(5-imidazole-1-yl)pentanoic acid methyl ester | 1619971-70-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (5-imidazole-1-yl)pentanoic acid methyl ester
• 英文别名: Methyl 5-imidazol-1-ylpentanoate
• CAS: 1619971-70-8
• 化学式: C₉H₁₄N₂O₂
• 分子量: 182.222
• InChiKey: AOJCPQABHBGKLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5-imidazole-1-yl)pentanoic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 1H-咪唑-1-戊酸
  参考文献：
  名称：

  制备含四嗪的99mTc [2 +1]配合物并使用生物正交逆电子需求Diels-Alder化学方法进行体内靶向

  摘要：

  这项工作的目的是合成和评估[2 + 1]含四嗪的99mTc（I）聚吡啶配合物，它与相应的Re（I）配合物一起代表了一类新的同构核和开启式发光探针，使用生物正交化学进行衍生和靶向。为此，[2 + 1]种类型为[99mTc（CO）3（N ^ N）（L）]的99mTc（I）络合物（N ^ N =邻菲咯啉二磺酸二磺酸盐（BPS）或2,2'-联吡啶（bipy）），其中单齿配体（L）是通过咪唑衍生物与金属连接的四嗪。通过将[99mTc（CO）3（N ^ N）（OH2）] n添加到咪唑-四嗪配体中并在60°C加热30分钟，可以以几乎定量的放射化学产率获得所需产物。在四嗪与（E）-环辛-4-烯醇之间的反应动力学的测量表明，在37°C下的二级速率常数为8.6×103 M-1s-1，适用于需要快速偶联的体内应用。稳定性研究表明，该金属配合物具有抗配体攻击的能力，并在体外具有合理的蛋白质结合能力。施用反式环辛烯

  DOI：

  10.1039/c7dt01497j
• 作为产物：
  描述：

  咪唑 、 5-溴戊酸甲酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 (5-imidazole-1-yl)pentanoic acid methyl ester
  参考文献：
  名称：

  制备含四嗪的99mTc [2 +1]配合物并使用生物正交逆电子需求Diels-Alder化学方法进行体内靶向

  摘要：

  这项工作的目的是合成和评估[2 + 1]含四嗪的99mTc（I）聚吡啶配合物，它与相应的Re（I）配合物一起代表了一类新的同构核和开启式发光探针，使用生物正交化学进行衍生和靶向。为此，[2 + 1]种类型为[99mTc（CO）3（N ^ N）（L）]的99mTc（I）络合物（N ^ N =邻菲咯啉二磺酸二磺酸盐（BPS）或2,2'-联吡啶（bipy）），其中单齿配体（L）是通过咪唑衍生物与金属连接的四嗪。通过将[99mTc（CO）3（N ^ N）（OH2）] n添加到咪唑-四嗪配体中并在60°C加热30分钟，可以以几乎定量的放射化学产率获得所需产物。在四嗪与（E）-环辛-4-烯醇之间的反应动力学的测量表明，在37°C下的二级速率常数为8.6×103 M-1s-1，适用于需要快速偶联的体内应用。稳定性研究表明，该金属配合物具有抗配体攻击的能力，并在体外具有合理的蛋白质结合能力。施用反式环辛烯

  DOI：

  10.1039/c7dt01497j

文献信息

• Bicyclic Pyrimidine Compounds
  申请人：Eli Lilly and Company

  公开号：US20140200231A1

  公开（公告）日：2014-07-17

  The present invention provides compounds of the Formula I: wherein X is a bond or CH 2 ; R is selected from the group consisting of R 1 and R 2 are each independently selected from the group consisting of CH and N; R 3 is H or CH 3 ; R 4 is H or CH 3 ; L is selected from the group consisting of —O(CH 2 ) 3 —, —C(O)NH(CH 2 ) 2 —, —CH 2 C(O)NH(CH 2 ) 2 —, —(CH 2 ) 3 N(C(O)CH 3 )CH 2 —, —(CH 2 ) 2 N(C(O)CH 3 )CH 2 —, —(CH 2 ) 3 NH—, (CH 2 ) 2 OCH 2 —, —(CH 2 ) 4 —, —(CH 2 ) 2 NHCH 2 —, —(CH 2 ) 3 O—, and —CH 2 O(CH 2 ) 2 —; or a pharmaceutically acceptable salt thereof. Compounds of this invention are autotaxin inhibitors.

