(trans)-8-(hydroxymethyl)-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decan-2-one | 1044271-22-8

• 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)-8-(hydroxymethyl)-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decan-2-one
• CAS: 1044271-22-8
• 化学式: C₁₃H₁₇N₃O₃
• 分子量: 263.296
• InChiKey: YYWHIHTZFZZRSG-MJHDQNEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.35
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  75.55
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (trans)-8-(hydroxymethyl)-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decan-2-one 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 生成 (trans)-2-oxo-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decane-8-carbaldehyde
  参考文献：
  名称：

  Discovery and structure–activity relationship of a novel spirocarbamate series of NPY Y5 antagonists

  摘要：

  A novel series of trans-8-aminomethyl-1-oxa-3-azaspiro[4.5] decan-2-one derivatives was identified with potent NPY Y5 antagonist activity. Optimization of the original lead furnished compounds 23p and 23u, which combine sub-nanomolar Y5 activity with metabolic stability, oral bioavailability, brain penetration and strong preclinical profile for development. Both compounds significantly inhibited the food intake induced by a Y5 selective agonist with minimal effective doses of 3 mg/kg po. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.041
• 作为产物：
  描述：

  (trans)-2-oxo-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decane-8-carboxylic acid 在 硼烷四氢呋喃络合物 、 盐酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.0h， 以64%的产率得到(trans)-8-(hydroxymethyl)-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decan-2-one
  参考文献：
  名称：

  Spiro Compounds As NPY Y5 Receptor Antagonists

  摘要：

  本发明涉及式(I)的新化合物或其药学上可接受的盐，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氧烷基、C1-C4卤代烷基、C1-C4卤代氧烷基、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是一个6-10成员芳基或杂芳基，可以被一个或多个卤素、C1-C4烷基、C1-C4氧烷基、C1-C4卤代烷基、C1-C4卤代氧烷基、氰基或—C(═O)—X取代；或—O(CH2)0-1R1；B是氢或是一个5-6成员杂芳基、或一个4-6成员杂环、或苯基，可以被一个或多个卤素、C1-C4烷基、C1-C4氧烷基、C1-C4卤代烷基、C1-C4卤代氧烷基、羟基、氰基取代；A和B通过任何原子连接；R1是—(C1-C4)烷基(C1-C4)氧基；或C3-C8环烷基；或R1是一个芳基或杂芳基，可以被一个或多个卤素、C1-C4烷基、C1-C4氧烷基、C1-C4卤代烷基、C1-C4卤代氧烷基、氰基取代；或R1是一个4-6成员杂环，可以被一个或多个卤素、C1-C4烷基、C1-C4氧烷基、C1-C4卤代烷基、C1-C4卤代氧烷基、氰基取代；X是OR2或NR3R4；R2是C1-C4烷基；R3是氢或与R4和氮一起形成一个5-6饱和成员环；R4是C3-C8环烷基；它们的制备方法，用于这些方法的中间体，含有它们的药物组合物以及它们作为NPY Y5受体拮抗剂和用于治疗和/或预防暴饮暴食等进食障碍的药物的用途。

  公开号：

  US20090203705A1

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。
• 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。
• 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
• [EN] 1-OXA-3-AZASPIRO(4.5)DECAN-2-ONE DERIVATIVES FOR THE TREATMENT OF EATING DISORDERS<br/>[FR] DÉRIVÉS DE 1-OXA-3-AZASPIRO [4,5] DÉCANE-2-ONE POUR LE TRAITEMENT DE TROUBLES DE L'ALIMENTATION
  申请人：GLAXO GROUP LTD

  公开号：WO2008092891A1

  公开（公告）日：2008-08-07

  [EN] 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.
  [FR] L'invention concerne de nouveaux composés ou un sel ou solvate pharmaceutiquement acceptable de ceux-ci, choisis dans le groupe composé de (trans)-8-([1-(2-fluorophényle)-1H-pyrazolo-3-yle]amino}méthyle)-3-(2-fluoro-3-pyridinyle)-1-oxa-3-azaspiro [4,5] décane-2-one; (trans)-8-([1-(2-fluorophényle)-1H-pyrazolo-3-yle]amino}méthyle)-3-(3-pyridazinyle)-1-oxa-3-azaspiro [4,5] décane-2-one; (trans)-8-([1-(2-fluorophényle)-1H-pyrazolo-3-yle]amino}méthyle)-3-(1-méthyle-1H-pyrazolo-3-yle)-1-oxa-3-azaspiro [4,5] décane-2-one. L'invention concerne également des procédés de fabrication de ces composés, des compositions pharmaceutiques contenant ces composés et leur utilisation en thérapie, en tant qu'antagonistes du récepteur de NPY Y5, et en tant qu'agents pour le traitement et/ou la prophylaxie de troubles de l'alimentation tels que la frénésie alimentaire.
• [EN] 1-OXA-3-AZASPIRO[4,5]DECAN--2-ONE DERIVATIVES FOR THE TREATMENT OF EATING DISORDERS<br/>[FR] DÉRIVÉS 1-OXA-3-AZASPIRO [4,5] DÉCANE-2-ONE POUR LE TRAITEMENT DE TROUBLES DE L'ALIMENTATION
  申请人：GLAXO GROUP LTD

  公开号：WO2008092888A1

  公开（公告）日：2008-08-07

  [EN] 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; Z₁ is H, C1-C4 alkyl or F; Z is CH₂, 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, C1-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.
  [FR] L'invention concerne de nouveaux composés de formule (I) ou un sel ou un solvate pharmaceutiquement acceptable de ceux-ci, R étant aryle ou hétéroaryle pouvant être substitué par halogène, C1-C4-alkyle, C1-C4-alcoxy, C1-C4-haloalkyle, C1-C4-haloalcoxy et/ou cyano; Z₁ étant H, C1-C4-alkyle ou F; Z étant CH₂, CH(C1-C4 alkyle), C(C1-C4 alkyle)₂ ou une liaison; A étant hétéroaryle à 5 éléments, pouvant être substitué par halogène, C1-C4-alkyle, C1-C4-alcoxy, C1-C4-haloalkyle, C1-C4-haloalcoxy et/ou cyano; B étant hydrogène ou un hétéroaryle ou phényle à 5 ou 6 éléments pouvant être substitué par halogène, C1-C4-alkyle, C1-C4-alcoxy, C1-C4-haloalkyle, C1-C4-haloalcoxy et/ou cyano; A et B étant liés par n'importe quel atome. L'invention concerne également des procédés de fabrication de ces composés, des intermédiaires employés dans ces procédés, des compositions pharmaceutiques contenant ces composés et leur utilisation en thérapie, en tant qu'antagonistes du récepteur de NPY Y5, et en tant qu'agents pour le traitement et/ou la prophylaxie de troubles de l'alimentation tels que la frénésie alimentaire.