4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N-methylbenzenamine | 683768-16-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N-methylbenzenamine
• 英文别名: [4-(6-iodoimidazo[1,2-a]pyridin-2-yl)phenyl]-N-methylamine；4-(6-iodoimidazo[1,2-a]pyridin-2-yl)-N-methylaniline；4-(6-iodoindolizin-2-yl)-N-methylbenzeneamine；6-iodo-2-(4'-N-methylamino)phenylimidazo[1,2-a]pyridine；4-(6-iodo-imidazo[1,2-a]pyridin-2-yl)-N-methylbenzenamine
• CAS: 683768-16-3
• 化学式: C₁₄H₁₂IN₃
• 分子量: 349.174
• InChiKey: CDORLHFBTIAZBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-[18F]fluoropropyl p-tosylate 、 4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N-methylbenzenamine 以 乙腈 为溶剂， 生成 6-iodo-2-[4'-N-(3-[18F]fluoropropyl)methylamino]phenylimidazo[1,2-a]pyridine
  参考文献：
  名称：

  Cai, L.; Chin, F. T.; Pike, V. W., Journal of labelled compounds and radiopharmaceuticals, 2003, vol. 46, p. S166 - S166

  摘要：

  DOI：
• 作为产物：
  描述：

  2,2,2-trifluoro-N-[4-(6-iodoimidazo[1,2-a]pyridin-2-yl)phenyl]-N-methylacetamide 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以88%的产率得到4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N-methylbenzenamine
  参考文献：
  名称：

  Synthesis and Evaluation of Two ¹⁸F-Labeled 6-Iodo-2-(4‘-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine Derivatives as Prospective Radioligands for β-Amyloid in Alzheimer's Disease

  摘要：

  This study evaluated F-18-labeled IMPY [6-iodo-2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine] derivatives as agents for imaging beta-amyloid plaque with positron emission tomography (PET). The precursor for radiolabeling and reference compounds was synthesized in up to five steps from commercially accessible starting materials. One of the two N-methyl groups of IMPY was substituted with either a 3-fluoropropyl (FPM-IMPY) or a 2-fluoroethyl (FEM-IMPY) group. FPM-IMPY and FEM-IMPY were found to have moderate affinity for Abeta-aggregates with K-i = 27 +/- 8 and 40 +/- 5 nM, respectively. A "one-pot" method for F-18-2-fluoroethylation and F-18-3-fluoropropylation of the precursor was developed. The overall decay-corrected radiochemical yields were 26-51%. In PET experiments with normal mouse, high uptake of activity was obtained in the brain after iv injection of each probe: 6.4% ID/g for [F-18]FEM-IMPY at 1.2 min, and 5.7% ID/g for [F-18]FPM-IMPY at 0.8 min. These values were similar to those of [I-123/I-123]IMPY (7.2% ID/g at 2 min). Polar and nonpolar radioactive metabolites were observed in both plasma and brain homogenates after injection of [F-18]FEM or [F-18]FPM-IMPY. In contrast to the single-exponential washout of [I-123/I-123]IMPY, the washouts of brain activity for the two fluorinated analogues were biphasic, with an initial rapid phase over 20 min and a subsequent much slower phase. Residual brain activity at 2 h, which may represent polar metabolites trapped in the brain, was 4.5% ID/g for [F-18] FEM-IMPY and 2.1% ID/g for [F-18]FPM-IMPY. Substantial skull uptake of [F-18]fluoride was also clearly observed. With a view to slow the metabolism of [F-18]FEM-IMPY, an analogue was prepared with deuteriums substituted for the four ethyl hydrogens. However, D-4-[F-18]FEM-IMPY showed the same brain uptake and clearance as the protio analogue. Metabolism of the [F-18]FEM-IMPY was appreciably slower in rhesus monkey than in mouse. Autoradiography of postmortem brain sections of human Alzheimer's disease patients with [F-18]FEM-IMPY showed high displaceable uptake in gray matter and low nonspecific binding in the white matter. This study demonstrates that the IMPY derivatives have favorable in vivo brain pharmacokinetics and a moderate affinity for imaging beta-amyloid plaques; however, further improvements are needed to reduce radioactive metabolites, increase binding affinity, and reduce lipophilicity.

