4-amino-5-chloro-N-<2-(dimethylamino)ethyl>-2-methoxybenzamide | 18094-92-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-amino-5-chloro-N-<2-(dimethylamino)ethyl>-2-methoxybenzamide
• 英文别名: 4-amino-5-chloro-N-<(dimethylamino)ethyl>-2-methoxybenzamide；4-amino-5-chloro-N-[2-(dimethylamino)ethyl]-2-methoxybenzamide
• CAS: 18094-92-3
• 化学式: C₁₂H₁₈ClN₃O₂
• 分子量: 271.747
• InChiKey: IYUGSTOVFNGBBA-UHFFFAOYSA-N

物化性质

• 熔点：
  169-171 °C
• 沸点：
  392.9±42.0 °C(Predicted)
• 密度：
  1.208±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  67.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-amino-5-chloro-N-<2-(dimethylamino)ethyl>-2-methoxybenzamide 以 二氯甲烷 、 氨 、 水 为溶剂， 生成 4-amino-5-chloro-N-[2-(dimethylamino)ethyl]-2-hydroxybenzamide
  参考文献：
  名称：

  Anti-emetic quinuclidinyl benzamides

  摘要：

  式中R1、R2、R3、R4、R5和A的定义如本文所述，新型取代苯甲酰胺用于治疗呕吐，特别是癌症患者的化疗引起的呕吐。其中一些化合物也用于治疗与胃动力减弱相关的疾病。

  公开号：

  US04820715A1
• 作为产物：
  描述：

  4-氨基-5-氯-2-甲氧基苯甲酸 在 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 4-amino-5-chloro-N-<2-(dimethylamino)ethyl>-2-methoxybenzamide
  参考文献：
  名称：

  4-氨基-5-氯-2-甲氧基苯甲酸的新酯作为有效的激动剂和5-HT4受体拮抗剂。

  摘要：

  合成了许多衍生自4-氨基-5-氯-2-甲氧基苯甲酸和取代的1-哌啶乙醇的苯甲酸酯，它们在豚鼠回肠的电刺激的肠神经丛和纵肌中是有效的5-HT4受体激动剂。和大鼠食道肌肉。哌啶环被Me，OH，NH-Ac或CONH2基团单取代后，化合物等效于7a（ML 10302），这是先前报道的具有纳摩尔摩尔亲和力的5-HT4受体激动剂。7a，k与5-羟色胺（5-HT）一样有效，但最大响应仅为5-HT的60-80％，表明这些化合物具有部分激动剂特性。在大鼠纹状体中用[3H] GR 113808进行结合测定，发现其中一些化合物对5-HT4受体具有纳摩尔摩尔亲和力（7a，Ki = 1.07 +/- 0.5 nM； 7k，Ki = 1。0 +/- 0.3 nM）。在哌啶环上引入两个甲基导致2-[（（顺式和反式-3,5-二甲基哌啶基）乙基] -4-氨基-5-氯-2-甲氧基苯甲酸酯）的药理学特性发生了显着变化， 7克，小时

  DOI：

  10.1021/jm960320m

文献信息

• Pharmacologically active substituted benzamides
  申请人：Bristol-Myers Company

  公开号：US04808624A1

  公开（公告）日：1989-02-28

  Novel substituted benzamides of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and A are as defined herein are useful in the treatment of emesis, and particularly chemotherapy-induced emesis in cancer patients. Some of the compounds are also useful in disorders relating to impaired gastric motility.

  式中R1、R2、R3、R4、R5和A为本发明所定义的取代苯甲酰胺类新化合物，用于治疗呕吐，特别是癌症患者的化疗诱导呕吐。其中一些化合物也用于治疗与胃动力受损相关的疾病。
• The interaction of ammonium, sulfonium, and sulfide analogs of metoclopramide with the dopamine D2 receptor
  作者：Marc W. Harrold、Anong Sriburi、Kazuhisa Matsumoto、Duane D. Miller、Tahira Farooqui、Norman Uretsky

  DOI：10.1021/jm00073a017

  日期：1993.10

  A series of permanently charged ammonium and sulfonium analogues of metoclopramide as well as a permanently uncharged sulfide analogue were synthesized and evaluated for their ability to inhibit apomorphine-induced responses on mouse striatal slices. Three of the four permanently charged analogues were found to inhibit apomorphine's effects, although at higher concentrations than either metoclopramide or its dimethyl analogue. In contrast, the sulfide analogue was inactive at concentrations up to 100 muM. These findings are consistent with earlier studies of chlorpromazine and sulpiride analogues and provide further evidence that dopamine antagonists bind in their charged molecular forms to anionic sites on the D2 receptor. Further, the results of this study in conjunction with those of our earlier sulpiride study would seem to indicate that differences in the biological profiles of metoclopramide, a type 1 benzamide useful as a gastric prokinetic agent, and sulpiride, a type 2 benzamide useful for its antipsychotic effects, are not due to any appreciable differences in the binding of the basic nitrogen atom of these molecules.
• Serotoninergic properties of new conformationally restricted benzamides
  作者：D Yang、B Brémont、S Shen、S Kefi、M Langlois

  DOI：10.1016/0223-5234(96)89139-2

  日期：1996.1

  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.
• US4808624A
  申请人：——

  公开号：US4808624A

  公开（公告）日：1989-02-28
• US4820715A
  申请人：——

  公开号：US4820715A

  公开（公告）日：1989-04-11