N-[2-(diethylamino)ethyl]-4-fluoro-6-(tributylstannyl)quinoline-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-[2-(diethylamino)ethyl]-4-fluoro-6-(tributylstannyl)quinoline-2-carboxamide
• 英文别名: N-[2-(diethylamino)ethyl]-4-fluoro-6-tributylstannylquinoline-2-carboxamide
• 化学式: C₂₈H₄₆FN₃OSn
• 分子量: 578.401
• InChiKey: AIYWXAJQBRVTMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  34
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[2-(diethylamino)ethyl]-4-fluoro-6-(tributylstannyl)quinoline-2-carboxamide 在 sodium iodide 、 chloroamine-T 作用下， 以 aq. buffer 为溶剂， 反应 0.75h， 生成 N-[2-(diethylamino)ethyl]-4-fluoro-6-(125I)iodanylquinoline-2-carboxamide
  参考文献：
  名称：

  Synthesis, radiolabeling and preliminary in vivo evaluation of multimodal radiotracers for PET imaging and targeted radionuclide therapy of pigmented melanoma

  摘要：

  Melanin pigment represents an attractive target to address specific treatment to melanoma cells, such as cytotoxic radionuclides. However, less than half of the patients have pigmented metastases. Hence, specific marker is required to stratify this patient population before proceeding with melanin-targeted radionuclide therapy. In such a context, we developed fluorinated analogues of a previously studied melanin-targeting ligand, N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide (ICF01012). These latter can be labeled either with F-18 or I-131/I-125 for positron emission tomography imaging (melanin-positive patient selection) and targeted radionuclide therapy purposes. Here we describe the syntheses, radiosyntheses and preclinical evaluations on melanoma-bearing mice model of several iodo- and fluoro(hetero)aromatic derivatives of the ICF01012 scaffold. After preliminary planar gamma scintigraphic and positron emission tomography imaging evaluations, [I-125]- and [F-18]-N-[2-(diethylamino)ethyl]-4-fluoro-3-iodobenzamides ([I-125]4, [F-18]4) were found to be chemically and biologically stable with quite similar tumor uptakes at 1 h p.i. (9.7 +/- 2.6% ID/g and 6.8 +/- 1.9% ID/g, respectively). (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.01.034
• 作为产物：
  描述：

  dimethyl 2-(4-iodophenylamino)maleate 在 potassium fluoride 、 四(三苯基膦)钯 、 三甲基铝 、 三氯氧磷 作用下， 以 二苯醚 、 正庚烷 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 32.0h， 生成 N-[2-(diethylamino)ethyl]-4-fluoro-6-(tributylstannyl)quinoline-2-carboxamide
  参考文献：
  名称：

  Synthesis, radiolabeling and preliminary in vivo evaluation of multimodal radiotracers for PET imaging and targeted radionuclide therapy of pigmented melanoma

  摘要：

  Melanin pigment represents an attractive target to address specific treatment to melanoma cells, such as cytotoxic radionuclides. However, less than half of the patients have pigmented metastases. Hence, specific marker is required to stratify this patient population before proceeding with melanin-targeted radionuclide therapy. In such a context, we developed fluorinated analogues of a previously studied melanin-targeting ligand, N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide (ICF01012). These latter can be labeled either with F-18 or I-131/I-125 for positron emission tomography imaging (melanin-positive patient selection) and targeted radionuclide therapy purposes. Here we describe the syntheses, radiosyntheses and preclinical evaluations on melanoma-bearing mice model of several iodo- and fluoro(hetero)aromatic derivatives of the ICF01012 scaffold. After preliminary planar gamma scintigraphic and positron emission tomography imaging evaluations, [I-125]- and [F-18]-N-[2-(diethylamino)ethyl]-4-fluoro-3-iodobenzamides ([I-125]4, [F-18]4) were found to be chemically and biologically stable with quite similar tumor uptakes at 1 h p.i. (9.7 +/- 2.6% ID/g and 6.8 +/- 1.9% ID/g, respectively). (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.01.034

文献信息

• LABELLED ANALOGUES OF HALOBENZAMIDES AS MULTIMODAL RADIOPHARMACEUTICALS AND THEIR PRECURSORS
  申请人：Chezal Jean-Michel

  公开号：US20110044899A1

  公开（公告）日：2011-02-24

  A compound of formula (I): in which R 1 represents a hydrogen atom, an optionally labelled halogen, a radionuclide or a Sn[(C 1 -C 4 )alkyl] 3 group, Ar represents an aryl group or a heteroaryl group, R 9 represents a hydrogen atom, a (C 1 -C 4 ) alkyl group or forms together with the group R 1 —Ar a ring fused with the Ar group, A represents a group of formula (β) or (δ): R 3 and R 4 independently represent a hydrogen atom, a (C 1 -C 6 )alkyl group, a (C 1 -C 6 ) alkenyl group or a group of formula (y): wherein R 11 represents an optionally labelled halogen, a radionuclide, an aryl or heteroaryl group optionally substituted by an optionally labelled halogen, a radionuclide, a —NO 2 group, a —NR 5 R 6 group, a N + R 5 R 6 R 7 X − group, or a —OSO 2 R 12 group, and their addition salts with pharmaceutically acceptable acids.

