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12 条记录 (耗时 0.012 秒)

    Use of propylene oxide as an acid scavenger in peptide synthesis
    1.
    发明授权
    Use of propylene oxide as an acid scavenger in peptide synthesis 失效
    在肽合成中使用环氧丙烷作为酸清除剂

    公开(公告)号：US5698676A

    公开(公告)日：1997-12-16

    申请号：US565465

    申请日：1995-11-30

    申请人： Madhup K. Dhaon

    发明人： Madhup K. Dhaon

    IPC分类号： C07K1/04 ,  A61K38/00 ,  C07K5/00 ,  C07K7/00 ,  C07K16/00

    CPC分类号： C07K1/04 ,  Y02P20/55

    摘要： A process of synthesizing a peptide using an alkylene oxide as an acid scavenger is provided. A process of the present invention can be used in a solid phase or solution phase synthetic process where peptide synthesis occurs by the sequential addition of N-.alpha.-amino-Boc-protected residues followed by acid deprotection of that N-.alpha.-amino protecting group and scavenging of the acid.

    摘要翻译： 提供了使用烯化氧作为酸清除剂合成肽的方法。 本发明的方法可以用于固相或溶液相合成过程，其中通过顺序加入N-α-氨基-Boc-保护的残基然后酸脱保护该N-N-氨基保护基来进行肽合成 并清除酸。

    Method of synthesizing the precursor pyruvamide
    2.
    发明授权
    Method of synthesizing the precursor pyruvamide 失效
    合成丙酮酸前体丙酮酰胺的方法

    公开(公告)号：US5312985A

    公开(公告)日：1994-05-17

    申请号：US43699

    申请日：1993-04-08

    申请人： Madhup K. Dhaon ,  John A. Houbion

    发明人： Madhup K. Dhaon ,  John A. Houbion

    IPC分类号： A61K31/19 ,  A61K31/195 ,  A61K31/40 ,  A61P3/04 ,  C07C231/02 ,  C07C235/72

    CPC分类号： A61K31/40 ,  A61K31/195 ,  Y10S514/866 ,  Y10S514/909

    摘要： A method for administering pyruvate is disclosed which comprises administering a therapeutically effective amount of a pyruvate precursor to a mammal in the form of pyruvamide or a pyruvyl-amino acid. The pyruvyl-amino acid is preferably selected from the group comprising pyruvyl-glycine, pyruvyl-alanine, pyruvyl-leucine, pyruvyl-valine, pyruvyl-isoleucine, pyruvyl-phenylalanine, pyruvyl-proline and pyruvyl-sarcosine, and their amides and esters as well as their salts. Associated with the administration of a pyruvate precursor to a mammal in accordance with this invention are improved insulin resistance, lower fasting insulin levels, and reduced fat gain. Novel methods of synthesizing several pyruvate precursors are also disclosed.

    摘要翻译： 公开了一种给予丙酮酸盐的方法，其包括给予哺乳动物治疗有效量的丙酮酸前体以丙酮酰胺或丙酮酸 - 氨基酸的形式。 丙酮酸氨基酸优选选自丙酮酸 - 甘氨酸，丙酮酸 - 丙氨酸，丙酮酸 - 亮氨酸，丙酮酸 - 缬氨酸，丙酮酸 - 异亮氨酸，丙酮酸 - 苯丙氨酸，丙酮酸 - 脯氨酸和丙酮酸 - 肌氨酸，其酰胺和酯为 以及它们的盐。 与根据本发明的哺乳动物的丙酮酸前体的施用相关联的是改善的胰岛素抵抗，降低的空腹胰岛素水平和降低的脂肪增加。 还公开了合成若干丙酮酸前体的新方法。

    Method for reducing insulin resistance in mammals
    3.
    发明授权
    Method for reducing insulin resistance in mammals 失效
    减少哺乳动物胰岛素抵抗的方法

    公开(公告)号：US5283260A

    公开(公告)日：1994-02-01

    申请号：US43720

    申请日：1993-04-08

    申请人： Robert H. Miller ,  Nickki L. Parlet ,  Kent L. Cipollo ,  Madhup K. Dhaon ,  John A. Houbion ,  Edwin O. Lundell

    发明人： Robert H. Miller ,  Nickki L. Parlet ,  Kent L. Cipollo ,  Madhup K. Dhaon ,  John A. Houbion ,  Edwin O. Lundell

