1-(3-(4-硝基苯氧基)丙基)吡咯烷 | 92033-81-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(3-(4-硝基苯氧基)丙基)吡咯烷
• 英文名称: 1-{3-[(4-nitrophenyl)oxy]propyl}pyrrolidine
• 英文别名: 1-(3-(4-nitrophenoxy)propyl)pyrrolidine；4-[3-(1-pyrrolidinyl)propoxy]-1-nitrobenzene；1-[3-(4-nitrophenoxy)propyl]pyrrolidine
• CAS: 92033-81-3
• 化学式: C₁₃H₁₈N₂O₃
• 分子量: 250.298
• InChiKey: JQLAYZSNLAOKEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  58.3
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  2-8°C，存于干燥密封条件下。

反应信息

• 作为反应物：
  描述：

  1-(3-(4-硝基苯氧基)丙基)吡咯烷 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 20.0h， 以97%的产率得到4-(3-(吡咯烷-1-基)丙氧基)苯胺
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships, and Biological Profiles of a Quinazolinone Class of Histamine H₃ Receptor Inverse Agonists

  摘要：

  A new series of quinazolinone derivatives was synthesized and evaluated as nonimidazole H(3) receptor inverse agonists. 2-Methyl-3-(4-{[3-(1-pyrrolidinyl)propy]oxy}phenyl)-5-(trifluoromethyl)-4(3H)-quinazolinone (1) was identified as a promising derivative for further evaluation following optimization of key parameters. Compound 1 has potent H3 inverse agonist activity and excellent selectivity over other histamine receptor subtypes and a panel of 115 unrelated diverse binding sites. Compound 1 also shows satisfactory pharmacokinetic profiles and brain penetrability in laboratory animals. Two hours after oral administration of 30 mg/kg of 1 to SD rats, significant elevation of brain histamine levels was observed where the brain H3 receptor was highly occupied (>90%). On the basis of species differences in P-glycoprotein (P-gp) susceptibility of I between human and rodent P-gps, the observed rodent brain permeability of I is significantly limited by P-gp mediated efflux in rodents, whereas the extent of P-gp mediated efflux in humans should be very small or negligible. The potential of 1 to be an efficacious drug was demonstrated by its excellent brain penetrability and receptor occupancy in P-gp-deficient CF-1 mice.

  DOI：

  10.1021/jm8003834
• 作为产物：
  描述：

  对氟硝基苯 在 苄基三乙基氯化铵 sodium hydroxide 作用下， 以 水 、 甲苯 为溶剂， 反应 0.83h， 以100%的产率得到1-(3-(4-硝基苯氧基)丙基)吡咯烷
  参考文献：
  名称：

  WO2007/4735

  摘要：

  公开号：

文献信息

• Crystal of 4(3H)-Quinazolinone Derivative
  申请人：Kanatani Akio

  公开号：US20080139589A1

  公开（公告）日：2008-06-12

  A substance that has a potency antagonistic to coupling of histamine with histamine H3 receptor or a potency of inhibiting the constant activity of histamine H3 receptor. There is provided a form I crystal of 2-methyl 3-4-[3-(1-pyrrolidinyl)propoxy]phenyl}-5-trifluoromethyl-4(3H)-quinazolinone that in the powder X- ray diffractometry, has peaks at 6.4°, 9.7°, 10.2°, 12.9°, 14.2°, 14.7°, 16.0°, 16.3°, 16.8°, 17.6°, 19.5°, 20.3°, 20.6°, 21.2°, 21.8°, 22.1°, 22.4°, 22.6°, 24.0°, 24.3°, 24.9°, 25.7°, 25.9°, 26.5°, 26.7°, 27.4°, 29.1°, 29.4°, 32.3° and 39.0° diffraction angles(2θ±0.2°).

  提供了一种物质，其具有对组胺与组胺H3受体的偶联具有拮抗作用或抑制组胺H3受体的恒定活性的效力。提供了一种2-甲基3-4-[3-(1-吡咯烷基)丙氧基]苯基}-5-三氟甲基-4(3H)-喹唑啉酮的I型晶体，在粉末X-射线衍射分析中，其在6.4°、9.7°、10.2°、12.9°、14.2°、14.7°、16.0°、16.3°、16.8°、17.6°、19.5°、20.3°、20.6°、21.2°、21.8°、22.1°、22.4°、22.6°、24.0°、24.3°、24.9°、25.7°、25.9°、26.5°、26.7°、27.4°、29.1°、29.4°、32.3°和39.0°衍射角度(2θ±0.2°)处具有峰值。
• Method for Producing 4(3H)-Quinazolinone Derivative
  申请人：Akao Atsushi

  公开号：US20090131664A1

  公开（公告）日：2009-05-21

  This invention is related to a method for producing 3-4-[3-(1-pyrrolidinyl)propoxy]phenyl}-5-trifluoromethyl-4(3H)-quinazolinone comprising a step for reacting 2-methyl-5-trifluoromethyl-4H-3,1-benzoxazin-4-one with 4-[3-(1-pyrrolidinyl)propoxy]aniline or an acid-addition salt thereof, or 4-(1-cyclobutyl-4-piperidinoy9oxyaniline or acid addition salt thereof in the presence of an acid catalyst.

