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    Methods and systems for treating cell proliferation disorders with psoralen derivatives
    1.
    发明授权
    Methods and systems for treating cell proliferation disorders with psoralen derivatives 有权
    用补骨脂素衍生物治疗细胞增殖障碍的方法和系统

    公开(公告)号：US08383836B2

    公开(公告)日：2013-02-26

    申请号：US12763404

    申请日：2010-04-20

    Applicant: Eric Toone ,  David Gooden ,  Tuan Vo-Dinh ,  Frederic A. Bourke, Jr.

    Inventor： Eric Toone ,  David Gooden ,  Tuan Vo-Dinh ,  Frederic A. Bourke, Jr.

    IPC: C07D493/00 ,  C07D215/38 ,  C07D211/32

    CPC classification number: C07D493/04 ,  A61K31/4433 ,  A61K31/453 ,  A61K31/4709 ,  A61K41/0066 ,  A61K45/06 ,  A61N5/062 ,  A61N5/10

    Abstract: Psoralen compounds of Formula (I): wherein (N+ Aryl) is a member selected from the group consisting of nitrogen containing aromatic heterocycles of formulae (i)-(iii): wherein Z is a group of formula: wherein R is C1-C30 hydrocarbyl, which may be linear, branched or cyclic and contains from 1 to 15 carbon-carbon double bonds, which may be conjugated or unconjugated with one another or may include an aryl ring, and may contain one or more substituents; R1 is hydrogen, aryl, heteroaryl, alkyl, cycloalkyl, heterocyclyl, alkenyl, alkynyl, alkene-aryl, alkene-heteroaryl, alkene-heterocyclyl, alkene-cycloalkyl, fused cycloalkylaryl, fused cycloalkylheteroaryl, fused heterocyclylaryl, fused heterocyclyheteroaryl, alkylene-fused cycloalkylaryl, alkylene-fused cycloalkylheteroaryl, alkylene-fused heterocyclylaryl, alkylene-fused heterocyclyheteroaryl; n is an integer from 1 to 8 and X is a pharmaceutically acceptable counter ion; and their use in methods for the treatment of a cell proliferation disorder in a subject, pharmaceutical compositions containing the psoralen derivatives, a kit for performing the method, and a method for causing an autovaccine effect in a subject using the method.

    Abstract translation: 式（I）的补骨脂素化合物：其中（N +芳基）是选自式（i） - （iii）的含氮芳族杂环的成员：其中Z是下式的基团：其中R是C1-C30 烃基，其可以是直链，支链或环状的并且含有1至15个碳 - 碳双键，其可以彼此共轭或非共轭或可以包括芳环，并且可以含有一个或多个取代基; R 1是氢，芳基，杂芳基，烷基，环烷基，杂环基，烯基，炔基，烯 - 芳基，烯 - 杂芳基，烯烃 - 杂环基，烯 - 环烷基，稠合环烷基芳基，稠合环烷基杂芳基，稠合杂环基芳基，稠合杂环杂芳基，亚烷基稠合环烷基芳基 亚烷基稠合的环烷基杂芳基，亚烷基稠合的杂环基芳基，亚烷基稠合的杂环杂芳基; n为1〜8的整数，X为药学上可接受的抗衡离子; 及其在治疗受试者的细胞增殖障碍的方法中的用途，含有补骨脂素衍生物的药物组合物，用于进行该方法的试剂盒以及使用该方法在受试者中引起自身疫苗效应的方法。

    C-Nitroso compounds and use thereof
    2.
    发明申请
    C-Nitroso compounds and use thereof 有权
    C-亚硝基化合物及其用途

    公开(公告)号：US20070258942A1

    公开(公告)日：2007-11-08

    申请号：US11822770

    申请日：2007-07-10

    Applicant: Jonathan Stamler ,  Eric Toone

    Inventor： Jonathan Stamler ,  Eric Toone

    IPC: A61K31/785 ,  A61F2/06 ,  A61K47/00 ,  A61P41/00

    CPC classification number: C07C245/04 ,  A61K31/00 ,  A61K31/195 ,  A61K31/785 ,  A61L31/10 ,  A61L31/16 ,  A61L2300/114 ,  A61L2300/606 ,  C07C207/00 ,  C07C207/04 ,  C07C219/06 ,  A61K2300/00

    Abstract: A C-nitroso compound having a molecular weight ranging from 225 to 1,000 (from 225 to 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to about 20, vascular relaxing effect is obtained at nanomolar concentrations without ghitathione. In another embodiment, a biocompatible polymer incorporates a C-nitroso moiety.