    IPC分类号： A61K31/19 ,  A61K31/195 ,  A61K31/40 ,  A61P3/04 ,  C07C231/02 ,  C07C235/72

    CPC分类号： A61K31/40 ,  A61K31/195 ,  Y10S514/866 ,  Y10S514/909

    摘要： A method for administering pyruvate is disclosed which comprises administering a therapeutically effective amount of a pyruvate precursor to a mammal in the form of pyruvamide or a pyruvyl-amino acid. The pyruvyl-amino acid is preferably selected from the group comprising pyruvyl-glycine, pyruvyl-alanine, pyruvyl-leucine, pyruvyl-valine, pyruvyl-isoleucine, pyruvylphenyl al anine, pyruvyl-proline and pyruvyl-sarcosine, and their amides and esters as well as their salts. Associated with the administration of a pyruvate precursor to a mammal in accordance with this invention are improved insulin resistance, lower fasting insulin levels, and reduced fat gain. Novel methods of synthesizing several pyruvate precursors are also disclosed.

    摘要翻译： 公开了一种给予丙酮酸盐的方法，其包括给予哺乳动物治疗有效量的丙酮酸前体以丙酮酰胺或丙酮酸 - 氨基酸的形式。 丙酮酸氨基酸优选选自丙酮酸 - 甘氨酸，丙酮酸 - 丙氨酸，丙酮酸 - 亮氨酸，丙酮酸 - 缬氨酸，丙酮酸 - 异亮氨酸，丙酮酰基苯胺，丙酮酸 - 脯氨酸和丙酮酸 - 肌氨酸，其酰胺和酯为 以及它们的盐。 与根据本发明的哺乳动物的丙酮酸前体的施用相关联的是改善的胰岛素抵抗，降低的空腹胰岛素水平和降低的脂肪增加。 还公开了合成若干丙酮酸前体的新方法。

    One pot synthesis of tetrazole derivatives of sirolimus
    4.
    发明申请
    One pot synthesis of tetrazole derivatives of sirolimus 有权
    一锅合成西罗莫司的四唑衍生物

    公开(公告)号：US20080167335A1

    公开(公告)日：2008-07-10

    申请号：US11300671

    申请日：2005-12-14

    申请人： Madhup K. Dhaon ,  Chi-nung Hsiao ,  Subhash R. Patel ,  Peter J. Bonk ,  Sanjay R. Chemburkar ,  Yong Y. Chen

    发明人： Madhup K. Dhaon ,  Chi-nung Hsiao ,  Subhash R. Patel ,  Peter J. Bonk ,  Sanjay R. Chemburkar ,  Yong Y. Chen

    IPC分类号： A61K31/436 ,  C07D267/00

    CPC分类号： C07D498/18

    摘要： A single-step, one-pot process to obtain zotarolimus and other rapamycin derivatives on large scale is presented, which improves currently available synthesis schemes. In one embodiment, dried rapamycin is dissolved in isopropylacetate (IPAc). The solution is cooled, and 2,6-Lutidine is added, followed slowly adding triflic anhydride at −30° C. Salts are then removed by filtration. Tetrazole, followed by a tert-base diisopropylethylamine (DIEA) is added to the triflate solution. After incubation at room temperature, the product is concentrated and purified by a silica gel column using THF/heptane as eluant. The fractions containing the product are collected, concentrated, and purified again using an acetone/heptane column. The product containing fractions are concentrated. The product is dissolved in t-BME and precipitated with heptane. The solids are dissolved in acetone, treated with butylated-hydroxy toluene (BHT), and the solution concentrated. The process is repeated twice with acetone to remove solvents. At least one stabilizing agent is added, such as BHT at 0.5% before drying.

    摘要翻译： 提出了大规模获得唑他莫司和其他雷帕霉素衍生物的单步一锅法，改进了现有的合成方案。 在一个实施方案中，将干燥的雷帕霉素溶于乙酸异丙酯（IPAc）中。 将溶液冷却，加入2,6-二甲基吡啶，然后在-30℃下缓慢加入三氟甲磺酸酐。然后通过过滤除去盐。 然后向该三氟甲磺酸酯溶液中加入四唑，然后加入叔丁基二异丙基乙胺（DIEA）。 在室温下孵育后，将产物浓缩并通过硅胶柱纯化，使用THF /庚烷作为洗脱剂。 收集含有产物的级分，浓缩并再次使用丙酮/庚烷柱纯化。 将含产物的级分浓缩。 将产物溶于t-BME中并用庚烷沉淀。 将固体溶解在丙酮中，用丁基化羟基甲苯（BHT）处理，浓缩溶液。 用丙酮重复该过程两次以除去溶剂。 在干燥前加入至少一种稳定剂，例如0.5％的BHT。

    Process for the preparation of midazolam
    5.
    发明授权
    Process for the preparation of midazolam 有权
    制备咪达唑仑的方法

    公开(公告)号：US06262260B1

    公开(公告)日：2001-07-17

    申请号：US09533160

    申请日：2000-03-23

    申请人： Madhup K. Dhaon

    发明人： Madhup K. Dhaon

    IPC分类号： C07D48704

    CPC分类号： C07D487/04

    摘要： The present invention provides a process for the synthesis of compounds of formula (II) or pharmaceutically acceptable salts thereof.

