7-chloro-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine | 1034047-10-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 7-chloro-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine
• 英文别名: 7-Chloro-2-(trifluoromethyl)-6,11-dihydro-5H-benzo[B]pyrido[2,3-E][1,4]diazepine；7-chloro-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[3,2-c][1,5]benzodiazepine
• CAS: 1034047-10-3
• 化学式: C₁₃H₉ClF₃N₃
• 分子量: 299.683
• InChiKey: TVTKACPFOMQBCR-UHFFFAOYSA-N

物化性质

• 沸点：
  395.9±42.0 °C(Predicted)
• 密度：
  1.396±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  37
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-chloro-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine 在 2-双环己基膦-2',6'-二甲氧基联苯 、 吡啶 、 4-二甲氨基吡啶 、 tris-(dibenzylideneacetone)dipalladium(0) 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.33h， 生成 7-cyano-6-{[4-(tert-butyl)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine
  参考文献：
  名称：

  Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity

  摘要：

  Extensive structure activity relationship studies of a series derived from atropisomer 1, a previously described chiral benzocliazepine sulfonamide series, led to a potent, brain penetrant and selective compound with excellent preclinical pharmacokinetic across species. We also describe the utilization of a high throughput mouse pharmacodynamic assay which allowed for expedient assessment of pharmacokinetic and brain distribution.

  DOI：

  10.1021/ml200304j
• 作为产物：
  描述：

  3-氯-2-硝基苯胺 在 platinum(IV) oxide 、 硼烷四氢呋喃络合物 、 氢气 作用下， 以 四氢呋喃 、 乙醇 、 乙二醇单丁醚 为溶剂， 150.0 ℃ 、101.33 kPa 条件下， 反应 26.0h， 生成 7-chloro-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine
  参考文献：
  名称：

  Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity

  摘要：

  Extensive structure activity relationship studies of a series derived from atropisomer 1, a previously described chiral benzocliazepine sulfonamide series, led to a potent, brain penetrant and selective compound with excellent preclinical pharmacokinetic across species. We also describe the utilization of a high throughput mouse pharmacodynamic assay which allowed for expedient assessment of pharmacokinetic and brain distribution.

  DOI：

  10.1021/ml200304j

文献信息

• SUBSTITUTED DIAZEPINE SULFONAMIDES AS BOMBESIN RECEPTOR SUBTYPE-1 MODULATORS
  申请人：Baker Robert K.

  公开号：US20100317645A1

  公开（公告）日：2010-12-16

  Certain novel substituted diazepine sulfonamides are ligands of the human bombesin receptor and, in particular, are selective ligands of the human bombesin receptor subtype-3 (BRS-3). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the modulation of BRS-3, such as obesity, and diabetes.

  某些新型取代二氮杂环磺酰胺是人体炸弹素受体的配体，特别是人体炸弹素受体亚型-3（BRS-3）的选择性配体。因此，它们可用于治疗、控制或预防对BRS-3调节敏感的疾病和障碍，如肥胖和糖尿病。
• SUBSTITUTED DIAZEPINE SULFONAMIDES AS BOMBESIN RECEPTOR SUBTYPE-3 MODULATORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2102201B1

  公开（公告）日：2010-10-13
• Discovery of Benzodiazepine Sulfonamide-Based Bombesin Receptor Subtype 3 Agonists and Their Unusual Chirality
  作者：Ping Liu、Thomas J. Lanza、Marc Chioda、Carrie Jones、Harry R. Chobanian、Yan Guo、Linda Chang、Theresa M. Kelly、Yanqing Kan、Oksana Palyha、Xiao-Ming Guan、Donald J. Marsh、Joseph M. Metzger、Katie Ramsay、Sheng-Ping Wang、Alison M. Strack、Randy Miller、Jianmei Pang、Kathy Lyons、Jasminka Dragovic、Jian G. Ning、Wes A. Schafer、Christopher J. Welch、Xiaoyi Gong、Ying-Duo Gao、Viktor Hornak、Richard G. Ball、Nancy Tsou、Marc L. Reitman、Matthew J. Wyvratt、Ravi P. Nargund、Linus S. Lin

  DOI：10.1021/ml200207w

  日期：2011.12.8

  We report herein the discovery of benzodiazepine sulfonamide-based bombesin receptor subtype 3 (BRS-3) agonists and their unusual chirality. Starting from a high-throughput screening lead, we prepared a series of BRS-3 agonists with improved potency and pharmacokinetic properties, of which compound 8a caused mechanism-based, dose-dependent food intake reduction and body weight loss after oral dosing in diet-induced obese mice. This effort also led to the discovery of a novel family of chiral molecules originated from the conformationally constrained seven-membered diazepine ring.
• US8153626B2
  申请人：——

  公开号：US8153626B2

  公开（公告）日：2012-04-10
• Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity
  作者：Harry R. Chobanian、Yan Guo、Ping Liu、Marc Chioda、Thomas J. Lanza、Linda Chang、Theresa M. Kelly、Yanqing Kan、Oksana Palyha、Xiao-Ming Guan、Donald J. Marsh、Joseph M. Metzger、Judith N. Gorski、Kate Raustad、Sheng-Ping Wang、Alison M. Strack、Randy Miller、Jianmei Pang、Maria Madeira、Kathy Lyons、Jasminka Dragovic、Marc L. Reitman、Ravi P. Nargund、Linus S. Lin

  DOI：10.1021/ml200304j

  日期：2012.3.8

  Extensive structure activity relationship studies of a series derived from atropisomer 1, a previously described chiral benzocliazepine sulfonamide series, led to a potent, brain penetrant and selective compound with excellent preclinical pharmacokinetic across species. We also describe the utilization of a high throughput mouse pharmacodynamic assay which allowed for expedient assessment of pharmacokinetic and brain distribution.