公开(公告)号：US20100056804A1

公开(公告)日：2010-03-04

申请号：US12203214

申请日：2008-09-03

申请人： Show-Wen LIU ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu ,  Cheng-Hsien Lin ,  Tsai-Yueh Luo ,  Lie-Hang Shen ,  Hwa-Jan Chen

发明人： Show-Wen LIU ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu ,  Cheng-Hsien Lin ,  Tsai-Yueh Luo ,  Lie-Hang Shen ,  Hwa-Jan Chen

IPC分类号： C07D207/30

CPC分类号： C07D207/46 ,  Y02P20/55

摘要： A compound containing carboxylate ester and N2S2 ligand bi-functional groups and a manufacturing method thereof are disclosed. The S in the N2S2 ligand of the compound containing carboxylate ester and N2S2 ligand bi-functional groups includes a protective group so as to avoid to be oxidized and easy storage. In a complex reaction, the protective group is automatically released As to the active carboxylate ester, it is for reacting with compounds having amino groups such as amines, amino acids, peptides, or protein etc while the N2S2 ligand is for bonding with technetium or rhenium so as to form neutral complex. The compound containing carboxylate ester and N2S2 ligand bi-functional groups is applied to radiopharmaceuticals such as contrast agents for tissues and target agents.

摘要翻译： 公开了含有羧酸酯和N 2 S 2配位体双官能团的化合物及其制备方法。 含有羧酸酯和N2S2配位体双官能团的化合物的N2S2配体中的S包括保护基，以避免被氧化并容易储存。 在复杂的反应中，保护基被自动释放对于活性羧酸酯，它是与具有氨基的化合物如胺，氨基酸，肽或蛋白质等反应，而N2S2配体与锝或铼键合 从而形成中性复合物。 含有羧酸酯和N 2 S 2配位体双功能基团的化合物被应用于放射性药物，例如用于组织和靶标的造影剂。

公开(公告)号：US07935833B2

公开(公告)日：2011-05-03

申请号：US12203214

申请日：2008-09-03

申请人： Show-Wen Liu ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu ,  Cheng-Hsien Lin ,  Tsai-Yueh Luo ,  Lie-Hang Shen ,  Haw-Jan Chen

发明人： Show-Wen Liu ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu ,  Cheng-Hsien Lin ,  Tsai-Yueh Luo ,  Lie-Hang Shen ,  Haw-Jan Chen

IPC分类号： C07D207/46

CPC分类号： C07D207/46 ,  Y02P20/55

摘要： A compound containing carboxylate ester and N2S2 ligand bi-functional groups and a manufacturing method thereof are disclosed. The S in the N2S2 ligand of the compound containing carboxylate ester and N2S2 ligand bi-functional groups includes a protective group so as to avoid to be oxidized and easy storage. In a complex reaction, the protective group is automatically released As to the active carboxylate ester, it is for reacting with compounds having amino groups such as amines, amino acids, peptides, or protein etc while the N2S2 ligand is for bonding with technetium or rhenium so as to form neutral complex. The compound containing carboxylate ester and N2S2 ligand bi-functional groups is applied to radiopharmaceuticals such as contrast agents for tissues and target agents.

摘要翻译： 公开了含有羧酸酯和N 2 S 2配位体双官能团的化合物及其制备方法。 含有羧酸酯和N2S2配位体双官能团的化合物的N2S2配体中的S包括保护基，以避免被氧化并容易储存。 在复杂的反应中，保护基被自动释放对于活性羧酸酯，它是与具有氨基的化合物如胺，氨基酸，肽或蛋白质等反应，而N2S2配体与锝或铼键合 从而形成中性复合物。 含有羧酸酯和N 2 S 2配位体双功能基团的化合物被应用于放射性药物，例如用于组织和靶标的造影剂。

公开(公告)号：US08258331B2

公开(公告)日：2012-09-04

申请号：US13087862

申请日：2011-04-15

申请人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu ,  Yu Chang

发明人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu ,  Yu Chang

IPC分类号： C07F7/22 ,  C07C217/00

CPC分类号： C07F7/2208

摘要： A method for preparation of N-methyl-3-(2-tributylstannylphenoxy)-3-phenylpropanamine is provided, which includes formation of N-methyl-3-(2-tributylstannylphenoxy)-3-phenylpropanamine, useful as a precursor of a norepinephrine transporter (NET) contrast label [123Iodine](R)—N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine ([123I]MIPP) with a leaving group Bu3Sn.

