β-(bromomethyl)-γ-phenylbutyric acid, methyl ester | 133496-52-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: β-(bromomethyl)-γ-phenylbutyric acid, methyl ester
• 英文别名: Methyl 3-benzyl-4-bromobutanoate
• CAS: 133496-52-3
• 化学式: C₁₂H₁₅BrO₂
• 分子量: 271.154
• InChiKey: YPOLLPDALQGVBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  β-(bromomethyl)-γ-phenylbutyric acid, methyl ester 在 PPA 、 sodium carbonate 、 potassium iodide 作用下， 以 various solvent(s) 为溶剂， 反应 25.0h， 生成 3-[4-(2-Methoxy-phenyl)-piperazin-1-ylmethyl]-3,4-dihydro-2H-naphthalen-1-one
  参考文献：
  名称：

  Synthesis and antidopaminergic activity of some 3-(aminomethyl)tetralones as analogs of butyrophenone

  摘要：

  Starting from beta-benzoylpropionic acid was synthesized 3-(aminomethyl)tetralones in which the amino substituent was 4-(N-piperazinyl)-p-fluorobutyrophenone (14), 4-benzoylpiperidine (15), 4-hydroxy-4-phenylpiperidine (16) or 4-(o-methoxyphenyl)piperazine (17). The possible dopamine antagonist activity of these compounds was investigated in both ''in vitro'' and ''in vivo'' experiments. These compounds potently inhibited [H-3]spiperone binding to D2 striatal receptors and moderately inhibited [H-3]SCH-23390 binding to D1 striatal receptors (K(i)s in the nanomolar and micromolar ranges, respectively). Apomorphine-induced stereotypies and amphetamine group toxicity were antagonized, to different extents, by the compounds under study, with a potency similar to that of haloperidol. Interestingly, no catalepsy was observed after administration of the new compounds (2-8 mg/kg). The most active compounds ''in vivo'' 14 and 15 possessed two butyrophenone pharmacophores. However, the tetralone moiety appeared not critical for their antidopaminergic activity, since all target compounds were less active than haloperidol. These studies provide a pharmacological basis for future research on these new compounds devoid of cataleptogenic activity.

  DOI：

  10.1021/jm00111a046
• 作为产物：
  描述：

  重氮甲烷 、 β-(bromomethyl)-γ-phenylbutyric acid 以 乙醚 为溶剂， 生成 β-(bromomethyl)-γ-phenylbutyric acid, methyl ester
  参考文献：
  名称：

  Synthesis and antidopaminergic activity of some 3-(aminomethyl)tetralones as analogs of butyrophenone

  摘要：

  Starting from beta-benzoylpropionic acid was synthesized 3-(aminomethyl)tetralones in which the amino substituent was 4-(N-piperazinyl)-p-fluorobutyrophenone (14), 4-benzoylpiperidine (15), 4-hydroxy-4-phenylpiperidine (16) or 4-(o-methoxyphenyl)piperazine (17). The possible dopamine antagonist activity of these compounds was investigated in both ''in vitro'' and ''in vivo'' experiments. These compounds potently inhibited [H-3]spiperone binding to D2 striatal receptors and moderately inhibited [H-3]SCH-23390 binding to D1 striatal receptors (K(i)s in the nanomolar and micromolar ranges, respectively). Apomorphine-induced stereotypies and amphetamine group toxicity were antagonized, to different extents, by the compounds under study, with a potency similar to that of haloperidol. Interestingly, no catalepsy was observed after administration of the new compounds (2-8 mg/kg). The most active compounds ''in vivo'' 14 and 15 possessed two butyrophenone pharmacophores. However, the tetralone moiety appeared not critical for their antidopaminergic activity, since all target compounds were less active than haloperidol. These studies provide a pharmacological basis for future research on these new compounds devoid of cataleptogenic activity.

  DOI：

  10.1021/jm00111a046

文献信息

• Piperazinomethyl Tetralines: Synthesis and Affinities for D1, D2 and 5-HT2A Receptors.
  作者：Enrique RAVINA、Jose CID、Jesus NEGREIRA、Maria E. CASTRO、Victor M. MOLDES、Tomas G-FERREIRO、Elizabeth ROSA、Jose MACALLEJA、Maria L. DE CEBALLOS

  DOI：10.1248/cpb.43.1234

  日期：——

  Starting from the methyl ester of β-(bromomethyl)-γ-phenylbutyric acid and its m-fluoro derivative, we have prepared 2-[4[3-(p-fluorobenzoyl)-1-propyl]piperazin-1-ylmethyl]tetraline (QF0105B) and the corresponding 7-fluoro derivative (QF0106B). The affinities of these compounds for D1 and D2 dopamine and 5-HT2A receptors was evaluated in vitro. The afinities of QF0105B and QF0106B for D2 receptors are less than that of haloperidol (pKi's for inhibition of [3H]spiperone binding : 7.72, 7.06 and 8.30, respectively) but all three compounds have similar affinities for 5-HT2A receptors (pKi'S for inhibition of [3H]ketanserine binding : 7.70, 7.36 and 7.70, respectively).

  从 β-（溴甲基）-γ-苯基丁酸甲酯及其间氟衍生物开始，我们制备了 2-[4-[3-（对氟苯甲酰基）-1-丙基]哌嗪-1-基甲基]四氢萘 (QF0105B) 和相应的 7-氟衍生物 (QF0106B)。体外评估了这些化合物对 D1 和 D2 多巴胺受体以及 5-HT2A 受体的亲和力。QF0105B 和 QF0106B 对 D2 受体的亲和力低于氟哌啶醇（抑制 [3H]spiperone 结合的 pKi 值分别为 7.72、7.06 和 8.30），但这三种化合物对 5-HT2A 受体的亲和力相似（抑制 [3H]ketanserine 结合的 pKi 值分别为 7.70、7.36 和 7.70）。