    Abstract translation: 一种分子量范围为225〜1000（口服给药时为225〜600）的C-亚硝基化合物，其中亚硝基连接到叔碳上，其通过具有pKa的碳酸的亚硝化而得到 小于约25，可用作NO供体。 当化合物从pKa小于约10的碳酸获得时，当以微摩尔浓度使用时，其提供血管松弛效果，并且该活性由以纳摩尔浓度获得的谷胱甘肽加强。 当化合物由pKa在约15至约20范围内的碳酸获得时，在毫摩尔浓度下获得血管松弛效果，而没有使用谷胱甘肽。 在另一个实施方案中，生物相容性聚合物包含C-亚硝基部分。

    Reactive oxygen generating enzyme inhibitor with nitric oxide bioactivity and uses thereof
    3.
    发明申请
    Reactive oxygen generating enzyme inhibitor with nitric oxide bioactivity and uses thereof 失效
    具有一氧化氮生物活性的活性氧发生酶抑制剂及其应用

    公开(公告)号：US20050239807A1

    公开(公告)日：2005-10-27

    申请号：US10829940

    申请日：2004-04-23

    Applicant: Jonathan Stamler ,  Eric Toone ,  Joshua Hare

    Inventor： Jonathan Stamler ,  Eric Toone ,  Joshua Hare

    IPC: A61K31/519 ,  C07D487/02 ,  C07D487/04

    CPC classification number: C07D487/04 ,  A61K31/519

    Abstract: A reactive oxygen generating enzyme inhibitor with NO donor bioactivity, e.g., nitrated allopurinol, e.g., 1,5-bis(3-nitrooxypropyyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one is useful to treat heart failure, stable angina, ischemic disorder, ischemic reperfusion injury, atherosclerosis, sickle cell disease, diabetes, Alzheimer's disease, Parkinson's disease, ALS and asthma and to obtain proper contraction of heart, skeletal and smooth muscle. Where the disorder is heart failure, administration of the enzyme inhibitor mediates amelioration of acute coronary symptoms and/or myocardial infarction.

    Abstract translation: 具有NO供体生物活性的活性氧产生酶抑制剂，例如硝化别嘌呤醇，例如1,5-双（3-硝基氧基丙基）-1,5-二氢-4H-吡唑并[3,4-d]嘧啶-4-酮 可用于治疗心力衰竭，稳定型心绞痛，缺血障碍，缺血再灌注损伤，动脉粥样硬化，镰状细胞病，糖尿病，阿尔茨海默氏病，帕金森病，ALS和哮喘，并获得心脏，骨骼和平滑肌的适当收缩。 在疾病是心力衰竭的地方，酶抑制剂的施用介导急性冠状动脉症状和/或心肌梗死的改善。

    C-nitroso compounds and use thereof
    4.
    发明申请
    C-nitroso compounds and use thereof 失效
    C-亚硝基化合物及其用途

    公开(公告)号：US20050187166A1

    公开(公告)日：2005-08-25

    申请号：US11052141

    申请日：2005-02-08

    Applicant: Jonathan Stamler ,  Eric Toone

    Inventor： Jonathan Stamler ,  Eric Toone

    IPC: A61K31/00 ,  A61K31/195 ,  C07C207/00 ,  C07C207/04 ,  C07C219/06 ,  C07C245/04 ,  A61K38/05 ,  A61K31/21 ,  A61K31/535 ,  A61K31/54 ,  A61K31/55 ,  A61K31/553 ,  A61K31/554

    CPC classification number: C07C245/04 ,  A61K31/00 ,  A61K31/195 ,  A61K31/785 ,  A61L31/10 ,  A61L31/16 ,  A61L2300/114 ,  A61L2300/606 ,  C07C207/00 ,  C07C207/04 ,  C07C219/06 ,  A61K2300/00

    Abstract: A C-nitroso compound having a molecular weight ranging from 225 to 1,000 (from 225 to 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to about 20, vascular relaxing effect is obtained at nanomolar concentrations without glutathione. In another embodiment, a biocompatible polymer incorporates a C-nitroso moiety.

    Abstract translation: 一种分子量范围为225〜1000（口服给药时为225〜600）的C-亚硝基化合物，其中亚硝基连接到叔碳上，其通过具有pKa的碳酸的亚硝化而得到 小于约25，可用作NO供体。 当化合物从pKa小于约10的碳酸获得时，当以微摩尔浓度使用时，其提供血管松弛效果，并且该活性由以纳摩尔浓度获得的谷胱甘肽加强。 当化合物由pKa为约15至约20的碳酸获得时，在没有谷胱甘肽的纳摩尔浓度下获得血管松弛效果。 在另一个实施方案中，生物相容性聚合物包含C-亚硝基部分。

    Methods of treating cardio pulmonary diseases with NO group compounds
    6.
    发明申请
    Methods of treating cardio pulmonary diseases with NO group compounds 审中-公开
    用NO组化合物治疗心肺疾病的方法

