2-(methoxycarbonyl)-3-[4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphtoxy)ethoxy]phenyl]propionic acid | 701294-91-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-(methoxycarbonyl)-3-[4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphtoxy)ethoxy]phenyl]propionic acid
• 英文别名: 2-(Methoxycarbonyl)-3-[4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthoxy)ethoxy]phenyl]propionic acid；3-methoxy-3-oxo-2-[[4-[2-[(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)oxy]ethoxy]phenyl]methyl]propanoic acid
• CAS: 701294-91-9
• 化学式: C₂₇H₃₄O₆
• 分子量: 454.563
• InChiKey: VDQRCWMYDWTXDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(methoxycarbonyl)-3-[4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphtoxy)ethoxy]phenyl]propionic acid 在 氯化亚砜 、 氨 作用下， 以 苯 、 水 为溶剂， 反应 1.5h， 以56%的产率得到methyl 2-carbamoyl-3-[4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphtoxy)ethoxy]phenyl]propionate
  参考文献：
  名称：

  [EN] NONCYCLIC 1,3-DICARBONYL COMPOUNDS AS DUAL PPAR AGONISTS WITH POTENT ANTIHYPERGLYCEMIC AND ANTIHYPERLIPIDEMIC ACTIVITY
  [FR] COMPOSES 1,3-DICARBONYLE NON CYCLIQUES UTILISES COMME DOUBLES AGONISTES DE PPAR PRESENTANT UNE ACTIVITE ANTIHYPERGLYCEMIQUE ET ANTIHYPERLIPIDEMIQUE

  摘要：

  本文披露了新型非环1,3-二酮化合物的制备和药用，其化学式为I，其中环A、环B、R'、R2、R3、R4、R5、X、Y、Z、Q、Ar和n如规范中定义。这些化合物作为过氧化物酶体增殖物激活受体（PPAR）的双激动剂，可作为RXR/PPARγ和RXR/PPARα异源二聚体的治疗和/或预防工具，用于治疗和/或预防2型糖尿病及相关代谢综合征，如高血压、肥胖、胰岛素抵抗、高脂血症、高血糖、高胆固醇血症、动脉粥样硬化、冠状动脉疾病和其他心血管疾病。

  公开号：

  WO2004048338A1
• 作为产物：
  描述：

  5,5,8,8-四甲基-5,6,7,8-四氢萘-2-醇 在 palladium on activated charcoal 氢氧化钾 、 sodium hydroxide 、 氢气 、 哌啶乙酸盐 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 2-(methoxycarbonyl)-3-[4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphtoxy)ethoxy]phenyl]propionic acid
  参考文献：
  名称：

  Design, synthesis, and evaluation of a new class of noncyclic 1,3-dicarbonyl compounds as PPARα selective activators

  摘要：

  Lipid accumulation in nonadipose tissues is increasingly linked to the development of type 2 diabetes in obese individuals. We report here the design, synthesis, and evaluation of a series of novel PPARalpha selective activators containing 1,3-dicarbonyl moieties. Structure-activity relationship studies led to the identification of PPARalpha selective activators (compounds 10, 14, 17, 18, and 21) with stronger potency and efficacy to activate PPARalpha over PPARgamma and PPARdelta. Experiments in vivo showed that compounds 10, 14, and 17 had blood glucose lowering effect in diabetic db/db mouse model after two weeks oral dosing. The data strongly support further testing of these lead compounds in other relevant disease animal models to evaluate their potential therapeutic benefits. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.04.053

文献信息

• [EN] NONCYCLIC 1,3-DICARBONYL COMPOUNDS AS DUAL PPAR AGONISTS WITH POTENT ANTIHYPERGLYCEMIC AND ANTIHYPERLIPIDEMIC ACTIVITY<br/>[FR] COMPOSES 1,3-DICARBONYLE NON CYCLIQUES UTILISES COMME DOUBLES AGONISTES DE PPAR PRESENTANT UNE ACTIVITE ANTIHYPERGLYCEMIQUE ET ANTIHYPERLIPIDEMIQUE
  申请人：SHENZHEN CHIPSCREEN BIOSCIENCE

  公开号：WO2004048338A1

  公开（公告）日：2004-06-10

  Disclosed are the preparation and pharmaceutical use of novel noncyclic 1,3-dicarbonyl compounds of formula I, wherein ring A, ring B, R', R2, R3, R4, R5, X, Y, Z, Q, Ar and n are as defined in the specification. These compounds, as peroxisome proliferator-activated receptor (PPAR) dual agonists for both RXR/PPARgamma and RXRIPPARalpha heterodimers, are useful in the treatment and/or prevention of type 2 diabetes and associated metabolic syndrome such as hypertension, obesity, insulin resistance, hyperlipidemia, hyperglycemia, hypercholesterolemia, atherosclerosis, coronary artery disease, and other cardiovascular disorders.

