公开(公告)号：US08624039B2

公开(公告)日：2014-01-07

申请号：US13395841

申请日：2010-03-04

申请人： Sang Eun Kim ,  Byung Chul Lee ,  Byung Seok Moon ,  Yu Kyeong Kim

发明人： Sang Eun Kim ,  Byung Chul Lee ,  Byung Seok Moon ,  Yu Kyeong Kim

IPC分类号： C07D207/09

CPC分类号： C07D207/09

摘要： A method for preparing [18F]fallypride is disclosed, which comprises a first step for trapping a fluorine-18 to a polymer ion exchange cartridge; a second step for extraction of fluorine-18 by inputting low base concentrations: 5.0˜25 μL of 40% TBAHCO3 or K2.2.2./K2CO3 (5˜25 mg/0.5˜3.0 mg) as a phase-transfer catalyst in a mixture of alcohol/water (1.0/0.2 (v/v)) or alcohol as a solvent into the polymer ion exchange cartridge trapped by the fluorine-18; a third step for preparing a [18F]fallypride product by removing the solvent from the trapped fluorine-18, by inputting tosylate precursor in CH3CN as a solvent into a reactor and by reacting the same for 5˜35 minutes at 50˜120° C.; and a fourth step for preparing a pure [18F]fallypride by purifying the prepared [18F]fallypride product.

摘要翻译： 公开了一种制备[18 F]菲拉必利的方法，其包括将氟-18捕获到聚合物离子交换盒的第一步骤; 通过输入低碱浓度来提取氟-18的第二步：将5.0〜25μl的40％TBAHCO 3或作为相转移催化剂的K2​​.2.2./K2CO3（5〜25mg / 0.5〜3.0mg）混合 的醇/水（1.0 / 0.2（v / v））或醇作为溶剂加入到被氟-18捕获的聚合物离子交换盒中; 通过在CH 3 CN中作为溶剂输入甲苯磺酸酯前体作为溶剂并通过在50〜120℃下反应5〜35分钟，通过从捕获的氟-18中除去溶剂来制备[18 F] fallypride产物的第三步骤 。 以及通过纯化制备的[18 F] fallypride产物制备纯的[18 F] fallypride的第四步骤。

公开(公告)号：US09439986B2

公开(公告)日：2016-09-13

申请号：US13699511

申请日：2011-05-24

申请人： Byung Chul Lee ,  Sang Eun Kim ,  Ji Sun Kim ,  Byung Seok Moon ,  Jae Ho Jung

发明人： Byung Chul Lee ,  Sang Eun Kim ,  Ji Sun Kim ,  Byung Seok Moon ,  Jae Ho Jung

IPC分类号： A61K51/00 ,  A61M36/14 ,  A61K51/08 ,  C07K7/64 ,  G01N33/574 ,  G01N33/60

CPC分类号： A61K51/088 ,  A61K51/082 ,  C07D273/06 ,  C07D498/06 ,  C07D498/16 ,  C07K7/64 ,  G01N33/574 ,  G01N33/60

摘要： The present invention relates to tricarbonyl technetium-99m or rhenium-188 labeled cyclic RGD derivatives, a preparation method thereof, and a pharmaceutical composition containing the derivative as an active ingredient for use in the diagnosis or treatment (radiotherapy) of angiogenesis-related diseases. The tricarbonyl technetium-99m or rhenium-188 labeled cyclic RGD derivatives of the present invention has a high subnanomolar affinity to integrin αvβ3 (also called as a vitronectin receptor) that is activated in an angiogenic action induced by a tumor, and acts exclusively upon cancer cells having selectively activated integrin αvβ3 because of a substantially low intake into the liver and intestines.

摘要翻译： 本发明涉及三羰基锝-99m或铼-188标记的环状RGD衍生物，其制备方法和含有该衍生物作为血管生成相关疾病的诊断或治疗（放射治疗）的有效成分的药物组合物。 本发明的三羰基锝-99m或铼-188标记的环状RGD衍生物在由肿瘤诱导的血管生成作用中被活化的整联蛋白αvβ3（也称为玻连蛋白受体）具有高的亚纳摩尔亲和力，并且仅起作用于癌症 由于肝和肠的摄入量实质上较低，细胞选择性地激活整合素αvβ3。

公开(公告)号：US20130064766A1

公开(公告)日：2013-03-14

申请号：US13699511

申请日：2011-05-24

申请人： Byung Chul Lee ,  Sang Eun Kim ,  Ji Sun Kim ,  Byung Seok Moon ,  Jae Ho Jung

发明人： Byung Chul Lee ,  Sang Eun Kim ,  Ji Sun Kim ,  Byung Seok Moon ,  Jae Ho Jung

