N-{3-[1-(3-aminopropyl)piperidin-4-yl]phenyl}acetamide | 387827-27-2

• 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: N-{3-[1-(3-aminopropyl)piperidin-4-yl]phenyl}acetamide
• 英文别名: N1-{3-[1-(3-aminopropyl)-4-piperidyl]phenyl}acetamide；N-{3-[1-(3-aminopropyl)-4-piperidinyl]phenyl}acetamide；N-{3-[1-(3-amino propyl)4-piperidinyl]phenyl}acetamide；N-[3-[1-(3-aminopropyl)piperidin-4-yl]phenyl]acetamide
• CAS: 387827-27-2
• 化学式: C₁₆H₂₅N₃O
• 分子量: 275.394
• InChiKey: HFWZERJLIXANPB-UHFFFAOYSA-N

物化性质

• 沸点：
  473.7±45.0 °C(Predicted)
• 密度：
  1.090±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  58.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-{3-[1-(3-aminopropyl)piperidin-4-yl]phenyl}acetamide 在 sodium hydride 、 氯磷酸二乙酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.83h， 以15%的产率得到N-(3-{1-[3-(5-phenyl-3H-benzo[e][1,4]diazepin-2-ylamino)propyl]piperidin-4-yl}phenyl)acetamide
  参考文献：
  名称：

  [EN] MEDICINAL USE OF RECEPTOR LIGANDS
  [FR] UTILISATION MEDICALE DE LIGANDS RECEPTEURS

  摘要：

  公开号：

  WO2006010446A3
• 作为产物：
  描述：

  tert-butyl N-(3-{4-[3-(acetylamino)phenyl]piperidino}propyl)-carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以96%的产率得到N-{3-[1-(3-aminopropyl)piperidin-4-yl]phenyl}acetamide
  参考文献：
  名称：

  SNAP-7941 的对映选择性合成：MCH1-R 的手性二氢嘧啶酮抑制剂。

  摘要：

  通过使用两种有机催化方法实现了 SNAP-7941（一种有效的黑色素浓缩激素受体拮抗剂）的对映选择性合成。用于合成富含对映体的二氢嘧啶酮核的第一种方法是金鸡纳生物碱催化的 β-酮酯曼尼希反应生成酰基亚胺，第二种方法是手性磷酸催化的 Biginelli 反应。通过在具有 3-(4-苯基哌啶-1-基)丙胺侧链片段的二氢嘧啶酮的 N3 位置选择性形成尿素来完成合成。SNAP-7921 的合成突出了不对称有机催化方法在构建一类重要的手性杂环中的实用性。

  DOI：

  10.1021/jo801463j

文献信息

• Substituted alkyl amido piperidines
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US20040186103A1

  公开（公告）日：2004-09-23

  This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of reducing the body mass of a subject which comprises administering to the subject an amount of a compound of the invention effective to reduce the body mass of the subject. This invention further provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of a compound of the invention effective to treat the subject's depression and/or anxiety.

  这项发明涉及选择性拮抗黑色素浓缩激素-1（MCH1）受体的化合物。该发明提供了一种包括该发明化合物的治疗有效量和药学上可接受的载体的药物组合物。该发明提供了一种由结合本发明化合物的治疗有效量和药学上可接受的载体制成的药物组合物。该发明还提供了一种制备药物组合物的方法，包括结合本发明化合物的治疗有效量和药学上可接受的载体。该发明还提供了一种减少受试者体重的方法，包括向受试者施用本发明化合物的有效量以减少受试者的体重。该发明还提供了一种治疗患有抑郁症和/或焦虑症的受试者的方法，包括向受试者施用本发明化合物的有效量以治疗受试者的抑郁症和/或焦虑症。
• Substituted anilinic piperidines as MCH selective antagonists
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US06727264B1

  公开（公告）日：2004-04-27

  This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therepeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier.

  这项发明涉及对黑素集中激素-1（MCH1）受体具有选择性的拮抗剂化合物。发明提供了一种药物组合物，包括治疗有效量的本发明化合物和药用可接受载体。本发明还提供了一种通过结合本发明的治疗有效量的化合物和药用可接受载体来制造的药物组合物。本发明进一步提供了一种制造药物组合物的方法，包括结合治疗有效量的本发明化合物和药用可接受载体。
• DNA encoding a human melanin concentrating hormone receptor (MCH1) and uses thereof
  申请人：——

  公开号：US20030082623A1

  公开（公告）日：2003-05-01

  This invention provides an isolated nucleic acid encoding a human MCH1 receptor, a purified human MCH1 receptor, vectors comprising isolated nucleic acid encoding a human MCH1 receptor, cells comprising such vectors, antibodies directed to a human MCH1 receptor, nucleic acid probes useful for detecting nucleic acid encoding human MCH1 receptors, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding human MCH1 receptors, transgenic, nonhuman animals which express DNA encoding a normal or mutant human MCH1 receptor, methods of isolating a human MCH1 receptor, methods of treating an abnormality that is linked to the activity of a human MCH1 receptor, as well as methods of determining binding of compounds to mammalian MCH1 receptors. This invention provides a method of modifying the feeding behavior of a subject which comprises administering to the subject an amount of an MCH1 antagonist effective to decrease the body mass of the subject and/or decrease the consumption of food by the subject. This invention further provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of an MCH1 antagonist effective to treat the subject's depression and/or anxiety.

