2-(三氟甲基)-6,11-二氢-5H-苯并[b]吡啶并[2,3-e][1,4]二氮杂革-7-醇 | 1039715-25-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 2-(三氟甲基)-6,11-二氢-5H-苯并[b]吡啶并[2,3-e][1,4]二氮杂革-7-醇
• 英文名称: 2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-7-ol
• 英文别名: 2-(Trifluoromethyl)-6,11-dihydro-5H-benzo[b]pyrido[2,3-e][1,4]diazepin-7-ol；2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[3,2-c][1,5]benzodiazepin-7-ol
• CAS: 1039715-25-7
• 化学式: C₁₃H₁₀F₃N₃O
• 分子量: 281.237
• InChiKey: PPTNLTCDCQOSER-UHFFFAOYSA-N

物化性质

• 沸点：
  410.7±45.0 °C(Predicted)
• 密度：
  1.398±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 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：
  57.2
• 氢给体数：
  3
• 氢受体数：
  7

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-(三氟甲基)-6,11-二氢-5H-苯并[b]吡啶并[2,3-e][1,4]二氮杂革-7-醇 在 2-双环己基膦-2',6'-二甲氧基联苯 、 吡啶 、 tris-(dibenzylideneacetone)dipalladium(0) 、 zinc(II) fluoride 、 苄基三乙基氯化铵 、 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2-[11-benzyl-6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5H-pyrido[3,2-c][1,5]benzodiazepin-7-yl]acetonitrile
  参考文献：
  名称：

  The design and synthesis of potent, selective benzodiazepine sulfonamide bombesin receptor subtype 3 (BRS-3) agonists with an increased barrier of atropisomerization

  摘要：

  Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein coupled receptor expressed primarily in the hypothalamus which plays a role in the onset of both diabetes and obesity. We report herein our progress made towards identifying a potent, selective bombesin receptor subtype-3 (BRS-3) agonist related to the previously described MK-7725(1) Chobanian et al. (2012) that would prevent atropisomerization through the increase of steric bulk at the C-2 position. This would thereby make clinical development of this class of compounds more cost effective by inhibiting racemization which can occur over long periods of time at room/elevated temperature. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.03.029
• 作为产物：
  描述：

  2-氯-6-三氟甲基烟酸 在 环丁砜 、 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 生成 2-(三氟甲基)-6,11-二氢-5H-苯并[b]吡啶并[2,3-e][1,4]二氮杂革-7-醇
  参考文献：
  名称：

  The design and synthesis of potent, selective benzodiazepine sulfonamide bombesin receptor subtype 3 (BRS-3) agonists with an increased barrier of atropisomerization

  摘要：

  Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein coupled receptor expressed primarily in the hypothalamus which plays a role in the onset of both diabetes and obesity. We report herein our progress made towards identifying a potent, selective bombesin receptor subtype-3 (BRS-3) agonist related to the previously described MK-7725(1) Chobanian et al. (2012) that would prevent atropisomerization through the increase of steric bulk at the C-2 position. This would thereby make clinical development of this class of compounds more cost effective by inhibiting racemization which can occur over long periods of time at room/elevated temperature. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.03.029

文献信息

• Substituted diazepine sulfonamides as bombesin receptor subtype-3 modulators
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08153626B2

  公开（公告）日：2012-04-10

  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类炸弹素受体的配体，特别是人类炸弹素受体亚型-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调节有响应的疾病和障碍，如肥胖症和糖尿病。
• 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