3α/β-amino-9-benzyl-9-azabicyclo<3.3.1>nonane | 76272-99-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3α/β-amino-9-benzyl-9-azabicyclo<3.3.1>nonane
• 英文别名: 9-Benzyl-9-azabicyclo[3.3.1]nonan-3-amine
• CAS: 76272-99-6
• 化学式: C₁₅H₂₂N₂
• mdl: MFCD13806395
• 分子量: 230.353
• InChiKey: UWEVJKJUENNRQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3α/β-amino-9-benzyl-9-azabicyclo<3.3.1>nonane 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 9-benzyl-9-azabicyclo[3.3.1]nonan-3-amine
  参考文献：
  名称：

  Fluorine-18 labeled benzamides for studying the dopamine D2 receptor with positron emission tomography

  摘要：

  Two series of (N-benzylpiperidin-4-yl)- and (9-azabicyclo[3.3.1]nonan-3beta-yl)benzamides were prepared, and in vitro binding assays were used to measure the affinity of these compounds for dopamine D2, dopamine D3, serotonin 5-HT2, and alpha2-adrenergic receptors. The results of these studies indicated compounds 23, 26b, and 34 have the selectivity needed for in vivo studies of the D2 (and possibly D3) receptors. F-18-Labeled analogues of 23, 26b and 34 were prepared by N-alkylation of the corresponding desbenzyl precursors with [F-18]-4-fluorobenzyl iodide. Preliminary in vivo studies demonstrated that [F-18]-23 and [F-18]-26b are suitable candidates for further evaluation in positron emission tomography imaging studies. The slow rate of washout of [F-18]-34 from nondopaminergic regions and its comparatively high lipophilicity indicates that this compound may not be suitable for imaging studies because of a high level of nonspecific binding.

  DOI：

  10.1021/jm00075a028
• 作为产物：
  描述：

  9-苄基-9-氮杂双环[3.3.1]壬烷-3-酮 在 ammonium hydroxide 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 14.0h， 生成 3α/β-amino-9-benzyl-9-azabicyclo<3.3.1>nonane
  参考文献：
  名称：

  一种2-（石榴皮烷-3-氨基）-4-四氢吲唑取代 的苯甲酰胺化合物及其应用

  摘要：

  本发明属于医药领域，具体涉及一种2‑(石榴皮烷‑3‑氨基)‑4‑四氢吲唑取代的苯甲酰胺化合物及其应用。所述的2‑(石榴皮烷‑3‑氨基)‑4‑四氢吲唑取代的苯甲酰胺化合物，具有式Ⅰ所示结构，其中，R1为氢基或烷基等；R2为氢基、烷基或杂原子取代的烷基等。该类化合物是将4‑四氢吲唑取代的苯甲酰胺的2‑号位用石榴皮烷‑3‑氨基进行取代得到的，能够抑制多种肿瘤细胞的生长并诱导其走向凋亡通道，在肿瘤治疗、辅助治疗等领域具有潜在的应用价值。

  公开号：

  CN104592230B

文献信息

• Synthesis of 2-(2,3-dimethoxyphenyl)-4-(aminomethyl)imidazole analogues and their binding affinities for dopamine D2 and D3 receptors
  作者：Yunsheng Huang、Robert R Luedtke、Rebekah A Freeman、Li Wu、Robert H Mach

  DOI：10.1016/s0968-0896(01)00175-4

  日期：2001.12

  same region resulted in a total loss of affinity for both dopamine receptor subtype binding sites. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinomethyl)imidazole (5i), which has a D(3) receptor affinity of 21nM and a 7-fold selectivity for D(3) versus D(2) receptors. The binding affinity for sigma(1) and sigma(2) receptors was

  制备了一系列的2-（2,3-二甲氧基苯基）-4-（氨基甲基）咪唑衍生物，并使用体外结合试验测量了它们对多巴胺D（2）和D（3）受体的亲和力。还制备了几种恶二唑类似物，并测试了它们对多巴胺D（2）和D（3）受体的亲和力。受体结合研究的结果表明，在苯环和碱性氮之间并入咪唑部分并不会显着增加对多巴胺D（3）受体的选择性，而在同一区域并入恶二唑会导致总的两个多巴胺受体亚型结合位点的亲和力丧失。该系列中选择性最高的化合物是2-（5-溴-2,3-二甲氧基苯基）-4-（6,7-二甲氧基-1,2,3,4-四氢异喹啉甲基）咪唑（5i），具有21nM的D（3）受体亲和力，对D（3）与D（2）受体的选择性是7倍。还测量了对sigma（1）和sigma（2）受体的结合亲和力，结果表明几种类似物是选择性的sigma（1）受体配体。
• Azabicyclo[3.3.1]nonanes
  申请人：Beecham Group p.l.c.

  公开号：US04705858A1

  公开（公告）日：1987-11-10

  Certain endo-9-lower-alkyl 9-azabicyclo[3.3.1]nonane-3-amines are valuable intermediates for the preparation of 2-methoxy-4-amino-5-halo-N-[9-lower-alkyl]-azabicyclo[3.3.1]nonanylbenzami des wherein said final products possess useful pharmacological activity, such as ability to regulate gastro-intestinal function, anti-emetic activity and CNS activity.