  这项发明提供了编码人类MCH1受体的孤立核酸，纯化的人类MCH1受体，包括编码人类MCH1受体的孤立核酸的载体，包含这种载体的细胞，针对人类MCH1受体的抗体，用于检测编码人类MCH1受体的核酸探针，互补于编码人类MCH1受体独特序列的反义寡核苷酸，表达编码正常或突变人类MCH1受体的转基因非人类动物，孤立人类MCH1受体的分离方法，治疗与人类MCH1受体活性相关的异常的方法，以及确定化合物与哺乳动物MCH1受体结合的方法。这项发明提供了一种修改受试者摄食行为的方法，包括向受试者投与足以减少受试者体重和/或减少受试者食物摄入量的MCH1拮抗剂的量。这项发明还提供了一种治疗患有抑郁和/或焦虑的受试者的方法，包括向受试者投与足以治疗受试者抑郁和/或焦虑的MCH1拮抗剂的量。
• Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof
  申请人：——

  公开号：US20030069261A1

  公开（公告）日：2003-04-10

  This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of modifying feeding behavior of a subject which comprises administering to the subject an amount of a compound of the invention effective to decrease the consumption of food by the subject. This invention further provides a method of treating a feeding disorder in a subject which comprises administering to the subject an amount of a compound of the invention effective to decrease the consumption of food by the subject. In an embodiment of the invention, the feeding disorder is bulimia, bulimia nervosa or obesity.

  这项发明涉及选择性拮抗黑素浓集激素-1（MCH1）受体的化合物。该发明提供了一种包括所述化合物的治疗有效量和药学可接受载体的药物组合物。该发明提供了一种通过结合本发明化合物的治疗有效量和药学可接受载体制备的药物组合物。该发明还提供了一种制备药物组合物的方法，包括结合本发明化合物的治疗有效量和药学可接受载体。该发明还提供了一种修改受试者进食行为的方法，包括向受试者投与本发明化合物的有效量以减少受试者的食物摄入量。该发明还提供了一种治疗受试者进食障碍的方法，包括向受试者投与本发明化合物的有效量以减少受试者的食物摄入量。在该发明实施方式中，进食障碍可以是暴食症、暴食症神经质或肥胖症。
• Synthesis and Structure–Activity Relationship of Naphtho[1,2-<i>b</i>]furan-2-carboxamide Derivatives as Melanin Concentrating Hormone Receptor 1 Antagonists
  作者：Chae Jo Lim、Jun Young Choi、Byung Ho Lee、Kwang-Seok Oh、Kyu Yang Yi

  DOI：10.1248/cpb.c13-00486

  日期：——

  The discovery that novel naphtho[1,2-b]furan-2-carboxamides containing linked piperidinylphenylacetamide groups serve as melanin concentrating hormone receptor 1 (MCH-R1) antagonists is described. An extensive structure–activity relationship (SAR) study, probing members of this family that contain a variety of aryl and heteroaryl groups at C-5 of the naphtho[1,2-b]furan-2-carboxamide skeleton and having different chain linker lengths, led to the identification of the 5-(4-pyridinyl) substituted analog 10b as a highly potent MCH-R1 antagonist with an IC50 value of 3 nM. This substance also displays good metabolic stability and it does not significantly inhibit cytochrome P450 (CYP450) enzymes. However, 10b has unacceptable oral bioavailability.

  研究发现，含有连接哌啶基苯乙酰胺基团的新型萘并[1,2-b]呋喃-2-甲酰胺可作为黑色素浓缩激素受体 1 (MCH-R1) 拮抗剂。通过对萘并[1,2-b]呋喃-2-甲酰胺骨架的 C-5 位含有各种芳基和杂芳基并具有不同链节长度的该家族成员进行广泛的结构-活性关系（SAR）研究，确定了 5-（4-吡啶基）取代的类似物 10b 是一种高效的 MCH-R1 拮抗剂，其 IC50 值为 3 nM。这种物质还具有良好的代谢稳定性，对细胞色素 P450（CYP450）酶的抑制作用不明显。不过，10b 的口服生物利用度令人难以接受。