1-(氯甲基)异喹啉盐酸盐 | 1263378-97-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 中文名称: 1-(氯甲基)异喹啉盐酸盐
• 英文名称: 1-(Chloromethyl)isoquinoline hydrochloride
• 英文别名: 1-(chloromethyl)isoquinoline;hydrochloride
• CAS: 1263378-97-7
• 化学式: C₁₀H₈ClN*ClH
• 分子量: 214.094
• InChiKey: HPJLBPAUOODQNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  12.9
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(氯甲基)异喹啉盐酸盐 在 sodium hydroxide 、 sodium azide 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 1-[[4-[3-(2H-tetrazol-5-yl)propoxy]phenoxy]methyl]isoquinoline
  参考文献：
  名称：

  Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 1. Initial structure-activity relationships

  摘要：

  This series of reports describes the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. Described in this first report are the structure-activity relationships that led to a more than a 20-fold improvement of the potency and selectivity of the initial chemical lead (RG 5901). From this series of compounds, RG 7152 (16) was identified and selected for further evaluation in the clinic as an antiasthmatic agent. Compound 16 competitively inhibits [3H]LTD4 binding to membranes from guinea pig lung (Ki = 38 +/- 6 nM) and the spasmogenic activity of LTC4, LTD4, and LTE4 in parenchymal lung strips from guinea pigs. Unlike the original lead (RG 5901), compound 16 does not inhibit 5-lipoxygenase from guinea pig PMNs. Following oral administration to guinea pigs, 16 blocks LTD4-induced dermal permeability (ED50 = 6.9 mg/kg), LTD4-induced bronchoconstriction (ED50 = 1.1 mg/kg), antigen-induced bronchoconstriction (ED50 = 2.5 mg/kg), and anaphylactic-induced mortality (ED50 = 16 mg/kg). These studies on structure-activity relationships indicate that there is a requirement for an acidic function and the presence of the (2-quinolinylmethoxy)phenyl moiety in a specific geometric arrangement.

  DOI：

  10.1021/jm00166a016

文献信息

• Heterocycles with inhibitory activity of 5-lipoxygenase
  申请人：ZENECA LIMITED

  公开号：EP0385662A2

  公开（公告）日：1990-09-05

  The invention concerns a heterocycle of the formula I wherein Q is an optionally substituted 6-membered monocyclic or 10-membered bicyclic heterocyclic moiety containing one or two nitrogen atoms; A is (1-6C)alkylene, (3-6C)alkenylene, (3-6C)alkynylene or cyclo(3-6C)alkylene; X is oxy, thio, sulphinyl, sulphonyl or imino; Ar is phenylene which may optionally bear one or two substituents or Ar is an optionally substituted 6-membered heterocyclene moiety containing up to three nitrogen atoms; R¹ is hydrogen, (1-6C)alkyl, (3-6C)alkenyl, (3-6C)alkynyl, cyano-(1-4C)alkyl or (2-4C)alkanoyl, or optionally substituted benzoyl; and R² and R³ together form a group of the formula -A²-X²-A³- which, together with the carbon atom to which A² and A³ are attached, defines a ring having 4 to 7 ring atoms, wherein A² and A³, which may be the same or different, each is (1-4C)alkylene and X² is oxy, thio, sulphinyl, sulphonyl or imino; or a pharmaceutically-acceptable salt thereof. The compounds of the invention are inhibitors of the enzyme 5-lipoxygenase.

  本发明涉及式 I 的杂环 其中 Q 是含有一个或两个氮原子的任选取代的 6 元单环或 10 元双环杂环分子； A是(1-6C)亚烷基、(3-6C)烯基、(3-6C)炔基或环(3-6C)亚烷基； X 是氧基、硫代、亚砜基、磺酰基或亚氨基； Ar 是亚苯基，可任选带有一个或两个取代基，或者 Ar 是任选被取代的含有最多三个氮原子的 6 元杂环分子； R¹是氢、(1-6C)烷基、(3-6C)烯基、(3-6C)炔基、氰基-(1-4C)烷基或(2-4C)烷酰基，或任选取代的苯甲酰基； 与 R² 和 R³ 一起形成式 -A²-X²-A³- 的基团，该基团与 A² 和 A³ 所连接的碳原子一起定义了一个具有 4 至 7 个环原子的环，其中 A² 和 A³ 可以相同或不同，各自为 (1-4C)烷基，X² 为氧基、硫基、亚砜基、磺酰基或亚氨基； 或其药学上可接受的盐。 本发明的化合物是 5-脂氧合酶的抑制剂。