2-[1-(2-chloro-ethyl)-2-methyl-propoxy]-4-methoxy-1-methyl-benzene | 478613-35-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-[1-(2-chloro-ethyl)-2-methyl-propoxy]-4-methoxy-1-methyl-benzene
• 英文别名: 2-(1-Chloro-4-methylpentan-3-yl)oxy-4-methoxy-1-methylbenzene
• CAS: 478613-35-3
• 化学式: C₁₄H₂₁ClO₂
• 分子量: 256.773
• InChiKey: GIMFZXUJUMJBKZ-UHFFFAOYSA-N

物化性质

• 沸点：
  347.8±27.0 °C(Predicted)
• 密度：
  1.033±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[1-(2-chloro-ethyl)-2-methyl-propoxy]-4-methoxy-1-methyl-benzene 在 palladium dihydroxide 氢气 、 三乙胺 、 sodium iodide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 82.0h， 生成 1-{1-[3-(5-Methoxy-2-methyl-phenoxy)-4-methylpentyl]-piperidin-4-yl}-3-(2-methylamino-ethyl)-1,3-dihydro-benzimidazol-2-one
  参考文献：
  名称：

  具有镇痛和镇静作用的N-3取代苯氧基丙基哌啶苯并咪唑-2-酮类似物作为NOP受体激动剂的合成和评价。

  摘要：

  已经发现了一系列3-苯氧丙基哌啶苯并咪唑-2-酮类似物作为新型的NOP受体激动剂。通过使用一系列功能性的苯并咪唑-2-酮的N-3取代，探索了构效关系。N-甲基乙酰胺衍生物（+）-7f被发现是一种高亲和力的强效NOP激动剂，其选择性是MOP受体的100倍以上。此外，当对啮齿动物静脉给药时，（+）-7f被证明具有镇痛和镇静作用。

  DOI：

  10.1016/j.bmc.2006.11.030
• 作为产物：
  描述：

  1-chloro-4-methyl-pentan-3-one 在 sodium tetrahydroborate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 42.0h， 生成 2-[1-(2-chloro-ethyl)-2-methyl-propoxy]-4-methoxy-1-methyl-benzene
  参考文献：
  名称：

  具有镇痛和镇静作用的N-3取代苯氧基丙基哌啶苯并咪唑-2-酮类似物作为NOP受体激动剂的合成和评价。

  摘要：

  已经发现了一系列3-苯氧丙基哌啶苯并咪唑-2-酮类似物作为新型的NOP受体激动剂。通过使用一系列功能性的苯并咪唑-2-酮的N-3取代，探索了构效关系。N-甲基乙酰胺衍生物（+）-7f被发现是一种高亲和力的强效NOP激动剂，其选择性是MOP受体的100倍以上。此外，当对啮齿动物静脉给药时，（+）-7f被证明具有镇痛和镇静作用。

  DOI：

  10.1016/j.bmc.2006.11.030

文献信息

• Structure–activity relationships and CoMFA of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic properties
  作者：Ronald Palin、John K. Clark、Louise Evans、Andrea K. Houghton、Philip S. Jones、Alan Prosser、Grant Wishart、Kazuya Yoshiizumi

  DOI：10.1016/j.bmc.2008.01.005

  日期：2008.3.15

  The N-3 position of a series of 3-phenoxypropyl piperidine benzimidazol-2-one analogues was optimised using the predictive power of a CoMFA model. The model was used to prioritise compounds for synthesis culminating in the triazole (+)-24. (+)-24 was found to be a high affinity, potent NOP agonist and demonstrated both antinociceptive and antiallodynic effects when administered iv to rodents.

