N'-hydroxy-1-[6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]cyclobutane-1-carboximidamide | 1039716-37-4

• 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: N'-hydroxy-1-[6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]cyclobutane-1-carboximidamide
• CAS: 1039716-37-4
• 化学式: C₂₅H₂₁F₆N₅O₄S
• 分子量: 601.529
• InChiKey: DGBJQRJGCOKCMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  N'-hydroxy-1-[6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]cyclobutane-1-carboximidamide 在 吡啶 、 甲醇 、 potassium carbonate 作用下， 以 乙醇 、 正己烷 为溶剂， 生成 2-[3-[1-[6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]cyclobutyl]-1,2,4-oxadiazol-5-yl]propan-2-ol
  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 2-双环己基膦-2',6'-二甲氧基联苯 、 吡啶 、 环丁砜 、 tris-(dibenzylideneacetone)dipalladium(0) 、 硼烷四氢呋喃络合物 、 zinc(II) fluoride 、 碘代三甲硅烷 、 苄基三乙基氯化铵 、 羟胺 、 sodium hydride 、 potassium carbonate 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 生成 N'-hydroxy-1-[6-[4-(trifluoromethoxy)phenyl]sulfonyl-2-(trifluoromethyl)-5,11-dihydropyrido[3,2-c][1,5]benzodiazepin-7-yl]cyclobutane-1-carboximidamide
  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-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。
• US8153626B2
  申请人：——

  公开号：US8153626B2

  公开（公告）日：2012-04-10
• [EN] SUBSTITUTED DIAZEPINE SULFONAMIDES AS BOMBESIN RECEPTOR SUBTYPE-3 MODULATORS<br/>[FR] SULFONAMIDES DE DIAZÉPINE SUBSTITUÉS UTILISÉS EN TANT QUE MODULATEURS DES RÉCEPTEURS DE SOUS-TYPE 3 DE LA BOMBÉSINE
  申请人：MERCK & CO INC

  公开号：WO2008073311A2

  公开（公告）日：2008-06-19

  [EN] 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.
  [FR] Certains nouveaux sulfonamides de diazépine substitués faisant l'objet de la présente invention sont des ligands du récepteur humain de la bombésine et, ils sont en particulier des ligands sélectifs du récepteur humain de sous-type 3 de la bombésine (BRS-3). Ils se révèlent de ce fait utiles pour le traitement, la régulation, ou la prévention de maladies et de troubles sensibles à la modulation du BRS-3, tels que l'obésité et le diabète.
• The design and synthesis of potent, selective benzodiazepine sulfonamide bombesin receptor subtype 3 (BRS-3) agonists with an increased barrier of atropisomerization
  作者：Harry R. Chobanian、Yan Guo、Ping Liu、Thomas J. Lanza、Marc Chioda、Linda Chang、Theresa M. Kelly、Yanqing Kan、Oksana Palyha、Xiao-Ming Guan、Donald J. Marsh、Joseph M. Metzger、Katie Raustad、Sheng-Ping Wang、Alison M. Strack、Judith N. Gorski、Randy Miller、Jianmei Pang、Kathy Lyons、Jasminka Dragovic、Jian G. Ning、Wes A. Schafer、Christopher J. Welch、Xiaoyi Gong、Ying-Duo Gao、Viktor Hornak、Marc L. Reitman、Ravi P. Nargund、Linus S. Lin

  DOI：10.1016/j.bmc.2012.03.029

  日期：2012.5

  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.