4-氨基-5-氯-2-甲氧基-N-(4-甲基哌啶)苯甲酰胺 | 654084-41-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氨基-5-氯-2-甲氧基-N-(4-甲基哌啶)苯甲酰胺
• 英文名称: 4-(4-amino-5-chloro-2-methoxyphenylcarbonylamino-methyl)piperidine bis hydrochloride salt
• 英文别名: 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)-benzamide dihydrochloride；4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide dihydrochloride；4-Amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide hydrochloride；4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide;hydrochloride
• CAS: 654084-41-0
• 化学式: C₁₄H₂₀ClN₃O₂*2ClH
• 分子量: 370.707
• InChiKey: AGVUBESCBQMUAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.08
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  76.4
• 氢给体数：
  4
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温且干燥

反应信息

• 作为反应物：
  描述：

  4-氨基-5-氯-2-甲氧基-N-(4-甲基哌啶)苯甲酰胺 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 4-amino-5-chloro-N-((1-(5-(N-benzylamino)pentyl)piperidin-4-yl)-methyl)-2-methoxybenzamide
  参考文献：
  名称：

  Design and synthesis of orally active benzamide derivatives as potent serotonin 4 receptor agonist

  摘要：

  A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide derivatives bearing an aralkylamino, alkylamino, benzoyl or phenylsulfonyl group at its side chain part at the I-position on the piperidine ring was synthesized. They were evaluated for serotonin 4 (5-HT4) receptor agonist activity by testing their ability to contract the isolated guinea-pig ascending colon. 4-Amino-5-chloro-2-methoxy-N-[1-[5-(1-methylindol-3-ylcarbonylamino)pentyl]piperidin-4-ylmethyl]benzamide (1a, Y-34959) and its related compounds possessed favorable pharmacological profiles for gastrointestinal motility. Unfortunately, the compound 1a showed low bioavailability when given orally presumably due to its poor intestinal absorption rate. Replacement of the 1-methylindol-3-yl carbonylamino moiety of 1a with an aralkylamino (or alkylamino) group did not improve the intestinal absorption rate. Replacement of the 1-methylindol-3-ylcarbonylamino moiety with a benzoyl or phenylsulfonyl group increased the intestinal absorption rate compared with 1a. These compounds revealed good pharmacological profiles for gastrointestinal motility and were superior to 1a in oral bioavailability. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00412-7
• 作为产物：
  描述：

  4-氨基-5-氯-2-甲氧基苯甲酸 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 4-氨基-5-氯-2-甲氧基-N-(4-甲基哌啶)苯甲酰胺
  参考文献：
  名称：

  Design and synthesis of orally active benzamide derivatives as potent serotonin 4 receptor agonist

  摘要：

  A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide derivatives bearing an aralkylamino, alkylamino, benzoyl or phenylsulfonyl group at its side chain part at the I-position on the piperidine ring was synthesized. They were evaluated for serotonin 4 (5-HT4) receptor agonist activity by testing their ability to contract the isolated guinea-pig ascending colon. 4-Amino-5-chloro-2-methoxy-N-[1-[5-(1-methylindol-3-ylcarbonylamino)pentyl]piperidin-4-ylmethyl]benzamide (1a, Y-34959) and its related compounds possessed favorable pharmacological profiles for gastrointestinal motility. Unfortunately, the compound 1a showed low bioavailability when given orally presumably due to its poor intestinal absorption rate. Replacement of the 1-methylindol-3-yl carbonylamino moiety of 1a with an aralkylamino (or alkylamino) group did not improve the intestinal absorption rate. Replacement of the 1-methylindol-3-ylcarbonylamino moiety with a benzoyl or phenylsulfonyl group increased the intestinal absorption rate compared with 1a. These compounds revealed good pharmacological profiles for gastrointestinal motility and were superior to 1a in oral bioavailability. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00412-7

文献信息

• Cyclic amine derivatives-CCR-3 receptor antagonists
  申请人：Syntex (U.S.A.) LLC

  公开号：US06339087B1

  公开（公告）日：2002-01-15

  This invention relates to certain cyclic amine derivatives of Formula (I) that are CCR-3 receptor antagonist, pharmaceutical compositions containing them, methods for their use and methods for preparing these compounds.

  这项发明涉及某些符合以下式（I）的环胺衍生物，它们是CCR-3受体拮抗剂，包含它们的药物组合物，以及它们的使用方法和制备这些化合物的方法。
• Benzoic acid compounds and use thereof as medicaments
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：US05864039A1

  公开（公告）日：1999-01-26

  Benzoic acid compounds of the formula ##STR1## wherein each symbol is as defined in the specification, optical isomers thereof and pharmaceutically acceptable salts thereof; pharmaceutical composition comprising this compound and pharmaceutically acceptable additive; and serotonin 4 receptor agonists, gastrointestinal prokinetic agents and therapeutic agents for various gastrointestinal diseases, which comprise this compound as active ingredient. The compounds of the present invention have high and selective affinity for serotonin 4 receptor, and show agonistic effects thereon. Accordingly, they are useful medications for the prophylaxis and treatment of various gastrointestinal diseases, central nervous disorders, cardiac function disorders, urinary diseases, and the like, as well as useful anti-nociceptors for analgesic use which increase threshold of pain.

