2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[3,2-c][1,5]benzodiazepine | 1034047-06-7

• 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: 2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[3,2-c][1,5]benzodiazepine
• 英文别名: 2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine
• CAS: 1034047-06-7
• 化学式: C₁₃H₁₀F₃N₃
• 分子量: 265.238
• InChiKey: RDGYGVKEMDUPND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 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：

  2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[3,2-c][1,5]benzodiazepine 、 3-苯氧基苯乙酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 以92%的产率得到2-(4-phenoxyphenyl)-1-[2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-6-yl]ethanone
  参考文献：
  名称：

  Synthesis and biological evaluation of novel chiral diazepine derivatives as bombesin receptor subtype-3 (BRS-3) agonists incorporating an antedrug approach

  摘要：

  Novel compounds based on the lead BRS-3 agonists from our HTS compounds 2a and 2b have been synthesized with the focus on obtaining peripheral BRS-3 agonists. To identify potent anti-obesity compounds without adverse effects on the central nerve system, a labile carboxylic ester with an antedrug functionality was introduced onto the terminal position. Through the extensive synthetic exploration and the pharmacokinetic studies of oral administration in mice, the phenol ester 17c was selected due to the most suitable pharmacological profile. In the evaluation of food intake suppression in B6 mice, 17c showed significant in vivo efficacy and no clear adverse effect on heart rate and blood pressure change in dog iv infusion. Our study paved the way for development of anti-diabetes and obesity drugs with a safer profile. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.018
• 作为产物：
  描述：

  邻苯二胺 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[3,2-c][1,5]benzodiazepine
  参考文献：
  名称：

  Synthesis and biological evaluation of novel chiral diazepine derivatives as bombesin receptor subtype-3 (BRS-3) agonists incorporating an antedrug approach

  摘要：

  Novel compounds based on the lead BRS-3 agonists from our HTS compounds 2a and 2b have been synthesized with the focus on obtaining peripheral BRS-3 agonists. To identify potent anti-obesity compounds without adverse effects on the central nerve system, a labile carboxylic ester with an antedrug functionality was introduced onto the terminal position. Through the extensive synthetic exploration and the pharmacokinetic studies of oral administration in mice, the phenol ester 17c was selected due to the most suitable pharmacological profile. In the evaluation of food intake suppression in B6 mice, 17c showed significant in vivo efficacy and no clear adverse effect on heart rate and blood pressure change in dog iv infusion. Our study paved the way for development of anti-diabetes and obesity drugs with a safer profile. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.018

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
• Synthesis and biological evaluation of novel chiral diazepine derivatives as bombesin receptor subtype-3 (BRS-3) agonists incorporating an antedrug approach
  作者：Tetsuyoshi Matsufuji、Kousei Shimada、Shozo Kobayashi、Masanori Ichikawa、Asuka Kawamura、Teppei Fujimoto、Tsuyoshi Arita、Takashi Hara、Masahiro Konishi、Rie Abe-Ohya、Masanori Izumi、Yoshitaka Sogawa、Yoko Nagai、Kazuhiro Yoshida、Yasuyuki Abe、Takako Kimura、Hisashi Takahashi

  DOI：10.1016/j.bmc.2014.11.018

  日期：2015.1

  Novel compounds based on the lead BRS-3 agonists from our HTS compounds 2a and 2b have been synthesized with the focus on obtaining peripheral BRS-3 agonists. To identify potent anti-obesity compounds without adverse effects on the central nerve system, a labile carboxylic ester with an antedrug functionality was introduced onto the terminal position. Through the extensive synthetic exploration and the pharmacokinetic studies of oral administration in mice, the phenol ester 17c was selected due to the most suitable pharmacological profile. In the evaluation of food intake suppression in B6 mice, 17c showed significant in vivo efficacy and no clear adverse effect on heart rate and blood pressure change in dog iv infusion. Our study paved the way for development of anti-diabetes and obesity drugs with a safer profile. (C) 2014 Elsevier Ltd. All rights reserved.