2-[4-(4-溴苯基)-哌嗪-1-基]-乙胺 | 199616-96-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 2-[4-(4-溴苯基)-哌嗪-1-基]-乙胺
• 英文名称: 4-(4-bromophenyl)-1-piperazineethanamine
• 英文别名: 2-[4-(4-Bromo-phenyl)-piperazin-1-YL]-ethylamine；2-[4-(4-bromophenyl)piperazin-1-yl]ethanamine
• CAS: 199616-96-1
• 化学式: C₁₂H₁₈BrN₃
• 分子量: 284.199
• InChiKey: IVYCDABPAPCTDJ-UHFFFAOYSA-N

物化性质

• 沸点：
  394.4±42.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[4-(4-溴苯基)-哌嗪-1-基]-乙胺 在 potassium carbonate 、 氯化铵 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 0.01h， 生成 2-benzyl-N-(2-(4-(4-bromophenyl)piperazin-1-yl)ethyl)-2-phenylhydrazine-1-carboxamide
  参考文献：
  名称：

  Benzyl Phenylsemicarbazides: A Chemistry-Driven Approach Leading to G Protein-Biased Dopamine D₄ Receptor Agonists with High Subtype Selectivity

  摘要：

  Many subtype-selective dopamine receptor ligands developed for the D-2-D-4 family incorporate a 1-arylpiperazine-derived primary recognition motif, which is connected to a lipophilic moiety occupying an extended binding pocket (EBP) of the receptor via an aliphatic linker of variable lengths. The evaluation of a novel group of dopamine receptor ligands now showed that highly subtype-selective ligands [up to K-i(D-4.4) = 0.25 nM, D-2L/D-4.4 = 320, D-3/D-4.4 = 710 for APH199 (17)] can be obtained by choosing a relatively large and conformationally flexible 1-benzyl-1-phenylsemicarbazide substructure to fill the EBP. The novel chemotype APH199 (17) was found to act as a full agonist at the D-4 receptor showing significant bias toward G protein activation over beta-arrestin recruitment in comparison to quinpirole.

  DOI：

  10.1021/acs.jmedchem.9b01085
• 作为产物：
  描述：

  1-(4-溴苯基)哌嗪盐酸盐 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 21.0h， 生成 2-[4-(4-溴苯基)-哌嗪-1-基]-乙胺
  参考文献：
  名称：

  Benzyl Phenylsemicarbazides: A Chemistry-Driven Approach Leading to G Protein-Biased Dopamine D₄ Receptor Agonists with High Subtype Selectivity

  摘要：

  Many subtype-selective dopamine receptor ligands developed for the D-2-D-4 family incorporate a 1-arylpiperazine-derived primary recognition motif, which is connected to a lipophilic moiety occupying an extended binding pocket (EBP) of the receptor via an aliphatic linker of variable lengths. The evaluation of a novel group of dopamine receptor ligands now showed that highly subtype-selective ligands [up to K-i(D-4.4) = 0.25 nM, D-2L/D-4.4 = 320, D-3/D-4.4 = 710 for APH199 (17)] can be obtained by choosing a relatively large and conformationally flexible 1-benzyl-1-phenylsemicarbazide substructure to fill the EBP. The novel chemotype APH199 (17) was found to act as a full agonist at the D-4 receptor showing significant bias toward G protein activation over beta-arrestin recruitment in comparison to quinpirole.

  DOI：

  10.1021/acs.jmedchem.9b01085

文献信息

• Radiolabelled alkylamino-benzothiazole and -benzoxazole derivatives and their use as D4 ligands
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1325917A1

  公开（公告）日：2003-07-09

  The present invention concerns the radiolabelled compounds of formula the N-oxide forms, the pharmaceutically acceptable acid addition salts and stereochemically isomeric forms thereof, wherein X is O or S; n is 2, 3, 4 or 5; R1 is hydrogen, C1-6alkyl, C1-6alkyloxy or halo; R2 is hydrogen, C1-6alkyl, phenyl, phenylC1-6alkyl or phenylcarbonyl; R3 and R4 each independently are selected from hydrogen, halo, nitro, C1-6alkyl, C1-6alkyloxy, haloC1-6alkyl, aminosulfonyl, mono- or di(C1-4alkyl)aminosulfonyl; or R3 and R4 may also be taken together to form a bivalent radical of formula -CH=CH-CH=CH- , characterized in that the compound has at least one halo which is a radioactive isotope of iodine, bromine or fluorine, or has at least one 11C-atom or tritium atom ; it further relates to a process of marking dopamine D4 receptor sites and a process for imaging an organ.

