(S)-1-(5-azaspiro[2.4]hept-6-yl)methanol | 1431322-86-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (S)-1-(5-azaspiro[2.4]hept-6-yl)methanol
• 英文别名: (S)-(5-Azaspiro[2.4]heptan-6-yl)methanol；[(6S)-5-azaspiro[2.4]heptan-6-yl]methanol
• CAS: 1431322-86-9
• 化学式: C₇H₁₃NO
• 分子量: 127.186
• InChiKey: WMRHLUMWSAZZMJ-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-1-(5-azaspiro[2.4]hept-6-yl)methanol 在 三苯基膦 、 sodium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 (S)-tert-butyl 6-((1,3-dioxoisoindolin-2-yl)methyl)-5-azaspiro[2.4]heptane-5-carboxylate
  参考文献：
  名称：

  发现，合成，选择性调制和DMPK表征5-氮杂螺[2.4]庚烷作为有效的食欲素受体拮抗剂。

  摘要：

  从orexin 1受体选择性拮抗剂4，4-二取代哌啶系列开始，发现了一种新型的有效的5-azaspiro [2.4]庚烷双重orexin 1和orexin 2受体拮抗剂。本文公开了该系列的SAR和药代动力学优化。铅化合物15在大鼠中表现出针对orexin 1和orexin 2受体的有效活性，以及​​低的细胞色素P450抑制潜能，良好的脑渗透性和口服生物利用度。

  DOI：

  10.1016/j.bmcl.2013.02.093
• 作为产物：
  描述：

  (3R,7aS)-6-methylene-3-phenyltetrahydropyrrolo[1,2-c]oxazol-5(1H)-one 在 lithium aluminium tetrahydride 、 palladium 10% on activated carbon 、 氢气 、 三甲基碘化亚砜 、 sodium hydride 作用下， 以 四氢呋喃 、 溶剂黄146 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-1-(5-azaspiro[2.4]hept-6-yl)methanol
  参考文献：
  名称：

  发现，合成，选择性调制和DMPK表征5-氮杂螺[2.4]庚烷作为有效的食欲素受体拮抗剂。

  摘要：

  从orexin 1受体选择性拮抗剂4，4-二取代哌啶系列开始，发现了一种新型的有效的5-azaspiro [2.4]庚烷双重orexin 1和orexin 2受体拮抗剂。本文公开了该系列的SAR和药代动力学优化。铅化合物15在大鼠中表现出针对orexin 1和orexin 2受体的有效活性，以及​​低的细胞色素P450抑制潜能，良好的脑渗透性和口服生物利用度。

  DOI：

  10.1016/j.bmcl.2013.02.093

文献信息

• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：ROTTAPHARM SPA

  公开号：WO2013092893A1

  公开（公告）日：2013-06-27

  The invention relates to a novel compound of formula (I) or a stereoisomer, or a racemate or a mixture or a pharmaceutically acceptable salt thereof: wherein: R is phenyl or a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from S, N and O, such rings may be optionally substituted with n groups Q; Q is selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN, SO2CH3 or a group -O[(CR1R2]pQ1; or Q may be a group Q2; Q1 is phenyl, which may be optionally substituted with n substituents selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN, or a group Q2; or corresponds to 2,2-difluoro- benzo[d][1,3]dioxol-4-yl; Q2 is a 5- or 6-membered heteroaryl containing at least one nitrogen atom, which may optionally substituted with n substituents selected from a group consisting of: C1 C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; P is a 6-membered heteroaryl or a 8-1 1 membered bicylic heteroaryl group, which may be substituted with n substituents selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; R1 is hydrogen or C1-C3 alkyl; R2 is hydrogen or C1-C3 alkyl; n is 1, 2 or 3; p is 0, 1 or 2; and with the proviso that when R corresponds to phenyl, P is substituted by at least one CF3; processes for the preparation of those compounds, pharmaceutical compositions containing one or more compounds of formula (I) and their use as dual antagonists of the Orexin 1 and Orexin 2 receptors.

