(trans)-3-(6-methyl-2-pyridinyl)-2-oxo-1-oxa-3-azaspiro[4.5]decane-8-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: (trans)-3-(6-methyl-2-pyridinyl)-2-oxo-1-oxa-3-azaspiro[4.5]decane-8-carboxylic acid
• 英文别名: 3-(6-Methylpyridin-2-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decane-8-carboxylic acid
• 化学式: C₁₅H₁₈N₂O₄
• 分子量: 290.319
• InChiKey: AGPXCOKNOZHSBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (trans)-3-(6-methyl-2-pyridinyl)-2-oxo-1-oxa-3-azaspiro[4.5]decane-8-carboxylic acid 在 对甲苯磺酸 吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 2.5h， 生成 (trans)-3-(6-methyl-2-pyridinyl)-8-{5-[(trifluoromethyl)oxy]-3H-benzimidazol-2-yl}-1-oxa-3-azaspiro[4.5]decan-2-one
  参考文献：
  名称：

  WO2008/129007

  摘要：

  公开号：
• 作为产物：
  描述：

  1-噁螺[2.5]辛烷-6-羧酸乙酯 在 copper(l) iodide 、 trans-1,2-cyclohexanediamine 甲醇 、 lithium hydroxide 、 potassium phosphate 、 potassium tert-butylate 、 水 作用下， 以 1,4-二氧六环 、 N,N-二甲基丙烯基脲 为溶剂， 反应 17.25h， 生成 (trans)-3-(6-methyl-2-pyridinyl)-2-oxo-1-oxa-3-azaspiro[4.5]decane-8-carboxylic acid
  参考文献：
  名称：

  WO2008/129007

  摘要：

  公开号：

文献信息

• Chemical Compounds
  申请人：Bentley Jonathan

  公开号：US20090042897A1

  公开（公告）日：2009-02-12

  The present invention relates to novel compounds or a pharmaceutically acceptable salt or solvate thereof, selected from a group consisting of: (trans)-8-([1-(2-fluorophenyl)-1H-pyrazol-3-yl]amino}methyl)-3-(2-fluoro-3-pyridinyl)-1-oxa-3-azaspiro[4.5]decan-2-one; (trans)-8-([1-(2-fluorophenyl)-1H-pyrazol-3-yl]amino}methyl)-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decan-2-one; (trans)-8-([1-(2-fluorophenyl)-1H-pyrazol-3-yl]amino}methyl)-3-(1-methyl-1H-pyrazol-3-yl)-1-oxa-3-azaspiro[4.5]decan-2-one; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as NPY Y5 receptor antagonists and as agents for the treatment and/or prophylaxis of eating disorders such as a binge eating disorder.

  本发明涉及一组新化合物或其药学上可接受的盐或溶剂，所述化合物从以下组中选择：（顺式）-8-（[1-（2-氟苯基）-1H-吡唑-3-基]氨基}甲基）-3-（2-氟-3-吡啶基）-1-氧杂-3-氮杂螺[4.5]癸烷-2-酮；（顺式）-8-（[1-（2-氟苯基）-1H-吡唑-3-基]氨基}甲基）-3-（3-吡嗪基）-1-氧杂-3-氮杂螺[4.5]癸烷-2-酮；（顺式）-8-（[1-（2-氟苯基）-1H-吡唑-3-基]氨基}甲基）-3-（1-甲基-1H-吡唑-3-基）-1-氧杂-3-氮杂螺[4.5]癸烷-2-酮；以及用于它们的制备的中间体，包含它们的药物组合物以及它们作为NPY Y5受体拮抗剂和治疗和/或预防暴食障碍等进食障碍的药物的用途。
• Benzimidazoles With A Hetero Spiro-Decane Residue As NPY-Y5 Antagonists
  申请人：Barton Nicholas Paul

  公开号：US20100216821A1

  公开（公告）日：2010-08-26

  The present invention relates to compounds of formula (I), or a pharmaceutically acceptable salts, solvates, stereoisomers thereof, R 1 may be C 1 -C 4 alkyl, aryl or heteroaryl, which may be substituted by one or more: halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, cyano; R 2 may be halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, cyano, nitro; or aryl, heteroaryl or heterocycle, which may be substituted by one or more: halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, cyano; or R 2 may correspond to —O—R 3 ; R 3 is a 6-membered aromatic carbocyclic ring which may contain 1 or 2 nitrogen X is carbon or oxygen; Z is carbon or nitrogen; G is a fused 6-membered aromatic carbocyclic ring which may contain 1 or 2 nitrogen; m may be 0 or an integer ranging from 1 to 4; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as NPY-Y5 receptor antagonists.

