1-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indazole-5-carboxylic acid ethyl ester | 277330-28-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 1-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indazole-5-carboxylic acid ethyl ester
• 英文别名: Ethyl 1-[2-(1,3-dioxoisoindolin-2-yl)ethyl]-1H-indazole-5-carboxylate；ethyl 1-[2-(1,3-dioxoisoindol-2-yl)ethyl]indazole-5-carboxylate
• CAS: 277330-28-6
• 化学式: C₂₀H₁₇N₃O₄
• 分子量: 363.373
• InChiKey: ROUOPGRWFNWDMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  81.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indazole-5-carboxylic acid ethyl ester 在 吡啶 、 sodium hydroxide 、 肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 37.0h， 生成 1-[2-(4,5-Dihydro-1H-imidazol-2-ylamino)-ethyl]-1H-indazole-5-carboxylic acid
  参考文献：
  名称：

  Disubstituted Indazoles as Potent Antagonists of the Integrin α_vβ₃

  摘要：

  A new series of indazole-containing alpha(v)beta(3) integrin antagonists is described. Starting with lead compound 18a, variations in a number of structural features were explored with respect to inhibition of the binding of beta(3)-transfected 293 cells to fibrinogen and to selectivity for alpha(v)beta(3) over GPIIbIIIa, another RGD-binding integrin. Indazoles attached to a 2-aminopyridine or 2-aminoimidazole by a propylene linker at the indazole 1-position and to a diaminopropionate derivative via a 5-carboxylate amide provided the best potency with moderate selectivity. Several differences in the SAR of the diaminopropionate moiety were observed between this series and a series of isoxazoline-based selective GPIIbIIIa antagonists. Compound 34a (SM256) was a potent antagonist of alpha(v)beta(3) (IC50 2.3 nM) with 9-fold selectivity over GPIIbIIIa.

  DOI：

  10.1021/jm990049j
• 作为产物：
  描述：

  N-(2-溴乙基)邻苯二甲酰亚胺 、 1H-吲唑-5-甲酸乙酯 在 18-冠醚-6 、 双(三甲基硅烷基)氨基钾 作用下， 以 甲苯 为溶剂， 反应 16.0h， 生成 2-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-2H-indazole-5-carboxylic acid ethyl ester 、 1-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indazole-5-carboxylic acid ethyl ester
  参考文献：
  名称：

  Disubstituted Indazoles as Potent Antagonists of the Integrin α_vβ₃

  摘要：

  A new series of indazole-containing alpha(v)beta(3) integrin antagonists is described. Starting with lead compound 18a, variations in a number of structural features were explored with respect to inhibition of the binding of beta(3)-transfected 293 cells to fibrinogen and to selectivity for alpha(v)beta(3) over GPIIbIIIa, another RGD-binding integrin. Indazoles attached to a 2-aminopyridine or 2-aminoimidazole by a propylene linker at the indazole 1-position and to a diaminopropionate derivative via a 5-carboxylate amide provided the best potency with moderate selectivity. Several differences in the SAR of the diaminopropionate moiety were observed between this series and a series of isoxazoline-based selective GPIIbIIIa antagonists. Compound 34a (SM256) was a potent antagonist of alpha(v)beta(3) (IC50 2.3 nM) with 9-fold selectivity over GPIIbIIIa.

  DOI：

  10.1021/jm990049j

文献信息

• SIMULTANEOUS IMAGING OF CARDIAC PERFUSION AND A VITRONECTIN RECEPTOR TARGETED IMAGING AGENT
  申请人：——

  公开号：US20040208823A1

  公开（公告）日：2004-10-21

  The present invention describes a method of concurrent imaging in a mammal comprising: a) administering to said mammal a vitronectin receptor targeted imaging agent and a perfusion imaging agent; and b) concurrently detecting the vitronectin receptor targeted imaging agent bound at the vitronectin receptor and the perfusion imaging agent; and c) forming an image from the detection of said vitronectin targeted imaging agent and said perfusion imaging agent.

  本发明描述了一种哺乳动物的并行成像方法，包括：a)向该哺乳动物注射一个定向于血管紧张素受体的成像剂和一个灌注成像剂；并b)同时检测定向于血管紧张素受体的成像剂在血管紧张素受体上的结合和灌注成像剂；并c)从检测到的血管紧张素受体定向成像剂和灌注成像剂形成图像。
• Vitronectin receptor antagonist pharmaceuticals
  申请人：Rajopadhye Milind

  公开号：US20050154185A1

  公开（公告）日：2005-07-14

  The present invention describes novel compounds of the formula: (Q) d -L n -C h , useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The present invention also provides novel compounds useful for imaging atherosclerosis, restenosis, cardiac ischemia, and myocardial reperfusion injury. The present invention also provides novel compounds useful for the treatment of rheumatoid arthritis. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

  本发明描述了新型化合物的公式：（Q）d-Ln-Ch，用于癌症的诊断和治疗，病人肿瘤成像方法以及病人癌症治疗方法。本发明还提供了新型化合物，用于监测治疗性血管生成和新血管生成的破坏。本发明还提供了新型化合物，用于成像动脉粥样硬化、再狭窄、心肌缺血和心肌再灌注损伤。本发明还提供了新型化合物，用于类风湿性关节炎的治疗。药物由结合到在血管生成期间上调的受体的靶向基团，可选的连接基团和治疗有效的放射性同位素或诊断有效的可成像基团组成。可成像基团是伽玛射线或正电子发射放射性同位素、磁共振成像对比剂、X射线对比剂或超声对比剂。
• VITRONECTIN RECEPTOR ANTAGONIST PHARMACEUTICALS
  申请人：Du Pont Pharmaceuticals Company

  公开号：EP1140203A2

  公开（公告）日：2001-10-10
• VITRONECTIN RECEPTOR ANTAGONIST PHARMACEUTICALS FOR USE IN COMBINATION THERAPY
  申请人：DuPont Pharmaceuticals Company

  公开号：EP1296678A2

  公开（公告）日：2003-04-02
• US6794518B1
  申请人：——

  公开号：US6794518B1

  公开（公告）日：2004-09-21