    公开(公告)号：US20070191478A1

    公开(公告)日：2007-08-16

    申请号：US11231162

    申请日：2005-09-20

    Applicant: Jonathan Stamler ,  Eric Toone ,  Andrew Gow

    Inventor： Jonathan Stamler ,  Eric Toone ,  Andrew Gow

    IPC: A61K31/21

    CPC classification number: C12N5/0641 ,  A61K31/197 ,  A61K31/21 ,  A61K33/00 ,  A61K33/04 ,  A61M2202/0275 ,  A61K2300/00

    Abstract: Treatment of pulmonary disorders associated with hypoxemia and/or smooth muscle constriction and/or inflammation comprises administering into the lungs as a gas a compound with an NO group which does not form NO2/NOx in the presence of oxygen or reactive oxygen species at body temperature. Treatment of cardiac and blood disorders, e.g., angina, myocardial infarction, heart failure, hypertension, sickle cell disease and clotting disorders, comprises administering into the lungs as a gas, a compound which reacts with cysteine in hemoglobin and/or dissolves in blood and has an NO group which is bound in said compound so that it does not form NO2/NOx in the presence of oxygen or reactive oxygen species at body temperature. Exemplary of the compound administered in each case is ethyl nitrite. Treatment of patient in need of improved oxygenation, blood flow of and/or thinning of blood comprises providing in the patient a therapeutic amount of red blood cells loaded with nitrosylated hemoglobin. A method is directed to screening drugs that increase level of nitrosoglutathione in airway lining fluid.

    Abstract translation: 与低氧血症和/或平滑肌收缩和/或炎症相关的肺部疾病的治疗包括以肺部作为气体给予具有不形成NO 2的NO组的化合物 在体温存在氧或活性氧的情况下。 治疗心脏和血液疾病，例如心绞痛，心肌梗死，心力衰竭，高血压，镰状细胞病和凝血障碍，包括作为气体给予肺，与血红蛋白中的半胱氨酸反应和/或溶解于血液中的化合物和 具有在所述化合物中结合的NO基团，使得其在体温存在氧或活性氧的情况下不形成NO 2 / NO x 2 x。 在每种情况下施用的化合物的实例是亚硝酸乙酯。 治疗需要改善氧合，血流和/或血液变薄的患者包括在患者体内提供加载有亚硝基化血红蛋白的治疗量的红细胞。 一种方法是用于筛选增加气道衬里液中亚硝基谷胱甘肽水平的药物。

    Carbon nanotubules for storage of nitric oxide
    8.
    发明申请
    Carbon nanotubules for storage of nitric oxide 审中-公开
    用于储存一氧化氮的碳纳米管

    公开(公告)号：US20050152891A1

    公开(公告)日：2005-07-14

    申请号：US10980616

    申请日：2004-11-03

    Applicant: Eric Toone ,  Jonathan Stamler

    Inventor： Eric Toone ,  Jonathan Stamler

    IPC: A61K33/00 ,  A61K45/06 ,  A61L29/10 ,  A61L29/16 ,  A61L31/08 ,  A61L31/16 ,  A61K33/44

    CPC classification number: A61K33/00 ,  A61K45/06 ,  A61L29/103 ,  A61L29/16 ,  A61L31/084 ,  A61L31/16 ,  A61L2300/114 ,  A61L2300/416 ,  A61L2300/432 ,  A61L2300/45 ,  A61L2300/624

    Abstract: Delivering nitric oxide to a treatment site, such as in the area of an implanted stent, over a period of hours or days is desirable; however, the storage and release of nitric oxide in medically-relevant situations and amounts is a challenge, in part due to the gaseous nature of nitric oxide and its instability in the presence of oxygen. The present invention provides a method of preparing compositions of matter, particularly those comprising nanotubules, containing nitric oxide or gases with nitric oxide-like biological activity, where the gas is non-covalently bound to the composition. These compositions allow for the storage of nitric oxide or a related gas, followed by controlled release of the gas. Compositions disclosed in the present invention include polymers, articles, pills, capsules, and medical devices.

    Abstract translation: 将一氧化氮递送至治疗部位，例如在植入支架的区域中，需要数小时或数天; 然而，一氧化氮在医学相关的情况和量中的储存和释放是一个挑战，部分是由于一氧化氮的气体性质及其在氧气存在下的不稳定性。 本发明提供了一种制备物质组合物的方法，特别是包含含有一氧化氮或具有一氧化氮样生物活性的气体的纳米管的组合物，其中气体与组合物非共价结合。 这些组合物允许一氧化氮或相关气体的储存，然后控制释放气体。 本发明公开的组合物包括聚合物，制品，丸剂，胶囊和医疗装置。

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