  该发明涉及以下式(I)的新化合物或其立体异构体、消旋体或混合物或其药学上可接受的盐：其中：R为苯基或含有1至3个来自S、N和O的杂原子的5-或6-成员杂芳环，这些环可以选择性地用n个基团Q取代；Q选自以下组成的一组：C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN、SO2CH3或一个基团-O[(CR1R2]pQ1；或Q可以是一个基团Q2；Q1为苯基，可以选择性地用n个取代基从以下组成的一组中取代：C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN或一个基团Q2；或对应于2,2-二氟苯并[d][1,3]二噁唑-4-基；Q2为含有至少一个氮原子的5-或6-成员杂芳基，可以选择性地用n个取代基从以下组成的一组中取代：C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN；P为6-成员杂芳基或8-11-成员双环杂芳基，可以选择性地用n个取代基从以下组成的一组中取代：C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN；R1为氢或C1-C3烷基；R2为氢或C1-C3烷基；n为1、2或3；p为0、1或2；并且在R对应于苯基时，P至少被一个CF3取代；制备这些化合物的方法，含有一个或多个式(I)化合物的药物组合物以及它们作为Orexin 1和Orexin 2受体的双重拮抗剂的用途。
• CHEMICAL COMPOUNDS
  申请人：Rottapharm Biotech S.r.I.

  公开号：US20140357653A1

  公开（公告）日：2014-12-04

  The invention relates to a novel compound of formula (I) or a stereoisomer, or a racemate or a mixture or a pharmaceutically acceptable salt thereof: wherein: R is phenyl or a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from S, N and O, such rings may be optionally substituted with n groups Q; Q is selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN, SO 2 CH 3 or a group —O[(CR 1 R 2 ]pQ 1 ; or Q may be a group Q 2 ; Q 1 is phenyl, which may be optionally substituted with n substituents selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN, or a group Q 2 ; or corresponds to 2,2-difluoro-benzo[d][1,3]dioxol-4-yl; Q2 is a 5- or 6-membered heteroaryl containing at least one nitrogen atom, which may optionally substituted with n substituents selected from a group consisting of: Cl C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; P is a 6-membered heteroaryl or a 8-1 1 membered bicyclic heteroaryl group, which may be substituted with n substituents selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; R 1 is hydrogen or C1-C3 alkyl; R 2 is hydrogen or C1-C3 alkyl; n is 1, 2 or 3; p is 0, 1 or 2; and with the proviso that when R corresponds to phenyl, P is substituted by at least one CF 3 ; processes for the preparation of those compounds, pharmaceutical compositions containing one or more compounds of formula (I) and their use as dual antagonists of the Orexin 1 and Orexin 2 receptors.

  该发明涉及以下式(I)的新化合物或其立体异构体、或其外消旋体或混合物或其药学上可接受的盐：其中：R为苯基或含有1至3个来自S、N和O的杂原子的5-或6-成员杂芳环，该环可以选择性地用n个基团Q取代；Q选自以下群体之一：C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN、SO2CH3或一个基团—O[(CR1R2]pQ1；或Q可以是一个基团Q2；Q1为苯基，可以选择性地用n个取代基团取代，所述取代基团选自以下群体之一：C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN，或一个基团Q2；或对应于2,2-二氟苯并[d][1,3]二噁唑-4-基；Q2为含有至少一个氮原子的5-或6-成员杂芳基，可以选择性地用n个取代基团取代，所述取代基团选自以下群体之一：Cl C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN；P为6-成员杂芳或8-11-成员双环杂芳基，可以选择性地用n个取代基团取代，所述取代基团选自以下群体之一：C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN；R1为氢或C1-C3烷基；R2为氢或C1-C3烷基；n为1、2或3；p为0、1或2；且条件是当R对应于苯基时，P至少被一个CF3取代；制备这些化合物的方法，含有一个或多个式(I)化合物的药物组合物以及它们作为Orexin 1和Orexin 2受体的双重拮抗剂的用途。
• [EN] IMIDAZOLE-CONTAINING INHIBITORS OF ALK2 KINASE<br/>[FR] INHIBITEURS DE LA KINASE ALK2 CONTENANT DE L'IMIDAZOLE
  申请人：BIOCRYST PHARM INC

  公开号：WO2018232094A1

  公开（公告）日：2018-12-20

  Disclosed are compounds of formula (I), (II), (III), and (IV), and pharmaceutically acceptable salts thereof. The compounds are inhibitors of ALK2 kinase. Also provided are pharmaceutical compositions comprising a compound of formula (I), (II), (III), or (IV), or pharmaceutically acceptable salt thereof, and methods involving use of the compounds or pharmaceutically acceptable salts thereof and compositions in the treatment and prevention of various diseases and conditions, such as fibrodysplasia ossificans progressiva.