  本发明涉及放射性标记的式化合物 其中X为O或S；n为2、3、4或5；R1为氢、C1-6烷基、C1-6烷氧基或卤代；R2 是氢、C1-6烷基、苯基、苯基 C1-6 烷基或苯基羰基； R3 和 R4 各自独立地选自氢、卤素、硝基、C1-6烷基、C1-6烷氧基、卤代 C1-6 烷基、氨磺酰基、单-或二(C1-4烷基)氨磺酰基；或 R3 和 R4 也可以结合在一起形成式-CH=CH-CH=CH-的二价基，其特征在于该化合物具有至少一个卤素，该卤素是碘、溴或氟的放射性同位素，或具有至少一个 11C 原子或氚原子；它还涉及一种标记多巴胺 D4 受体位点的工艺和一种器官成像工艺。
• ALKYLAMINOBENZOTHIAZOLE AND -BENZOXAZOLE DERIVATIVES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0912533A1

  公开（公告）日：1999-05-06
• US6103725A
  申请人：——

  公开号：US6103725A

  公开（公告）日：2000-08-15
• US6224849B1
  申请人：——

  公开号：US6224849B1

  公开（公告）日：2001-05-01
• [EN] ALKYLAMINOBENZOTHIAZOLE AND -BENZOXAZOLE DERIVATIVES<br/>[FR] DERIVES DE L'ALKYLAMINOBENZOTHIAZOLE ET ALKYLAMINOBENZOXAZOLE
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1997043271A1

  公开（公告）日：1997-11-20

  (EN) The present invention concerns the compounds of formula (I) the $i(N)-oxide forms, the pharmaceutically acceptable acid addition salts and stereochemically isomeric forms thereof, wherein X is O or S; n is 2, 3, 4 or 5; R1 is hydrogen, C1-6alkyl, C1-6alkyloxy or halo; R2 is hydrogen, C1-6alkyl, phenyl, phenylC1-6alkyl or phenylcarbonyl; R3 and R4 each independently are selected from hydrogen, halo, nitro, C1-6alkyl, C1-6alkyloxy, haloC1-6alkyl, aminosulfonyl, mono-or di(C1-4alkyl)aminosulfonyl; or R3 and R4 may also be taken together to form a bivalent radical of formula -CH=CH-CH=CH-; it further relates to processes for their preparation, compositions comprising them as well as their use as a medicine; compounds of formula (I) containing a radioactive isotope; a process of marking dopamine D4 receptor sites; and a process for imaging an organ are disclosed.(FR) La présente invention concerne les composés de la formule (I), les formes N-oxyde, les sels d'addition d'acide pharmaceutiquement acceptables et les formes stéréochimiquement isomériques de ces derniers. Dans la formule, X est O ou S; n est 2, 3, 4 ou 5; R1 est hydrogène, C1-6alkyle, C1-6alkyloxy ou halo; R2 est hydrogène, C1-6alkyle, phényle, phénylC1-6alkyle ou phénylcarbonyle,; R3 et R4 sont chacun indépendamment sélectionnés parmi hydrogène, halo, nitro, C1-6alkyle, C1-6alkyloxy, haloC1-6alkyle, aminosulfonyle, mono ou di(C1-4alkyl)aminosulfonyle; ou R3 et R4 peuvent être pris ensemble pour former un radical bivalent de la formule -CH=CH-CH=CH-. L'invention traite aussi de procédés pour leur préparation, de compositions les comprenant ainsi que de leur utilisation comme médicaments. L'invention a aussi pour objet des composés de la formule (I) comprenant un isotope radioactif, un procédé de marquage des sites du récepteur D4 de la dopamine et un procédé pour observer un organe par imagerie.