trans-3-oxo-3H-spiro[5-aza-2-benzofuran-1,1'-cyclohexane]-4'-carboxylic acid | 328233-18-7

• 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: trans-3-oxo-3H-spiro[5-aza-2-benzofuran-1,1'-cyclohexane]-4'-carboxylic acid
• CAS: 328233-18-7
• 化学式: C₁₃H₁₃NO₄
• 分子量: 247.251
• InChiKey: WKGDDMKDIRTPTG-XCSCGOTBSA-N

物化性质

• 密度：
  1.41

计算性质

• 辛醇/水分配系数(LogP)：
  1.72
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  76.49
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  trans-3-oxo-3H-spiro[5-aza-2-benzofuran-1,1'-cyclohexane]-4'-carboxylic acid 、 2-氨基-5-苯基吡嗪 在 吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以43%的产率得到trans-3-oxo-N-(5-phenylpyrazin-2-yl)-3H-spiro[5-aza-2-benzofuran-1,1'-cyclohexane]-4'-carboxamide
  参考文献：
  名称：

  Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′-cyclohexane]-4′-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist

  摘要：

  A series of trans-3-oxospiro[(aza)isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide derivatives were synthesized to identify potent NPY Y5 receptor antagonists. Of the compounds, 21j showed high Y5 binding affinity, metabolic stability and brain and cerebrospinal fluid (CSF) penetration, and low susceptibility to P-glycoprotein transporters. Oral administration of 21j significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 1 mg/kg. This compound was selected for proof-of-concept studies in human clinical trials. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.019
• 作为产物：
  描述：

  trans-3-oxo-3H-spiro[5-aza-2-benzofuran-1,1'-cyclohexane]-4'-carbonitrile 在 硫酸 、 水 作用下， 以92%的产率得到trans-3-oxo-3H-spiro[5-aza-2-benzofuran-1,1'-cyclohexane]-4'-carboxylic acid
  参考文献：
  名称：

  Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′-cyclohexane]-4′-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist

  摘要：

  A series of trans-3-oxospiro[(aza)isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide derivatives were synthesized to identify potent NPY Y5 receptor antagonists. Of the compounds, 21j showed high Y5 binding affinity, metabolic stability and brain and cerebrospinal fluid (CSF) penetration, and low susceptibility to P-glycoprotein transporters. Oral administration of 21j significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 1 mg/kg. This compound was selected for proof-of-concept studies in human clinical trials. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.019

文献信息

• Method for producing alkoxy malonic acid dinitriles
  申请人：——

  公开号：US20030144538A1

  公开（公告）日：2003-07-31

  1 The invention relates to a method for producing alkoxy malonic acid dinitriles of general formula (I), wherein R 1 means C 1 - 6 -alkyl or halogen-substituted C 1-6 -alkyl. The method is characterised in that the corresponding alkoxy malonic acid diamides of general formula (II), wherein R 1 has the aforementioned meaning, are converted by means of a dehydrating agent. The invention also relates to the intermediate products of general formula (III), whereby said products are formed during dehydration.

  这项发明涉及一种制备通式（I）中的烷氧基丙二酸二腈的方法，其中R1代表C1-6烷基或卤素取代的C1-6烷基。该方法的特点在于，通过脱水剂将通式（II）中的相应烷氧基丙二酸二酰胺转化而成，其中R1具有上述含义。该发明还涉及通式（III）的中间产物，这些产物在脱水过程中形成。
• Novel spiro compounds
  申请人：——

  公开号：US20030220499A1

  公开（公告）日：2003-11-27

  Compounds of the general formula (I): 1 (wherein Ar 1 represents optionally substituted aryl or heteroaryl; n represents 0 or 1; T, U, V and W represent independently nitrogen atom or optionally substituted methine group, where at least two of them represent the said methine group; X represents methine or nitrogen; Y represents optionally substituted imino or oxygen atom) exhibit NPY antagonistic activities and are useful as agents for the treatment of various diseases related to NPY, for example, cardiovascular disorders such as hypertension, nephropathy, heart disease, vasospasm, arteriosclerosis and the like, central nervous system disorders such as bulimia, depression, anxiety, seizure, epilepsy, dementia, pain, alcoholism, drug withdrawal and the like, metabolic diseases such as obesity, diabetes, hormone abnormality, hypercholesterolemia, hyperlipidemia and the like, sexual and reproductive dysfunction, gastrointestinal disorder, respiratory disorder, inflammation or glaucoma, and the like.