  本发明涉及一种制备3-4-[3-(1-吡咯烷基)丙氧基]苯基}-5-三氟甲基-4(3H)-喹唑啉酮的方法，其中包括通过在酸催化剂存在下将2-甲基-5-三氟甲基-4H-3,1-苯并噁唑啉-4-酮与4-[3-(1-吡咯烷基)丙氧基]苯胺或其酸加成盐，或4-(1-环丁基-4-哌啶氧基)苯胺或其酸加成盐反应的步骤。
• CRYSTAL OF 4(3H)-QUINAZOLINONE DERIVATIVE
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1852423A1

  公开（公告）日：2007-11-07

  A substance that has a potency antagonistic to coupling of histamine with histamine H3 receptor or a potency of inhibiting the constant activity of histamine H3 receptor. There is provided a form I crystal of 2-methy 3-4-[3-(1-pyrrolidinyl)propoxy]phenyl}-5-trifluoromethyl-4(3H)-quinazolinone that in the powder X- ray diffractometry, has peaks at 6.4°, 9.7°, 10.2°, 12.9°, 14.2°, 14.7°, 16.0°, 16.3°, 16.8°, 17.6°, 19.5°, 20.3°, 20.6°, 21.2°, 21.8°, 22.1°, 22.4°, 22.6°, 24.0°, 24.3°, 24.9°, 25.7°, 25.9°, 26.5°, 26.7°, 27.4°, 29.1°, 29.4°, 32.3° and 39.0° diffraction angles(2θ ± 0.2°).

  一种物质，具有拮抗组胺与组胺 H3 受体偶联的效力或抑制组胺 H3 受体恒定活性的效力。本发明提供了 2-甲基 3-4-[3-(1-吡咯烷基)丙氧基]苯基}-5-三氟甲基-4(3H)-喹唑啉酮的 I 型晶体，在粉末 X 射线衍射仪中，该晶体在 6.4°、9.7°、10.2°、12.9°、14.2°、14.7°、16.0°、16.3°、16.8°、17.6°、19.5°、20.3°、20.6°、21.2°、21.8°、22.1°、22.4°、22.6°、24.0°、24.3°、24.9°、25.7°、25.9°、26.5°、26.7°、27.4°、29.1°、29.4°、32.3°和 39.0°衍射角（2θ ± 0.2°）。
• METHOD FOR PRODUCING 4(3H)-QUINAZOLINONE DERIVATIVE
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1903040A1

  公开（公告）日：2008-03-26

  This invention is related to a method for producing 3-4-[3-(1-pyrrolidinyl)propoxy]phenyl}-5-trifluoromethyl-4(3H)-quinazolinone comprising a step for reacting 2-methyl-5-trifluoromethyl-4H-3,1-benzoxazin-4-one with 4-[3-(1-pyrrolidinyl)propoxy]aniline or an acid-addition salt thereof, or 4-(1-cyclobutyl-4-piperidiny9oxyaniline or acid addition salt thereof in the presence of an acid catalyst.

  本发明涉及一种生产 3-4-[3-(1-吡咯烷基)丙氧基]苯基}-5-三氟甲基-4(3H)-喹唑啉酮的方法，包括以下步骤：将 2-甲基-5-三氟甲基-4H-3、1-苯并恶嗪-4-酮与 4-[3-(1-吡咯烷基)丙氧基]苯胺或其酸加成盐或 4-(1-环丁基-4-哌啶基9-氧代苯胺或其酸加成盐在酸催化剂存在下反应的步骤。
• Discovery of potent and selective rhodanine type IKKβ inhibitors by hit-to-lead strategy
  作者：Hyeseung Song、Yun Suk Lee、Eun Joo Roh、Jae Hong Seo、Kwang-Seok Oh、Byung Ho Lee、Hogyu Han、Kye Jung Shin

  DOI：10.1016/j.bmcl.2012.06.088

  日期：2012.9

  Regulation of NF-kappa B activation through the inhibition of IKK beta has been identified as a promising target for the treatment of inflammatory and autoimmune disease such as rheumatoid arthritis. In order to develop novel IKK beta inhibitors, we performed high throughput screening toward around 8000 library compounds, and identified a hit compound containing rhodanine moiety. We modified the structure of hit compound to obtain potent and selective IKK beta inhibitors. Throughout hit-to-lead studies, we have discovered optimized compounds which possess blocking effect toward NF-kappa B activation and TNF alpha production in cell as well as inhibition activity against IKK beta. Among them, compound 3q showed the potent inhibitory activity against IKK beta, and excellent selectivity over other kinases such as p38 alpha, p38 beta, JNK1, JNK2, and JNK3 as well as IKK alpha. (C) 2012 Elsevier Ltd. All rights reserved.