  DOI：

  10.1021/jm030477w

文献信息

• Radiosyntheses and reactivities of novel [18F]2-fluoroethyl arylsulfonates
  作者：John L. Musachio、Jay Shah、Victor W. Pike

  DOI：10.1002/jlcr.991

  日期：2005.9

  [18F]2-Fluoroethyl tosylate ([18F]FEOX, X=Ts) is widely used for labeling radiotracers for positron emission tomography (PET). Little work has been reported on syntheses of other [18F]2-fluoroethyl arylsulfonates ([18F]FEOX) that bear a less electron-rich aryl group, even though these might offer enhanced reactivities. Thus, a series of novel [18F]FEOX (X=benzenesulfonyl, brosyl, nosyl, 3,4-dibromobenzenesulfonyl) were synthesized and reactivities compared to [18F]FEOTs. Precursors for radiolabeling (bis-ethylene glycol arylsulfonates) and reference FEOX were synthesized (alcohol+arylsulfonyl chloride+KOSiMe3 in THF). Regardless of substitution pattern, [18F]FEOX (110°C, 5 min, acetonitrile) were obtained in similar decay-corrected isolated radiochemical yields (RCY; 47–53%). All [18F]FEOX gave excellent RCYs (64–87%) of the dopamine uptake radioligand, [18F]FECNT (130°C, 10 min, acetonitrile). The 3,4-dibromobenzensulfonate gave the highest RCY of [18F]FECNT (87%) and this HPLC-purified labeling agent was used directly for efficient [18F]FECNT production. When the secondary aniline of an amyloid probe (HM-IMPY) or p-nitrophenol was reacted with [18F]FEOX, RCYs were appreciably higher for brosylate and nosylate than for tosylate, while 3,4-dibromobenzenesulfonate again gave the highest RCY. Owing to the high reactivity of the new [18F]FEOX and their ease of syntheses via stable precursors, such agents (particularly 3,4-dibromobenzenesulfonate) should be considered as alternatives to [18F]FEOTs. Copyright © 2005 John Wiley & Sons, Ltd.

  [18F]2-氟乙基对甲苯磺酸酯([18F]FEOX, X=Ts)广泛用于正电子发射断层扫描(PET)示踪剂的标记。尽管可能具有增强的反应性,但关于合成其他[18F]2-氟乙基芳磺酸酯([18F]FEOX)的研究报道很少,特别是含有较少电富集芳基的化合物。因此,合成了一系列新型[18F]FEOX(X=苯磺酰基、对溴苯磺酰基、对硝基苯磺酰基、3,4-二溴苯磺酰基)并比较了其与[18F]FEOTs的反应活性。放射性标记前体(双乙二醇芳磺酸酯)和参考FEOX通过以下方法合成:乙醇+芳磺酰氯+KOSiMe3(在四氢呋喃中)。无论取代模式如何,[18F]FEOX(110°C, 5 min, 乙腈)均以相似的衰减校正的放射化学产率(RCY; 47–53%)获得。所有[18F]FEOX均提供了优异的多巴胺摄取放射配体[18F]FECNT的RCY(64–87%)(130°C, 10 min, 乙腈)。3,4-二溴苯磺酸酯提供了最高的[18F]FECNT的RCY(87%),该高效液相色谱纯化的标记试剂直接用于高效生产[18F]FECNT。当与淀粉样蛋白探针(HM-IMPY)的二级苯胺或对硝基苯酚反应时,[18F]FEOX的RCY明显高于对溴苯磺酸酯和对硝基苯磺酸酯,而3,4-二溴苯磺酸酯再次提供了最高的RCY。由于新型[18F]FEOX的高反应性和通过稳定前体合成的简便性,这些试剂(特别是3,4-二溴苯磺酸酯)应被视为[18F]FEOTs的替代品。版权所有 © 2005 John Wiley & Sons, Ltd.
• Synthesis and Structure−Affinity Relationships of New 4-(6-Iodo-<i>H</i>-imidazo[1,2-<i>a</i>]pyridin-2-yl)-<i>N</i>-dimethylbenzeneamine Derivatives as Ligands for Human β-Amyloid Plaques
  作者：Lisheng Cai、Jessica Cuevas、Sebastian Temme、Mary M. Herman、Claudio Dagostin、David A. Widdowson、Robert B. Innis、Victor W. Pike