  通式（I）的化合物：1（其中Ar1代表可选取代的芳基或杂环芳基；n代表0或1；T、U、V和W分别独立地代表氮原子或可选取代的甲烷基，其中至少两个代表所述的甲烷基；X代表甲烷或氮；Y代表可选取代的亚胺基或氧原子）表现出NPY拮抗活性，并且可用作治疗与NPY相关的各种疾病的药物，例如心血管疾病如高血压、肾病、心脏病、血管痉挛、动脉硬化等，中枢神经系统疾病如暴食症、抑郁症、焦虑症、癫痫、痴呆、疼痛、酗酒、药物戒断等，代谢性疾病如肥胖症、糖尿病、激素异常、高胆固醇血症、高脂血症等，性和生殖功能障碍、胃肠道疾病、呼吸系统疾病、炎症或青光眼等。
• Aza-Substituted Spiro Derivatives
  申请人：Jitsuoka Makoto

  公开号：US20090258871A1

  公开（公告）日：2009-10-15

  A compound of the following formula (I) or its pharmaceutically-acceptable salt is provided: [wherein X, Y, Z and W each independently represent a methine group or a nitrogen atom, provided that a case where all of X, Y, Z and W are methine group; A represents —O— or the like, B represents —C(O)— or the like, D represent —(CH 2 )m 2 -, —O— or the like, and m2 represents 0 or 1; Q represents a methine group or a nitrogen atom; and R represents a group represented by the following formula (II-1) (wherein R 6 , R 7 and R 8 independently represent a lower alkyl group or the like].

  提供以下式子（I）的化合物或其药学上可接受的盐：[其中X、Y、Z和W各自独立地表示甲基基团或氮原子，前提是当X、Y、Z和W全部为甲基基团时；A表示—O—或类似物，B表示—C（O）—或类似物，D表示—（CH2）m2-、—O—或类似物，m2表示0或1；Q表示甲基基团或氮原子；R表示由以下式子（II-1）表示的基团（其中R6、R7和R8各自独立地表示较低的烷基基团或类似物）。
• AZA-SUBSTITUTED SPIRO DERIVATIVES
  申请人：Jitsuoka Makoto

  公开号：US20120149703A1

  公开（公告）日：2012-06-14

  A compound of the following formula (I) or its pharmaceutically-acceptable salt is provided: [wherein X, Y, Z and W each independently represent a methine group or a nitrogen atom, provided that a case where all of X, Y, Z and W are methine group; A represents —O— or the like, B represents —C(O)— or the like, D represent —(CH 2 )m 2 -, —O— or the like, and m2 represents 0 or 1; Q represents a methine group or a nitrogen atom; and R represents a group represented by the following formula (II-1) (wherein R 6 , R 7 and R 8 independently represent a lower alkyl group or the like].

  提供以下式子（I）或其药学上可接受的盐的化合物： 其中X、Y、Z和W各自独立地表示一个甲基基团或氮原子，前提是X、Y、Z和W全部都是甲基基团的情况除外；A表示—O—或类似物，B表示—C（O）—或类似物，D表示—（CH2）m2-、—O—或类似物，m2表示0或1；Q表示一个甲基基团或氮原子；R表示以下式子（II-1）所表示的基团（其中R6、R7和R8各自独立地表示低级烷基或类似物）。
• Method for producing alkoxymalononitriles
  申请人：——

  公开号：US20040063987A1

  公开（公告）日：2004-04-01

  A process for preparing 2-cyno-2-alkoxyacetamides of the formula: 1 where R 1 is C 1-16 -alkyl or halogen-substituted C 1-16 -alkyl, wherein appropriate alkoxymalonamides of the general formula: 2 where R 1 is as defined above, are reacted with a dehydrating agent and the reaction is stopped before the reaction continues to 2-cyano-2-alkoxyacetamides (I).

  一种制备式 2-氰基-2-烷氧基乙酰胺的工艺： 1 其中 R 1 是 C 1-16 -烷基或卤素取代的 C 1-16 -烷基，其中适当的烷氧基丙二酰胺的通式为 2 其中 R 1 与脱水剂反应，并在反应继续进行之前停止反应，生成 2-氰基-2-烷氧基乙酰胺 (I)。