4-(4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)-7-(4-(trifluoromethyl)phenyl)-2-naphthoic acid | 1160271-35-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 4-(4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)-7-(4-(trifluoromethyl)phenyl)-2-naphthoic acid
• 英文别名: 4-[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]phenyl]-7-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxylic acid
• CAS: 1160271-35-1
• 化学式: C₃₄H₃₂F₃NO₄
• 分子量: 575.628
• InChiKey: VEENHJHHQFFAMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.3
• 重原子数：
  42
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)-7-(4-(trifluoromethyl)phenyl)-2-naphthoic acid 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 PPTN
  参考文献：
  名称：

  A Selective High-Affinity Antagonist of the P2Y₁₄ Receptor Inhibits UDP-Glucose–Stimulated Chemotaxis of Human Neutrophils

  摘要：

  1

  DOI：

  10.1124/mol.113.085654
• 作为产物：
  描述：

  7-溴-4-羟基-2-萘羧酸乙酯 在 吡啶 、 甲醇 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 rhodium contaminated with carbon 、 氢气 、 potassium acetate 、 sodium carbonate 、 potassium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， -78.0~110.0 ℃ 、689.49 kPa 条件下， 反应 13.5h， 生成 4-(4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)-7-(4-(trifluoromethyl)phenyl)-2-naphthoic acid
  参考文献：
  名称：

  A Selective High-Affinity Antagonist of the P2Y₁₄ Receptor Inhibits UDP-Glucose–Stimulated Chemotaxis of Human Neutrophils

  摘要：

  1

  DOI：

  10.1124/mol.113.085654

文献信息

• [EN] SUBSTITUTED 2-NAPHTHOIC ACIDS AS ANTAGONISTS OF GPR105 ACTIVITY<br/>[FR] ACIDES 2-NAPHTOÏQUE SUBSTITUÉS EN TANT QU'ANTAGONISTES DE L'ACTIVITÉ DE GPR105
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2009070873A1

  公开（公告）日：2009-06-11

  Substituted 2-naphthoic acids of structural formula I are effective as antagonists of the biological activity of GPR105 protein. They are useful for the treatment, control or prevention of disorders responsive to antagonism of this receptor, such as diabetes, particularly, Type 2 diabetes, insulin resistance, hyperglycemia, lipid disorders, obesity, atherosclerosis, and conditions associated with the Metabolic Syndrome.

  结构式I中的2-萘甲酸替代物对GPR105蛋白的生物活性具有拮抗作用。它们可用于治疗、控制或预防对该受体拮抗有响应的疾病，如糖尿病，特别是2型糖尿病，胰岛素抵抗，高血糖，脂质紊乱，肥胖，动脉粥样硬化以及与代谢综合征相关的疾病。
• [EN] HETEROCYCLIC P2Y14 RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES HÉTÉROCYCLIQUES DU RÉCEPTEUR P2Y14
  申请人：US HEALTH

  公开号：WO2019157417A1

  公开（公告）日：2019-08-15

  Disclosed are compounds of formulas (I)-(IX) for treating or preventing a disease or disorder responsive to antagonism of a P2Y14R receptor agonist in a mammal in need thereof, wherein R1-R8, X, Y, Z, X', Y', Z', and A are as defined herein, that are useful in treating an inflammatory such as asthma, cystic fibrosis, and sterile inflammation of the kidney.

  揭示了以下化合物的结构式（I）-（IX），用于治疗或预防对P2Y14R受体激动剂拮抗敏感的哺乳动物患者的疾病或紊乱，其中R1-R8、X、Y、Z、X'、Y'、Z'和A的定义如下，这些化合物可用于治疗炎症性疾病，如哮喘、囊性纤维化和肾脏的无菌性炎症。
• SUBSTITUTED 2-NAPHTHOIC ACIDS AS ANTAGONISTS OF GPR105 ACTIVITY
  申请人：Belley Michel

  公开号：US20100298347A1

  公开（公告）日：2010-11-25

  Substituted 2-naphthoic acids of structural formula are effective as antagonists of the biological activity of GPR105 protein. They are useful for the treatment, control or prevention of disorders responsive to antagonism of this receptor, such as diabetes, particularly, Type 2 diabetes, insulin resistance, hyperglycemia, lipid disorders, obesity, atherosclerosis, and conditions associated with the Metabolic Syndrome.