IPC分类号： A61K51/08 ,  C07K1/13 ,  A61P9/00 ,  C07K7/64

CPC分类号： A61K51/088 ,  A61K51/082 ,  C07D273/06 ,  C07D498/06 ,  C07D498/16 ,  C07K7/64 ,  G01N33/574 ,  G01N33/60

摘要： The present invention relates to tricarbonyl technetium-99m or rhenium-188 labeled cyclic RGD derivatives, a preparation method thereof, and a pharmaceutical composition containing the derivative as an active ingredient for use in the diagnosis or treatment (radiotherapy) of angiogenesis-related diseases. The tricarbonyl technetium-99m or rhenium-188 labeled cyclic RGD derivatives of the present invention has a high subnanomolar affinity to integrin αvβ3 (also called as a vitronectin receptor) that is activated in an angiogenic action induced by a tumor, reflects a high tumor image of the tricatvonyl technetium-99m labeled cyclic RGD derivative after initial intake in an animal in which cancer cells are transplanted, and acts exclusively upon cancer cells having selectively activated integrin αvβ3 because of a substantially low intake into the liver and intestines, compared to existing known radioactive isotope labeled cyclic RGD derivatives. These results show that the rhenium-188 labeled derivative, a therapeutic nuclide using the same precursor as used in the technetium-99m labeling, effectively inhibits the growth of a tumor and demonstrates therapeutic efficacy when administered via tail vein injection to an animal model bearing tumor, compared to a case where only saline has been injected, thereby making it useful as a medicine for the diagnosis or treatment of angiogenesis-related diseases.

摘要翻译： 本发明涉及三羰基锝-99m或铼-188标记的环状RGD衍生物，其制备方法和含有该衍生物作为血管生成相关疾病的诊断或治疗（放射治疗）的有效成分的药物组合物。 本发明的三羰基锝-99m或铼-188标记的环状RGD衍生物在由肿瘤诱导的血管生成作用中被激活的整联蛋白αv＆bgr 3（也称为玻连蛋白受体）具有高亚纳摩尔亲和力，反映了高 在移植了癌细胞的动物中，首先摄入三氯乙酰锝-99m标记的环状RGD衍生物的肿瘤图像，并且完全作用于具有选择性活化整联蛋白αv＆bgr3的癌细胞，因为进入肝脏和肠的摄入量很低， 与现有已知的放射性同位素标记的环状RGD衍生物相比。 这些结果表明，使用与锝-99m标记中使用的相同前体的治疗性核素的铼-188标记的衍生物有效地抑制肿瘤的生长，并且当通过尾静脉注射施用于携带肿瘤的动物模型时显示出治疗功效 ，与仅注射盐水的情况相比，可以用作诊断或治疗血管发生相关疾病的药物。

公开(公告)号：US20120178920A1

公开(公告)日：2012-07-12

申请号：US13395841

申请日：2010-03-04

申请人： Sang Eun Kim ,  Byung Chul Lee ,  Byung Seok Moon ,  Yu Kyeong Kim

发明人： Sang Eun Kim ,  Byung Chul Lee ,  Byung Seok Moon ,  Yu Kyeong Kim

IPC分类号： C07D207/09 ,  C07H19/052 ,  C07C253/30 ,  C07D451/02

CPC分类号： C07D207/09

摘要： A method for preparing [18F]fallypride is disclosed, which comprises a first step for trapping a fluorine-18 to a polymer ion exchange cartridge; a second step for extraction of fluorine-18 by inputting low base concentrations: 5.0˜25 μL of 40% TBAHCO3 or K2.2.2./K2CO3 (5˜25 mg/0.5˜3.0 mg) as a phase-transfer catalyst in a mixture of alcohol/water (1.0/0.2 (v/v)) or alcohol as a solvent into the polymer ion exchange cartridge trapped by the fluorine-18; a third step for preparing a [18F]fallypride product by removing the solvent from the trapped fluorine-18, by inputting tosylate precursor in CH3CN as a solvent into a reactor and by reacting the same for 5˜35 minutes at 50˜120° C.; and a fourth step for preparing a pure [18F]fallypride by purifying the prepared [18F]fallypride product.

摘要翻译： 公开了一种制备[18 F]菲拉必利的方法，其包括将氟-18捕获到聚合物离子交换盒的第一步骤; 通过输入低碱浓度来提取氟-18的第二步：将5.0〜25μL的40％TBAHCO 3或作为相转移催化剂的K2​​.2.2./K2CO3（5〜25mg / 0.5〜3.0mg）混合 的醇/水（1.0 / 0.2（v / v））或醇作为溶剂加入到被氟-18捕获的聚合物离子交换盒中; 通过将CH 3 CN中的甲苯磺酸酯前体作为溶剂输入到反应器中并通过在50〜120℃下反应5〜35分钟，通过从捕获的氟-18中除去溶剂来制备[18 F] fallypride产物的第三步骤 。 以及通过纯化制备的[18 F] fallypride产物制备纯的[18 F] fallypride的第四步骤。