1-(3-Methylbutyl)-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carboxylic acid | 885485-13-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(3-Methylbutyl)-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carboxylic acid
• CAS: 885485-13-2
• 化学式: C₁₇H₂₅NO₃
• 分子量: 291.39
• InChiKey: IFPFTGMAWXVUBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-Methylbutyl)-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carboxylic acid 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 甲苯 为溶剂， 反应 0.5h， 生成 1-(3-Methylbutyl)-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonyl chloride
  参考文献：
  名称：

  Selective CB2 agonists with anti-pruritic activity: Discovery of potent and orally available bicyclic 2-pyridones

  摘要：

  The CB2 receptor has emerged as a potential target for the treatment of pruritus as well as pain without CB1-mediated side effects. We previously identified 2-pyridone derivatives 1 and 2 as potent CB2 agonists; however, this series of compounds was found to have unacceptable pharmacokinetic profiles with no significant effect in vivo. To improve these profiles, we performed further structural optimization of 1 and 2, which led to the discovery of bicyclic 2-pyridone 18e with improved CB2 affinity and selectivity over CB1. In a mouse pruritus model, 18e inhibited compound 48/80 induced scratching behavior at a dose of 100 mg/kg. In addition, the docking model of 18e with an active-state CB2 homology model indicated the structural basis of its high affinity and selectivity over CB1. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2013.03.030
• 作为产物：
  描述：

  在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 1-(3-Methylbutyl)-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carboxylic acid
  参考文献：
  名称：

  Selective CB2 agonists with anti-pruritic activity: Discovery of potent and orally available bicyclic 2-pyridones

  摘要：

  The CB2 receptor has emerged as a potential target for the treatment of pruritus as well as pain without CB1-mediated side effects. We previously identified 2-pyridone derivatives 1 and 2 as potent CB2 agonists; however, this series of compounds was found to have unacceptable pharmacokinetic profiles with no significant effect in vivo. To improve these profiles, we performed further structural optimization of 1 and 2, which led to the discovery of bicyclic 2-pyridone 18e with improved CB2 affinity and selectivity over CB1. In a mouse pruritus model, 18e inhibited compound 48/80 induced scratching behavior at a dose of 100 mg/kg. In addition, the docking model of 18e with an active-state CB2 homology model indicated the structural basis of its high affinity and selectivity over CB1. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2013.03.030

文献信息

• 3-Carbamoyl-2-Pyridone Derivative
  申请人：Ishizuka Natsuki

  公开号：US20080103139A1

  公开（公告）日：2008-05-01

  The present invention provides compounds having an agonistic activity to the cannabinoid receptor, which is represented by the formula (I): wherein R 1 is optionally substituted C1-C8 alkyl and the like; R 2 is C1-C6 alkyl; R 3 is C1-C6 alkyl and the like; or R 2 and R 3 taken together with may form an optionally substituted 5 to 10 membered non-aromatic carbon ring; R 4 is hydrogen and the like; G is a group selected from the groups shown by the formula an the like: wherein R 5 is hydrogen and the like; X 1 is a single bond and the like; X 2 is optionally substituted C1-C8 alkylene that may be replaced by one or two groups of —O—, or —N(R 6 )—, wherein R 6 is hydrogen and the like, and the like; X 3 is a single bond and the like; a pharmaceutically acceptable salt or a solvate thereof, and pharmaceutical compositions, atopic dermatitis treating agents, and anti-pruritus agents, especially anti-pruritus agents for oral used and for external application, which each contains the said compound as an active ingredient.

  本发明提供了具有激动大麻素受体的作用的化合物，其由式（I）表示：其中，R1是可选取的取代的C1-C8烷基等；R2是C1-C6烷基；R3是C1-C6烷基等；或R2和R3共同形成可选取代的5至10个成员的非芳香碳环；R4是氢等；G是由式等所示的基团中选取的基团：其中，R5是氢等；X1是单键等；X2是可选取代的C1-C8烷基，可以被一或两个-O-或-N（R6）-的基团替代，其中R6是氢等；X3是单键等；其药学上可接受的盐或其溶剂，以及制药组合物、治疗特应性皮炎的制剂和抗瘙痒剂，特别是口服和外用的抗瘙痒剂，每种制剂均以所述化合物为活性成分。
• 3-CARBAMOYL-2-PYRIDONE DERIVATIVES
  申请人：ISHIZUKA Natsuki

  公开号：US20120208813A1

  公开（公告）日：2012-08-16

  The present invention provides compounds having an agonistic activity to the cannabinoid receptor, which is represented by the formula (I): wherein R 1 , R 2 , R 3 , R 4 , and G are defined as herein, a pharmaceutically acceptable salt or a solvate thereof, and pharmaceutical compositions, atopic dermatitis treating agents, and anti-pruritus agents, especially anti-pruritus agents for oral used and for external application, which each contains the said compound as an active ingredient.

  本发明提供了具有激动大麻素受体的活性的化合物，该受体由公式（I）表示：其中R1、R2、R3、R4和G如本文所定义，其药学上可接受的盐或溶剂，以及制备该化合物为活性成分的药物组合物、治疗特应性皮炎的药剂和抗瘙痒剂，尤其是用于口服和外用的抗瘙痒剂。
• 3-CARBAMOYL-2-PYRIDONE DERIVATIVE
  申请人：SHIONOGI & CO., LTD.

  公开号：EP1806342A1

  公开（公告）日：2007-07-11

  The present invention provides compounds having an agonistic activity to the cannabinoid receptor, which is represented by the formula (I): wherein R1 is optionally substituted C1-C8 alkyl and the like; R2 is C1-C6 alkyl; R3 is C1-C6 alkyl and the like; or R2 and R3 taken together with may form an optionally substituted 5 to 10 membered non-aromatic carbon ring; R4 is hydrogen and the like; G is a group selected from the groups shown by the formula an the like: wherein R5 is hydrogen and the like; X1 is a single bond and the like; X2 is optionally substituted C1-C8 alkylene that may be replaced by one or two groups of -O-, or -N(R6)-, wherein R6 is hydrogen and the like, and the like; X3 is a single bond and the like; a pharmaceutically acceptable salt or a solvate thereof, and pharmaceutical compositions, atopic dermatitis treating agents, and anti-pruritus agents, especially anti-pruritus agents for oral used and for external application, which each contains the said compound as an active ingredient.

  本发明提供了对大麻素受体具有激动活性的化合物，该受体由式 (I) 表示： 其中 R1 是任选取代的 C1-C8 烷基及类似物；R2 是 C1-C6 烷基；R3 是 C1-C6 烷基及类似物；或 R2 和 R3 一起可形成任选取代的 5 至 10 个成员的非芳香族碳环；R4 是氢及类似物；G 是选自式所示基团及类似物的基团： 其中 R5 是氢和类似物；X1 是单键和类似物；X2 是可被一个或两个基团-O-或-N(R6)-取代的任选取代的 C1-C8 亚烷基，其中 R6 是氢和类似物；X3 是单键和类似物； 其药学上可接受的盐或溶液，以及药物组合物、特应性皮炎治疗剂和止痒剂，尤其是口服和外用的止痒剂，其中每一种都含有上述化合物作为活性成分。
• US8178681B2
  申请人：——

  公开号：US8178681B2

  公开（公告）日：2012-05-15
• US8367666B2
  申请人：——

  公开号：US8367666B2

  公开（公告）日：2013-02-05