  揭示了化合物的公式（I）、（II）、（III）和（IV），以及它们的药用盐。这些化合物是ALK2激酶的抑制剂。还提供了包含公式（I）、（II）、（III）或（IV）的化合物或其药用盐的药物组合物，以及涉及使用这些化合物或其药用盐和组合物治疗和预防各种疾病和病况的方法，如纤维性骨化进行性疾病。
• Chemical compounds
  申请人：Rottapharm Biotech S.r.l.

  公开号：US09062033B2

  公开（公告）日：2015-06-23

  The invention relates to a novel compound of formula (I) or a stereoisomer, or a racemate or a mixture or a pharmaceutically acceptable salt thereof: wherein: R is phenyl or a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from S, N and O, such rings may be optionally substituted with n groups Q; Q is selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN, SO2CH3 or a group —O[(CR1R2]pQ1; or Q may be a group Q2; Q1 is phenyl, which may be optionally substituted with n substituents selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN, or a group Q2; or corresponds to 2,2-difluoro-benzo[d][1,3]dioxol-4-yl; Q2 is a 5- or 6-membered heteroaryl containing at least one nitrogen atom, which may optionally substituted with n substituents selected from a group consisting of: C1 C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; P is a 6-membered heteroaryl or a 8-1 1 membered bicyclic heteroaryl group, which may be substituted with n substituents selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; R1 is hydrogen or C1-C3 alkyl; R2 is hydrogen or C1-C3 alkyl; n is 1, 2 or 3; p is 0, 1 or 2; and with the proviso that when R corresponds to phenyl, P is substituted by at least one CF3; processes for the preparation of those compounds, pharmaceutical compositions containing one or more compounds of formula (I) and their use as dual antagonists of the Orexin 1 and Orexin 2 receptors.

  本发明涉及一种新型化合物，其化学式为（I）或其立体异构体、外消旋体、混合物或药物可接受的盐：其中：R为苯基或含有1至3个S、N和O杂原子的5-或6元杂环，这些环可以选择性地用n个基团Q取代；Q选自由以下组：C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN、SO2CH3或—O[(CR1R2]pQ1的基团；或Q可以是Q2基团；Q1为苯基，可以选择性地用n个取代基团来自以下组：C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN或Q2基团；或对应于2,2-二氟苯并[d][1,3]二氧杂环-4-基基团；Q2为含有至少一个氮原子的5-或6元杂环，可以选择性地用n个取代基团来自以下组：C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN；P为6元杂环或8-11元双环杂环基团，可以选择性地用n个取代基团来自以下组：C1-C4烷基、卤素、卤代C1-C4烷基、C1-C4烷氧基、CN；R1为氢或C1-C3烷基；R2为氢或C1-C3烷基；n为1、2或3；p为0、1或2；条件是当R对应于苯基时，P被至少一个CF3取代；制备这些化合物的方法，含有一种或多种化合物的制药组合物以及它们作为Orexin 1和Orexin 2受体的双重拮抗剂的用途。
• PROCESSES FOR THE PREPARATION OF NOVEL BENZIMIDAZOLE DERIVATIVES
  申请人：ENANTA PHARMACEUTICALS, INC.

  公开号：US20140316143A1

  公开（公告）日：2014-10-23

  The present invention relates to processes and intermediates for the preparation of novel benzimidazole derivatives, especially in the synthesis of hepatitis C virus NS5A inhibitors. In particular, the present invention relates to processes and intermediates for the preparation of compounds of formulae (I-a):

  本发明涉及制备新型苯并咪唑衍生物的方法和中间体，尤其是在合成丙型肝炎病毒NS5A抑制剂方面。特别是，本发明涉及制备式（I-a）化合物的方法和中间体：