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    Apoptosis inhibitors
    2.
    发明授权
    Apoptosis inhibitors 有权
    凋亡抑制剂

    公开(公告)号：US07816352B2

    公开(公告)日：2010-10-19

    申请号：US11885463

    申请日：2006-03-10

    申请人： Dennis A. Carson ,  Howard B. Cottam ,  Sylvie Barchéchath ,  Mary Patricia Corr

    发明人： Dennis A. Carson ,  Howard B. Cottam ,  Sylvie Barchéchath ,  Mary Patricia Corr

    IPC分类号： A61K31/535 ,  A61K31/47 ,  A61K31/497 ,  C07D213/56 ,  C07D217/00 ,  C07D215/38

    CPC分类号： C07D513/04 ,  C07D213/20 ,  C07D215/227

    摘要： The present invention provides compounds that act as selective agents to protect against unintentional cell death or tissue damage and can relieve side effects of cancer treatment such as, for example, oral mucositis, hair loss, diarrhea due to damage to the gastrointestinal epithelium, and myelosuppression. In addition, these compounds can be used to prevent premature cell death when the cell death is caused by signals from damaged cells, for example, signals generated as the result of a traumatic incident or an ischemic episode.

    摘要翻译： 本发明提供了用作选择剂以防止无意的细胞死亡或组织损伤并可以减轻癌症治疗的副作用的化合物，例如口腔粘膜炎，脱发，胃肠上皮损伤引起的腹泻和骨髓抑制 。 此外，当细胞死亡是由受损细胞的信号引起的，例如作为创伤事件或缺血发作的结果产生的信号，这些化合物可用于防止过早的细胞死亡。

    Use of etodolac to treat hyperplasia
    4.
    发明授权
    Use of etodolac to treat hyperplasia 失效

    公开(公告)号：US07211599B2

    公开(公告)日：2007-05-01

    申请号：US10667208

    申请日：2003-09-19

    申请人： Dennis A. Carson ,  Lorenzo M. Leoni ,  Mary Patricia Corr

    发明人： Dennis A. Carson ,  Lorenzo M. Leoni ,  Mary Patricia Corr

    IPC分类号： A61K31/40 ,  A61K31/56 ,  A61K31/50 ,  A61K31/18 ,  A61K31/12

    CPC分类号： A61K31/12 ,  A61K31/18 ,  A61K31/40 ,  A61K31/407 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/50 ,  A61K31/56 ,  A61K31/675 ,  A61K31/7052

    摘要： The present invention provides a therapeutic method to treat non-malignant diseases characterized by the excessive tissue growth, e.g., hyperplastic diseases, comprising administering to a mammal (e.g., human) afflicted with excessive tissue growth, an effective amount of a derivative of an indole compound of formula (I):formula (I): wherein R1 is lower alkyl, (hydroxy)lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, phenyl, benzyl or 2-thienyl; R2, R3, R4 and R5 are the same or different and are each hydrogen or lower alkyl; each R6 is individually hydrogen, lower alkyl, hydroxy, (hydroxy)lower alkyl, lower alkoxy, benzyloxy, lower alkanoyloxy, nitro or halo, R7 is hydrogen, lower alkyl or lower alkenyl, X is oxy and thio, Y is carbonyl, —(CH2)1-3—, —(C1-C3)alkyl(CO)—, or —(CH2)1-3SO2—; Z is hydroxy, lower alkoxy, (C2-C4)acyloxy, —N(R8)(R9), phenylamino, (ω-(4-pyridyl)(C2-C4 alkoxy), (ω-((R8)(R9)amino)(C2-C4 alkoxy), an amino acid ester of (ω-(HO)(C2-C4))alkoxy, —N(R8)CH(R8)CO2H, 1′-D-glucuronyloxy, —SO3H, —PO4H2, —N(NO)(OH), —SO2NH2, —PO(OH)(NH2), —OCH2CH2N(CH3)3+, or tetrazolyl; wherein R8 and R9 are each H, (C1-C3)alkyl or together with N are a 5- or 6-membered heterocyclic ring comprising 1-3 N(R8), S or nonperoxide O; n is 0, 1, 2, or 3; wherein R8 and R9 are each H, (C1-C3)alkyl or together with N are a 5- or 6-membered heterocyclic ring comprising 1-3 N(R8), S or nonperoxide O; each alkyl or phenyl group of R1, R2, R3, R4, R5, R6, R7 and Z is optionally substituted with 1, 2, or 3 (C1-C4)alkyl groups; or a pharmaceutically acceptable salt thereof.

    Method for inhibiting adenylosuccinate synthetase activity in malignant methylthioadenosine phosphorylase deficient cells
    10.
    发明授权
    Method for inhibiting adenylosuccinate synthetase activity in malignant methylthioadenosine phosphorylase deficient cells 失效
    恶性甲基硫代腺苷磷酸化酶缺陷型细胞中腺苷酸琥珀酸合成酶抑制活性的方法

    公开(公告)号：US06214571B1

    公开(公告)日：2001-04-10

    申请号：US09199137

    申请日：1998-11-24

    申请人： Carlos J. Carrera ,  Dennis A. Carson ,  Howard B. Cottam ,  Tsutomu Nobori

    发明人： Carlos J. Carrera ,  Dennis A. Carson ,  Howard B. Cottam ,  Tsutomu Nobori

    IPC分类号： C12Q134

    CPC分类号： C12Q1/6886 ,  A61K31/198 ,  C12N9/1077

    摘要： An in vivo method for depleting mammalian cells of adenosine 5′-monophosphate (AMP) useful in the treatment of certain cancers is provided. According to the method, a population of cells is obtained from a host and assayed for loss of methylthioadenosine phosphorylase (MTAse) activity. MTAse catabolizes methylthioadenosine to adenine for endogenous salvage incorporation into the intracellular AMP pool. The preferred method for assaying loss of MTAse activity is a hybridization technique for detection of a homozygous loss of the gene which encodes MTAse. Hosts having MTAse deficient tumors are treated with a therapeutically effective amount of an agent which inhibits the activity of adenylsuccinate synthetase, which converts inosine 5-monophosphate to AMP, thus depleting the tumor cells of substrates for de novo AMP production. L-alanosine is the preferred ASS inhibitory agent for use in the method of the invention.

    摘要翻译： 提供了用于消除用于治疗某些癌症的腺苷5'-单磷酸（AMP）的哺乳动物细胞的体内方法。 根据该方法，从宿主获得细胞群并测定甲硫基腺苷磷酸化酶（MTAse）活性的损失。 MTAs将甲基硫代腺苷分解为腺嘌呤，用于内源性补救并入细胞内AMP库。 用于测定MTAse活性丧失的优选方法是用于检测编码MTAse的基因的纯合丢失的杂交技术。 具有MTAse缺陷肿瘤的宿主用治疗有效量的抑制腺苷酸琥珀酸合成酶活性的药物进行治疗，其将5-单磷酸肌苷转化为AMP，从而消耗底物的肿瘤细胞用于从头AMP产生。 L-肌氨酸是用于本发明方法的优选的ASS抑制剂。