N-(4-氨基-2-甲基-6-喹啉)-2-[(4-乙基苯氧基)甲基]苯甲酰胺 | 244218-93-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: N-(4-氨基-2-甲基-6-喹啉)-2-[(4-乙基苯氧基)甲基]苯甲酰胺
• 英文名称: N-(4-amino-2-methylquinoline-6-yl)-2-((4-ethylphenoxy)methyl)benzamide
• 英文别名: N-(4-amino-2-methylquinolin-6-yl)-2-((4-ethylphenoxy)methyl)benzamide；N-(4-amino-2-methylquinolin-6-yl)-2-[(4-ethylphenoxy)methyl]benzamide；JTC-801；N-(4-amino-2-methyl-6-quinolyl)-2-[(4-ethylphenoxy)methyl]benzamide；JTC-801 free base
• CAS: 244218-93-7
• 化学式: C₂₆H₂₅N₃O₂
• 分子量: 411.503
• InChiKey: VTGBZWHPJFMTKS-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C(Solv: ethanol (64-17-5))
• 沸点：
  580.9±50.0 °C(Predicted)
• 密度：
  1.240±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  77.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-溴甲基苯甲酸甲酯 在 吡啶 、 sodium hydroxide 、 草酰氯 、 potassium carbonate 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.0h， 生成 N-(4-氨基-2-甲基-6-喹啉)-2-[(4-乙基苯氧基)甲基]苯甲酰胺
  参考文献：
  名称：

  4-Aminoquinolines:  Novel Nociceptin Antagonists with Analgesic Activity

  摘要：

  Small-molecule nociceptin antagonists were synthesized to examine their therapeutic potential. After a 4-aminoquinoline derivative was found to bind with the human ORL1 receptor, a series of 4-aminoquinolines and related compounds were synthesized and their binding was evaluated. Elucidation of structure-activity relationships eventually led to the optimum compounds. One of the se compounds, N-(4-amino-2-methylquinolin-6-yl) -2-(4-ethylphenoxymethyl)benzamide hydrochloride (11) not only antagonized nociceptin-induced allodynia in mice but also showed analgesic effect in a hot plate test using mice and in a formalin test using rats. Its analgesic effect was not antagonized by the opioid antagonist naloxone. These results indicate that this nociceptin antagonist has the potential to become a novel type of analgesic that differs from mu -opioid agonists.

  DOI：

  10.1021/jm0002073

文献信息

• [EN] NOCICEPTIN RECEPTOR ORL-1 AGONISTS FOR USE IN TREATING COUGH<br/>[FR] AGONISTES DU RECEPTEUR ORL-1 DE LA NOCICEPTINE UTILISES POUR LE TRAITEMENT DE LA TOUX
  申请人：SCHERING CORP

  公开号：WO2001007050A1

  公开（公告）日：2001-02-01

  The present invention relates to the use of ORL-1 receptor agonists for the treatment of cough, alone or in combination with one or more agents for the treatment of cough, allergy or asthma symptoms, in particular to the use of ORL-1 agonists of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein: the dotted line represents and optional double bond; X1 is optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl; X2 is-CHO, -CN, optionally substituted amino, alkyl, or aryl; or X1 is optionally substituted benzofused heterocyclyl and X2 is hydrogen; or X?1 and X2¿ together form an optionally benzofused spiro heterocyclyl group R?1, R2, R3 and R4¿ are independently H and alkyl, or (R?1 and R4) or (R2 and R3) or (R1 and R3) or (R2 and R4¿) together can form an alkylene bridge of 1 to 3 carbon atoms; Z1 is optionally substituted alkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, or -CO¿2?(alkyl or substituted amino) or CN; Z?2¿ is H or Z1; Z3 is H or alkyl; or Z?1, Z2 and Z3¿, together with the carbon to which they are attached, form bicyclic saturated or unsaturated rings.

