trans-3-oxospiro[isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxylic acid | 328233-08-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: trans-3-oxospiro[isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxylic acid
• 英文别名: trans-3-oxo-3H-spiro[2-benzofuran-1,1'-cyclohexane]-4'-carboxylic acid；trans-3'oxospiro[cyclohexane-1,1'(3'H)-isobenzofuran]-4-carboxylic acid
• CAS: 328233-08-5
• 化学式: C₁₄H₁₄O₄
• 分子量: 246.263
• InChiKey: CDDYQAWKPYEZMD-KMHCFJFGSA-N

物化性质

• 沸点：
  504.8±50.0 °C(Predicted)
• 密度：
  1.35

计算性质

• 辛醇/水分配系数(LogP)：
  2.33
• 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：
  0.43
• 拓扑面积：
  63.6
• 氢给体数：
  1.0
• 氢受体数：
  3.0

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  甲基-(2-哌啶-1-乙基)-胺 、 trans-3-oxospiro[isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxylic acid 在 2-chloro-1,3-dimethyl imidazolium chloride 、 三乙胺 作用下， 以 氯仿 为溶剂， 反应 1.0h， 以87%的产率得到(1r,4r)-N-methyl-3'-oxo-N-(2-(piperidin-1-yl)ethyl)-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-4-carboxamide
  参考文献：
  名称：

  Synthesis and evaluation of a spiro-isobenzofuranone class of histamine H3 receptor inverse agonists

  摘要：

  Spiro-isobenzofuranones 1a and 1b were discovered as potent, selective, and brain-penetrable non-imidazole H-3 receptor inverse agonists. Our corporate sample collection was screened to identify 2a as a lead. Recognizing the right-hand portion of 2a as an essential pharmacophore, an extensive screen of the left-hand piperidine portion was carried out to yield the potent spiro-derivatives 2t-x. Spiro-isobenzofuranone 2x, the most potent among the derivatives, was converted to the corresponding amide 1a, which possessed dramatically improved H3 activity (IC50 = 0.72 nM; more than 20-fold improvement over 2x). Further elaboration led to the identification of 1b, a 5-methoxy derivative with an IC50 of 0.54 nM. Our studies demonstrated that derivatives 1a and 1b to be potent, selective, and brain-penetrable H-3 inverse agonists. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.125
• 作为产物：
  描述：

  trans-3-oxo-3H-spiro[2-benzofuran-1,1'-cyclohexane]-4'-carbonitrile 在 硫酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 以96%的产率得到trans-3-oxospiro[isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxylic acid
  参考文献：
  名称：

  新型，强效和选择性反式-2- [3-氧螺环[异苯并呋喃-1（3H），1'-环己基] -4'-基]苯并咪唑NPY Y5受体拮抗剂的合成及构效关系。

  摘要：

  描述了新型的2- [3-氧杂螺[异苯并呋喃-1（3H），1'-环己基] -4'-基]苯并咪唑NPY Y5受体拮抗剂的合成及其构效关系。通过将取代基并入苯并咪唑核心部分的5位或5位和6位两者中来优化前导化合物2a导致鉴定出5-（5-甲基-1,2,4-恶二唑-2 -基）苯并咪唑（2r：IC（50）= 3.3 nM）和5-（2-甲基四唑-5-基）苯并咪唑（2u：IC（50）= 5.9 nM），两者都是有效的，选择性的和口服的可生物利用的Y5受体拮抗剂。

  DOI：

  10.1016/j.bmcl.2008.08.021

文献信息

• Novel spiro compounds
  申请人：——

  公开号：US20020188124A1

  公开（公告）日：2002-12-12

  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 each independently represent nitrogen atom or optionally substituted methine group, where at least two of them represent the said methine group; X represents methine or hydroxy substituted methine; Y represents an optionally substituted imino or oxygen atom are described and claimed. These novel spiro compounds are useful as neuropeptide Y receptor antagonists and as agents for the treatment of various kinds of cardiovascular disorders, central nervous system disorders, metabolic diseases and the like.

  通式(I)的化合物： 1 其中Ar 1 代表可选地取代的芳基或杂芳基； n代表0或1； T、U、V和W各自独立地代表氮原子或可选地取代的次甲基基团，其中至少有两个代表所述次甲基基团； X代表次甲基或羟基取代的次甲基； Y代表可选地取代的亚氨基或氧原子被描述和声称。这些新型的螺环化合物作为神经肽Y受体拮抗剂以及用于治疗各种心血管疾病、中枢神经系统疾病、代谢性疾病等的药物是有用的。
• Syntheses and structure–activity relationships of novel, potent, and selective trans-2-[3-oxospiro[isobenzofuran-1(3H),1′-cyclohexan]-4′-yl]benzimidazole NPY Y5 receptor antagonists
  作者：Yoshio Ogino、Norikazu Ohtake、Yoshikazu Nagae、Kenji Matsuda、Makoto Ishikawa、Minoru Moriya、Maki Kanesaka、Yuko Mitobe、Junko Ito、Tetsuya Kanno、Akane Ishihara、Hisashi Iwaasa、Tomoyuki Ohe、Akio Kanatani、Takehiro Fukami

