5-碘-2-(1H-吡咯-1-基)吡啶 | 338748-93-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 5-碘-2-(1H-吡咯-1-基)吡啶
• 英文名称: 5-iodo-2-(1H-pyrrol-1-yl)pyridine
• 英文别名: 5-iodo-2-pyrrol-1-ylpyridine
• CAS: 338748-93-9
• 化学式: C₉H₇IN₂
• mdl: MFCD01315196
• 分子量: 270.072
• InChiKey: MKIBDODBOFHHHO-UHFFFAOYSA-N

物化性质

• 沸点：
  327.7±27.0 °C(Predicted)
• 密度：
  1.75±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1’-BOC-1,2-二氢-2-氧代-螺[3H-吲哚-3,4’-哌啶] 、 5-碘-2-(1H-吡咯-1-基)吡啶 在 copper(l) iodide 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  1,3,8-Triazaspiro[4.5]decane-2,4-diones as Efficacious Pan-Inhibitors of Hypoxia-Inducible Factor Prolyl Hydroxylase 1–3 (HIF PHD1–3) for the Treatment of Anemia

  摘要：

  The discovery of 1,3,8-triazaspiro[4.5]decane-2,4-diones (spirohydantoins) as a structural class of pan-inhibitors of the prolyl hydroxylase (PHD) family of enzymes for the treatment of anemia is described. The initial hit class, spirooxindoles, was identified through affinity selection mass spectrometry (AS-MS) and optimized for PHD2 inhibition and optimal PK/PD profile (short-acting PHDi inhibitors). 1,3,8-Triazaspiro[4.5]decane-2,4-diones (spirohydantoins) were optimized as an advanced lead class derived from the original spiroindole hit. A new set of general conditions for C-N coupling, developed using a high-throughput experimentation (HTE) technique, enabled a full SAR analysis of the spirohydantoins. This rapid and directed SAR exploration has resulted in the first reported examples of hydantoin derivatives with good PK in preclinical species. Potassium channel off-target activity (hERG) was successfully eliminated through the systematic introduction of acidic functionality to the molecular structure. Undesired upregulation of alanine aminotransferese (ALT) liver enzymes was mitigated and a robust on-/off-target margin was achieved. Spirohydantoins represent a class of highly efficacious, short-acting PHD1-3 inhibitors causing a robust erythropoietin (EPO) upregulation in vivo in multiple preclinical species. This profile deems spirohydantoins as attractive short-acting PHDi inhibitors with the potential for treatment of anemia.

  DOI：

  10.1021/jm201542d

文献信息

• Phenylethynyl-substituted heterocycles inhibit cyclin D1 and induce the expression of cyclin-dependent kinase inhibitor p21^Wif1/Cip1in colorectal cancer cells
  作者：Vitaliy M. Sviripa、Liliia M. Kril、Wen Zhang、Yanqi Xie、Przemyslaw Wyrebek、Larissa Ponomareva、Xifu Liu、Yaxia Yuan、Chang-Guo Zhan、David S. Watt、Chunming Liu

  DOI：10.1039/c7md00393e

  日期：——

  heterocycles including pyridines, indoles, 1H-indazoles, quinolines, and isoquinolines inhibited the proliferation of LS174T colon cancer cells in which the inhibition of cyclin D1 and induction of the cyclin-dependent kinase inhibitor-1 (i.e., p21Wif1/Cip1) served as readouts for antineoplastic activity at a cellular level. At a molecular level, these agents, particularly 4-((2,6-difluorophenyl)et

  氟苯基乙炔基取代的杂环具有N-甲基氨基或与N，N-二甲基氨基连接的杂环，包括吡啶，吲哚，1 H-吲唑，喹啉和异喹啉，可抑制LS174T结肠癌细胞的增殖，其中Cyclin的抑制作用D1和细胞周期蛋白依赖性激酶抑制剂-1（即p21 Wif1 / Cip1）的诱导用作细胞水平抗肿瘤活性的读数。在分子水平上，这些试剂，特别是4-（（2,6-二氟苯基）乙炔基）-N-甲基异喹啉-1-胺和4-（（2,6-二氟苯基）乙炔基）-N，N-二甲基异喹啉-1-胺结合并抑制蛋氨酸S-腺苷基转移酶2（MAT2A）的催化亚基。
• Imaging Agents Useful for Identifying AD Pathology
  申请人：Kolb Hartmuth C.

  公开号：US20100098634A1

  公开（公告）日：2010-04-22

  Provided herein are compounds and compositions which comprise the formulae as disclosed herein, wherein the compound is an amyloid binding compound. An amyloid binding compound according to the invention may be administered to a patient in amounts suitable for in vivo imaging of amyloid deposits, and distinguish between neurological tissue with amyloid deposits and normal neurological tissue. Amyloid probes of the invention may be used to detect and quantitate amyloid deposits in diseases including, for example, Down's syndrome, familial Alzheimer's Disease. In another embodiment, the compounds may be used in the treatment or prophylaxis of neurodegenerative disorders. Also provided herein are methods of allowing the compound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal is suffering from or is at risk of developing a neurodegenerative disease.

  本文提供的化合物和组合物包含如下所述的公式，其中该化合物是一种淀粉样蛋白结合化合物。本发明的淀粉样蛋白结合化合物可以以适量的方式用于体内成像淀粉样沉积物，以区分含有淀粉样沉积物的神经组织和正常神经组织。本发明的淀粉样探针可以用于检测和定量测量包括唐氏综合症、家族性阿尔茨海默病在内的疾病中的淀粉样沉积物。在另一实施例中，这些化合物可以用于治疗或预防神经退行性疾病。本文还提供了一种使化合物分布到脑组织中并成像脑组织的方法，其中与正常结合水平相比，化合物与脑组织的结合增加表明哺乳动物正在患有或有发展神经退行性疾病的风险。
• IMAGING AGENTS USEFUL FOR IDENTIFYING AD PATHOLOGY
  申请人：Siemens Medical Solutions USA, Inc.

  公开号：EP2323697A2

  公开（公告）日：2011-05-25
• US8420052B2
  申请人：——

  公开号：US8420052B2

  公开（公告）日：2013-04-16
• [EN] IMAGING AGENTS USEFUL FOR IDENTIFYING AD PATHOLOGY<br/>[FR] AGENTS D'IMAGERIE UTILES POUR IDENTIFIER UNE PATHOLOGIE
  申请人：SIEMENS MEDICAL SOLUTIONS

  公开号：WO2010011964A2

  公开（公告）日：2010-01-28

  Provided herein are compounds and compositions which comprise the formulae as disclosed herein, wherein the compound is an amyloid binding compound. An amyloid binding compound according to the invention may be administered to a patient in amounts suitable for in vivo imaging of amyloid deposits, and distinguish between neurological tissue with amyloid deposits and normal neurological tissue. Amyloid probes of the invention may be used to detect and quantitate amyloid deposits in diseases including, for example, Down's syndrome, familial Alzheimer's Disease. In another embodiment, the compounds may be used in the treatment or prophylaxis of neurodegenerative disorders.. Also provided herein are methods of allowing the compound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal is suffering from or is at risk of developing a neurodegenerative disease.