N-tert-butyloxycarbonyl-4-(4-amino-5-chloro-2-methoxyphenylcarbonylaminomethyl)piperidine | 188973-04-8

• 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: N-tert-butyloxycarbonyl-4-(4-amino-5-chloro-2-methoxyphenylcarbonylaminomethyl)piperidine
• 英文别名: tert-butyl 4-[[(4-amino-5-chloro-2-methoxybenzoyl)amino]methyl]piperidine-1-carboxylate；4-amino-N-[1-(tert-butoxycarbonyl)piperidin-4-ylmethyl]-5-chloro-2-methoxybenzamide；4-amino-5-chloro-2-methoxy-N-(1-(tert-butoxycarbonyl)piperidin-4-ylmethyl)benzamide；4-amino-5-chloro-N-(1-tert-butoxycarbonylpiperidin-4-ylmethyl)-2-methoxybenzamide；tertiary butyl 4-((4-amino-5-chloro-2-methoxybenzamido)methyl)piperidine-1-carboxylate；4-amino-5-chloro-2-methoxy-N-((1-tert-butoxycarbonyl)piperidin-4-ylmethyl)benzamide
• CAS: 188973-04-8
• 化学式: C₁₉H₂₈ClN₃O₄
• 分子量: 397.902
• InChiKey: HFIKHLIQLQRIPR-UHFFFAOYSA-N

物化性质

• 沸点：
  522.3±50.0 °C(Predicted)
• 密度：
  1.210±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  93.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-tert-butyloxycarbonyl-4-(4-amino-5-chloro-2-methoxyphenylcarbonylaminomethyl)piperidine 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-amino-5-chloro-2-methoxy-N-((1-(6-oxo-6-phenylhexyl)piperidin-4-yl)methyl)benzamide
  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：

  1-BOC-4-甲磺酰基氧甲基哌啶 在 sodium azide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 N-tert-butyloxycarbonyl-4-(4-amino-5-chloro-2-methoxyphenylcarbonylaminomethyl)piperidine
  参考文献：
  名称：

  发现新型 4-甲基哌啶基苯甲酰胺衍生物作为 5-HT4 受体激动剂用于治疗胃肠道疾病

  摘要：

  合成了新型 4-甲基哌啶基苯甲酰胺衍生物，并评估了体外和体内的促运动活性。在这些衍生物中，去甲西沙必利的 3-甲氧基哌啶部分、西沙必利的药效团和 DA-6650 被替换为没有手性中心的 4-甲基哌啶基部分。在这些衍生物中，化合物28b具有强效的 5-HT 4受体结合亲和力 (IC 50  = 0.067 μM)，并且在不抑制 CYP3A4 (IC 50  = 7.272 μM) 和阻断人类 ether-à-go-go-related 的情况下提高了安全性基因 (hERG) 通道 (IC 50  > 10 μM)。体内大鼠模型，化合物28b与对照组相比，胃排空率提高 (68.2%)，排便重量增加两倍以上。此外，它在刺激大鼠模型中显示出内脏超敏反应的缓解作用。因此，化合物28b被选为临床前候选药物，作为促动力剂，具有良好的安全性，可用于治疗胃肠道疾病。

  DOI：

  10.1002/bkcs.12667

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。
• A Multivalent Approach to the Design and Discovery of Orally Efficacious 5-HT₄ Receptor Agonists
  作者：R. Murray McKinnell、Scott R. Armstrong、David T. Beattie、Seok-Ki Choi、Paul R. Fatheree、Roland A. L. Gendron、Adam Goldblum、Patrick P. Humphrey、Daniel D. Long、Daniel G. Marquess、J. P. Shaw、Jacqueline A. M. Smith、S. Derek Turner、Ross G. Vickery

  DOI：10.1021/jm900881j

  日期：2009.9.10

  nitrogen atom of common ligands, occupying what may be termed a “secondary” binding site. Using a multivalent approach to lead discovery, we have investigated how varying the position and nature of the secondary binding group can be used as a strategy to achieve the desired 5-HT4 agonist pharmacological profile. During this study, we discovered the ability of amine-based secondary binding groups to impart

  5-HT 4受体激动剂（例如替加色罗）已证明可治疗便秘为主的肠易激综合症（IBS-C），该病症是一种高度流行的疾病，其特征在于慢性便秘和肠道推进功能受损，腹胀和疼痛。5-HT 4受体结合位点可以容纳连接至常见配体的胺氮原子的功能和空间上不同的基团，占据所谓的“第二”结合位点。使用多价方法进行前导发现，我们研究了如何将二级结合基团的位置和性质变化用作实现所需5-HT 4的策略。激动剂药理学资料。在这项研究过程中，我们发现了基于胺的二级结合基团能够在5-HT 4激动剂的结合亲和力，选择性和功能效能方面获得非凡的收益。通过这种方法产生的前导物的优化提供了化合物26，其为一种选择性的，口服有效的5-HT 4激动剂，可用于治疗胃肠动力相关的疾病。
• 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。
• Agent containing quinonimine derivatives and used to colour keratin fibres, and associated method
  申请人：——

  公开号：US20030182736A1

  公开（公告）日：2003-10-02

  The invention relates to an agent for colouring fibres (A). Said agent is produced by mixing two constituents (A1) and (A2), and is characterised in that the constituent (A1) contains at least one quinonimine derivative of formula (I), and the constituent (A2) contains at least one compound from the group consisting of aromatic amines and phenols. The invention also relates to a method for colouring keratin fibres using the inventive agent. 1

  该发明涉及一种用于染色纤维的药剂（A）。该药剂由混合两种成分（A1）和（A2）制备而成，其特征在于成分（A1）至少含有一个式（I）的醌亚胺衍生物，而成分（A2）至少含有一种来自芳香胺和酚的化合物。该发明还涉及一种使用该创新药剂染色角蛋白纤维的方法。
• 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。