  苯甲酸化合物的化学式为##STR1##，其中每个符号如规范中定义，其光学异构体及其药用可接受盐；包括该化合物和药用可接受添加剂的药物组合物；以及将该化合物作为活性成分的5-羟色胺4受体激动剂、胃肠促动力剂和用于各种胃肠疾病的治疗剂。本发明的化合物具有对5-羟色胺4受体的高度和选择性亲和力，并显示出激动效应。因此，它们可用于预防和治疗各种胃肠疾病、中枢神经障碍、心脏功能障碍、泌尿系统疾病等，同时还可用作提高疼痛阈值的镇痛用途的有用抗痛觉剂。
• Synthesis and pharmacological properties of benzamide derivatives as selective serotonin 4 receptor agonists
  作者：Shuji Sonda、Kenichi Katayama、Toshio Kawahara、Noriko Sato、Kiyoshi Asano

  DOI：10.1016/j.bmc.2004.02.036

  日期：2004.5

  selective 5-HT4 receptor agonist offering potential as a novel prokinetic with reduced side effects derived from 5-HT3- and dopamine D2 receptor-binding affinity. In the oral route of administration, this compound enhanced gastric emptying and defecation in mice, and has a possibility as a prokinetic agent, which is effective on both the upper and the lower gastrointestinal tract.

  合成了一系列在哌啶环的1-位具有极性取代基的4-氨基-5-氯-2-甲氧基-N-（哌啶-4-基甲基）苯甲酰胺，并评估了其对胃肠动力的影响。苯甲酰基，苯磺酰基和苄基磺酰基衍生物加速胃排空并增加排便频率。其中一种是选择性的5-HT 4，即4-氨基-N- [1- [3- [苄基磺酰基）丙基]哌啶-4-基甲基] -5-氯-2-甲氧基苯甲酰胺（13a，Y-36912）。受体激动剂具有潜力，可作为一种新型的促运动药物，具有降低的由5-HT3-和多巴胺D2受体结合亲和力产生的副作用。在口服给药途径中，该化合物可增强小鼠的胃排空和排便能力，并有可能作为促运动剂，
• 5-HTX MODULATORS
  申请人：Klaveness Jo

  公开号：US20090029979A1

  公开（公告）日：2009-01-29

  This invention relates to compounds which bind to serotonin receptors inside or outside the central nervous system, in particular compounds which bind to the 5-HT 2 or 5-HT 7 receptors, their preparation and use, compositions containing them, and methods of treatment using them.

  本发明涉及与中枢神经系统内或外的血清素受体结合的化合物，特别是与5-HT2或5-HT7受体结合的化合物，其制备和使用，包含它们的组合物以及使用它们的治疗方法。
• Modulators of Preripheral 5-Ht Receptors
  申请人：Klaveness Jo

  公开号：US20070254874A1

  公开（公告）日：2007-11-01

  Novel modulators of 5-HT4 receptors have been developed which have a selectivity for peripheral receptors rather than those of the central nervous systems. Theses include novel derivatives of known modulators as well as entirely novel entities. Surprisingly, the derivatised compounds of the known modulators maintain a high binding affinity to 5-HT4 receptors, despite the presence of an acidic moiety at the end of an optional chain. The entirely novel entities also exhibit good binding affinity to 5-HT4 receptors. All of the compounds of the invention have a common motif which includes a basic nitrogen moiety and an acidic moiety. The compounds of the invention, due at least in part to their high ionisation potential at physiological pH, have the unique properties of selectively for peripheral 5HT4 receptors over those of the CNS, good binding affinity, and selectively of 5HT4 receptors over other serotonin receptors.

  已经开发出了5-HT4受体的新型调节剂，其选择性针对的是外周受体而非中枢神经系统受体。其中包括已知调节剂的新型衍生物以及全新的实体。令人惊讶的是，已知调节剂的衍生物化合物尽管在可选链的末端存在酸性基团，但仍保持对5-HT4受体的高结合亲和力。全新的实体也表现出良好的5-HT4受体结合亲和力。发明中的所有化合物都具有一个共同的基团，其中包括一种碱性氮基团和一种酸性基团。该发明中的化合物，至少部分原因是由于它们在生理pH值下具有高离化电位，具有选择性地作用于外周5-HT4受体而非中枢神经系统受体，具有良好的结合亲和力，并且对5-HT4受体的选择性高于其他血清素受体。