N-(2-(diethylamino)ethyl)-6-iodoquinoxaline-2-carboxamide | 1005029-85-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(2-(diethylamino)ethyl)-6-iodoquinoxaline-2-carboxamide
• 英文别名: N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide；N-[2-(diethylamino)ethyl]-6-iodoquinoxaline-2-carboxamide
• CAS: 1005029-85-5
• 化学式: C₁₅H₁₉IN₄O
• 分子量: 398.247
• InChiKey: COGTVQOVSQHRIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  58.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-diethylaminoethyl)-6-(tributylstannyl)quinoline-2-carboxamide 、 N-(2-(diethylamino)ethyl)-6-iodoquinoxaline-2-carboxamide 在 alumina 、 cyclohexane, ethyl acetate 作用下， 生成 N-(2-diethylaminoethyl)-6-i(tributylstannyl)quinoxaline-2-carboxamide
  参考文献：
  名称：

  LABELLED ANALOGUES OF HALOBENZAMIDES AS RADIOPHARMACEUTICALS

  摘要：

  本发明涉及使用式（I）化合物：其中R1代表放射性核素，Ar代表芳香环，m为2到4的整数，R2和R3代表独立的氢原子，（C1-C6）烷基，（C1-C6）烯基或苯基，所述苯基选择自苯基，苄基，咪唑基，吡啶基，嘧啶基，吡嗪基，吲哚基，吲唑基，呋喃基和噻吩基，并且它们与药学上可接受的酸的加成盐，用于制备放射性药物组合物，用于诊断和/或治疗黑色素瘤。

  公开号：

  US20100061928A1
• 作为产物：
  描述：

  6-碘喹喔啉-2-羧酸乙酯 、 N,N-二乙基乙二胺 在 三甲基铝 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 7.0h， 以77%的产率得到N-(2-(diethylamino)ethyl)-6-iodoquinoxaline-2-carboxamide
  参考文献：
  名称：

  N-（2-二乙基氨基乙基）-4-碘代苯甲酰胺的放射性标记（杂）芳族类似物的评估，用于黑色素瘤的成像和放射性核素治疗。

  摘要：

  使用对黑素瘤组织具有特定亲和力的放射性碘化化合物的靶向放射性核素治疗是弥散性黑素瘤的一种有前途的治疗方法，但具有理想动力学特征的候选药物仍有待发现。靶向放射性核素疗法集中了对肿瘤细胞的作用，从而提高了疗效并降低了放射疗法的发病率。在这种情况下，N-（2-二乙基氨基乙基）-4-碘代苯甲酰胺（BZA）的类似物是令人关注的。合成了多种BZA的（杂）芳族类似物5并用（125）I进行了放射性碘标记，并在静脉注射后研究了它们在荷黑素瘤小鼠中的生物分布。大多数[（125）I] 5标记的化合物似乎与黑素瘤肿瘤特异性结合并且具有中到高亲和力。5h和5k这两种化合物，

  DOI：

  10.1021/jm701424g

文献信息

• Labelled quinoxaline derivatives as multimodal radiopharmaceuticals and their precursors
  申请人：Institut National de la Santé et de la Recherche Médicale

  公开号：EP2657213A1

  公开（公告）日：2013-10-30

  The present invention relates to the compound of formula (I): in which R1 represents Sn(R)3, B(OH)2, B(OR)2, a halogen atom, NO2, a radionuclide or a -N+(R)3 group, where R is a (C1-C6) alkyl group, R2 represents a hydrogen atom or a (C1-C6)alkyl group, R3 represents: - a -(CH2CH2O)n2-(CH2)n3-X group, or - a ―(CH2CH2O)n4-(CH2)n5-Y group with Y representing a -C=C-H, a -N3 or a -Ar-(CH2)n6-(OCH2CH2)n7-X group, and X represents a halogen atom, a radionuclide or a -OSO2R' group, where R' is a CF3, CH3, t-Bu, Ph, p-NO2Ph, p-BrPh or p-CH3Ph 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.

