7,8-tetrahydronaphthalenes and evaluated their activity as hMCHR1 antagonists. Modification of the biphenylcarbonylamino group revealed that the biphenyl moiety played a crucial role in the interaction of the antagonist with the receptor. The stereoselective effect of the chiral center on binding affinity generated the novel 6-aminomethyl-7,8-dihydronaphthalene scaffold without a chiral center. Optimization of the amino group led to the identification of a potent antagonist 2s (4'-fluoro-N[6-(1-pyrrolidinylmethyl)-7,8-dihydro-2-naphthalenyl][1,1'-biphenyl]-4-carboxamide), which significantly inhibited the nocturnal food intake in rats after oral administration. Pharmacokinetic analysis confirmed that 2s had good oral bioavailability and brain penetrance. This antagonist appears to be a viable lead compound that can be used to develop a promising therapy for obesity. (C) 2011 Elsevier Ltd. All rights reserved.