1-(二甲基氨基)环丁烷甲腈 | 176445-74-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 1-(二甲基氨基)环丁烷甲腈
• 英文名称: 1-(dimethylamino)cyclobutanecarbonitrile
• 英文别名: 1-dimethylamino-cyclobutanecarbonitrile；1-(dimethylamino)cyclobutane-1-carbonitrile
• CAS: 176445-74-2
• 化学式: C₇H₁₂N₂
• 分子量: 124.186
• InChiKey: ZZEAKIPYKTYAIS-UHFFFAOYSA-N

物化性质

• 沸点：
  205.3±23.0 °C(Predicted)
• 密度：
  0.98±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(二甲基氨基)环丁烷甲腈 在 lithium aluminium tetrahydride 、 硫酸 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 4-amino-5-chloro-N-<1-(dimethylamino)-1-cyclobutyl>methyl-2-methoxybenzamide
  参考文献：
  名称：

  Serotoninergic properties of new conformationally restricted benzamides

  摘要：

  A new series of benzamides derived from metoclopramide have been synthesized, in which the vicinal carbon of the basic nitrogen atom of the ethyl chain is situated on the C-3, C-4, C-5 and C-6 rings. The diamino derivatives were prepared through Strecker's reaction from the corresponding ketones except for the cyclopropyl derivatives where 1-ethoxy-1-trimethylsiloxy cyclopropane was used as the starting material. The benzamides were prepared using the mixed anhydride method. They were tested in binding assays for D-2, 5-HT3 and 5-HT4 receptors. The results show a marked increase in the selectivity and potency of these derivatives for 5-HT3 receptors with regard to metoclopramide (compound 1d: 5-HT3 K-i = 9.03 nM; 5-HT4 K-i > 5000; D-2 K-i > 5000). The influences of steric hindrance and hydrophobic properties on the affinity of benzamide derivatives for 5-HT3 receptors were also emphasized by these data. The X-ray crystal structure of compound 1d was compared with that of the minimal energy conformer of BRL 24682, a reference 5-HT3 receptor antagonist benzamide, determined using the Random Search program. Superimposition of the two structures showed a suitable fit between the pharmacophore groups previously determined to be important for 5-HT3 receptor antagonists. On the other hand, the hydrophobic parts of the basic moieties had different spatial occupancies.

  DOI：

  10.1016/0223-5234(96)89139-2
• 作为产物：
  描述：

  环丁酮 、 盐酸二甲胺 、 氰化钾 以 水 为溶剂， 以85%的产率得到1-(二甲基氨基)环丁烷甲腈
  参考文献：
  名称：

  Serotoninergic properties of new conformationally restricted benzamides

  摘要：

  A new series of benzamides derived from metoclopramide have been synthesized, in which the vicinal carbon of the basic nitrogen atom of the ethyl chain is situated on the C-3, C-4, C-5 and C-6 rings. The diamino derivatives were prepared through Strecker's reaction from the corresponding ketones except for the cyclopropyl derivatives where 1-ethoxy-1-trimethylsiloxy cyclopropane was used as the starting material. The benzamides were prepared using the mixed anhydride method. They were tested in binding assays for D-2, 5-HT3 and 5-HT4 receptors. The results show a marked increase in the selectivity and potency of these derivatives for 5-HT3 receptors with regard to metoclopramide (compound 1d: 5-HT3 K-i = 9.03 nM; 5-HT4 K-i > 5000; D-2 K-i > 5000). The influences of steric hindrance and hydrophobic properties on the affinity of benzamide derivatives for 5-HT3 receptors were also emphasized by these data. The X-ray crystal structure of compound 1d was compared with that of the minimal energy conformer of BRL 24682, a reference 5-HT3 receptor antagonist benzamide, determined using the Random Search program. Superimposition of the two structures showed a suitable fit between the pharmacophore groups previously determined to be important for 5-HT3 receptor antagonists. On the other hand, the hydrophobic parts of the basic moieties had different spatial occupancies.

  DOI：

  10.1016/0223-5234(96)89139-2

文献信息

• GlyT1 RECEPTOR ANTAGONISTS
  申请人：Kolczewski Sabine

  公开号：US20100048531A1

  公开（公告）日：2010-02-25

  The present invention relates to a compound of formula I wherein R 1 , R 2 , X, Ar 1 and Ar 2 are as defined herein and to pharmaceutically acceptable acid addition salts, to a racemic mixtures, or to their corresponding enantiomers and/or optical isomers thereof. Compounds of the invention are good inhibitors of the glycine transporter 1 (GlyT-1), and have a good selectivity to glycine transporter 2 (GlyT-2) inhibitors.

