(4R)-1,2,3,5-tetrahydro-spiro[4H-1-benzazepine-4,1'-[2]cyclopentene]-3'-carboxylic acid ethyl ester | 813426-23-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: (4R)-1,2,3,5-tetrahydro-spiro[4H-1-benzazepine-4,1'-[2]cyclopentene]-3'-carboxylic acid ethyl ester
• 英文别名: (4R)-1,2,3,5-tetrahydro-spiro[4H-1-benzazepine-4,1'-[2]cylopentene]-3'-carboxylic acid ethyl ester；(R)-3-carboethoxy-4-aza-[6,4]-spiro-[5,6]-benzoundec-2'-ene；ethyl (4R)-spiro[1,2,3,5-tetrahydro-1-benzazepine-4,3'-cyclopentene]-1'-carboxylate
• CAS: 813426-23-2
• 化学式: C₁₇H₂₁NO₂
• 分子量: 271.359
• InChiKey: KKMGANWNTXBHMQ-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4R)-1,2,3,5-tetrahydro-spiro[4H-1-benzazepine-4,1'-[2]cyclopentene]-3'-carboxylic acid ethyl ester 、 3-甲氧基-4-硝基苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以77%的产率得到(R)-4-(3-dethoxy4-nitrobenzoyl)-4-aza-3'-(carboethoxy)-[6,4]-spiro-[5,6]-benzoundec-2'-ene
  参考文献：
  名称：

  Substituted spirobenzazepines

  摘要：

  该发明涉及一种公式I的非肽替代苯并哌啶，其可用作抗利尿素受体拮抗剂，用于治疗与利尿素受体活性相关的病症，如涉及增加血管阻力和心脏功能不全的病症，包括充血性心力衰竭、低钠血症和高血压等。还披露了包含公式I化合物的药物组合物以及治疗高血压、充血性心力衰竭、心脏功能不全、冠状动脉痉挛、心肌缺血、肝硬化、低钠血症、肾脏痉挛、肾功能衰竭、糖尿病肾病、脑水肿、脑缺血、中风、血栓形成或水潴留等病症的治疗方法。

  公开号：

  US20040266752A1
• 作为产物：
  描述：

  (4R)-1,2,3,5-tetrahydrospiro[4H-1-benzazepine-4,1'-[2]cyclopentene]-3'-carboxylic acid 、 乙醇 在 硫酸 作用下， 生成 (4R)-1,2,3,5-tetrahydro-spiro[4H-1-benzazepine-4,1'-[2]cyclopentene]-3'-carboxylic acid ethyl ester
  参考文献：
  名称：

  Process for the preparation of nonpeptide substituted spirobenzoazepine derivatives

  摘要：

  新型螺合苯并氮杂环庚烷化合物，用于制备非肽替代螺合苯并氮杂环庚烷衍生物的新工艺，以及用于制备这类衍生物制备中间体的新工艺。用于制备非肽替代螺合苯并氮杂环庚烷衍生物的新中间体。

  公开号：

  US20040259857A1

文献信息

• Novel solid forms of (4R)-1-[2-chloro-5-fluorobenzoyl)amino-3-methoxybenzoyl]-1,2,3,5- tetrahydro-spiro[4h-1-benzazepine-4,1'-[2]cyclopentene]-3'-carboxylic acid
  申请人：Huang Lian

  公开号：US20070173490A1

  公开（公告）日：2007-07-26

  The present invention relates to novel solid forms of (4R)-1-[4-(2-chloro-5-fluorobenzoyl)amino-3-methoxybenzoyl]-1,2,3,5-tetrahydro-spiro[4H-1-benzazepine-4,1′-[2]cyclopentene]-3′-carboxylic acid (formula (I)) useful for treating and/or preventing conditions such as diabetic nephropathy, renal disease, renal failure and congestive heart failure.

  本发明涉及一种新型固态形式的(4R)-1-[4-(2-氯-5-氟苯甲酰)氨基-3-甲氧基苯甲酰]-1,2,3,5-四氢-螺[4H-1-苯并氮杂环-4,1′-[2]环戊烯]-3′-羧酸（式（I）），其用于治疗和/或预防糖尿病肾病、肾病、肾衰竭和充血性心力衰竭等疾病。
• SUBSTITUTED SPIROBENZAZEPINES
  申请人：Patel Mona

  公开号：US20070179128A1

  公开（公告）日：2007-08-02

  The invention is directed to nonpeptide substituted benzazepines of Formula I, which are useful as vasopressin receptor antagonists for treating conditions associated with vasopressin receptor activity such as those involving increased vascular resistance and cardiac insufficiency, including congestive heart failure, hyponatremia, and hypertension, among others disclosed. Pharmaceutical compositions comprising a compound of Formula I and methods of treating conditions such as hypertension, congestive heart failure, cardiac insufficiency, coronary vasospasm, cardiac ischemia, liver cirrhosis, hyponatremia, renal vasospasm, renal failure, diabetic nephropathy, cerebral edema, cerebral ischemia, stroke, thrombosis, or water retention are also disclosed.

  本发明涉及式I的非肽替代苯并噁唑，其可用作抗利尿激素受体拮抗剂，用于治疗与利尿激素受体活性有关的疾病，例如涉及增加血管阻力和心脏功能不全的疾病，包括充血性心力衰竭、低钠血症和高血压等。还公开了包含式I化合物的制药组合物和治疗高血压、充血性心力衰竭、心脏功能不全、冠状动脉痉挛、心肌缺血、肝硬化、低钠血症、肾血管痉挛、肾功能衰竭、糖尿病肾病、脑水肿、脑缺血、中风、血栓或水肿等疾病的方法。
• PROCESS FOR THE PREPARATION OF NONPEPTIDE SUBSTITUTED SPIROBENZOAZEPINE DERIVATIVES
  申请人：Deng Xiaohu

  公开号：US20090105220A1

  公开（公告）日：2009-04-23

  Novel spirobenzoazepine compounds, novel processes for the preparation of nonpeptide substituted spirobenzoazepine derivatives, and novel processes for the preparation of intermediates in the preparation of such derivatives. Novel intermediates in the preparation of nonpeptide substituted spirobenzoazepine derivatives.

  新型螺苯并氮杂环化合物，制备非肽取代螺苯并氮杂环衍生物的新型方法，以及制备此类衍生物的中间体的新型方法。制备非肽取代螺苯并氮杂环衍生物的新型中间体。
• Next-generation spirobenzazepines: Identification of RWJ-676070 as a balanced vasopressin V1a/V2 receptor antagonist for human clinical studies
  作者：Min Amy Xiang、Philip J. Rybczynski、Mona Patel、Robert H. Chen、David F. McComsey、Han-Cheng Zhang、Joseph W. Gunnet、Richard Look、Yuanping Wang、Lisa K. Minor、H. Marlon Zhong、Frank J. Villani、Keith T. Demarest、Bruce P. Damiano、Bruce E. Maryanoff

  DOI：10.1016/j.bmcl.2007.09.059

  日期：2007.12

  We have continued to explore spirobenzazepines as vasopressin receptor antagonists to follow up on RWJ-339489 (2), which had advanced into preclinical development. Further structural modi. cations were pursued to find a suitable backup compound for human clinical studies. Thus, we identified carboxylic acid derivative 3 (RWJ-676070; JNJ-17158063) as a potent, balanced vasopressin V-1a/V-2 receptor antagonist with favorable properties for clinical development. Compound 3 is currently undergoing human clinical investigation. (c) 2007 Elsevier Ltd. All rights reserved.
• US7687494B2
  申请人：——

  公开号：US7687494B2

  公开（公告）日：2010-03-30