8-chloro-11-(1-(pyridin-2-ylmethyl)piperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并环庚烷吡啶
• 英文名称: 8-chloro-11-(1-(pyridin-2-ylmethyl)piperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
• 英文别名: VUF15714；13-Chloro-2-[1-(pyridin-2-ylmethyl)piperidin-4-ylidene]-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene；13-chloro-2-[1-(pyridin-2-ylmethyl)piperidin-4-ylidene]-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene
• 化学式: C₂₅H₂₄ClN₃
• 分子量: 401.939
• InChiKey: UOWDGRXBJGRHBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  29
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(溴甲基)吡啶氢溴酸盐 、 地氯雷他定 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以62%的产率得到8-chloro-11-(1-(pyridin-2-ylmethyl)piperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
  参考文献：
  名称：

  Route to Prolonged Residence Time at the Histamine H₁ Receptor: Growing from Desloratadine to Rupatadine

  摘要：

  Drug-target binding kinetics are an important predictor of in vivo drug efficacy, yet the relationship between ligand structures and their binding kinetics is often poorly understood. We show that both rupatadine (1) and desloratadine (2) have a long residence time at the histamine H-1 receptor (H1R). Through development of a [H-3]levocetirizine radiolabel, we find that the residence time of 1 exceeds that of 2 more than 10-fold. This was further explored with 22 synthesized rupatadine and desloratadine analogues. Methylene-linked cycloaliphatic or beta-branched substitutions of desloratadine increase the residence time at the H1R, conveying a longer duration of receptor antagonism. However, cycloaliphatic substituents directly attached to the piperidine amine (i.e., lacking the spacer) have decreased binding affinity and residence time compared to their methylene-linked structural analogues. Guided by docking studies, steric constraints within the binding pocket are hypothesized to explain the observed differences in affinity and binding kinetics between analogues.

  DOI：

  10.1021/acs.jmedchem.9b00447

文献信息

• HETEROCYCLIC COMPOUND AND H1 RECEPTOR ANTAGONIST
  申请人：Okada Makoto

  公开号：US20130085127A1

  公开（公告）日：2013-04-04

  A heterocyclic compound useful as an antiallergic agent is provided. A compound represented by the following formula (1) or a salt thereof: wherein the ring A is a homocyclic or heterocyclic ring; the ring B is a heterocyclic ring which contains G and nitrogen atom N as constituent atoms thereof, wherein G is CH or N; R 1 is a carbonyl group or an alkylene group; R 2a and R 2b are an alkyl group, a cycloalkyl group, an aryl group, or a heterocyclic group; X is an oxygen atom or a sulfur atom; Z is a hydroxyl group, an alkoxy group, a cycloalkyloxy group, an aryloxy group, an aralkyloxy group, an amino group, or an N-substituted amino group; and n is 0 or 1; with the proviso that when the ring A is a benzene ring or when the ring B is a piperazine ring, R 1 is an alkylene group which may have a substituent.

  提供一种作为抗过敏剂使用的杂环化合物。所述化合物由以下式（1）或其盐表示：其中环A是同环或杂环；环B是一个杂环，其中包含G和氮原子N作为其组成原子，其中G是CH或N；R1是一个羰基或一个烷基基团；R2a和R2b是烷基基团、环烷基基团、芳基团或杂环基团；X是一个氧原子或硫原子；Z是一个羟基、烷氧基、环烷氧基、芳氧基、芳基氧基、氨基或N-取代氨基；n为0或1；但条件是当环A为苯环或环B为哌嗪环时，R1是可能有取代基的烷基基团。
• US9365553B2
  申请人：——

  公开号：US9365553B2

  公开（公告）日：2016-06-14