1-phenyl-4H-<1,2,4>-triazolo<4,3-a><1,5>benzodiazepin-5(6H)-one | 137731-25-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-phenyl-4H-<1,2,4>-triazolo<4,3-a><1,5>benzodiazepin-5(6H)-one
• 英文别名: 1-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5(6H)-one；1-phenyl-4H,6H-2,3,6,10b-tetraaza-benzo[e]azulen-5-one；1-phenyl-4H-[1,2,4]-triazolo[4,3-a][1,5]benzodiazepin-5(6H)-one；1-phenyl-4,6-dihydro-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-one
• CAS: 137731-25-0
• 化学式: C₁₆H₁₂N₄O
• 分子量: 276.297
• InChiKey: MBMNHMPNVGGMPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  59.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-phenyl-4H-<1,2,4>-triazolo<4,3-a><1,5>benzodiazepin-5(6H)-one 在 palladium 10% on activated carbon 氢气 、 双(三甲基硅烷基)氨基钾 、 sodium hydride 、 1-丙基磷酸酐 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， -20.0~40.0 ℃ 、411.6 kPa 条件下， 反应 104.0h， 生成 {4-[(1-{2-[methyl(propyl)amino]-2-oxoethyl}-1H-indazol-3-yl)methyl]-5-oxo-1-phenyl-4,5-dihydro-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-6-yl}acetic acid.
  参考文献：
  名称：

  [EN] 1,2,4 TRIAZOLO [4, 3 -A] [1,5] BENZODIAZEPIN-5 (6H) -ONES AS AGONISTS OF THE CHOLECYSTOKININ-1 RECEPTOR (CCK-IR)
  [FR] 1,2,4 TRIAZOLO[4,3-A][1,5] BENZODIAZÉPIN-5(6H)-ONES UTILISÉES COMME AGONISTES DU RÉCEPTEUR DE LA CHOLÉCYSTOKININE-1 (CCK-1R)

  摘要：

  这项发明涉及到式（I）中的CCK-1 R激动剂，其中R1-R5和X如规范中所定义，以及含有这些化合物的药物组合物和这些化合物和组合物的使用方法。这些化合物在治疗肥胖症、2型糖尿病及相关疾病方面是有用的。

  公开号：

  WO2010067233A1
• 作为产物：
  描述：

  4-ethoxy-1,3-dihydro-benzo[b][1,4]diazepin-2-one 、 苯甲酰肼 以 溶剂黄146 为溶剂， 反应 2.0h， 生成 1-phenyl-4H-<1,2,4>-triazolo<4,3-a><1,5>benzodiazepin-5(6H)-one
  参考文献：
  名称：

  Tetraazabenzo[e]azulene derivatives and analogs thereof

  摘要：

  这项发明涉及公式（I）中的CCK-A激动剂， 其中R1-R4，A，B，X，D，E和G如规范中所定义，以及包含这些化合物的药物组合物和这些化合物和组合物的使用方法。这些化合物在治疗肥胖症方面是有用的。

  公开号：

  US20050267100A1

文献信息

• 1,5-Benzodiazepines Part XIII. Substituted 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amines and 4H-imidazo[1,2-a][1,5]benzodiazepin-5-amines as analgesic, anti-inflammatory and/or antipyretic agents with low acute toxicity
  作者：G Grossi

  DOI：10.1016/s0223-5234(02)01400-9

  日期：2002.12.1

  kg(-1) os dose, some compounds 3 and 4 showed notable analgesic or anti-inflammatory activity but no antipyretic properties, whereas the 5-(dibutylamino) derivatives 5b and 5f proved to be significantly endowed with all these activities. Almost all the compounds 3, 4 and 5 did not show acute toxicity in mice up to 800 mg kg(-1) os dose.

  适当的N，N-二烷基-4H- [1,2,4]三唑[4,3-a] [1,5]苯并二氮杂-5-胺（1）与N-氯代琥珀酰亚胺的反应得到其4-氯代衍生物3依次用环胺处理，得到相应的4,5-二氨基衍生物4。N，N-二烷基-4H-咪唑并[1,2-a] [1,5]苯并二氮杂-5-胺（5）为由适合的4-（二烷基氨基）-1,3-二氢-2H-1,5-苯并二氮杂-2--2-酮（8）开始，通过多步合成路线制备。在200 mg kg（-1）os剂量下，某些化合物3和4表现出明显的止痛或抗炎活性，但没有解热特性，而5-（二丁基氨基）衍生物5b和5f被证明具有所有这些活性。 。几乎所有化合物3、4和5在800 mg kg（-1）os剂量的小鼠中均未显示急性毒性。
• TETRAAZABENZO[E]AZULENE DERIVATIVES AND ANALOGS THEREOF
  申请人：Elliott L. Richard

  公开号：US20070265193A1

  公开（公告）日：2007-11-15

  This invention relates to CCK-A agonists of Formula (I) wherein R 1 -R 4 , A, B, X, D, E and G are as defined in the specification, as well as, among other things, pharmaceutical compositions containing the compounds and methods of use of the compounds and compositions. The compounds are useful in treating diabetes.