    摘要翻译： 本发明提供了合成式（II）化合物或其药学上可接受的盐的方法。

    One pot synthesis of tetrazole derivatives of rapamycin
    8.
    发明授权
    One pot synthesis of tetrazole derivatives of rapamycin 有权
    雷帕霉素四唑衍生物的一锅合成

    公开(公告)号：US08129521B2

    公开(公告)日：2012-03-06

    申请号：US12711072

    申请日：2010-02-23

    申请人： Madhup K. Dhaon ,  Chi-nung Hsiao ,  Subhash R. Patel ,  Peter J. Bonk ,  Sanjay R. Chemburkar ,  Yong Y. Chen

    发明人： Madhup K. Dhaon ,  Chi-nung Hsiao ,  Subhash R. Patel ,  Peter J. Bonk ,  Sanjay R. Chemburkar ,  Yong Y. Chen

    IPC分类号： C07D498/18

    CPC分类号： C07D498/18

    摘要： A single-step, one-pot process to obtain zotarolimus and other rapamycin derivatives on large scale is presented, which improves currently available synthesis schemes. In one embodiment, dried rapamycin is dissolved in isopropylacetate (IPAc). The solution is cooled, and 2,6-Lutidine is added, followed slowly adding triflic anhydride at −30° C. Salts are then removed by filtration. Tetrazole, followed by a tert-base diisopropylethylamine (DIEA) is added to the triflate solution. After incubation at room temperature, the product is concentrated and purified by a silica gel column using THF/heptane as eluant. The fractions containing the product are collected, concentrated, and purified again using an acetone/heptane column. The product containing fractions are concentrated. The product is dissolved in t-BME and precipitated with heptane. The solids are dissolved in acetone, treated with butylated-hydroxy toluene (BHT), and the solution concentrated. The process is repeated twice with acetone to remove solvents. At least one stabilizing agent is added, such as BHT at 0.5% before drying.

    摘要翻译： 提出了大规模获得唑他莫司和其他雷帕霉素衍生物的单步一锅法，改进了现有的合成方案。 在一个实施方案中，将干燥的雷帕霉素溶于乙酸异丙酯（IPAc）中。 将溶液冷却，加入2,6-二甲基吡啶，然后在-30℃下缓慢加入三氟甲磺酸酐。然后通过过滤除去盐。 然后向该三氟甲磺酸酯溶液中加入四唑，然后加入叔丁基二异丙基乙胺（DIEA）。 在室温下孵育后，将产物浓缩并通过硅胶柱纯化，使用THF /庚烷作为洗脱剂。 收集含有产物的级分，浓缩并再次使用丙酮/庚烷柱纯化。 将含产物的级分浓缩。 将产物溶于t-BME中并用庚烷沉淀。 将固体溶解在丙酮中，用丁基化羟基甲苯（BHT）处理，浓缩溶液。 用丙酮重复该过程两次以除去溶剂。 在干燥前加入至少一种稳定剂，例如0.5％的BHT。

    ONE POT SYNTHESIS OF TETRAZOLE DERIVATIVES OF RAPAMYCIN
    9.
    发明申请
    ONE POT SYNTHESIS OF TETRAZOLE DERIVATIVES OF RAPAMYCIN 有权
    一种合成RAPAMYCIN的四唑衍生物的方法

    公开(公告)号：US20100204466A1

    公开(公告)日：2010-08-12

    申请号：US12711072

    申请日：2010-02-23

    申请人： Madhup K. Dhaon ,  Chi-nung Hsiao ,  Subhash R. Patel ,  Peter J. Bonk ,  Sanjay R. Chemburkar ,  Yong Chen

    发明人： Madhup K. Dhaon ,  Chi-nung Hsiao ,  Subhash R. Patel ,  Peter J. Bonk ,  Sanjay R. Chemburkar ,  Yong Chen