  本发明涉及一种具有式I的化合物 其中 R 1 ，R 2 ，X，Ar 1 和Ar 2 如本文所定义，并且涉及药学上可接受的酸盐加合物，外消旋混合物，或其相应的对映体和/或光学异构体。本发明的化合物是甘氨酸转运蛋白1（GlyT-1）的良好抑制剂，并且对甘氨酸转运蛋白2（GlyT-2）抑制剂具有良好的选择性。
• N-[(1-dimethylaminocycloalkyl)methyl]benzamide derivatives
  申请人：——

  公开号：US20040242685A1

  公开（公告）日：2004-12-02

  The present invention relates to N-[(1-dimethylaminocycloalkyl)methyl]benzamide derivatives having the general formula I 1 wherein n is 0, 1, 2 or 3; R 1 and R 2 are independently H, (C 1-4 )alkyl or (C 1-4 )alkyloxy; R 3 is (C 3-8 )alkyl, (C 4-7 )cycloalkyl, (C 4-7 )cycloalkyl (C 1-3 )alkyl, (C 6-12 )aryl(C 1-3 )alkyl (wherein the aryl moiety is optionally substituted with 1-3 substituents selected from (C 1-4 )alkyl, (C 1-4 )alkyloxy, halogen, trifluoromethyl and methoxycarbonyl), or (C 4-9 )heteroaryl(C 1-3 )alkyl; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said derivatives, and to the use of these N-[(1-dimethylaminocycloalkyl)methyl]benzamide derivatives in the treatment of disorders or conditions which are responsive to inhibition of the GlyT-2 transporter, such as muscle spasticity, epilepsy and, particularly, acute, chronic and neuropathic pain.

  本发明涉及具有一般式I1的N-［（1-二甲氨基环烷基）甲基］苯甲酰胺衍生物，其中n为0、1、2或3；R1和R2分别为H、（C1-4）烷基或（C1-4）烷氧基；R3为（C3-8）烷基、（C4-7）环烷基、（C4-7）环烷基（C1-3）烷基、（C6-12）芳基（C1-3）烷基（其中芳基基团可选地被1-3个取自（C1-4）烷基、（C1-4）烷氧基、卤素、三氟甲基和甲氧羰基的取代基所取代），或（C4-9）杂环芳基（C1-3）烷基；或其药学上可接受的盐。本发明还涉及包含所述衍生物的制药组合物，以及在治疗对GlyT-2转运体抑制有反应的疾病或病况，例如肌肉痉挛、癫痫和特别是急性、慢性和神经病理性疼痛中使用这些N-［（1-二甲氨基环烷基）甲基］苯甲酰胺衍生物的用途。
• GlyT1 receptor antagonists
  申请人：Hoffmann-La Roche Inc.

  公开号：US08063098B2

  公开（公告）日：2011-11-22

  The present invention relates to a compound of formula I wherein R1, R2, X, Ar1 and Ar2 are as defined herein and to pharmaceutically acceptable acid addition salts, to a racemic mixtures, or to their corresponding enantiomers and/or optical isomers thereof. Compounds of the invention are good inhibitors of the glycine transporter 1 (GlyT-1), and have a good selectivity to glycine transporter 2 (GlyT-2) inhibitors.

  本发明涉及式I的化合物，其中R1，R2，X，Ar1和Ar2如本文所定义，并涉及药物可接受的酸加盐、外消旋混合物或其对应的对映体和/或光学异构体。本发明的化合物是良好的甘氨酸转运体1（GlyT-1）抑制剂，并具有良好的选择性对甘氨酸转运体2（GlyT-2）抑制剂。
• NOVEL COMPOUNDS
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：US20160176806A1

  公开（公告）日：2016-06-23

  Compounds of the formula in which the substituents are as defined in claim 1 , are suitable for use as nematicides.

  公式中的化合物，其中取代基如权利要求1所定义的那样，适用于作为线虫杀剂的用途。
• 4-MEMBERED RING CARBOXAMIDES USED AS NEMATICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：US20160157485A1

  公开（公告）日：2016-06-09

  Compounds of the formula (I), in which the substituents are as defined in claim 1 , are suitable for use as nematicides.

  公式(I)的化合物，其中取代基的定义如权利要求书1所述，适用于用作线虫灭除剂。