  具有以下结构式的2-萘甲酸替代物是GPR105蛋白生物活性的拮抗剂，对于治疗、控制或预防对此受体的拮抗作用有响应的疾病非常有效，包括糖尿病，特别是2型糖尿病，胰岛素抵抗，高血糖，脂质异常，肥胖症，动脉粥样硬化以及与代谢综合征相关的疾病。
• Applying the pro-drug approach to afford highly bioavailable antagonists of P2Y14
  作者：Joël Robichaud、Jean-François Fournier、Sébastien Gagné、Jacques Yves Gauthier、Martine Hamel、Yongxin Han、Martin Hénault、Stacia Kargman、Jean-François Levesque、Yaël Mamane、Joseph Mancini、Nicolas Morin、Erin Mulrooney、Jin Wu、W. Cameron Black

  DOI：10.1016/j.bmcl.2010.12.113

  日期：2011.7

  Our series of competitive antagonists against the G-protein coupled receptor P2Y(14) were found to be highly shifted in the presence of serum (>99% protein bound). A binding assay using 2% human serum albumin (HSA) was developed to guide further SAR studies and led to the identification of the zwitterion 2, which is substantially less shifted (18-fold) than our previous lead compound 1 (323-fold). However, as the bioavailability of 2 was low, a library of ester pro-drugs was prepared (7a-7j) and assessed in vitro. The most interesting candidates were then profiled in vivo and led to the identification of the pro-drug 7j, which possesses a substantially improved pharmacokinetic profile. (C) 2011 Published by Elsevier Ltd.
• Exploration of Alternative Scaffolds for P2Y₁₄ Receptor Antagonists Containing a Biaryl Core
  作者：Young-Hwan Jung、Jinha Yu、Zhiwei Wen、Veronica Salmaso、Tadeusz P. Karcz、Ngan B. Phung、Zhoumou Chen、Sierra Duca、John M. Bennett、Steven Dudas、Daniela Salvemini、Zhan-Guo Gao、Donald N. Cook、Kenneth A. Jacobson

  DOI：10.1021/acs.jmedchem.0c00745

  日期：2020.9.10

  Various heteroaryl and bicyclo-aliphatic analogues of zwitterionic biaryl P2Y(14) receptor (P2Y(14)R) antagonists were synthesized, and affinity was measured in P2Y(14)R-expressing Chinese hamster ovary cells by flow cytometry. Given this series' low water solubility, various polyethylene glycol derivatives of the distally binding piperidin-4-yl moiety of moderate affinity were synthesized. Rotation of previously identified 1,2,3-triazole attached to the central m-benzoic acid core (25) provided moderate affinity but not indole and benzimidazole substitution of the aryl-triazole. The corresponding P2Y(14)R region is predicted by homology modeling as a deep, sterically limited hydrophobic pocket, with the outward pointing piperidine moiety being the most flexible. Bicyclic-substituted piperidine ring derivatives of naphthalene antagonist 1, e.g., quinuclidine 17 (MRS4608, IC50 approximate to 20 nM at hP2Y(14)R/mP2Y(14)R), or of triazole 2, preserved affinity. Potent antagonists 1, 7a, 17, and 23 (10 mg/kg) protected in an ovalbumin/Aspergillus mouse asthma model, and PEG conjugate 12 reduced chronic pain. Thus, we expanded P2Y(14)R antagonist structure-activity relationship, introducing diverse physical-chemical properties.