  某些9-内酰基-9-低烷基-3-胺基-9-氮杂双环[3.3.1]壬烷是制备2-甲氧基-4-氨基-5-卤代-N-[9-低烷基]-氮杂双环[3.3.1]壬基苯甲酰胺的有价值中间体，其中所述最终产物具有有用的药理活性，例如调节胃肠功能、抗恶心活性和中枢神经系统活性。
• Pharmaceutically active aza-bicyclo-benzamide derivatives
  申请人：Beecham Group, Limited

  公开号：US04273778A1

  公开（公告）日：1981-06-16

  This invention relates to novel substituted benzamides having useful pharmacological properties, to pharmaceutical compositions containing them, and to a process for their preparation. N-(2-Diethylaminoethyl)-2-methoxy-4-amino-5-chlorobenzamide, 1-ethyl-2(2-methoxy-5-sulphamoylbenzamidomethyl)pyrrolidine and N-[4'-(1"-benzyl)-piperidyl]-2-methoxy-4-amino-5-chlorobenzamide are well known compounds having useful pharmacological activity such as the ability to regulate the gastro-intestinal function anti-emetic activity and CNS activity. It has now been found that a certain structurally distinct class of substituted benzamides also has useful pharmacological activity, in particular dopamine antagonist activity.

  本发明涉及具有有用的药理特性的新型取代苯甲酰胺、含有它们的制药组合物以及它们的制备方法。N-(2-二乙氨基乙基)-2-甲氧基-4-氨基-5-氯苯甲酰胺、1-乙基-2(2-甲氧基-5-磺酰胺基苯甲酰胺甲基)吡咯烷和N-[4'-(1"-苄基)-哌啶基]-2-甲氧基-4-氨基-5-氯苯甲酰胺是已知的具有有用药理活性的化合物，如调节胃肠功能、抗恶心活性和中枢神经系统活性。现在发现一类结构上独特的取代苯甲酰胺也具有有用的药理活性，特别是多巴胺拮抗活性。
• Pharmaceutically active tropanes
  申请人：Beecham Group p.l.c.

  公开号：US04544660A1

  公开（公告）日：1985-10-01

  A compound of the formula (I), and pharmaceutically acceptable salts thereof: ##STR1## wherein: R.sub.1 is a C.sub.1-6 alkoxy group; R.sub.2 and R.sub.3 are the same or different and are hydrogen, halogen, CF.sub.3, C.sub.2-7 acyl, C.sub.2-7 acylamino, or amino, aminocarbonyl or aminosulphone optionally substituted by one or two C.sub.1-6 alkyl groups, C.sub.1-6 alkylsulphone or nitro; R.sub.5 is hyrogen or C.sub.1-6 alkyl; R.sub.6 is C.sub.1-7 alkyl or a group --(CH.sub.2).sub.s R.sub.7 where s is 0 to 2 and R.sub.7 is a C.sub.3-8 cycloalkyl group, or a group --(CH.sub.2).sub.t R.sub.8 where t is 1 or 2 and R.sub.8 is C.sub.2-5 alkenyl or a phenyl group optionally substituted by one or two substituents selected from C.sub.1-6 alkyl, C.sub.1-4 alkoxy, trifluoromethyl and halogen; and n, p and q are independently 0 to 2; have useful pharmacological activity.

  化合物的化学式（I）及其药学上可接受的盐：##STR1## 其中：R.sub.1是C.sub.1-6烷氧基团；R.sub.2和R.sub.3相同或不同，可以是氢、卤素、CF.sub.3、C.sub.2-7酰基、C.sub.2-7酰胺基、氨基、氨基甲酰基或氨基磺酰基，可选地被一个或两个C.sub.1-6烷基、C.sub.1-6烷基磺酰基或硝基取代；R.sub.5是氢或C.sub.1-6烷基；R.sub.6是C.sub.1-7烷基或一个基团--(CH.sub.2).sub.sR.sub.7，其中s为0至2，R.sub.7是C.sub.3-8环烷基，或一个基团--(CH.sub.2).sub.tR.sub.8，其中t为1或2，R.sub.8是C.sub.2-5烯基或一个苯基，可选地被一个或两个C.sub.1-6烷基、C.sub.1-4烷氧基、三氟甲基和卤素中的一种或两种取代；n、p和q独立地为0至2；具有有用的药理活性。
• Certain aza-bicyclo-benzamide derivatives and pharmaceutical
  申请人：Beecham Group Limited

  公开号：US04336259A1

  公开（公告）日：1982-06-22

  Substituted benzamides having useful pharmacological properties, pharmaceutical compositions containing the same, pharmaceutically acceptable salts thereof, and procedure for administering said compositions. The active compounds have dopamine antagonist activity which is an effective amount of a compound of formula (I) and the compositions are particularly useful for the treatment of humans suffering from emesis impaired gastro-intestinal motility and disorders of the central nervous system. The administration of the compositions overcomes these disorders of the central nervous system and ordinary additions. The active compounds are characterized by having the formula (I), wherein R.sub.2 and/or R.sub.3 are sulphone groups, preferably either R.sub.2 or R.sub.3 being an aminosulphone or alkylsulphone group, which groups may optionally be substituted by 1 or 2 C.sub.1-6 alkyl groups.

  具有有用药理特性的取代苯甲酰胺，含有该化合物的制药组合物，其药学上可接受的盐，以及用于给予该组合物的方法。活性化合物具有多巴胺拮抗剂活性，其为公式(I)化合物的有效量，该组合物特别适用于治疗患有呕吐，受损胃肠运动和中枢神经系统障碍的人类。给予该组合物可以克服这些中枢神经系统障碍和常规添加物。活性化合物的特征在于具有公式(I)，其中R.sub.2和/或R.sub.3是磺酰基，最好是R.sub.2或R.sub.3是氨基磺酰基或烷基磺酰基，这些基团可以选择地被1或2个C.sub.1-6烷基取代。