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    Methods of inhibiting invasion and metastasis of malignant solid tumors
    1.
    发明授权
    Methods of inhibiting invasion and metastasis of malignant solid tumors 失效
    抑制恶性实体瘤侵袭转移的方法

    公开(公告)号：US5880129A

    公开(公告)日：1999-03-09

    申请号：US906542

    申请日：1997-08-05

    申请人： Elise C. Kohn ,  Lance A. Liotta ,  Christian C. Felder

    发明人： Elise C. Kohn ,  Lance A. Liotta ,  Christian C. Felder

    IPC分类号： A61K31/12 ,  A61K31/41 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4192 ,  C07D233/90 ,  C07D249/04 ,  A61K31/495 ,  A61K31/505 ,  C07D239/26 ,  C07D241/10

    CPC分类号： A61K31/12 ,  A61K31/41 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4192 ,  C07D233/90 ,  C07D249/04

    摘要： A discovery underlying this invention is the concordance between particular cellular signaling mechanisms and cancer cell growth and metastasis. It has now been discovered that certain compounds inhibit the signal transduction required for the maintenance and driving of the malignant process. These compounds are also effective for the in vivo treatment of solid tumors and related disease states. This invention provides a method for the use of these compounds to inhibit the invasion and metastasis of malignant solid tumors in mammals. This invention further provides a method for using related compounds to treat diseases involving aberrant signal transduction pathways. Some of the compounds used in the methods of the present invention are novel and constitute another aspect of this invention.

    摘要翻译： 本发明的发现是特定细胞信号传导机制与癌细胞生长和转移之间的一致性。 现在已经发现某些化合物抑制维持和驱动恶性过程所需的信号转导。 这些化合物对于实体瘤和相关疾病状态的体内治疗也是有效的。 本发明提供了一种使用这些化合物抑制哺乳动物恶性实体瘤侵袭和转移的方法。 本发明还提供了使用相关化合物治疗涉及异常信号转导途径的疾病的方法。 在本发明的方法中使用的一些化合物是新的，构成本发明的另一方面。

    Signal transduction inhibitor triazole and diazole compounds
    2.
    发明授权
    Signal transduction inhibitor triazole and diazole compounds 失效
    信号转导抑制剂三唑和二唑化合物

    公开(公告)号：US5482954A

    公开(公告)日：1996-01-09

    申请号：US270181

    申请日：1994-07-01

    申请人： Elise C. Kohn ,  Lance A. Liotta ,  Christian C. Felder

    发明人： Elise C. Kohn ,  Lance A. Liotta ,  Christian C. Felder

    IPC分类号： A61K31/12 ,  A61K31/41 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4192 ,  A61P35/00 ,  C07D233/90 ,  C07D249/04 ,  C07D249/06

    CPC分类号： A61K31/4164 ,  A61K31/12 ,  A61K31/41 ,  A61K31/415 ,  A61K31/4192 ,  C07D233/90 ,  C07D249/04

    摘要： A discovery underlying this invention is the concordance between particular cellular signaling mechanisms and cancer cell growth and metastasis. It has now been discovered that certain compounds inhibit the signal transduction required for the maintenance and driving of the malignant process. These compounds are also effective for the in vivo treatment of solid tumors and related disease states. This invention provides a method for the use of these compounds to inhibit the invasion and metastasis of malignant solid tumors in mammals. This invention further provides a method for using related compounds to treat diseases involving aberrant signal transduction pathways. Some of the compounds used in the methods of the present invention are novel and constitute another aspect of this invention.

    摘要翻译： 本发明的发现是特定细胞信号传导机制与癌细胞生长和转移之间的一致性。 现在已经发现某些化合物抑制维持和驱动恶性过程所需的信号转导。 这些化合物对于实体瘤和相关疾病状态的体内治疗也是有效的。 本发明提供了一种使用这些化合物抑制哺乳动物恶性实体瘤侵袭和转移的方法。 本发明还提供了使用相关化合物治疗涉及异常信号转导途径的疾病的方法。 在本发明的方法中使用的一些化合物是新的，构成本发明的另一方面。

    Signal transduction inhibitor compounds
    4.
    发明授权
    Signal transduction inhibitor compounds 失效
    信号转导抑制剂化合物

    公开(公告)号：US5705514A

    公开(公告)日：1998-01-06

    申请号：US455825

    申请日：1995-05-31

    申请人： Elise C. Kohn ,  Lance A. Liotta ,  Christian C. Felder

    发明人： Elise C. Kohn ,  Lance A. Liotta ,  Christian C. Felder

    IPC分类号： A61K31/12 ,  A61K31/41 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4192 ,  A61P35/00 ,  C07D233/90 ,  C07D249/04

