(R)-2-ethoxy-3-(3-(4,5-dihydro-5-(4-fluorophenyl)isooxazol-3-yl)phenyl)propionic acid | 1033781-59-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (R)-2-ethoxy-3-(3-(4,5-dihydro-5-(4-fluorophenyl)isooxazol-3-yl)phenyl)propionic acid
• 英文别名: (R)-2-ethoxy-3-(3-(5-(4-fluorophenyl)-4,5-dihydroisoxazole-3-yl)phenyl)propanoic acid；(2R)-2-ethoxy-3-[3-[5-(4-fluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]phenyl]propanoic acid
• CAS: 1033781-59-7
• 化学式: C₂₀H₂₀FNO₄
• 分子量: 357.382
• InChiKey: SHEXHMGVCDIUNB-MUMRKEEXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  68.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  甲醇 、 (R)-2-ethoxy-3-(3-(4,5-dihydro-5-(4-fluorophenyl)isooxazol-3-yl)phenyl)propionic acid 在 三甲基氯硅烷 作用下， 生成 (R)-methyl 2-ethoxy-3-(3-(4,5-dihydro-5-(4-fluorophenyl)isoxazol-3-yl)phenyl)propionate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Constrained meta-Substituted Phenyl Propanoic Acids as Peroxisome Proliferator-Activated Receptor α and γ Dual Agonists

  摘要：

  In an effort to develop dual PPAR alpha/gamma activators with improved therapeutic efficacy, a series of diaryl alpha-ethoxy propanoic acid compounds comprising two aryl groups linked by rigid oxime ether or isoxazoline ring were designed and synthesized and their biological activities were examined. Most of the compounds possessing an oxime ether linker were more potent PPAR gamma activators than the lead PPAR alpha/gamma dual agonist, tesaglitazar in vitro. Compound 18, one of the derivatives with an oxime ether linker, was found to selectively transactivate PPAR gamma (EC(50) = 0.028 mu M) over PPAR alpha (EC(50) = 7.22 mu M) in vitro and lower blood glucose in db/db mice more than muraglitazar after oral treatment for 11 days.

  DOI：

  10.1021/jm8003416
• 作为产物：
  描述：

  (2R)-2-ethoxy-3-[3-[5-(4-fluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]phenyl]-N-[(1R)-2-hydroxy-1-phenylethyl]propanamide 在 硫酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 生成 (R)-2-ethoxy-3-(3-(4,5-dihydro-5-(4-fluorophenyl)isooxazol-3-yl)phenyl)propionic acid
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Constrained meta-Substituted Phenyl Propanoic Acids as Peroxisome Proliferator-Activated Receptor α and γ Dual Agonists

  摘要：

  In an effort to develop dual PPAR alpha/gamma activators with improved therapeutic efficacy, a series of diaryl alpha-ethoxy propanoic acid compounds comprising two aryl groups linked by rigid oxime ether or isoxazoline ring were designed and synthesized and their biological activities were examined. Most of the compounds possessing an oxime ether linker were more potent PPAR gamma activators than the lead PPAR alpha/gamma dual agonist, tesaglitazar in vitro. Compound 18, one of the derivatives with an oxime ether linker, was found to selectively transactivate PPAR gamma (EC(50) = 0.028 mu M) over PPAR alpha (EC(50) = 7.22 mu M) in vitro and lower blood glucose in db/db mice more than muraglitazar after oral treatment for 11 days.

  DOI：

  10.1021/jm8003416

文献信息

• 2-에톡시프로피온산 유도체 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 일주기 연관성 질환의 예방 또는 치료용 약학적 조성물
  申请人：Seoul National University R&DB Foundation 서울대학교산학협력단(120070509242) Corp. No ▼ 114371-0009224BRN ▼119-82-03684

  公开号：KR101497577B1

  公开（公告）日：2015-03-02

  본 발명은 2-에톡시프로피온 산 유도체 또는 이의 약학적으로 허용가능한 염을 포함하는 일주기 연관성 질환의 예방 또는 치료용 약학적 조성물에 관한 것으로, 본 발명에 따른 2-에톡시프로피온산 유도체는 CRY1/2의 기능을 억제하여 CLOCK:BMAL1 이합체의 활성을 촉진함으로써, 유전적 혹은 환경적인 요인으로 깨진 생체시계 분자 네트워크를 효과적으로 조절할 수 있으므로 2-에톡시프로피온산 유도체 또는 이의 허용 가능한 염을 유효성분으로 포함하는 조성물은 일주기 연관성 질환인 수면장애, 대사장애, 기분장애, 암의 예방 또는 치료에 유용하게 사용할 수 있다.

  该专利涉及一种用于预防或治疗与日常节律相关性疾病的药学组合物，其中包括2-乙氧基丙酸衍生物或其药学上可接受的盐。根据该专利，2-乙氧基丙酸衍生物通过抑制CRY1/2的功能，从而促进CLOCK:BMAL1复合物的活性，可以有效调节由遗传或环境因素破坏的生物钟分子网络，因此包含2-乙氧基丙酸衍生物或其可接受的盐作为有效成分的组合物可用于有助于预防或治疗日常节律相关性疾病，如睡眠障碍、代谢紊乱、情绪障碍、癌症。
• Design, Synthesis, and Biological Evaluation of Novel Constrained <i>meta</i>-Substituted Phenyl Propanoic Acids as Peroxisome Proliferator-Activated Receptor α and γ Dual Agonists
  作者：Young-Ger Suh、Nam-Jung Kim、Bon-Woong Koo、Kwang-Ok Lee、Sung-Hyun Moon、Dong-Hyung Shin、Jong-Wha Jung、Seung-Mann Paek、Dong-Jo Chang、Funan Li、Hyun-Jin Kang、Tuong Vy Thi Le、Yu Na Chae、Chang Yell Shin、Mi-Kyung Kim、Joong In Lim、Jae-Sang Ryu、Hyun-Ju Park

  DOI：10.1021/jm8003416

  日期：2008.10.23

  In an effort to develop dual PPAR alpha/gamma activators with improved therapeutic efficacy, a series of diaryl alpha-ethoxy propanoic acid compounds comprising two aryl groups linked by rigid oxime ether or isoxazoline ring were designed and synthesized and their biological activities were examined. Most of the compounds possessing an oxime ether linker were more potent PPAR gamma activators than the lead PPAR alpha/gamma dual agonist, tesaglitazar in vitro. Compound 18, one of the derivatives with an oxime ether linker, was found to selectively transactivate PPAR gamma (EC(50) = 0.028 mu M) over PPAR alpha (EC(50) = 7.22 mu M) in vitro and lower blood glucose in db/db mice more than muraglitazar after oral treatment for 11 days.