  本发明涉及使用ORL-1受体激动剂治疗咳嗽，单独或与一种或多种用于治疗咳嗽、过敏或哮喘症状的药物组合使用，特别是使用式（I）的ORL-1激动剂或其药学上可接受的盐或溶剂，其中：虚线代表可选的双键；X1是可选的取代基的烷基、环烷基、芳基、杂芳基或杂环烷基；X2是-CHO、-CN、可选的取代氨基、烷基或芳基；或X1是可选的取代苯并杂环基，X2是氢；或X1和X2一起形成可选的苯并螺杂环基团；R1、R2、R3和R4独立地为H和烷基，或（R1和R4）或（R2和R3）或（R1和R3）或（R2和R4）一起形成1至3个碳原子的烷基桥；Z1是可选的取代基的烷基、芳基、杂芳基、环烷基或杂环烷基，或-CO2（烷基或取代氨基）或-CN；Z2是H或Z1；Z3是H或烷基；或Z1、Z2和Z3，与它们连接的碳一起，形成二环饱和或不饱和环。
• Antipruritics
  申请人：——

  公开号：US20040116450A1

  公开（公告）日：2004-06-17

  The present invention relates to an antipruritic agent comprising a nociceptin antagonist as an active ingredient. The nociceptin antagonist can be used as a preventive or remedy for diseases associated with itching (for example, atopic dermatitis and urticaria), local pruritus cutaneous caused by insect excretion and secretion, nodular prurigo, kidney dialysis, diabetes, blood disease, liver disease, kidney disease, incretion and metabolic disorder, viscera malignant tumor, hyperthyroidism, autoimmune disease, multiple sclerosis, neurologic disease, psychoneurosis, allergic conjunctivitis, spring catarrh, atopic keratoconjunctivitis, or itching caused by excess use of laxuries and drugs because it has excellent scrtaching behavior suppressing effect, that is, antiitching effect and antipruritic effect.

  本发明涉及一种抗瘙痒剂，其包含一种镇痛肽拮抗剂作为活性成分。该镇痛肽拮抗剂可用作与瘙痒有关的疾病的预防或治疗（例如，特应性皮炎和荨麻疹），由昆虫排泄物和分泌物引起的局部皮肤瘙痒，结节性瘙痒，肾透析，糖尿病，血液疾病，肝脏疾病，肾脏疾病，内分泌和代谢紊乱，内脏恶性肿瘤，甲状腺功能亢进，自身免疫疾病，多发性硬化症，神经系统疾病，精神神经症，过度使用泻药和药物引起的瘙痒，因为它具有出色的抓痒行为抑制作用，即抗瘙痒作用和抗瘙痒作用。
• Amide derivatives and nociceptin antagonists
  申请人：Japan Tobacco Inc.

  公开号：US20030055087A1

  公开（公告）日：2003-03-20

  The present invention relates to a compound of the formula [1′] 1 wherein R 2 is lower alkyl optionally substituted by hydroxy, amino and the like, ring B is phenyl, thienyl and the like, E is a single bond, —O—, —S— and the like, ring G is aryl, heterocyclic group and the like, R 5 is halogen atom, hydroxy, lower alkyl optionally substituted by halogen atom etc., and the like, t is 0 or an integer of 1 to 5, when t is an integer of 2 to 5, each R 5 may be the same or different, m is 0 or an integer of 1 to 8, and n is 0 or an integer of 1 to 4, and a nociceptin antagonist containing compound [1′] as an active ingredient. The compound [1′] shows, due to nociceptin antagonistic action, analgesic effect against sharp pain such as postoperative pain and the like. The present invention also relates to the use of certain amide derivative inclusive of compound [1′] as a nociceptin antagonist or analgesic.