  DOI：10.1021/jm0702231

  日期：2007.9.1

  extensive set of 4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N-dimethylbenzeneamine (IMPY) derivatives was synthesized and assayed for affinity toward human Abeta plaques. 6-Ethylthio- (12h), 6-cyano- (12e), 6-nitro- (12f), and 6-p-methoxybenzylthio- (15d) analogues were discovered to have high affinity (KI < 10 nM). However, introduction of a hydrophilic thioether group in the 6-position (15a-c, 15e-g) reduced

  合成了一组新的4-（6-碘-H-咪唑并[1,2-a]吡啶-2-基）-N-二甲基苯胺（IMPY）衍生物，并测定了对人Abeta斑块的亲和力。发现6-乙基硫基-（12h），6-氰基-（12e），6-硝基-（12f）和6-对甲氧基苄基硫基-（15d）类似物具有高亲和力（KI <10 nM）。然而，在6-位（15a-c，15e-g）中引入亲水性硫醚基降低或消除了亲和力。在仲N-甲基类似物中，相邻环位置的溴取代基（14a）具有高亲和力（KI = 7.4 nM），而甲基取代基则没有（14c）。对6位非亲水性硫醚取代基的耐受性开辟了开发新的敏感正电子发射断层显像放射配体的可能性，以对阿尔茨海默氏病中的人Abeta斑块进行成像，尤其是考虑到硫醚易于通过S-烷基化反应被碳11或氟18标记。在这项研究中揭示的结构活性关系扩展了对人类Abeta斑块中IMPY样配体结合位点的形貌的了解。
• PROCESS OF PREPARING A RADIOACTIVE COMPOUND CONTAINING A FLUORINE-18 ISOTOPE
  申请人：CHO Zang Hee

  公开号：US20100292478A1

  公开（公告）日：2010-11-18

  A process of preparing a radioactive compound containing a fluorine-18 isotope is provided. In one embodiment, the process may comprise forming a [ 18 F] fluoroalkyl triflate by triflating a [ 18 F] fluoroalkyl compound with AgOTf, and forming a [ 18 F] fluoroalkylated radioactive compound through alkylation between the [ 18 F] fluoroalkyl triflate and a radioactive compound precursor having at least one group selected from NH, OH and SH.

  提供一种制备含氟-18同位素的放射性化合物的过程。在一个实施例中，该过程可能包括通过使用AgOTf对氟-18氟烷基化合物进行三氟甲基化，形成[18F]氟烷基三氟甲基酯，然后通过[18F]氟烷基三氟甲基酯与具有NH、OH和SH中至少一种基团的放射性化合物前体之间的烷基化反应，形成[18F]氟烷基化放射性化合物。
• Compounds and methods useful for rescuing cells from beta-amyloid toxicity and treatment of Alzheimer's disease
  申请人：Jin Lee-Way

  公开号：US20070254889A1

  公开（公告）日：2007-11-01

  The present invention is directed to pharmaceutical compositions comprising one or more compounds of Formulae I, II, III, IV, V, VI, VII, VIII, IX and X, or pharmaceutically acceptable salts thereof and excipients. The present invention provides a method of inhibiting β-amyloid plaque aggregation, the method comprising introducing into a mammal an aggregation-inhibiting amount of a compound of Formula I, II, III, IV, V, VI, VII, VIII, IX or X or a pharmaceutically acceptable salt, ester, amide or prodrug thereof. By inhibiting amyloid aggregation, this method is capable of rescuing cells that otherwise would be susceptible or further damaged by amyloidosis.

  本发明涉及一种制药组合物，包括式I、II、III、IV、V、VI、VII、VIII、IX和X中的一个或多个化合物，或其药学上可接受的盐和辅料。本发明提供了一种抑制β-淀粉样斑块聚集的方法，该方法包括向哺乳动物中引入式I、II、III、IV、V、VI、VII、VIII、IX或X中的一种化合物或其药学上可接受的盐、酯、酰胺或前药的抑制聚集量。通过抑制淀粉样聚集，该方法能够挽救那些本来易受淀粉样蛋白病损伤的细胞。
• WO2007/124345
  申请人：——

  公开号：——

  公开（公告）日：——