摘要翻译： 提供了制备N-甲基-3-（2-三丁基甲锡烷基苯氧基）-3-苯基丙胺的方法，包括形成N-甲基-3-（2-三丁基甲锡烷基苯氧基）-3-苯基丙胺，可用作去甲肾上腺素的前体 转运蛋白（NET）对比标记物[123碘]（R）-N-甲基-3-（2-碘苯氧基）-3-苯基丙胺（[123 I] MIPP）与离去基团Bu 3 Sn。

公开(公告)号：US08551447B2

公开(公告)日：2013-10-08

申请号：US13087664

申请日：2011-04-15

申请人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Yu Chang ,  Cheng-Fang Hsu ,  Tsyh-Lang Lin

发明人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Yu Chang ,  Cheng-Fang Hsu ,  Tsyh-Lang Lin

IPC分类号： A61K38/00

CPC分类号： C07H15/04

摘要： A bifunctional compound with a monosaccharide and a N2S2 ligand, and more particularly, a bifunctional compound with a N2S2 ligand and aminohexylacetyl galactosamine (ah-GalNAc4) is provided. A method for preparing the bifunctional compound with a monosaccharide and a N2S2 ligand is also provided, including activating a carboxyl group in an organic ligand, reacting the activated carboxyl group with a galactopyranoside through amidation, and then hydrolyzing. The bifunctional compound of the present invention is widely useful in nuclear medicine for preparation of liver imaging agents for assisting in correct diagnosis of diseases.

摘要翻译： 提供了具有单糖和N2S2配体的双官能化合物，更具体地，提供了具有N 2 S 2配体和氨基己基乙酰基半乳糖胺（ah-GalNAc 4）的双官能化合物。 还提供了用单糖和N 2 S 2配体制备双功能化合物的方法，包括活化有机配体中的羧基，通过酰胺化使活化的羧基与吡喃半乳糖苷反应，然后水解。 本发明的双功能化合物在制备用于辅助正确诊断疾病的肝成像剂的核医学中广泛有用。

公开(公告)号：US08329879B2

公开(公告)日：2012-12-11

申请号：US12558911

申请日：2009-09-14

申请人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

发明人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

IPC分类号： C07F13/00

CPC分类号： C07C323/41 ,  C07F13/005

摘要： H3LMN series compounds used as radioactive agents for treatment of liver cancer and a manufacturing method thereof are revealed. 2-thioethylamine hydrochloride is reacted with triphenylmethanol for protection of thiol to obtain 2-[(triphenylmethyl)thio]ethylamine. Then obtain N-[2-((triphenylmethyl)thio)ethyl]chloroacetamide by a transamidation reaction between 2-[(triphenylmethyl)thio]ethylamine and chloroactyl chloride. Next produce a amine-amide-thiol ligand-N-[2-((triphenylmethyl)thio)ethyl][2-((triphenylmethyl)thio)ethylamino]acetamide by a substitution reaction of N-[2-((triphenylmethyl)thio)ethyl]chloroacetamide and 2-[(triphenylmethyl)thio]ethylamine. After respective reaction with 1-bromotetradecane, 1-bromohexadecane and ethyl 16-bromohexadecanoate, H3LMN series compounds are obtained. These amine-amide-dithiols quadridentate ligands can react with MO3+ (M=Tc or Re) to produce electrically neutral complexes. The complexes have high lipophilicity, allowing them soluble in lipiodol to be applied to radiation therapy for liver cancer.

摘要翻译： 揭示了用作肝癌治疗放射剂的H3LMN系列化合物及其制造方法。 将2-硫代乙胺盐酸盐与三苯基甲醇反应以保护硫醇，得到2 - [（三苯基甲基）硫代]乙胺。 然后通过2 - [（三苯基甲基）硫代]乙胺和氯代酰氯的酰胺化反应获得N- [2 - （（三苯基甲基）硫基）乙基]氯乙酰胺。 接着通过N- [2 - （（三苯基甲基）硫代）的取代反应生成胺 - 酰胺 - 硫醇配体-N- [2 - （（三苯基甲基）硫代）乙基] [2 - （（三苯基甲基）硫基）乙基氨基] ）乙基]氯乙酰胺和2 - [（三苯甲基）硫基]乙胺。 在与1-溴十四烷，1-溴十六烷和16-溴十六烷酸乙酯反应后，得到H3LMN系列化合物。 这些胺 - 酰胺 - 二硫醇三元配体可以与MO3 +（M = Tc或Re）反应以产生电中性络合物。 复合物具有高亲脂性，使其可溶于碘油以适用于放射治疗肝癌。