  本发明提供了Formula I的化合物： 其中X是键或CH2； R从以下组中选择： R1和R2分别独立地从CH和N组中选择； R3是H或CH3； R4是H或 ； L从以下组中选择：—O( )3—、—C(O)NH( )2—、— C(O)NH( )2—、—( )3N(C(O) ) —、—( )2N(C(O) ) —、—( )3NH—、( )2O —、—( )4—、—( )2NH —、—( )3O—和— O( )2—； 或其药学上可接受的盐。 本发明的化合物是自体脂肪酶抑制剂。
• Bicyclic pyrimidine compounds
  申请人：Eli Lilly and Company

  公开号：US08969555B2

  公开（公告）日：2015-03-03

  The present invention provides compounds of the Formula I: wherein X is a bond or CH2; R is selected from the group consisting of R1 and R2 are each independently selected from the group consisting of CH and N; R3 is H or CH3; R4 is H or CH3; L is selected from the group consisting of —O(CH2)3—, —C(O)NH(CH2)2—, —CH2C(O)NH(CH2)2—, —(CH2)3N(C(O)CH3)CH2—, —(CH2)2N(C(O)CH3)CH2—, —(CH2)3NH—, (CH2)2OCH2—, —(CH2)4—, —(CH2)2NHCH2—, —(CH2)3O—, and —CH2O(CH2)2—; or a pharmaceutically acceptable salt thereof. Compounds of this invention are autotaxin inhibitors.

  本发明提供了公式I的化合物：其中X为键或CH2；R选自以下组：R1和R2各自独立地选自CH和N；R3为H或CH3；R4为H或 ；L选自以下组：—O( )3—、—C(O)NH( )2—、— C(O)NH( )2—、—( )3N(C(O) ) —、—( )2N(C(O) ) —、—( )3NH—、( )2O —、—( )4—、—( )2NH —、—( )3O—和— O( )2—；或其药学上可接受的盐。本发明的化合物是自动脂肪酸酰肽酶抑制剂。
• Novel Autotaxin Inhibitors for the Treatment of Osteoarthritis Pain: Lead Optimization via Structure-Based Drug Design
  作者：Spencer B. Jones、Lance A. Pfeifer、Thomas J. Bleisch、Thomas J. Beauchamp、Jim D. Durbin、V. Joseph Klimkowski、Norman E. Hughes、Christopher J. Rito、Yen Dao、Joseph M. Gruber、Hai Bui、Mark G. Chambers、Srinivasan Chandrasekhar、Chaohua Lin、Denis J. McCann、Daniel R. Mudra、Jennifer L. Oskins、Craig A. Swearingen、Kannan Thirunavukkarasu、Bryan H. Norman

  DOI：10.1021/acsmedchemlett.6b00207

  日期：2016.9.8

  In an effort to develop a novel therapeutic agent aimed at addressing the unmet need of patients with osteoarthritis pain, we set out to develop an inhibitor for autotaxin with excellent potency and physical properties to allow for the clinical investigation of autotaxin-induced nociceptive and neuropathic pain. An initial hit identification campaign led to an aminopyrimidine series with an autotaxin IC50 of 500 nM. X-ray crystallography enabled the optimization to a lead compound that demonstrated favorable potency (IC50 = 2 nM), PK properties, and a robust PK/PD relationship.
• Imidazole-Based [2 + 1] Re(I)/^99mTc(I) Complexes as Isostructural Nuclear and Optical Probes
  作者：Abdolreza Yazdani、Nancy Janzen、Laura Banevicius、Shannon Czorny、John F. Valliant

  DOI：10.1021/ic502663p

  日期：2015.2.16

  The synthesis, stability, and photophysical properties of [2 + 1] Re(I)/Tc(I) complexes derived from bipyridine and a series of imidazole derivatives were investigated as a means of identifying complexes suitable for creating targeted isostructural optical/nuclear molecular imaging probes. To prepare the desired complexes, [Re(CO)(3)(H2O)(3)]Br was combined with 2,2'-bipyridine (bipy) to give [Re(CO)(3)(bipy)Br], which in turn was converted to the desired complexes by treatment with functionalized imidazoles, yielding crystal structures of two new Re complexes. The corresponding Tc-99m complexes [Tc-99m(CO)(3)(bipy)(L)](+) (L = imidazole derivatives) were prepared by combining [Tc-99m(CO)(3)(bipy)((HO)-O-2)]Cl with the same series of ligands and heating at 40 or 60 degrees C for 30 min. Quantitative transformation to the final products was confirmed in all cases by HPLC, and the nature of the complexes was verified by comparison to the authentic Re standards. Incubation in saline and plasma, and amino acid challenge experiments showed that N-substituted imidazole derivatives, bearing electron donating groups, exhibited superior stability to analogous metal complexes derived from less basic ligands. Imaging studies in mice revealed that with the appropriate choice of monodentate ligand, it is possible to prepare robust [2 + 1] Tc complexes that can be used as the basis for preparing targeted isostructural optical and nuclear probes.
• PYRIDO- OR PYRROLO-FUSED PYRIMIDINE DERIVATIVES AS AUTOTAXIN INHIBITORS FOR TREATING PAIN
  申请人：Eli Lilly and Company

  公开号：EP2943494B1

  公开（公告）日：2017-02-22