4'-[(R)-3-[(E)-hydroxyimino]-3-(1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-1-o-tolyl-propyl]-biphenyl-4-carboxylic acid | 1354810-76-6

• 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: 4'-[(R)-3-[(E)-hydroxyimino]-3-(1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-1-o-tolyl-propyl]-biphenyl-4-carboxylic acid
• 英文别名: 4-[4-[(1R,3E)-3-hydroxyimino-3-(1-methyl-6-oxopyridin-3-yl)-1-(2-methylphenyl)propyl]phenyl]benzoic acid
• CAS: 1354810-76-6
• 化学式: C₂₉H₂₆N₂O₄
• 分子量: 466.536
• InChiKey: RSVRJXDRUUJGOO-XWGMSIGLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(4-溴-苯基)-2-氰基-丙烯酸乙酯 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 正丁基锂 、 硫酸 、 盐酸羟胺 、 水 、 sodium acetate 、 sodium carbonate 、 potassium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 1,4-二氧六环 、 乙醇 、 N,N-二甲基乙酰胺 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 4'-[(R)-3-[(E)-hydroxyimino]-3-(1-methyl-6-oxo-1,6-dihydro-pyridin-3-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

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-HYDROXYIMINO-3-PHENYL-PROPANES
  申请人：Bissantz Caterina

  公开号：US20120010190A1

  公开（公告）日：2012-01-12

  This invention relates to novel 1-hydroxyimino-3-phenyl-propanes of the formula wherein R 1 to R 10 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.

  本发明涉及一种新的1-羟基亚胺基-3-苯基-丙烷的化合物，其结构式如下： 其中R1至R10的定义见说明书和权利要求书，以及其制备的药学上可接受的盐。这些化合物是GPBAR1激动剂，可用作治疗2型糖尿病等疾病的药物。
• US8765730B2
  申请人：——

  公开号：US8765730B2

  公开（公告）日：2014-07-01
• Discovery and optimisation of 1-hydroxyimino-3,3-diphenylpropanes, a new class of orally active GPBAR1 (TGR5) agonists
  作者：Henrietta Dehmlow、Rubén Alvarez Sánchez、Stephan Bachmann、Caterina Bissantz、Fritz Bliss、Karin Conde-Knape、Martin Graf、Rainer E. Martin、Ulrike Obst Sander、Susanne Raab、Hans G.F. Richter、Sabine Sewing、Urs Sprecher、Christoph Ullmer、Patrizio Mattei

  DOI：10.1016/j.bmcl.2013.06.017

  日期：2013.8

  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.