(R)-2-methyl-1-{3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxyl]propyl}pyrrolidine | 1005403-35-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (R)-2-methyl-1-{3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxyl]propyl}pyrrolidine
• 英文别名: (R)-2-methyl-1-{3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-propyl}-pyrrolidine；(2R)-2-methyl-1-[3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]propyl]pyrrolidine
• CAS: 1005403-35-9
• 化学式: C₂₀H₃₂BNO₃
• 分子量: 345.29
• InChiKey: VLBONGZLBZCKLC-MRXNPFEDSA-N

物化性质

• 熔点：
  148-150 °C
• 沸点：
  459.8±30.0 °C(Predicted)
• 密度：
  1.04±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.24
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-2-methyl-1-{3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxyl]propyl}pyrrolidine 生成 (R)-2-methyl-1-{3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-propyl}-pyrrolidine hydrochloride
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIDAZINE DERIVATIVES WHICH HAVE HISTAMINE H3 ANTAGONIST ACTIVITY
  [FR] DÉRIVÉS DE PYRIDAZINE SUBSTITUÉS À ACTIVITÉ ANTAGONISTE DES RÉCEPTEURS H3 DE L'HISTAMINE

  摘要：

  本发明涉及具有组胺H3拮抗活性的化合物，以及它们的使用和制备方法。

  公开号：

  WO2009097306A1
• 作为产物：
  描述：

  4-羟基苯硼酸频哪醇酯 在 potassium carbonate 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 84.0h， 生成 (R)-2-methyl-1-{3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxyl]propyl}pyrrolidine
  参考文献：
  名称：

  发现和表征6- {4- [3-（R）-2-甲基吡咯烷基-1-基）丙氧基]苯基} -2 H-哒嗪-3-酮（CEP-26401，依达比松）：有效的选择性组胺H 3受体反向激动剂

  摘要：

  新型哒嗪-3-一组胺H 3受体（H 3 R）拮抗剂/反向激动剂的优化确定了6- {4- [3-（R）-2-甲基吡咯烷-1-基）丙氧基]苯基}- 2 H-哒嗪-3-酮（8a，CEP-26401； irdabisant）作为潜在候选药物可用于治疗注意力和认知障碍。8a对人（K i = 2.0 nM）和大鼠（K i = 7.2 nM）H 3 Rs具有高亲和力，在hH 1 R，hH 2 R和hH 4上的选择性大于1000倍R组胺受体亚型，在418 G蛋白偶联受体，离子通道，转运蛋白和酶的体外实验中。图8a证明了CNS药物在水溶性，渗透性和亲脂性方面的理想药物特性，并且与人血浆蛋白的结合性低。它微弱地抑制了重组细胞色素P450亚型和与人类醚相关的基因。大鼠，小鼠，狗和人肝微粒体中的8a代谢极少，并且具有良好的种间药代动力学特性。图8a在大鼠中剂量依赖性地抑制了H 3 R激动剂诱导的成遗传（ED 50＝

  DOI：

  10.1021/jm200401v

文献信息

• Substituted pyridazine derivatives
  申请人：Cephalon, Inc.

  公开号：US08076331B2

  公开（公告）日：2011-12-13

  The present invention is directed to compounds having histamine H3 antagonist activity, as well as methods of their use and preparation.

  本发明涉及具有组胺H3受体拮抗活性的化合物，以及它们的使用和制备方法。
• Substituted Pyridazine Derivatives
  申请人：Hudkins Robert L.

  公开号：US20120004231A1

  公开（公告）日：2012-01-05

  The present invention is directed to compounds having histamine H 3 antagonist activity, as well as methods of their use and preparation.

  本发明涉及具有组胺H3拮抗活性的化合物，以及它们的使用和制备方法。
• Synthesis and evaluation of 4- and 5-pyridazin-3-one phenoxypropylamine analogues as histamine-3 receptor antagonists
  作者：Nadine C. Becknell、Jacquelyn A. Lyons、Lisa D. Aimone、Zeqi Huang、John A. Gruner、Rita Raddatz、Robert L. Hudkins

  DOI：10.1016/j.bmc.2012.04.028

  日期：2012.6

  A novel series of 4-pyridazin-3-one and 5-pyridazin-3-one analogues were designed and synthesized as H3R antagonists. Structure-activity relationship revealed the 5-pyridazin-3-ones 8a and S-methyl 8b had excellent human and rat H3R affinities, and acceptable pharmacokinetic properties. In vivo evaluation of 8a showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG/EMG model. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of pyridone-phenoxypropyl-R-2-methylpyrrolidine analogues as histamine H3 receptor antagonists
  作者：Nadine C. Becknell、Jacquelyn A. Lyons、Lisa D. Aimone、John A. Gruner、Joanne R. Mathiasen、Rita Raddatz、Robert L. Hudkins

  DOI：10.1016/j.bmcl.2011.09.091

  日期：2011.12

  6-4-[3-(R)-2-Methylpyrrolidin-1-yl) propoxy]-phenyl}-2H-pyridazin-3-one 6 (Irdabisant; CEP-26401) was recently reported as a potent H3R antagonist with excellent drug-like properties and in vivo activity that advanced into clinical evaluation. A series of pyridone analogs of 6 was synthesized and evaluated as H3R antagonists. Structure-activity relationships revealed that the 5-pyridone regiomer was optimal for H3R affinity. N-Methyl 9b showed excellent H3R affinity, acceptable pharmacokinetics and pharmaceutical properties. In vivo evaluation of 9b showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG model. (C) 2011 Elsevier Ltd. All rights reserved.