  DOI：10.1016/j.bmcl.2008.08.021

  日期：2008.9

  ole NPY Y5 receptor antagonists are described. Optimization of the lead compound 2a by incorporating substituents into the 5-position or into both the 5- and 6-positions of the benzimidazole core part led to the identification of 5-(5-methyl-1,2,4-oxadiazol-2-yl)benzimidazole (2r: IC(50)=3.3 nM) and 5-(2-methyltetrazol-5-yl)benzimidazole (2u: IC(50)=5.9 nM), both of which are potent, selective, and

  描述了新型的2- [3-氧杂螺[异苯并呋喃-1（3H），1'-环己基] -4'-基]苯并咪唑NPY Y5受体拮抗剂的合成及其构效关系。通过将取代基并入苯并咪唑核心部分的5位或5位和6位两者中来优化前导化合物2a导致鉴定出5-（5-甲基-1,2,4-恶二唑-2 -基）苯并咪唑（2r：IC（50）= 3.3 nM）和5-（2-甲基四唑-5-基）苯并咪唑（2u：IC（50）= 5.9 nM），两者都是有效的，选择性的和口服的可生物利用的Y5受体拮抗剂。
• Novel azole derivatives
  申请人：Otake Norikazu

  公开号：US20060111380A1

  公开（公告）日：2006-05-25

  The present invention relates to a compound of the formula (I): wherein Az is a group comprising a monocyclic azole or a bicyclic aromatic ring of the same or different fused azoles; T, U, V and W are independently methine or nitrogen, said methine being optionally substituted by a substituent, and at least two of T, U, V and W are said methine groups; and X is nitrogen or methine. The compounds of the present invention are useful as agents for the treatment of various kinds of diseases related to NPY, for example, cardiovascular disorders, nervous system disorders, genitative diseases, metabolic diseases, genital or reproductive disorders, gastrointestinal disorders, respiratory disorders, inflammatory diseases or glaucoma, and the like.

  本发明涉及一种式子为(I)的化合物：其中，Az是包含单环唑或同种或不同融合唑的双环芳香环的基团；T、U、V和W独立地是亚甲基或氮，所述亚甲基可以选用取代基进行取代，且至少有两个T、U、V和W是所述亚甲基基团；而X是氮或亚甲基。本发明的化合物可用作治疗与NPY相关的各种疾病的药剂，例如心血管疾病、神经系统疾病、遗传性疾病、代谢性疾病、生殖器或生殖系统疾病、胃肠疾病、呼吸系统疾病、炎症性疾病或青光眼等。
• Spiro compounds
  申请人：——

  公开号：US20040259890A1

  公开（公告）日：2004-12-23

  Compounds of the formula (I): 1 (wherein A is an optionally substituted straight-chain hydrocarbon having 1 to 6 carbon atoms, which is optionally intervened by oxygen or nitrogen atom; Ar 1 is aryl or heteroaryl, any of which is optionally substituted; n is 0 or 1; R 0 is hydrogen, or lower alkylene attached to an arbitrary, bondable position of A; T, U, V and W are independently nitrogen atom or optionally substituted methine, and at least two of T, U, V and W are said methine group; X is —N(SO 2 R 1 )—, —N(COR 2 )— or —CO—; Y is —C(R 3 )(R 4 )—, —O— or —N(R 5 )—; Z is methine or nitrogen 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, etc., central nervous system disorders such as bulimia, depression, anxiety, seizure, epilepsy, dementia, pain, alcoholism, drug withdrawal, circadian rhythm disorders, schizophrenia, etc., metabolic diseases such as obesity, diabetes, hormone abnormality, hypercholesterolemia, hyperlipidemia, etc., sexual and reproductive dysfunctions, and gastro-intestinal motility disorder.

  化合物的结构式为(I):1（其中A是具有1到6个碳原子的直链烃基，可以是选用的取代基，也可以由氧或氮原子插入；Ar1是芳基或杂环芳基，任何一种都可以是选用的取代基；n为0或1；R0为氢或连接到A的任意可结合位置的低碳烷基；T、U、V和W分别是氮原子或选用的甲烷基，其中至少两个是甲烷基；X为—N(SO2R1)—、—N(COR2)—或—CO—；Y为—C(R3)(R4)—、—O—或—N(R5)—；Z为甲烷基或氮原子），具有NPY拮抗活性，并可用作治疗与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贪食症、抑郁症、焦虑症、癫痫、痴呆、疼痛、酗酒、戒毒、昼夜节律紊乱、精神分裂症等，代谢疾病如肥胖症、糖尿病、激素异常、高胆固醇血症、高脂血症等，性和生殖功能障碍以及胃肠动力障碍。
• NOVEL SPIRO COMPOUNDS
  申请人：——

  公开号：US20020052371A1

  公开（公告）日：2002-05-02

  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, gastro-intestinal disorder, respiratory disorder, inflammation or glaucoma, and the like.

  通式（I）化合物（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独立地代表氮原子或可选取代的甲基基团，其中至少有两个代表所述甲基基团；X代表甲基或氮原子；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剂，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、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。