  本发明涉及式(I)的CCK-A激动剂，其中R1-R4，A，B，X，D，E和G如规范中所定义，以及包含该化合物的药物组合物和使用该化合物和组合物的方法，该化合物在治疗糖尿病方面有用。
• Discovery of N-benzyl-2-[(4S)-4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-6-yl]-N-isopropylacetamide, an orally active, gut-selective CCK1 receptor agonist for the potential treatment of obesity
  作者：Richard L. Elliott、Kimberly O. Cameron、Janice E. Chin、Jeremy A. Bartlett、Elena E. Beretta、Yue Chen、Paul Da Silva Jardine、Jeffrey S. Dubins、Melissa L. Gillaspy、Diane M. Hargrove、Amit S. Kalgutkar、Janet A. LaFlamme、Mary E. Lame、Kelly A. Martin、Tristan S. Maurer、Nancy A. Nardone、Robert M. Oliver、Dennis O. Scott、Dexue Sun、Andrew G. Swick、Catherine E. Trebino、Yingxin Zhang

  DOI：10.1016/j.bmcl.2010.08.115

  日期：2010.11

  We describe the design, synthesis, and structure-activity relationships of triazolobenzodiazepinone CCK1 receptor agonists. Analogs in this series demonstrate potent agonist activity as measured by in vitro and in vivo assays for CCK1 agonism. Our efforts resulted in the identification of compound 4a which significantly reduced food intake with minimal systemic exposure in rodents. (C) 2010 Elsevier Ltd. All rights reserved.
• 1,5-Benzodiazepines IX. A new route to substituted 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amines with analgesic and/or anti-inflammatory activities
  作者：G Roma、GC Grossi、M Di Braccio、M Ghia、F Mattioli

  DOI：10.1016/0223-5234(91)90144-c

  日期：1991.7

  A new two-step synthetic pathway to substituted 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amines 2a-p is described. The cyclocondensation of (dimethylamino)benzodiazepinone 1a with hydrazides afforded triazolobenzodiazepinones 5 which in turn reacted with suitable primary or secondary amines, in the presence of titanium tetrachloride, to give the desired 5-amino-derivatives 2a-p. When compounds 5 were treated with the Lawesson's reagent thiolactams 6 were obtained, which then reacted with sodium hydride and proper alkyl halides to yield 5-(alkylthio)derivatives 7a-d. Compounds 2a-h, j-p, and 7a-d were tested for their analgesic and anti-inflammatory activities, as well as for their acute toxicity and gross behavioral effects. The analgesic activity appeared noteworthy in the writhing test, where fifteen compounds were more effective than both the reference drugs acetylsalicylic acid and dipyrone, but was less evident in the hot plate test. An anti-inflammatory activity, lower than that of indomethacin but reaching the level of statistical significance, was displayed in the carrageenin-induced edema assay by five of the nineteen test compounds.
• Discovery of new piperidine amide triazolobenzodiazepinones as intestinal-selective CCK1 receptor agonists
  作者：Kimberly O. Cameron、Elena E. Beretta、Yue Chen、Margaret Chu-Moyer、Dilinie Fernando、Hua Gao、Jeffrey Kohrt、Sophie Lavergne、Paul Da Silva Jardine、Angel Guzman-Perez、Christopher Hoth、David A. Perry、John R. Hadcock、Denise Gautreau、Michael Makowski、Sylvie Perez、Jana Polivkova、Lucy Rogers、Dennis O. Scott、Andrew G. Swick、Lucinda Thiede、Catherine E. Trebino、Richard V. Trilles、Julie Wilmowski、Yingxin Zhang

  DOI：10.1016/j.bmcl.2012.02.049

  日期：2012.4

  New cholecystokinin-1 receptor (CCK1R) agonist 'triggers' were identified using iterative library synthesis. Structural activity relationship studies led to the discovery of compound 10e, a potent CCK1R agonist that demonstrated robust weight loss in a diet-induced obese rat model with very low systemic exposure. Pharmacokinetic data suggest that efficacy is primarily driven through activation of CCK1R's located within the intestinal wall. (C) 2012 Elsevier Ltd. All rights reserved.