4-chloro-2-[(2R)-1-methyl-2-pyrrolidinylmethyl]-1(2H)-phthalazinone | 1279126-23-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-chloro-2-[(2R)-1-methyl-2-pyrrolidinylmethyl]-1(2H)-phthalazinone
• 英文别名: 4-chloro-2-[[(2R)-1-methylpyrrolidin-2-yl]methyl]phthalazin-1-one
• CAS: 1279126-23-6
• 化学式: C₁₄H₁₆ClN₃O
• 分子量: 277.754
• InChiKey: VCFZBKHUFICMJS-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  35.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  Boc-D-脯氨醇 在 盐酸 、 甲酸 、 偶氮二甲酸二叔丁酯 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 3.25h， 生成 4-chloro-2-[(2R)-1-methyl-2-pyrrolidinylmethyl]-1(2H)-phthalazinone
  参考文献：
  名称：

  The Discovery of Phthalazinone-Based Human H₁ and H₃ Single-Ligand Antagonists Suitable for Intranasal Administration for the Treatment of Allergic Rhinitis

  摘要：

  A series of potent phthalazinone-based human H-1 and H-3 bivalent histamine receptor antagonists, suitable for intranasal administration for the potential treatment of allergic rhinitis, were identified. Blockade of H-3 receptors is thought to improve efficacy on nasal congestion, a symptom of allergic rhinitis that is currently not treated by current antihistamines. Two analogues (56a and 56b) had slightly lower H-1, potency (pA(2) 9.1 and 8.9, respectively, vs 9.7 for the clinical gold-standard azelastine, and H-3 potency (pK(i) 9.6 and 9.5, respectively, vs 6.8 for azelastine). Compound 56a had longer duration of action than azelastine, low brain penetration, and low oral bioavailability, which coupled with the predicted low clinical dose, should limit the potential of engaging CNS-related side-effects associated with H-1 or H-3 antagonism.

  DOI：

  10.1021/jm1013874

文献信息

• The Discovery of Phthalazinone-Based Human H₁ and H₃ Single-Ligand Antagonists Suitable for Intranasal Administration for the Treatment of Allergic Rhinitis
  作者：Panayiotis A. Procopiou、Christopher Browning、Jennifer M. Buckley、Kenneth L. Clark、Lise Fechner、Paul M. Gore、Ashley P. Hancock、Simon T. Hodgson、Duncan S. Holmes、Michael Kranz、Brian E. Looker、Karen M. L. Morriss、Daniel L. Parton、Linda J. Russell、Robert J. Slack、Steven L. Sollis、Sadie Vile、Clarissa J. Watts

  DOI：10.1021/jm1013874

  日期：2011.4.14

  A series of potent phthalazinone-based human H-1 and H-3 bivalent histamine receptor antagonists, suitable for intranasal administration for the potential treatment of allergic rhinitis, were identified. Blockade of H-3 receptors is thought to improve efficacy on nasal congestion, a symptom of allergic rhinitis that is currently not treated by current antihistamines. Two analogues (56a and 56b) had slightly lower H-1, potency (pA(2) 9.1 and 8.9, respectively, vs 9.7 for the clinical gold-standard azelastine, and H-3 potency (pK(i) 9.6 and 9.5, respectively, vs 6.8 for azelastine). Compound 56a had longer duration of action than azelastine, low brain penetration, and low oral bioavailability, which coupled with the predicted low clinical dose, should limit the potential of engaging CNS-related side-effects associated with H-1 or H-3 antagonism.