1,4,10-trioxadispiro[4.2.4⁸.2⁵]tetradecan-9-one | 109006-14-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,4,10-trioxadispiro[4.2.4⁸.2⁵]tetradecan-9-one
• 英文别名: 2-oxaspiro[4.5]decane-1,8-dione ethylene ketal；1,4,10-trioxadispiro[4.2.4.2]tetradecan-9-one；1-Oxo-2-oxaspiro[4.5]decan-8-one, ethylene ketal；1,4,10-Trioxa-dispiro[4.2.4.2]tetradecan-9-one；3,9,12-trioxadispiro[4.2.48.25]tetradecan-4-one
• CAS: 109006-14-6
• 化学式: C₁₁H₁₆O₄
• 分子量: 212.246
• InChiKey: QQPAQCIBECWHPI-UHFFFAOYSA-N

物化性质

• 沸点：
  393.6±42.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,4,10-trioxadispiro[4.2.4⁸.2⁵]tetradecan-9-one 在 吡啶 、 lithium aluminium tetrahydride 、 正丁基锂 、 溶剂黄146 、 二异丙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 、 三氯氧磷 作用下， 以 四氢呋喃 、 正己烷 、 水 为溶剂， 反应 73.0h， 生成
  参考文献：
  名称：

  Property- and Structure-Guided Discovery of a Tetrahydroindazole Series of Interleukin-2 Inducible T-Cell Kinase Inhibitors

  摘要：

  Interleukin-2 inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, plays a major role in T-cell signaling downstream of the T-cell receptor (TCR), and considerable efforts have been directed toward discovery of ITK-selective inhibitors as potential treatments of inflammatory disorders such as asthma. Using a previously disclosed indazole series of inhibitors as a starting point, and using X-ray crystallography and solubility forecast index (SFI) as guides, we evolved a series of tetrahydroindazole inhibitors with improved potency, selectivity, and pharmaceutical properties. Highlights include identification of a selectivity pocket above the ligand plane, and identification of appropriate lipophilic substituents to occupy this space. This effort culminated in identification of a potent and selective ITK inhibitor (GNE-9822) with good ADME properties in preclinical species.

  DOI：

  10.1021/jm500550e
• 作为产物：
  描述：

  ethyl 8-(2-(benzyloxy)ethyl)-1,4-dioxaspiro[4.5]decane-8-carboxylate 在 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 生成 1,4,10-trioxadispiro[4.2.4⁸.2⁵]tetradecan-9-one
  参考文献：
  名称：

  CARBOXAMIDE DERIVATIVES

  摘要：

  本发明提供了化合物(I)或其药学上可接受的盐； 一种制造本发明化合物的方法，以及其治疗用途。本发明还提供了药理活性剂的组合和药物组成。

  公开号：

  US20150329529A1

文献信息

• Analgesic 2-oxa-spirocyclic compounds
  申请人：The Upjohn Company

  公开号：US04588591A1

  公开（公告）日：1986-05-13

  Analgesic 2-oxa-spirocyclic compounds of the formula ##STR1## where the wavy line bonds, p, n, m, A, q, X, Y, R, R.sub.1, R.sub.2 and E are as defined in the specification, e.g., trans-4-bromo-N-methyl-N-[7-(1-pyrrolidinyl)-2-oxaspiro[4.5]dec-8-yl]benza mide, and trans-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)-2-oxaspiro[4.5]dec-8-yl] benzeneacetamide, and acid addition salts thereof. Pharmaceutical compositions and methods of using these compounds as analgesics are disclosed. Processes for preparing the class of compounds are also disclosed.

  镇痛药2-氧代螺环化合物的化学式为##STR1##其中波浪线键，p，n，m，A，q，X，Y，R，R.sub.1，R.sub.2和E的定义如规范中所述，例如，trans-4-溴-N-甲基-N-[7-(1-吡咯烷基)-2-氧代螺[4.5]癸-8-基]苯甲酰胺，以及trans-3,4-二氯-N-甲基-N-[7-(1-吡咯烷基)-2-氧代螺[4.5]癸-8-基]苯乙酰胺，及其酸盐。公开了将这些化合物用作镇痛药的药物组合物和使用方法。还公开了制备这类化合物的过程。
• PYRAZOLE CARBOXAMIDE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Genentech, Inc.

  公开号：US20150158851A1

  公开（公告）日：2015-06-11

  Provided herein are compounds of formula (AA): stereoisomers or a pharmaceutically acceptable salt thereof, wherein A, R a , p, R 5 and R 6 are defined herein, compositions including the compounds and methods of manufacturing and using the compounds for the treatment of diseases.

  本文提供了式（AA）的化合物：其立体异构体或其药学上可接受的盐，其中A、Ra、p、R5和R6在此定义，包括该化合物的组合物以及制造和使用该化合物治疗疾病的方法。
• ARGININE METHYLTRANSFERASE INHIBITORS AND USES THEREOF
  申请人：EPIZYME, INC.

  公开号：US20160024016A1

  公开（公告）日：2016-01-28

  Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds described herein are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

  本文描述了式(I)的化合物，其药学上可接受的盐以及其制药组合物。所述化合物可用于抑制精氨酸甲基转移酶活性。本文还描述了使用这些化合物治疗精氨酸甲基转移酶介导的疾病的方法。
• Carboxamide derivatives
  申请人：Novartis AG

  公开号：US09403810B2

  公开（公告）日：2016-08-02

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了式(I)的化合物或其药学上可接受的盐；一种制造本发明化合物的方法，以及其治疗用途。本发明还提供了一种药理活性剂的组合和制药组合物。
• Arginine methyltransferase inhibitors and uses thereof
  申请人：Epizyme, Inc.

  公开号：US10800743B2

  公开（公告）日：2020-10-13

  Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds described herein are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

  本文描述了式（I）化合物、其药学上可接受的盐及其药物组合物。本文所述化合物可用于抑制精氨酸甲基转移酶活性。还描述了使用这些化合物治疗精氨酸甲基转移酶介导的疾病的方法。