5-[3-phenyl-4-(4-(2-quinolylmethyloxy)phenyl)butyl]tetrazole | 129649-43-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 5-[3-phenyl-4-(4-(2-quinolylmethyloxy)phenyl)butyl]tetrazole
• 英文别名: 2-[[4-[2-phenyl-4-(2H-tetrazol-5-yl)butyl]phenoxy]methyl]quinoline
• CAS: 129649-43-0
• 化学式: C₂₇H₂₅N₅O
• 分子量: 435.528
• InChiKey: IEISNEYLXZRMDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  76.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苯乙酸乙酯 在 palladium on activated charcoal sodium hydroxide 、 lithium aluminium tetrahydride 、 sodium azide 、 氨 、 氢气 、 sodium 、 sodium hydride 、 氯化铵 、 ferric nitrate 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 25.0~120.0 ℃ 、344.73 kPa 条件下， 反应 27.33h， 生成 5-[3-phenyl-4-(4-(2-quinolylmethyloxy)phenyl)butyl]tetrazole
  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

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：——
• YOUSSEFYEH, RAYMOND;CNAKRABORTY, UTPAL;MAGNIEN, ERNEST;DESAI, ROHIT;LEE, +
  作者：YOUSSEFYEH, RAYMOND、CNAKRABORTY, UTPAL、MAGNIEN, ERNEST、DESAI, ROHIT、LEE, +

  DOI：——

  日期：——
• QUINOLINYL ETHER OR THIOETHER TETRAZOLES AS AGENTS FOR THE TREATMENT OF HYPERSENSITIVE AILMENTS
  申请人：RORER INTERNATIONAL (OVERSEAS) INC. (a Delaware corporation)

  公开号：EP0260305A1

  公开（公告）日：1988-03-23
• EP0260305A4
  申请人：——

  公开号：EP0260305A4

  公开（公告）日：1988-07-04
• US4874769A
  申请人：——

  公开号：US4874769A

  公开（公告）日：1989-10-17