    CPC分类号： A61K31/4164 ,  A61K31/12 ,  A61K31/41 ,  A61K31/415 ,  A61K31/4192 ,  C07D233/90 ,  C07D249/04

    摘要： A method of inhibiting the invasion and metastasis of malignant solid tumors in mammals, said method comprising administering to said mammal an anti-proliferative, anti-invasive and anti-metastasis effective amount of a compound selected from the group of formulas consisting of: ##STR1## wherein: p is an integer of from 0 to 4; Ar.sup.1 is a moiety selected from the group consisting of --Ar.sup.2 --X--Ar.sup.3, phenyl, trioxaadamantyl, anthracenyl, anthraquinonyl, naphthyl, phenanthryl, and substituted versions thereof; Ar.sup.2 and Ar.sup.3 are each aromatic moieties independently selected from the group consisting of phenyl, naphthyl, and substituted versions thereof; X is a linking moiety selected from the group consisting of O, S, SO.sub.2 2, CO, CHCN, straight chain alkyl, alkoxy, and alkoxyalkyl; and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl and substituted versions thereof, said heterocyclic moieties being attached to the --(CH.sub.2).sub.p -- portion of the molecule at the N1 position of the heterocycle.

    摘要翻译： 一种抑制哺乳动物恶性实体瘤侵袭和转移的方法，所述方法包括对所述哺乳动物施用抗增殖，抗侵袭和抗转移的有效量的选自下组的化合物：Z（ CH 2）pAr 1（I）和（II）其中：p是0至4的整数; Ar1是选自-Ar2-X-Ar3，苯基，三氧杂金刚烷基，蒽基，蒽醌基，萘基，菲基及其取代形式的部分; Ar 2和Ar 3各自独立地选自苯基，萘基及其取代形式的芳族部分; X是选自O，S，SO22，CO，CHCN，直链烷基，烷氧基和烷氧基烷基的连接部分; 并且Z是选自咪唑基，1,2,3-三唑基，1,2,4-三唑基及其取代形式的含氮杂环部分，所述杂环部分连接到 - （CH 2）p - 分子在杂环的N1位的部分。

    Method for inhibiting metalloproteinase expression
    6.
    发明授权
    Method for inhibiting metalloproteinase expression 失效
    抑制金属蛋白酶表达的方法

    公开(公告)号：US5602156A

    公开(公告)日：1997-02-11

    申请号：US209089

    申请日：1994-03-10

    申请人： Elise C. Kohn ,  Lance A. Liotta

    发明人： Elise C. Kohn ,  Lance A. Liotta

    IPC分类号： A61K31/41 ,  A61K31/415

    CPC分类号： A61K31/415 ,  A61K31/41

    摘要： Calcium homeostasis is an important regulator of MMP-2 transcription, activation and activity. Disclosed herein are compounds which inhibit the expression of matrix metalloproteinases in cells. Pharmaceutical application of these compounds to inhibit the expression of MMPs offers a new approach to cancer treatment as well as treatment for nerve healing, degenerative cartilagenous diseases, decubitus ulcers, arthritis, Alzheimer's disease, wound healing, proliferative retinopathy, proliferative renal diseases, corneal ulcers and fertility problems.

    摘要翻译： 钙稳态是MMP-2转录，激活和活性的重要调节因子。 本文公开了抑制细胞中基质金属蛋白酶表达的化合物。 这些化合物抑制MMP表达的药物应用提供了一种新的治疗方法，以及治疗神经愈合，退行性软骨疾病，褥疮性溃疡，关节炎，阿尔茨海默氏病，伤口愈合，增殖性视网膜病变，增殖性肾病，角膜溃疡 和生育问题。

    Inhibition of retroviral LTR promoters by calcium response modifiers
    8.
    发明授权
    Inhibition of retroviral LTR promoters by calcium response modifiers 失效
    通过钙反应调节剂抑制逆转录病毒LTR启动子

    公开(公告)号：US6057346A

    公开(公告)日：2000-05-02

    申请号：US353765

    申请日：1994-12-12

    申请人： Elise C. Kohn ,  Lance A. Liotta ,  Kevin L. Gardner

    发明人： Elise C. Kohn ,  Lance A. Liotta ,  Kevin L. Gardner

    IPC分类号： A61K31/4174 ,  A61K31/4192 ,  A61K31/41 ,  A01N43/64

    CPC分类号： A61K31/4174 ,  A61K31/4192

    摘要： A class of calcium-response modification compounds is disclosed which inhibits the activation of retroviral LTR promoters, including the HIV-LTR. This class of compounds are used to delay or suppress the transition of a retroviral infection from a latent to a virulent condition, thereby ameliorating retrovirally caused diseases such as AIDS. The compounds are also useful in cancer treatment, allowing for coordinated therapeutic approaches to retroviral diseases and related cancers such as AIDS and Kaposi's Sarcoma. The compounds are also useful in standardizing in vitro assays of clinical and experimental importance.

    摘要翻译： 公开了一类钙响应修饰化合物，其抑制包括HIV-LTR在内的逆转录病毒LTR启动子的活化。 这类化合物用于延缓或抑制逆转录病毒感染从潜伏状态转变为有毒状态，从而改善逆转录病毒引起的疾病如艾滋病。 该化合物也可用于癌症治疗，允许对逆转录病毒疾病和相关癌症如AIDS和卡波西肉瘤的协调治疗方法。 该化合物还可用于标准化临床和实验重要性的体外测定。