  本发明涉及具有以下结构的化合物（I）： 其中 R1代表Sn（R）3，B（OH）2，B（OR）2，卤素原子，NO2，放射性核素或-N+（R）3基团，其中R是（C1-C6）烷基基团， R2代表氢原子或（C1-C6）烷基基团， R3代表： - 一个-(CH2CH2O)n2-(CH2)n3-X基团，或 - 一个―(CH2CH2O)n4-(CH2)n5-Y基团，其中Y代表-C=C-H，-N3或-Ar-(CH2)n6-(OCH2CH2)n7-X基团，而X代表卤素原子，放射性核素或-OSO2R'基团，其中R'是CF3，CH3，t-Bu，Ph，p-NO2Ph，p-BrPh或p-CH3Ph基团，并且它们与药学上可接受的酸形成的加合盐， 本发明还涉及包含它们的药物组合物，以及它们在诊断中的使用，特别是与SPECT或PET成像一起以及在黑色素瘤的治疗中，通过靶向放射性核素治疗。
• PEGylation enhances the tumor selectivity of melanoma-targeted conjugates
  作者：Mathieu André、Sophie Besse、Jean-Michel Chezal、Emmanuelle Mounetou

  DOI：10.1039/c4ob01751j

  日期：——

  Three preselected conjugates of 5-iodo-2′-deoxyuridine (IUdR) to the ICF01012 melanoma-carrier, PEGylated and non-PEGylated, were radiolabelled with iodine-125, and their in vivo distribution profile was evaluated for potential intratumoural selective delivery.

  三种预选的5-碘-2'-脱氧尿嘧啶（IUdR）与ICF01012黑色素瘤载体结合物，包括PEG化和非PEG化的结合物，被标记了碘-125，并评估了它们的体内分布特性，以用于潜在的肿瘤内选择性递送。
• 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 radiopharmaceuticals
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP2363399A1

  公开（公告）日：2011-09-07

  The present invention relates to the use of a compound of formula (I): in which R1 represents a radionuclide, Ar represents an aromatic nucleus, m is an integer varying from 2 to 4, R2 and R3 represent, independently of one another, a hydrogen atom, a (C1-C6)alkyl group, a (C1-C6)alkenyl group or an aryl group chosen from a phenyl, benzyl, imidazolyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, indazolyl, furyl and thienyl group, and their addition salts with pharmaceutically acceptable acids, in the preparation of a radiopharmaceutical composition intended for the diagnosis and/or treatment of melanoma.

  本发明涉及式（I）化合物的用途： 其中 R1 代表放射性核素 Ar 代表芳香核 m 是 2 至 4 之间的整数、 R2和R3相互独立地代表氢原子、(C1-C6)烷基、(C1-C6)烯基或选自苯基、苄基、咪唑基、吡啶基、嘧啶基、吡嗪基、吲哚基、吲唑基、呋喃基和噻吩基的芳基，以及它们与药学上可接受的酸的加成盐，用于制备诊断和/或治疗黑色素瘤的放射性药物组合物。
• Synthesis and in Vivo Evaluation of [¹²³I]Melanin-Targeted Agents
  作者：Maxine P. Roberts、Vu Nguyen、Mark E. Ashford、Paula Berghofer、Naomi A. Wyatt、Anwen M. Krause-Heuer、Tien Q. Pham、Stephen R. Taylor、Leena Hogan、Cathy D. Jiang、Benjamin H. Fraser、Nigel A. Lengkeek、Lidia Matesic、Marie-Claude Gregoire、Delphine Denoyer、Rodney J. Hicks、Andrew Katsifis、Ivan Greguric

  DOI：10.1021/acs.jmedchem.5b00777

  日期：2015.8.13

  study reports the synthesis, [I-123]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [I-131]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [I-123]4 (ICF01012). The most favorable compounds ([I-123]20, [I-123]23, [I-123] 41, and [I-123]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [I-123]20 and [I-123]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [I-123]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [I-123]41 and [I-123]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [I-123]53 displays favorable in vivo pharrnacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [I-131] therapeutic evaluation.