  本发明涉及式（I）的化合物，或其药学上可接受的盐，溶剂化合物和立体异构体，其中R1可以是C1-C4烷基，芳基或杂芳基，可以被一个或多个卤素，C1-C4烷基，C1-C4烷氧基，C1-C4卤代烷基，C1-C4卤代烷氧基，氰基取代；R2可以是卤素，C1-C4烷基，C1-C4烷氧基，C1-C4卤代烷基，C1-C4卤代烷氧基，氰基，硝基或芳基，杂芳基或杂环，可以被一个或多个卤素，C1-C4烷基，C1-C4烷氧基，C1-C4卤代烷基，C1-C4卤代烷氧基，氰基取代；或者R2可以对应于—O—R3；R3是一个含有1或2个氮原子的6元芳香环；X是碳或氧；Z是碳或氮；G是一个融合的含有1或2个氮原子的6元芳香环；m可以是0或一个范围在1到4之间的整数；本发明还涉及制备这些化合物的方法，用于这些方法的中间体，包含它们的制药组合物以及它们作为NPY-Y5受体拮抗剂在治疗中的应用。
• 1-OXA-3-Azaspiro[4,5]Decan--2-One Derivatives For The Treatment Of Eating Disorders
  申请人：Bentley Jonathan

  公开号：US20100286151A1

  公开（公告）日：2010-11-11

  The present invention relates to novel compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R is an aryl or heteroaryl; which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; Z 1 is H, C1-C4 alkyl or F; Z is CH 2 , CH(C1-C4 alkyl), C(C1-C4 alkyl) 2 or a bond; A is a 5 membered heteroaryl, which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, Cl C4 haloalkoxy, cyano; B is hydrogen or is a 5-6 membered heteroaryl, or phenyl, which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; being A and B linked via any atom; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as NPY Y5 receptor antagonists and as agents for the treatment and/or prophylaxis of eating disorders such as a binge eating disorder.

  本发明涉及公式（I）的新化合物，或其药学上可接受的盐或溶剂，其中R是芳基或杂芳基; 可以被一个或多个卤素，C1-C4烷基，C1-C4烷氧基，C1-C4卤代烷基，C1-C4卤代烷氧基，氰基取代; Z1是H，C1-C4烷基或F; Z是CH2，CH（C1-C4烷基），C（C1-C4烷基）2或键; A是5成员杂芳基，可以被一个或多个卤素，C1-C4烷基，C1-C4烷氧基，C1-C4卤代烷基，Cl C4卤代烷氧基，氰基取代; B是氢或是5-6成员杂芳基或苯基，可以被一个或多个卤素，C1-C4烷基，C1-C4烷氧基，C1-C4卤代烷基，C1-C4卤代烷氧基，氰基取代; A和B通过任何原子连接; 用于制备它们的过程，用于这些过程中使用的中间体，包含它们的制药组合物以及它们作为NPY Y5受体拮抗剂和作为治疗和/或预防进食障碍（如暴饮暴食障碍）的药物的用途。
• Design, synthesis and SAR of a novel series of benzimidazoles as potent NPY Y5 antagonists
  作者：Domenica Antonia Pizzi、Colin Philip Leslie、Angelica Mazzali、Catia Seri、Matteo Biagetti、Jonathan Bentley、Thorsten Genski、Romano Di Fabio、Stefania Contini、Fabio Maria Sabbatini、Laura Zonzini、Laura Caberlotto

  DOI：10.1016/j.bmcl.2010.09.064

  日期：2010.12

  A novel class of benzimidazole NPY Y5 receptor antagonists was prepared exploiting a privileged spirocarbamate moiety. The structure-activity relationship of this series and efforts to achieve a profile suitable for further development and an appropriate pharmacokinetic profile in rat are described. Optimisation led to the identification of the brain penetrant, orally bioavailable Y5 antagonist 9b which significantly inhibited the food intake induced by a Y5 selective agonist with a minimal effective dose of 30 mg/kg po. (C) 2010 Elsevier Ltd. All rights reserved.
• 1-OXA-3-AZASPIRO[4,5]DECAN-2-ONE DERIVATIVES FOR THE TREATMENT OF EATING DISORDERS
  申请人：Glaxo Group Limited

  公开号：EP2118097A1

  公开（公告）日：2009-11-18