公开(公告)号：US20110065904A1

公开(公告)日：2011-03-17

申请号：US12558911

申请日：2009-09-14

申请人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

发明人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

IPC分类号： C07F13/00 ,  C07C237/04 ,  C07C69/003

CPC分类号： C07C323/41 ,  C07F13/005

摘要： H3LMN series compounds used as radioactive agents for treatment of liver cancer and a manufacturing method thereof are revealed. 2-thioethylamine hydrochloride is reacted with triphenylmethanol for protection of thiol to obtain 2-[(triphenylmethyl)thio]ethylamine. Then obtain N-[2-((triphenylmethyl)thio)ethyl]chloroacetamide by a transamidation reaction between 2-[(triphenylmethyl)thio]ethylamine and chloroactyl chloride. Next produce a amine-amide-thiol ligand-N-[2-((triphenylmethyl)thio)ethyl][2-((triphenylmethyl)thio)ethylamino]acetamide by a substitution reaction of N-[2-((triphenylmethyl)thio)ethyl]chloroacetamide and 2-[(triphenylmethyl)thio]ethylamine. After respective reaction with 1-bromotetradecane, 1-bromohexadecane and ethyl 16-bromohexadecanoate, H3LMN series compounds are obtained. These amine-amide-dithiols quadridentate ligands can react with MO3+ (M=Tc or Re) to produce electrically neutral complexes. The complexes have high lipophilicity, allowing them soluble in lipiodol to be applied to radiation therapy for liver cancer.

摘要翻译： 揭示了用作肝癌治疗放射剂的H3LMN系列化合物及其制造方法。 将2-硫代乙胺盐酸盐与三苯基甲醇反应以保护硫醇，得到2 - [（三苯基甲基）硫代]乙胺。 然后通过2 - [（三苯基甲基）硫代]乙胺和氯代酰氯的酰胺化反应获得N- [2 - （（三苯基甲基）硫基）乙基]氯乙酰胺。 接着通过N- [2 - （（三苯基甲基）硫代）的取代反应生成胺 - 酰胺 - 硫醇配体-N- [2 - （（三苯基甲基）硫代）乙基] [2 - （（三苯基甲基）硫基）乙基氨基] ）乙基]氯乙酰胺和2 - [（三苯甲基）硫基]乙胺。 在与1-溴十四烷，1-溴十六烷和16-溴十六烷酸乙酯反应后，得到H3LMN系列化合物。 这些胺 - 酰胺 - 二硫醇三元配体可以与MO3 +（M = Tc或Re）反应，产生电中性络合物。 复合物具有高亲脂性，使其可溶于碘油以适用于放射治疗肝癌。

公开(公告)号：US20110040123A1

公开(公告)日：2011-02-17

申请号：US12540467

申请日：2009-08-13

申请人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

发明人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

IPC分类号： C07C237/10

CPC分类号： C07C323/41 ,  Y02P20/55

摘要： A bifunctional compound containing an amino group and diaminedithiol ligand and a manufacturing method thereof are revealed, the bifunctional compound includes at least one amino group and a diaminedithiol (N2S2) ligand. The amino groups is for reacting with compounds containing carboxylic acids or halogens while the N2S2 ligand binds with technetium or rhenium so as to form an anion complex. The thiol group in the N2S2 ligand is protected by a protecting group for prevention of oxidation and easy storage. This protecting group is released easily during complex reactions. Due to the bifunctional property, the compound is applied to preparation of radiopharmaceuticals such as imaging agents and targeted agents.

公开(公告)号：US07964752B2

公开(公告)日：2011-06-21

申请号：US12540467

申请日：2009-08-13

申请人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

发明人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

IPC分类号： C07C233/05 ,  C07C237/10

CPC分类号： C07C323/41 ,  Y02P20/55

摘要： A bifunctional compound containing an amino group and diaminedithiol ligand and a manufacturing method thereof are revealed, the bifunctional compound includes at least one amino group and a diaminedithiol (N2S2) ligand. The amino groups is for reacting with compounds containing carboxylic acids or halogens while the N2S2 ligand binds with technetium or rhenium so as to form an anion complex. The thiol group in the N2S2 ligand is protected by a protecting group for prevention of oxidation and easy storage. This protecting group is released easily during complex reactions. Due to the bifunctional property, the compound is applied to preparation of radiopharmaceuticals such as imaging agents and targeted agents.

摘要翻译： 显示含有氨基和二硫代二醇配体的双官能化合物及其制备方法，双官能化合物包括至少一个氨基和二硫代二醇（N 2 S 2）配体。 氨基用于与含有羧酸或卤素的化合物反应，而N2S2配体与锝或铼结合形成阴离子络合物。 N2S2配体中的硫醇基团被保护基团保护，以防止氧化和容易储存。 这种保护基团在复杂的反应过程中容易释放。 由于双功能性，该化合物被用于制备放射性药物如成像剂和靶向剂。

