(S)-3-(4-bromo-phenyl)-N-methoxy-N-methyl-3-o-tolyl-propionamide | 1354810-20-0

• 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: (S)-3-(4-bromo-phenyl)-N-methoxy-N-methyl-3-o-tolyl-propionamide
• 英文别名: (S)-3-(4-bromophenyl)-N-methoxy-N-methyl-3-o-tolylpropanamide；(3S)-3-(4-bromophenyl)-N-methoxy-N-methyl-3-(2-methylphenyl)propanamide
• CAS: 1354810-20-0
• 化学式: C₁₈H₂₀BrNO₂
• 分子量: 362.266
• InChiKey: ZHCXHSYGCGRRIL-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-3-(4-bromo-phenyl)-N-methoxy-N-methyl-3-o-tolyl-propionamide 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 正丁基锂 、 盐酸羟胺 、 sodium acetate 、 sodium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 为溶剂， 生成 4'-[(S)-3-[(E)-hydroxyimino]-3-(2-methyl-pyridin-4-yl)-1-o-tolyl-propyl]-biphenyl-4-carboxylic acid
  参考文献：
  名称：

  Discovery and optimisation of 1-hydroxyimino-3,3-diphenylpropanes, a new class of orally active GPBAR1 (TGR5) agonists

  摘要：

  A series of non-steroidal GPBAR1 (TGR5) agonists was developed from a hit in a high-throughput screening campaign. Lead identification efforts produced biphenyl-4-carboxylic acid derivative (R)-22, which displayed a robust secretion of PYY after oral administration in a degree that can be correlated with the unbound plasma concentration. Further optimisation work focusing on reduction of the lipophilicity provided the 1-phenylpiperidine-4-carboxylic acid derivative (R)-29 (RO5527239), which showed an improved secretion of PYY and GLP-1, translating into a significant reduction of postprandial blood glucose excursion in an oral glucose tolerance test in DIO mice. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.017
• 作为产物：
  描述：

  3-(4-溴-苯基)-2-氰基-丙烯酸乙酯 在 硫酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 溶剂黄146 、 三乙胺 作用下， 以 2-甲基四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 (S)-3-(4-bromo-phenyl)-N-methoxy-N-methyl-3-o-tolyl-propionamide
  参考文献：
  名称：

  Discovery and optimisation of 1-hydroxyimino-3,3-diphenylpropanes, a new class of orally active GPBAR1 (TGR5) agonists

  摘要：

  A series of non-steroidal GPBAR1 (TGR5) agonists was developed from a hit in a high-throughput screening campaign. Lead identification efforts produced biphenyl-4-carboxylic acid derivative (R)-22, which displayed a robust secretion of PYY after oral administration in a degree that can be correlated with the unbound plasma concentration. Further optimisation work focusing on reduction of the lipophilicity provided the 1-phenylpiperidine-4-carboxylic acid derivative (R)-29 (RO5527239), which showed an improved secretion of PYY and GLP-1, translating into a significant reduction of postprandial blood glucose excursion in an oral glucose tolerance test in DIO mice. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.017

文献信息

• [EN] 1-HYDROXYIMINO-3-PHENYL-PROPANES<br/>[FR] 1-HYDROXYIMINO-3-PHÉNYL-PROPANES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012007365A1

  公开（公告）日：2012-01-19

  This invention relates to novel 1-hydroxyimino-3-phenyl-propanes of the formula (I) wherein R1 to R10 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may be used as medicaments for the treatment of diseases such as type II diabetes.

  这项发明涉及式(I)中的新型1-羟基亚胺基-3-苯基丙烷，其中R1至R10如描述和权利要求书中所定义，并且其药学上可接受的盐。这些化合物是GPBAR1激动剂，可用作治疗疾病如2型糖尿病的药物。
• 1-CYCLOALKYL- OR 1-HETEROCYCLYL-HYDROXYIMINO-3-PHENYL-PROPANES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20130109718A1

  公开（公告）日：2013-05-02

  This invention relates to novel 1-cycloalkyl- or 1-heterocyclyl-hydroxyimino-3-phenyl-propanes of the formula wherein R 1 to R 7 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may therefore be useful as medicaments for the treatment of diseases such as type II diabetes.

  这项发明涉及新颖的1-环烷基或1-杂环烷基-羟胺基-3-苯基丙烷的化合物，其结构如下式所示：其中R1至R7如描述和权利要求中所定义，并且其药学上可接受的盐。这些化合物是GPBAR1激动剂，因此可能用作治疗疾病如2型糖尿病的药物。
• [EN] 1-CYCLOALKYL- OR 1-HETEROCYCLYL-HYDROXYIMINO-3-PHENYL-PROPANES<br/>[FR] 1-CYCLOALKYL- OU 1-HÉTÉROCYCLYL-HYDROXYIMINO-3-PHÉNYL-PROPANES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013060653A1

  公开（公告）日：2013-05-02

  This invention relates to novel 1-cycloalkyl- or l-heterocyclyl-hydroxyimino-3-phen propanes of the formula wherein R1 to R7 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may therefore be useful as medicaments for the treatment of diseases such as type II diabetes.

  这项发明涉及新颖的1-环烷基或1-杂环烷基-羟胺基-3-苯基丙烷类化合物的公式，其中R1至R7如描述和索赔中定义，并且其药学上可接受的盐。这些化合物是GPBAR1激动剂，因此可能作为治疗疾病如2型糖尿病的药物而有用。
• [EN] 1-PYRIDAZINYL-HYDROXYIMINO- 3- PHENYL- PROPANES AS GPBAR1 AGONISTS<br/>[FR] 1-PYRIDAZINYLHYDROXYIMINO-3-PHÉNYLPROPANES UTILISÉS COMME AGONISTES DE GPBAR1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013072265A1

  公开（公告）日：2013-05-23

  This invention relates to 1-pyridazinyl-hydroxyimino-3-phenyl-propanes of the formula (I) wherein R1 to R7 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may therefore be useful as medicaments for the treatment of diseases such as type II diabetes.

  该发明涉及式(I)的1-吡啶嗪基-羟亚胺-3-苯基-丙烷，其中R1至R7如描述和权利要求中定义的，以及其药学上可接受的盐。这些化合物是GPBAR1激动剂，因此可能用作治疗疾病如2型糖尿病的药物。
• 1-PYRIDAZINYL-HYDROXYIMINO-3-PHENYL-PROPANES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20130123267A1

  公开（公告）日：2013-05-16

  This invention relates to 1-pyridazinyl-hydroxyimino-3-phenyl-propanes of the formula wherein R 1 to R 7 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may therefore be useful as medicaments for the treatment of diseases such as type II diabetes.

  该发明涉及一种1-吡啶嗪基-羟肟基-3-苯基-丙烷的化合物，其分子式如下，其中R1至R7如描述和权利要求中定义的那样，以及其药学上可接受的盐。这些化合物是GPBAR1激动剂，因此可能作为治疗疾病如2型糖尿病的药物而有用。