  本文披露了新型非环1,3-二酮化合物的制备和药用，其化学式为I，其中环A、环B、R'、R2、R3、R4、R5、X、Y、Z、Q、Ar和n如规范中定义。这些化合物作为过氧化物酶体增殖物激活受体（PPAR）的双激动剂，可作为RXR/PPARγ和RXR/PPARα异源二聚体的治疗和/或预防工具，用于治疗和/或预防2型糖尿病及相关代谢综合征，如高血压、肥胖、胰岛素抵抗、高脂血症、高血糖、高胆固醇血症、动脉粥样硬化、冠状动脉疾病和其他心血管疾病。
• Noncyclic 1,3-dicarbonyl compounds as dual PPAR agonists with potent antihyperglycemic and antihyperlipidemic activity
  申请人：——

  公开号：US20040138211A1

  公开（公告）日：2004-07-15

  Disclosed are the preparation and pharmaceutical use of novel noncyclic 1,3-dicarbonyl compounds of formula I, wherein ring A, ring B, R 1 , R 2 , R 3 , R 4 , R 5 , X, Y, Z, Q, Ar and n are as defined in the specification. These compounds, as peroxisome proliferator-activated receptor (PPAR) dual agonists for both RXR/PPARgamma and RXR/PPARalpha heterodimers, are useful in the treatment and/or prevention of type 2 diabetes and associated metabolic syndrome such as hypertension, obesity, insulin resistance, hyperlipidemia, hyperglycemia, hypercholesterolemia, atherosclerosis, coronary artery disease, and other cardiovascular disorders. 1

  本发明涉及一种非环状1,3-二羰基化合物的制备和药用，其化学式为I，其中环A、环B、R1、R2、R3、R4、R5、X、Y、Z、Q、Ar和n如规范中定义。这些化合物作为过氧化物酶体增殖物激活受体（PPAR）双激动剂，对RXR/PPARgamma和RXR/PPARalpha异源二聚体都有作用，可用于治疗和/或预防2型糖尿病及相关代谢综合征，如高血压、肥胖症、胰岛素抵抗、高脂血症、高血糖、高胆固醇血症、动脉粥样硬化、冠状动脉疾病和其他心血管疾病。1
• Noncyclic 1,3-Dicarbonyl compounds as dual PPAR agonists with potent antihyperglycemic and antihyperlipidemic activity
  申请人：Lu Xian-Ping

  公开号：US20070142427A1

  公开（公告）日：2007-06-21

  Disclosed are the preparation and pharmaceutical use of novel noncyclic 1,3-dicarbonyl compounds of formula I, wherein ring A, ring B, R 1 , R 2 , R 3 , R 4 , R 5 , X, Y, Z, Q, Ar and n are as defined in the specification. These compounds, as peroxisome proliferator-activated receptor (PPAR) dual agonists for both RXR/PPARgamma and RXR/PPARalpha heterodimers, are useful in the treatment and/or prevention of type 2 diabetes and associated metabolic syndrome such as hypertension, obesity, insulin resistance, hyperlipidemia, hyperglycemia, hypercholesterolemia, atherosclerosis, coronary artery disease, and other cardiovascular disorders.

  本发明涉及一种新型非环状1,3-二羰基化合物的制备和药用，其化学式为I，其中环A、环B、R1、R2、R3、R4、R5、X、Y、Z、Q、Ar和n的定义如规范所述。这些化合物作为过氧化物酶体增殖物激活受体（PPAR）双重激动剂，可用于治疗和/或预防2型糖尿病和相关代谢综合症，如高血压、肥胖症、胰岛素抵抗、高脂血症、高血糖、高胆固醇血症、动脉粥样硬化、冠状动脉疾病和其他心血管疾病。
• US7192970B2
  申请人：——

  公开号：US7192970B2

  公开（公告）日：2007-03-20
• Design, synthesis, and evaluation of a new class of noncyclic 1,3-dicarbonyl compounds as PPARα selective activators
  作者：Zhibin Li、Chenzhong Liao、Ben C.B. Ko、Song Shan、Edith H.Y. Tong、Zihui Yin、Desi Pan、Vincent K.W. Wong、Leming Shi、Zhi-Qiang Ning、Weiming Hu、Jiaju Zhou、Stephen S.M. Chung、Xian-Ping Lu

  DOI：10.1016/j.bmcl.2004.04.053

  日期：2004.7

  Lipid accumulation in nonadipose tissues is increasingly linked to the development of type 2 diabetes in obese individuals. We report here the design, synthesis, and evaluation of a series of novel PPARalpha selective activators containing 1,3-dicarbonyl moieties. Structure-activity relationship studies led to the identification of PPARalpha selective activators (compounds 10, 14, 17, 18, and 21) with stronger potency and efficacy to activate PPARalpha over PPARgamma and PPARdelta. Experiments in vivo showed that compounds 10, 14, and 17 had blood glucose lowering effect in diabetic db/db mouse model after two weeks oral dosing. The data strongly support further testing of these lead compounds in other relevant disease animal models to evaluate their potential therapeutic benefits. (C) 2004 Elsevier Ltd. All rights reserved.