4-[(1E)-3-(7,8-dihydro-8,8-dimethyl-5-(2-phenylethynyl)-naphthalen-2-yl)-3-oxoprop-1-en-1-yl]-benzoic acid | 1178898-41-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 4-[(1E)-3-(7,8-dihydro-8,8-dimethyl-5-(2-phenylethynyl)-naphthalen-2-yl)-3-oxoprop-1-en-1-yl]-benzoic acid
• 英文别名: 4-[(E)-3-[8,8-dimethyl-5-(2-phenylethynyl)-7H-naphthalen-2-yl]-3-oxoprop-1-enyl]benzoic acid
• CAS: 1178898-41-3
• 化学式: C₃₀H₂₄O₃
• 分子量: 432.519
• InChiKey: PBDVJEQWCQCWTG-GZTJUZNOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[(1E)-3-(7,8-dihydro-8,8-dimethyl-5-(2-phenylethynyl)-naphthalen-2-yl)-3-oxoprop-1-en-1-yl]-benzoic acid 在 盐酸羟胺 、 sodium acetate 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以93%的产率得到4-[3-(8,8-dimethyl-5-(phenylethynyl)-7,8-dihydronaphthalen-2-yl)-4,5-dihydroisoxazol-5-yl]benzoic acid
  参考文献：
  名称：

  Retinoid receptor subtype-selective modulators through synthetic modifications of RARγ agonists

  摘要：

  A series of retinoids designed to interfere with the repositioning of H12 have been synthesized to identify novel RAR gamma antagonists based on the structure of known RAR gamma agonists. The transcriptional activities of the novel ligands were revealed by cell-based reporting assays, using engineered cells containg RAR subtype-selective fusions of the RAR ligand-binding domains with the yeast GAL4 activator DNA-binding domain and the cognate luciferase reporter gene. Whereas none of the ligands exhibited features of a selective RAR gamma antagonist, some of them are endowed with interesting activities. In particular 24a acts as a pan-RAR agonist that induces at high concentration a higher transactivation potential on RAR alpha than TTNPB and synergizes at low concentration with TTNPB-bound RAR alpha but not RAR beta or RAR gamma. Similarly, 24c synergizes with TTNPB-bound RAR gamma and exhibits RAR alpha,beta antagonist activity. Compounds 24b and 25b are strong RAR alpha,beta-selective antagonists without agonist or antagonist activities for RAR gamma. Compounds 24b and 24c display weak RXR antagonist activity. In addition several pan-antagonists and partial agonist/antagonists have been defined. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.05.035
• 作为产物：
  描述：

  1-[7,8-dihydro-8,8-dimethyl-5-(2-phenylethynyl)-naphthalen-2-yl]-ethan-1-one 、 4-甲酰基苯甲酸乙酯 在 sodium hydroxide 、 水 、 盐酸 作用下， 以 甲醇 为溶剂， 反应 15.0h， 以78%的产率得到4-[(1E)-3-(7,8-dihydro-8,8-dimethyl-5-(2-phenylethynyl)-naphthalen-2-yl)-3-oxoprop-1-en-1-yl]-benzoic acid
  参考文献：
  名称：

  Retinoid receptor subtype-selective modulators through synthetic modifications of RARγ agonists

  摘要：

  A series of retinoids designed to interfere with the repositioning of H12 have been synthesized to identify novel RAR gamma antagonists based on the structure of known RAR gamma agonists. The transcriptional activities of the novel ligands were revealed by cell-based reporting assays, using engineered cells containg RAR subtype-selective fusions of the RAR ligand-binding domains with the yeast GAL4 activator DNA-binding domain and the cognate luciferase reporter gene. Whereas none of the ligands exhibited features of a selective RAR gamma antagonist, some of them are endowed with interesting activities. In particular 24a acts as a pan-RAR agonist that induces at high concentration a higher transactivation potential on RAR alpha than TTNPB and synergizes at low concentration with TTNPB-bound RAR alpha but not RAR beta or RAR gamma. Similarly, 24c synergizes with TTNPB-bound RAR gamma and exhibits RAR alpha,beta antagonist activity. Compounds 24b and 25b are strong RAR alpha,beta-selective antagonists without agonist or antagonist activities for RAR gamma. Compounds 24b and 24c display weak RXR antagonist activity. In addition several pan-antagonists and partial agonist/antagonists have been defined. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.05.035

文献信息

• Methods of stratifying patients for treatment with retinoic acid receptor-alpha agonists
  申请人：Syros Pharmaceuticals, Inc.

  公开号：US10167518B2

  公开（公告）日：2019-01-01

  The invention provides methods that define cellular populations that are sensitive to RARA agonists and identify patient subgroups that will benefit from treatment with RARA agonists. The invention also provides packaged pharmaceutical compositions that comprise a RARA agonist and instructions for determining if such agonist is suitable for use in treatment.

  本发明提供的方法可确定对 RARA 激动剂敏感的细胞群，并识别将从 RARA 激动剂治疗中获益的患者亚群。本发明还提供了包含 RARA 激动剂的包装药物组合物，以及确定这种激动剂是否适合用于治疗的说明。
• Methods of stratifying patients for treatment with retinoic acid receptor-α agonists
  申请人：Syros Pharmaceuticals, Inc.

  公开号：US11053552B2

  公开（公告）日：2021-07-06

  Described herein are methods that define cellular populations that are sensitive to RARA agonists and identify patient populations that will benefit from treatment with RARA agonists. The methods may comprise administering RARA agonists to patient populations.

  本文描述的方法可确定对 RARA 激动剂敏感的细胞群，并识别将从 RARA 激动剂治疗中获益的患者群。这些方法可包括向患者群施用 RARA 激动剂。
• METHODS OF STRATIFYING PATIENTS FOR TREATMENT WITH RETINOIC ACID RECEPTOR-AGONISTS
  申请人：Syros Pharmaceuticals, Inc.

  公开号：EP3277272B1

  公开（公告）日：2021-08-04
• METHODS OF STRATIFYING PATIENTS FOR TREATMENT WITH RETINOIC ACID RECEPTOR-ALPHA AGONISTS
  申请人：SYROS PHARMACEUTICALS, INC.

  公开号：US20160355888A1

  公开（公告）日：2016-12-08

  The invention provides methods that define cellular populations that are sensitive to RARA agonists and identify patient subgroups that will benefit from treatment with RARA agonists. The invention also provides packaged pharmaceutical compositions that comprise a RARA agonist and instructions for determining if such agonist is suitable for use in treatment.
• METHODS OF STRATIFYING PATIENTS FOR TREATMENT WITH RETINOIC ACID RECEPTOR-ALPHA AGONISTS
  申请人：Syros Pharmaceuticals, Inc.

  公开号：US20180087115A1

  公开（公告）日：2018-03-29

  The invention provides methods that define cellular populations that are sensitive to RARA agonists and identify patient subgroups that will benefit from treatment with RARA agonists. The invention also provides packaged pharmaceutical compositions that comprise a RARA agonist and instructions for determining if such agonist is suitable for use in treatment.