  本发明涉及一种化合物，其化学式为[1′]1，其中R2是低碳基，可选择性地被羟基、氨基等取代，环B是苯基、噻吩基等，E是单键，-O-，-S-等，环G是芳基、杂环基等，R5是卤素原子、羟基、低碳基，可选择性地被卤素原子等取代，t为0或1至5的整数，当t为2至5的整数时，每个R5可能相同也可能不同，m为0或1至8的整数，n为0或1至4的整数，以及一种含有化合物[1′]作为活性成分的镇痛剂。由于其镇痛剂作用，化合物[1′]对于术后疼痛等尖锐疼痛具有镇痛效果。本发明还涉及某些酰胺衍生物的使用，其中包括化合物[1′]作为镇痛剂或镇痛剂拮抗剂。
• AMIDE DERIVATIVES AND NOCICEPTIN ANTAGONISTS
  申请人：Japan Tobacco Inc.

  公开号：EP1072263A1

  公开（公告）日：2001-01-31

  The present invention relates to a compound of the formula [1' ] wherein R2 is lower alkyl optionally substituted by hydroxy, amino and the like, ring B is phenyl, thienyl and the like, E is a single bond, -O-,-S- and the like, ring G is aryl, heterocyclic group and the like, R5 is halogen atom, hydroxy, lower alkyl optionally substituted by halogen atom etc., and the like, t is 0 or an integer of 1 to 5, when t is an integer of 2 to 5, each R5 may be the same or different, m is 0 or an integer of 1 to 8, and n is 0 or an integer of 1 to 4, and a nociceptin antagonist containing compound [1' ] as an active ingredient The compound [1' ] shows, due to nociceptin antagonistic action, analgesic effect against sharp pain such as postoperative pain and the like. The present invention also relates to the use of certain amide derivative inclusive of compound [1' ] as a nociceptin antagonist or analgesic.

  本发明涉及一种式 [1' ]的化合物。 其中 R2 是任选被羟基、氨基等取代的低级烷基，环 B 是苯基、噻吩基等，E 是单键、-O-、-S- 等，环 G 是芳基、杂环基等，R5 是卤素原子、羟基、任选被卤素原子等取代的低级烷基，t 是 0 或 1 至 5 的整数，当 t 是 2 至 5 的整数时，每个 R5 可以是相同的、等，t 为 0 或 1 至 5 的整数，当 t 为 2 至 5 的整数时，每个 R5 可以相同或不同，m 为 0 或 1 至 8 的整数，n 为 0 或 1 至 4 的整数，以及含有化合物[1']作为活性成分的痛觉素拮抗剂。本发明还涉及包含化合物[1' ]的某些酰胺衍生物作为痛觉素拮抗剂或镇痛剂的用途。
• ANTIPRURITICS
  申请人：Nippon Shinyaku Co., Ltd.

  公开号：EP1371376A1

  公开（公告）日：2003-12-17

  The present invention relates to an antipruritic agent comprising a nociceptin antagonist as an active ingredient. The nociceptin antagonist can be used as a preventive or remedy for diseases associated with itching (for example, atopic dermatitis and urticaria), local pruritus cutaneous caused by insect excretion and secretion, nodular prurigo, kidney dialysis, diabetes, blood disease, liver disease, kidney disease, incretion and metabolic disorder, viscera malignant tumor, hyperthyroidism, autoimmune disease, multiple sclerosis, neurologic disease, psychoneurosis, allergic conjunctivitis, spring catarrh, atopic keratoconjunctivitis, or itching caused by excess use of laxuries and drugs because it has excellent scrtaching behavior suppressing effect, that is, antiitching effect and antipruritic effect.

  本发明涉及一种止痒剂，其活性成分包括一种神经痛素拮抗剂。痛觉素拮抗剂可用于预防或治疗与瘙痒有关的疾病（例如特应性皮炎和荨麻疹）、昆虫排泄和分泌物引起的局部皮肤瘙痒症、结节性瘙痒症、肾透析、糖尿病、血液病、肝病、肾病、增生和代谢紊乱、内脏恶性肿瘤、甲状腺机能亢进症、自身免疫性疾病、多发性硬化症、神经系统疾病、精神神经症、过敏性结膜炎、春季白内障、特应性角结膜炎，或过量使用泻药和药物引起的瘙痒，因为它具有出色的抑制瘙痒行为的效果，即止痒效果和止痒效果。