5-p-hydroxyphenyl-4-methyl-valeronitrile | 114497-62-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-p-hydroxyphenyl-4-methyl-valeronitrile
• 英文别名: 5-(4-Hydroxyphenyl)-4-methylpentanenitrile
• CAS: 114497-62-0
• 化学式: C₁₂H₁₅NO
• 分子量: 189.257
• InChiKey: UPESTUHLQFABGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-p-hydroxyphenyl-4-methyl-valeronitrile 在 sodium hydroxide 、 sodium azide 、 氯化铵 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 RG 12175
  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：

  5-(p-benzyloxyphenyl)-4-methyl-2,4-pentadienenitrile 生成 5-p-hydroxyphenyl-4-methyl-valeronitrile
  参考文献：
  名称：

  YOUSSEFYEH, RAYMOND;CNAKRABORTY, UTPAL;MAGNIEN, ERNEST;DESAI, ROHIT;LEE, +

  摘要：

  DOI：

文献信息

• Quinolinyl ether or thioether tetrazoles as agents for the treatment of
  申请人：Rorer Pharmaceutical Corporation

  公开号：US04874769A1

  公开（公告）日：1989-10-17

  This invention relates to certain quinolyl ether and thioether tetrazoles and their use as valuable pharmaceutical agents for the treatment of hypersensitive ailments, particularly as lipoxygenase inhibitors and/or leukotriene antagonists possessing anti-inflammatory and antiallergic properties.

  这项发明涉及某些喹诺醚和硫醚四唑，以及它们作为有价值的药用剂治疗过敏病症的用途，特别是作为脂氧合酶抑制剂和/或白三烯拮抗剂，具有抗炎和抗过敏特性。
• Quinoline derivatives, their use in the treatment of hypersensitive ailments and a pharmaceutical composition containing the same
  申请人：RHONE-POULENC RORER INTERNATIONAL (HOLDINGS) INC.

  公开号：EP0315399A2

  公开（公告）日：1989-05-10

  This invention relates to quinoline derivatives, their use in the treatment of hypersensitive ailments and a pharmaceutical composition containing the same. The quinoline derivatives of the invention are a particular class of quinolinyl-diaryl compounds and they are especially valuable as lipoxygenase inhibitors and/or leukotriene antagonists, typically antagonists of leukotriene D4, possessing anti-inflammatory and anti-allergic properties.

  本发明涉及喹啉衍生物、它们在治疗过敏性疾病中的用途以及含有喹啉衍生物的药物组合物。 本发明的喹啉衍生物是一类特殊的喹啉基二元化合物，它们作为脂氧合酶抑制剂和/或白三烯拮抗剂（通常是白三烯 D4 拮抗剂）特别有价值，具有抗炎和抗过敏特性。
• 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：——
• YOUSSEFYEH, RAYMOND;CNAKRABORTY, UTPAL;MAGNIEN, ERNEST;DESAI, ROHIT;LEE, +
  作者：YOUSSEFYEH, RAYMOND、CNAKRABORTY, UTPAL、MAGNIEN, ERNEST、DESAI, ROHIT、LEE, +

  DOI：——

  日期：——
• HUANG, FU-CHI;GALEMMO, ROBERT A. (JR);CAMPBELL, HENRY F.
  作者：HUANG, FU-CHI、GALEMMO, ROBERT A. (JR)、CAMPBELL, HENRY F.

  DOI：——

  日期：——