  使用CoMFA模型的预测能力，优化了一系列3-苯氧基丙基哌啶苯并咪唑-2-一类似物的N-3位置。该模型用于对化合物进行优先排序，最终合成出三唑（+）-24。（+）-24被发现是一种高亲和力，强效的NOP激动剂，并在静脉内施用给啮齿动物后表现出抗伤害感受和抗痛觉过敏的作用。
• Synthesis and SAR studies of 3-phenoxypropyl piperidine analogues as ORL1 (NOP) receptor agonists
  作者：Ronald Palin、David R. Barn、John K. Clark、Jean E. Cottney、Phillip M. Cowley、Marc Crockatt、Louise Evans、Helen Feilden、Richard R. Goodwin、Frank Griekspoor、Simon J.A. Grove、Andrea K. Houghton、Philip S. Jones、Richard J. Morphy、Alasdair R.C. Smith、Hardy Sundaram、David Vrolijk、Mark A. Weston、Grant Wishart、Paul Wren

  DOI：10.1016/j.bmcl.2004.11.049

  日期：2005.2

  A series of 3-phenoxypropyl piperidine analogues have been discovered as novel ORL1 receptor agonists. Structure-activity relationships have been explored around the 3-phenoxypropyl region with several potent and selective analogues identified. (C) 2004 Elsevier Ltd. All rights reserved.
• [EN] 1-(3-PHENYLOXYPROPYL)PIPERIDINE DERIVATIVES<br/>[FR] DERIVES DE 1-(3-PHENYLOXYPROPYL)PIPERIDINE
  申请人：AKZO NOBEL NV

  公开号：WO2002100861A1

  公开（公告）日：2002-12-19

  The present invention relates to 1(3-phenyloxypropyl)-piperidine derivative having general Formula (I), wherein R1 is (C1-6)alkyl or (C4-8)cycloalkyl or phenyl, optionally substituted with (C1-6)alkyl, (C1-6)alkyloxy or halogen; R2 is H or (C1-6)alkyl; or R1 and R2 form together with the carbon atom to which they are bound (C4-8)cycloalkyl, optionally substitutes with (C1-6)alkyloxy or halogen; R3 is H, OH, (C1-6)alkyloxy or (C1-6)alkylcarbonyloxy; R4 represents 1-5 substituents independently selected from H, (C1-6)alkyl, (C1-6)alkyloxy and halogen; Y represents (a), (b) and Z is H; or Y and Z together with the carbon atom to which they are bound represent the spiro atom in the spiro atom in the spiro system formed with (c) *represents the spiro carbon atom; R6 is H, (C1-6)alkyl or (CO)n-(CH2)m-R12; n is 0 or 1; m is 1-4; R8 and R10 are independently H or(C1-6)alkyl; R7, R9 and R11 are independently H, (C1-6)alkyl, (C1-6)alkyloxy or halogen; R12 is hydroxy, (C1-4)alkyloxy, (C1-4)alkylthio, (C1-4)alkyloxycarbonyl, (C1-4)alkylcarbonyloxy, 2-tetrahydrofuranyl, 4-morpholinyl or di(C1-4)alkylamino; or a pharmaceutically acceptable salt thereof. The present invention also relates to pharmaceutical compositions comprising said derivatives, as well as to the use of these 1-(3-phenyloxypropyl)-piperidine derivatives in therapy.
• Synthesis and evaluation of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic and sedative properties
  作者：Ronald Palin、Anton Bom、John K. Clark、Louise Evans、Helen Feilden、Andrea K. Houghton、Philip S. Jones、Brian Montgomery、Mark A. Weston、Grant Wishart

  DOI：10.1016/j.bmc.2006.11.030

  日期：2007.2

  A series of 3-phenoxypropyl piperidine benzimidazol-2-one analogues have been discovered as novel NOP receptor agonists. Structure-activity relationships have been explored via N-3 substitution of the benzimidazol-2-one with a range of functionality. The N-methyl acetamide derivative (+)-7f was found to be a high-affinity, potent NOP agonist with greater than 100-fold selectivity over the MOP receptor

  已经发现了一系列3-苯氧丙基哌啶苯并咪唑-2-酮类似物作为新型的NOP受体激动剂。通过使用一系列功能性的苯并咪唑-2-酮的N-3取代，探索了构效关系。N-甲基乙酰胺衍生物（+）-7f被发现是一种高亲和力的强效NOP激动剂，其选择性是MOP受体的100倍以上。此外，当对啮齿动物静脉给药时，（+）-7f被证明具有镇痛和镇静作用。