公开(公告)号：US08076499B2

公开(公告)日：2011-12-13

申请号：US12540448

申请日：2009-08-13

申请人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

发明人： Show-Wen Liu ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

IPC分类号： C07F3/10 ,  C07F7/00

CPC分类号： C07C277/08 ,  C07B2200/05 ,  C07C279/06

摘要： A method for preparing a precursor of radioactive 3-iodobenzylguanidine- N,N′-bis(tert-butyloxycarbonyl)-3-(tri-n-butyltin)benzylguanidine) (MSnBG) is revealed. The method includes following steps. Firstly, obtain 3-iodobenzylguanidine bicarbonate by an addition reaction between 3-iodobenzylamine hydrochloride and cyanamide. Use di-tert-butyl dicarbonate as a protecting agent for NH group and convert 3-iodobenzylguanidine bicarbonate into N,N′-bis(tert-butyloxycarbonyl)-N-(3-iodobenzyl) guanidine. At last, under catalysis of bis(triphenylphosphine) palladium dichloride, obtain a final product MSnBG by a substitution reaction between N,N′-bis(tert-butyloxycarbonyl)-N-(3-iodobenzyl) guanidine and bis(tri-n-butyltin). MSnBG is used in no-carrier-added synthesis of [*l]MIBG.

摘要翻译： 揭示了制备放射性3-碘苄基胍-N，N'-双（叔丁氧基羰基）-3-（三正丁基锡）苄基胍）前体的方法（MSnBG）。 该方法包括以下步骤。 首先，通过3-碘苄胺盐酸盐和氨腈之间的加成反应获得3-碘苄基胍碳酸氢盐。 使用二碳酸二叔丁酯作为NH基团的保护剂，并将3-碘苄基胍碳酸氢盐转化成N，N'-双（叔丁氧基羰基）-N-（3-碘苄基）胍。 最后，在双（三苯基膦）二氯化钯的催化下，通过N，N'-双（叔丁氧基羰基）-N-（3-碘苄基）胍与双（三正丁基）二氯化钯的取代反应得到最终产物MSnBG， 丁基锡）。 MSnBG用于[* 1] MIBG的无载体添加合成。

公开(公告)号：US20110040119A1

公开(公告)日：2011-02-17

申请号：US12540448

申请日：2009-08-13

申请人： Show-Wen LIU ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

发明人： Show-Wen LIU ,  Cheng-Hsien Lin ,  Tsyh-Lang Lin ,  Cheng-Fang Hsu

IPC分类号： C07C271/20

CPC分类号： C07C277/08 ,  C07B2200/05 ,  C07C279/06

摘要： A method for preparing a precursor of radioactive 3-iodobenzylguanidine-N,N′-bis(tert-butyloxycarbonyl)-3-(tri-n-butyltin)benzylguanidine) (MSnBG) is revealed. The MSnBG is a precursor of [*I]MIBG that is used as radioactive imaging agents and antineoplastic drugs. The method includes following steps. Firstly, obtain 3-iodobenzylguanidine bicarbonate by an addition reaction between 3-iodobenzylamine hydrochloride and cyanamide. Use di-tert-butyl dicarbonate as a protecting agent for NH group and convert 3-iodobenzylguanidine bicarbonate into N,N′-bis(tert-butyloxycarbonyl)-N-(3-iodobenzyl) guanidine. At last, under catalysis of bis(triphenylphosphine) palladium dichloride, obtain a final product MSnBG by a substitution reaction between N,N′-bis(tert-butyloxycarbonyl)-N-(3-iodobenzyl) guanidine and bis(tri-n-butyltin). MSnBG is used in no-carrier-added synthesis of [*I]MIBG. The [*I]MIBG obtained by this method has better effect on neuroblastoma treatment than that obtained by conventional, carrier-added method.

摘要翻译： 揭示了制备放射性3-碘苄基胍-N，N'-双（叔丁氧基羰基）-3-（三正丁基锡）苄基胍）（MSnBG）的前体的方法。 MSnBG是用作放射性成像剂和抗肿瘤药物的[* I] MIBG的前体。 该方法包括以下步骤。 首先，通过3-碘苄胺盐酸盐和氨腈之间的加成反应获得3-碘苄基胍碳酸氢盐。 使用二碳酸二叔丁酯作为NH基团的保护剂，并将3-碘苄基胍碳酸氢盐转化成N，N'-双（叔丁氧基羰基）-N-（3-碘苄基）胍。 最后，在双（三苯基膦）二氯化钯的催化下，通过N，N'-双（叔丁氧基羰基）-N-（3-碘苄基）胍与双（三正丁基）二氯化钯的取代反应得到最终产物MSnBG， 丁基锡）。 MSnBG用于[* I] MIBG的无载体添加合成。 通过该方法获得的[* I] MIBG对于神经母细胞瘤治疗比通过常规的载体添加方法获得的效果更好。