    IPC分类号： C07D498/18

    CPC分类号： C07D498/18

    摘要： A single-step, one-pot process to obtain zotarolimus and other rapamycin derivatives on large scale is presented, which improves currently available synthesis schemes. In one embodiment, dried rapamycin is dissolved in isopropylacetate (IPAc). The solution is cooled, and 2,6-Lutidine is added, followed slowly adding triflic anhydride at −30° C. Salts are then removed by filtration. Tetrazole, followed by a tert-base diisopropylethylamine (DIEA) is added to the triflate solution. After incubation at room temperature, the product is concentrated and purified by a silica gel column using THF/heptane as eluant. The fractions containing the product are collected, concentrated, and purified again using an acetone/heptane column. The product containing fractions are concentrated. The product is dissolved in t-BME and precipitated with heptane. The solids are dissolved in acetone, treated with butylated-hydroxy toluene (BHT), and the solution concentrated. The process is repeated twice with acetone to remove solvents. At least one stabilizing agent is added, such as BHT at 0.5% before drying.

    摘要翻译： 提出了大规模获得唑他莫司和其他雷帕霉素衍生物的单步一锅法，改进了现有的合成方案。 在一个实施方案中，将干燥的雷帕霉素溶于乙酸异丙酯（IPAc）中。 将溶液冷却，加入2,6-二甲基吡啶，然后在-30℃下缓慢加入三氟甲磺酸酐。然后通过过滤除去盐。 然后向该三氟甲磺酸酯溶液中加入四唑，然后加入叔丁基二异丙基乙胺（DIEA）。 在室温下孵育后，将产物浓缩并通过硅胶柱纯化，使用THF /庚烷作为洗脱剂。 收集含有产物的级分，浓缩并再次使用丙酮/庚烷柱纯化。 将含产物的级分浓缩。 将产物溶于t-BME中并用庚烷沉淀。 将固体溶解在丙酮中，用丁基化羟基甲苯（BHT）处理，浓缩溶液。 用丙酮重复该过程两次以除去溶剂。 在干燥前加入至少一种稳定剂，例如0.5％的BHT。

    One pot synthesis of tetrazole derivatives of rapamycin
    10.
    发明授权
    One pot synthesis of tetrazole derivatives of rapamycin 有权
    雷帕霉素四唑衍生物的一锅合成

    公开(公告)号：US07700614B2

    公开(公告)日：2010-04-20

    申请号：US11300671

    申请日：2005-12-14

    申请人： Madhup K. Dhaon ,  Chi-nung Hsiao ,  Subhash R. Patel ,  Peter J. Bonk ,  Sanjay R. Chemburkar ,  Yong Chen

    发明人： Madhup K. Dhaon ,  Chi-nung Hsiao ,  Subhash R. Patel ,  Peter J. Bonk ,  Sanjay R. Chemburkar ,  Yong Chen

    IPC分类号： C07D498/18

    CPC分类号： C07D498/18

    摘要： A single-step, one-pot process to obtain zotarolimus and other rapamycin derivatives on large scale is presented, which improves currently available synthesis schemes. In one embodiment, dried rapamycin is dissolved in isopropylacetate (IPAc). The solution is cooled, and 2,6-Lutidine is added, followed slowly adding triflic anhydride at −30° C. Salts are then removed by filtration. Tetrazole, followed by a tert-base diisopropylethylamine (DIEA) is added to the triflate solution. After incubation at room temperature, the product is concentrated and purified by a silica gel column using THF/heptane as eluant. The fractions containing the product are collected, concentrated, and purified again using an acetone/heptane column. The product containing fractions are concentrated. The product is dissolved in t-BME and precipitated with heptane. The solids are dissolved in acetone, treated with butylated-hydroxy toluene (BHT), and the solution concentrated. The process is repeated twice with acetone to remove solvents. At least one stabilizing agent is added, such as BHT at 0.5% before drying.

    摘要翻译： 提出了大规模获得唑他莫司和其他雷帕霉素衍生物的单步一锅法，改进了现有的合成方案。 在一个实施方案中，将干燥的雷帕霉素溶于乙酸异丙酯（IPAc）中。 将溶液冷却，加入2,6-二甲基吡啶，然后在-30℃下缓慢加入三氟甲磺酸酐。然后通过过滤除去盐。 然后向该三氟甲磺酸酯溶液中加入四唑，然后加入叔丁基二异丙基乙胺（DIEA）。 在室温下孵育后，将产物浓缩并通过硅胶柱纯化，使用THF /庚烷作为洗脱剂。 收集含有产物的级分，浓缩并再次使用丙酮/庚烷柱纯化。 将含产物的级分浓缩。 将产物溶于t-BME中并用庚烷沉淀。 将固体溶解在丙酮中，用丁基化羟基甲苯（BHT）处理，浓缩溶液。 用丙酮重复该过程两次以除去溶剂。 在干燥前加入至少一种稳定剂，例如0.5％的BHT。