5-(4-methoxyphenyl)-5-oxo-3,3-tetramethylenepentanoic acid | 403481-48-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(4-methoxyphenyl)-5-oxo-3,3-tetramethylenepentanoic acid
• 英文别名: {1-[2-(4-Methoxy-phenyl)-2-oxo-ethyl]-cyclopentyl}-acetic acid；2-[1-[2-(4-methoxyphenyl)-2-oxoethyl]cyclopentyl]acetic acid
• CAS: 403481-48-1
• 化学式: C₁₆H₂₀O₄
• 分子量: 276.332
• InChiKey: NAKUOLIRKVYQOD-UHFFFAOYSA-N

物化性质

• 沸点：
  470.8±15.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(4-methoxyphenyl)-5-oxo-3,3-tetramethylenepentanoic acid 在 palladium on activated charcoal 氢溴酸 、 氢气 作用下， 以 溶剂黄146 为溶剂， 反应 4.0h， 生成 5-(4-hydroxyphenyl)-3,3-tetramethylenepentanoic acid
  参考文献：
  名称：

  The development of a novel series of (quinolin-2-ylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 3. Structural variation of the acidic side chain to give antagonists of enhanced potency

  摘要：

  This paper is the third in a series outlining the development of orally active sulfido peptide leukotriene antagonists containing a (quinolin-2-ylmethoxy)phenyl moiety. In this work the systematic variation of the acid side chain substituents led to dramatic and reproducible changes in the oral activity of these compounds, presumably due to alterations in their pharmacokinetic properties. The most potent compound identified, 5-[4-[4-(quinolin-2-yl-methoxy)phenyl]-3-methylbutyl]tetrazole (32), represents a convergence of good in vitro antagonist activity and a 3-10-fold improvement in oral potency over the current clinical candidate 2. The new findings from these optimization studies are as follows: oxygen substitution in the acid side chain was not necessary for antagonist activity, in vitro and in vivo activity was enhanced by alkyl or phenyl substitution on the gamma-carbon of the acid side chain of para-substituted (quinolin-2-ylmethoxy)phenyl derivatives, and free rotation about the side chain carbon atom adjacent to the (quinolin-2-ylmethoxy)phenyl ring was required for activity. The lead compound of this report (32) is a competitive inhibitor of [3H]LTD4 binding to receptor membrane purified from guinea pig lung (Ki = 12 +/- 3 nM) and of the spasmogenic activity of LTC4, LTD4, and LTE4 in guinea pig lung strip. Dosed orally in guinea pigs, this compound blocks LTD4-induced bronchoconstriction (ED50 0.8 mg/kg) and antigen-induced systemic anaphylaxis (ED50 = 1.2 mg/kg).

  DOI：

  10.1021/jm00172a024
• 作为产物：
  描述：

  3,3-四亚甲基戊二酸酐 、 苯甲醚 在 aluminum (III) chloride 作用下， 以 neat (no solvent) 为溶剂， 反应 2.0h， 以79%的产率得到5-(4-methoxyphenyl)-5-oxo-3,3-tetramethylenepentanoic acid
  参考文献：
  名称：

  失活的烯烃酸的对映选择性溴化

  摘要：

  已经开发出使用双官能氨基脲催化剂的α，β-不饱和酮的新型对映选择性溴化。该反应的范围由具有各种官能度的卤代内酯的23个实例证明，产率高达99％，er为99：1 er。与需要缺乏电子的取代基来增强氢键强度的典型尿素催化剂不同，有趣的是，在这种情况下，富含电子的脲对于高对映选择性是必不可少的。此外，实验数据表明，卤代内酯化合物对LPS诱导的RAW 264.7细胞具有相当大的抗炎作用。

  DOI：

  10.1021/acs.orglett.8b01125

文献信息

• GALEMMO, ROBERT A.;JOHNSON, WILLIAM H. (JR);LEARN, KEITH S.;LEE, THOMAS D+, J. MED. CHEM., 33,(1990) N0, C. 2828-2841
  作者：GALEMMO, ROBERT A.、JOHNSON, WILLIAM H. (JR)、LEARN, KEITH S.、LEE, THOMAS D+

  DOI：——

  日期：——
• Enantioselective Bromolactonization of Deactivated Olefinic Acids
  作者：Xiaojian Jiang、Shenghui Liu、Si Yang、Mei Jing、Lipeng Xu、Pei Yu、Yuqiang Wang、Ying-Yeung Yeung

  DOI：10.1021/acs.orglett.8b01125

  日期：2018.6.1

  A novel enantioselective bromolactonization of α,β-unsaturated ketones using bifunctional amino-urea catalysts has been developed. The scope of the reaction is evidenced by 23 examples of halolactones bearing various functionalities with up to 99% yield and 99:1 er. Unlike typical urea catalysts that require electron-deficient substituents to enhance the hydrogen bond strength, it is interesting to

  已经开发出使用双官能氨基脲催化剂的α，β-不饱和酮的新型对映选择性溴化。该反应的范围由具有各种官能度的卤代内酯的23个实例证明，产率高达99％，er为99：1 er。与需要缺乏电子的取代基来增强氢键强度的典型尿素催化剂不同，有趣的是，在这种情况下，富含电子的脲对于高对映选择性是必不可少的。此外，实验数据表明，卤代内酯化合物对LPS诱导的RAW 264.7细胞具有相当大的抗炎作用。
• The development of a novel series of (quinolin-2-ylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 3. Structural variation of the acidic side chain to give antagonists of enhanced potency
  作者：Robert A. Galemmo、William H. Johnson、Keith S. Learn、Thomas D. Y. Lee、Fu Chih Huang、Henry F. Campbell、Raymond Youssefyeh、Susan V. O'Rourke、Glenn Schuessler

  DOI：10.1021/jm00172a024

  日期：1990.10

  This paper is the third in a series outlining the development of orally active sulfido peptide leukotriene antagonists containing a (quinolin-2-ylmethoxy)phenyl moiety. In this work the systematic variation of the acid side chain substituents led to dramatic and reproducible changes in the oral activity of these compounds, presumably due to alterations in their pharmacokinetic properties. The most potent compound identified, 5-[4-[4-(quinolin-2-yl-methoxy)phenyl]-3-methylbutyl]tetrazole (32), represents a convergence of good in vitro antagonist activity and a 3-10-fold improvement in oral potency over the current clinical candidate 2. The new findings from these optimization studies are as follows: oxygen substitution in the acid side chain was not necessary for antagonist activity, in vitro and in vivo activity was enhanced by alkyl or phenyl substitution on the gamma-carbon of the acid side chain of para-substituted (quinolin-2-ylmethoxy)phenyl derivatives, and free rotation about the side chain carbon atom adjacent to the (quinolin-2-ylmethoxy)phenyl ring was required for activity. The lead compound of this report (32) is a competitive inhibitor of [3H]LTD4 binding to receptor membrane purified from guinea pig lung (Ki = 12 +/- 3 nM) and of the spasmogenic activity of LTC4, LTD4, and LTE4 in guinea pig lung strip. Dosed orally in guinea pigs, this compound blocks LTD4-induced bronchoconstriction (ED50 0.8 mg/kg) and antigen-induced systemic anaphylaxis (ED50 = 1.2 mg/kg).