azetidin-1-yl(4-bromophenyl)methanone | 925423-97-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: azetidin-1-yl(4-bromophenyl)methanone
• 英文别名: 1-(4-Bromobenzoyl)azetidine；azetidin-1-yl-(4-bromophenyl)methanone
• CAS: 925423-97-8
• 化学式: C₁₀H₁₀BrNO
• mdl: MFCD26397592
• 分子量: 240.099
• InChiKey: DZQKIBIXQBMKRW-UHFFFAOYSA-N

物化性质

• 沸点：
  351.0±25.0 °C(Predicted)
• 密度：
  1.546±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  azetidin-1-yl(4-bromophenyl)methanone 在 copper(l) iodide 、 2,2,6,6-四甲基-3,5-庚二酮 、 偶氮二甲酸二异丙酯 、 caesium carbonate 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 (S)-3-(4-(azetidine-1-carbonyl)phenoxy)-5-((1-methoxypropan-2-yl)oxy)-N-(5-(2-oxo-1,2-dihydropyridin-4-yl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)benzamide
  参考文献：
  名称：

  Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation

  摘要：

  Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected beta-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.051
• 作为产物：
  描述：

  对溴苯乙烯 在 三乙烯二胺 、 dipotassium peroxodisulfate 、 silver nitrate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 36.0h， 生成 azetidin-1-yl(4-bromophenyl)methanone
  参考文献：
  名称：

  胺诱导 2,2,2-三氟乙基羰基选择性 C-C 键断裂用于合成脲和酰胺

  摘要：

  据报道，2,2,2-三氟乙基羰基与胺有效且选择性地转化为脲/酰胺。该方案允许在无过渡金属和无氧化剂的条件下选择性裂解 2,2,2-三氟乙基羰基的 C-C 键，这与类似的 C-F 或 C-CF 3 键功能化相反。该反应揭示了 2,2,2-三氟乙基羰基的未开发反应性，并表现出广泛的底物范围和良好的官能团耐受性。

  DOI：

  10.1021/acs.joc.3c00979

文献信息

• Chemoselective Ketone Synthesis by the Addition of Organometallics to <i>N</i>-Acylazetidines
  作者：Chengwei Liu、Marcel Achtenhagen、Michal Szostak

  DOI：10.1021/acs.orglett.6b00842

  日期：2016.5.20

  A general and highly chemoselective method for the synthesis of ketones by the addition of organometallics to N-acylazetidines via stable tetrahedral intermediates is reported for the first time. The transformation is characterized by its wide substrate scope and exquisite selectivity for the ketone products even when a large excess of nucleophilic reagents is used. Even of broader interest is the

  首次报道了通过将有机金属通过稳定的四面体中间体加到N-酰基氮杂啶中来合成酮的通用且高度化学选择性的方法。即使使用大量过量的亲核试剂，该转化的特征也在于其广泛的底物范围和对酮产物的精妙选择性。甚至更广泛的兴趣是使用N-酰基氮杂胞苷作为稳定的，容易获得的酰胺酰化试剂，其中反应性通过酰胺金字塔化和四元环的应变来控制，以提供合成上有价值的结构单元。
• New Pyridinones and Isoquinolinones as Inhibitors of the Bromodomain BRD9
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20180044335A1

  公开（公告）日：2018-02-15

  The present invention encompasses compounds of general formula (I) wherein the groups R 1 to R 9 , X 1 and X 2 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation, e.g. cancer, pharmaceutical preparations containing such compounds and their uses as a medicament.

  本发明涵盖了一般式（I）的化合物，其中基团R1至R9，X1和X2的含义如权利要求和说明书中所述。本发明的化合物适用于治疗由细胞过度或异常增殖所特征化的疾病，例如癌症，含有这种化合物的制药制剂以及它们作为药物的用途。
• FUSED PHENYL AMIDO HETEROCYCLIC COMPOUNDS
  申请人：Bai Hao

  公开号：US20080280875A1

  公开（公告）日：2008-11-13

  The present invention relates to a compound of formula (I): or a pharmaceutically acceptable salt or solvate thereof, wherein: Ring A is (4-12)-membered heterocyclyl; Ring B is a fused benzene ring selected from the group consisting of: Ring A, ring B, ring C, R 1 , R 1a , R 2 , R 3 , R 4 , L 2 , n, t, w, and z are as defined in the specification. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating a condition that is mediated by the modulation of glucokinase, the method comprising administering to a mammal an effective amount of a compound of formula (I).

  本发明涉及以下式(I)的化合物：或其药用可接受的盐或溶剂，其中：环A为(4-12)成员杂环基；环B是从以下组中选择的融合苯环之一：环A、环B、环C、R1、R1a、R2、R3、R4、L2、n、t、w和z如规范中所定义。本发明还涉及包括式(I)的化合物的药物组合物以及治疗通过调节葡萄糖激酶介导的疾病的方法，该方法包括向哺乳动物施用有效量的式(I)的化合物。
• Pyrimidine Derivatives and Their Use in Therapy as well as the Use of Pyrimidine Derivatives in the Manufacture of a Medicament for Prevention and/or Treatment of Alzheimer's Disease
  申请人：Andersson Lars

  公开号：US20090105252A1

  公开（公告）日：2009-04-23

  Compounds of formula I wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are as defined in the specification as a base or a pharmaceutically acceptable salt, solvate or solvate of salt thereof, processes for their preparation, new intermediates used therein, pharmaceutical formulations containing said compounds and to the use of said compounds in therapy.

  该专利涉及式I的化合物，其中R1，R2，R3，R4，R5，R6，R7，R8和R9如规范中所定义，作为基础物质或药物可接受的盐，溶剂或其盐的溶剂，以及制备它们的方法，其中使用了新的中间体，含有所述化合物的制药配方以及在治疗中使用所述化合物的用途。
• Fused phenyl amido heterocyclic compounds
  申请人：Pfizer Inc

  公开号：US07842713B2

  公开（公告）日：2010-11-30

  The present invention relates to a compound of formula (I): or a pharmaceutically acceptable salt or solvate thereof, wherein: Ring A is (4-12)-membered heterocyclyl; Ring B is a fused benzene ring selected from the group consisting of: Ring A, ring B, ring C, R1, R1a, R2, R3, R4, L2, n, t, w, and z are as defined in the specification. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating a condition that is mediated by the modulation of glucokinase, the method comprising administering to a mammal an effective amount of a compound of formula (I).

  本发明涉及式（I）的化合物：或其药学上可接受的盐或溶剂，其中：环A是（4-12）成员的杂环；环B是选自以下组的融合苯环：环A，环B，环C，R1，R1a，R2，R3，R4，L2，n，t，w和z在规范中定义。本发明还涉及包括式（I）的化合物的制药组合物和治疗通过调节葡萄糖激酶介导的疾病的方法，该方法包括向哺乳动物施用式（I）的化合物的有效量。