  化合物的化学式为(I)：其中R1代表氢原子、可选择标记的卤素、放射性核素或Sn[(C1-C4)烷基]3基团，Ar代表芳基或杂芳基，R9代表氢原子、(C1-C4)烷基或与基团R1-Ar共同形成与Ar基团融合的环，A代表化学式(β)或(δ)的基团：R3和R4分别独立地代表氢原子、(C1-C6)烷基、(C1-C6)烯基或化学式(y)的基团：其中R11代表可选择标记的卤素、放射性核素、可选择取代的芳基或杂芳基，取代基可以是可选择标记的卤素、放射性核素、—NO2基团、—NR5R6基团、N+R5R6R7X−基团或—OSO2R12基团，以及它们与药物可接受的酸形成的加合物。
• Labelled analogues of halobenzamides as multimodal radiopharmaceuticals and their precursors
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：US09125937B2

  公开（公告）日：2015-09-08

  The present invention relates to the compound of formula (I): in which R1 represents a hydrogen atom, an optionally labelled halogen, a radionuclide or a Sn[(C1-C4)alkyl]3 group, Ar represents an aryl group or a heteroaryl group, R9 represents a hydrogen atom, a (C1-C4)alkyl group or forms together with the group R1—Ar a ring fused with the Ar group, A represents a group of formula (β) or (δ): R3 and R4 independently represent a hydrogen atom, a (C1-C6)alkyl group, a (C1-C6)alkenyl group or a group of formula (γ): —Y—Z—W—R11  (γ) wherein R11 represents an optionally labelled halogen, a radionuclide, an aryl or heteroaryl group optionally substituted by an optionally labelled halogen, a radionuclide, a —NO2 group, a —NR5R6 group, a —N+R5R6R7X− group, or a —OSO2R12 group, and their addition salts with pharmaceutically acceptable acids. The present invention also relates to pharmaceutical compositions comprising them and to their use in diagnosis, in particular with SPECT or PET imaging and in therapy of melanoma via targeted radionuclide therapy.

  本发明涉及公式（I）的化合物： 其中，R1代表氢原子，可选择标记的卤素，放射性核素或Sn[(C1-C4)烷基]3基团； Ar代表芳基或杂芳基； R9代表氢原子，(C1-C4)烷基或与基团R1-Ar一起形成与Ar基团融合的环； A代表公式（β）或（δ）的基团： R3和R4独立地代表氢原子，(C1-C6)烷基，(C1-C6)烯基或公式（γ）的基团： -Y-Z-W-R11（γ） 其中，R11代表可选择标记的卤素，放射性核素，芳基或杂芳基，可选择地被可选择标记的卤素，放射性核素，-NO2基团，-NR5R6基团，-N+R5R6R7X-基团或-OSO2R12基团取代； 以及与药学上可接受的酸形成的加成盐。 本发明还涉及包含它们的制药组合物以及它们在诊断中的应用，特别是在SPECT或PET成像中以及通过靶向放射性核素治疗黑色素瘤的治疗中的应用。
• Synthesis, radiolabeling and preliminary in vivo evaluation of multimodal radiotracers for PET imaging and targeted radionuclide therapy of pigmented melanoma
  作者：Emilie M.F. Billaud、Aurélie Maisonial-Besset、Latifa Rbah-Vidal、Aurélien Vidal、Sophie Besse、Jean-Baptiste Béquignat、Caroline Decombat、Françoise Degoul、Laurent Audin、Jean-Bernard Deloye、Frédéric Dollé、Bertrand Kuhnast、Jean-Claude Madelmont、Sébastien Tarrit、Marie-Josèphe Galmier、Michèle Borel、Philippe Auzeloux、Elisabeth Miot-Noirault、Jean-Michel Chezal

  DOI：10.1016/j.ejmech.2015.01.034

  日期：2015.3

  Melanin pigment represents an attractive target to address specific treatment to melanoma cells, such as cytotoxic radionuclides. However, less than half of the patients have pigmented metastases. Hence, specific marker is required to stratify this patient population before proceeding with melanin-targeted radionuclide therapy. In such a context, we developed fluorinated analogues of a previously studied melanin-targeting ligand, N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide (ICF01012). These latter can be labeled either with F-18 or I-131/I-125 for positron emission tomography imaging (melanin-positive patient selection) and targeted radionuclide therapy purposes. Here we describe the syntheses, radiosyntheses and preclinical evaluations on melanoma-bearing mice model of several iodo- and fluoro(hetero)aromatic derivatives of the ICF01012 scaffold. After preliminary planar gamma scintigraphic and positron emission tomography imaging evaluations, [I-125]- and [F-18]-N-[2-(diethylamino)ethyl]-4-fluoro-3-iodobenzamides ([I-125]4, [F-18]4) were found to be chemically and biologically stable with quite similar tumor uptakes at 1 h p.i. (9.7 +/- 2.6% ID/g and 6.8 +/- 1.9% ID/g, respectively). (C) 2015 Elsevier Masson SAS. All rights reserved.