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    Methods for detection and use of differentially expressed genes in disease states
    5.
    发明授权
    Methods for detection and use of differentially expressed genes in disease states 有权
    在疾病状态下检测和使用差异表达基因的方法

    公开(公告)号：US06709855B1

    公开(公告)日：2004-03-23

    申请号：US09461912

    申请日：1999-12-15

    申请人： Lawrence W. Stanton ,  R. Tyler White ,  Deborah L. Damm ,  John A. Lewicki ,  Alison Joly ,  George F. Schreiner

    发明人： Lawrence W. Stanton ,  R. Tyler White ,  Deborah L. Damm ,  John A. Lewicki ,  Alison Joly ,  George F. Schreiner

    IPC分类号： C12M134

    CPC分类号： C12Q1/6876 ,  C12Q1/6837 ,  C12Q2600/158

    摘要： The present invention relates to methods and compositions for the detection, diagnosis, prevention and treatment of a disease, specifically cardiac, kidney or inflammatory disease, and related disorders. The present invention also relates to compositions and methods useful in the diagnosis, prevention and therapeutic treatment of a disease, specifically cardiac, kidney or inflammatory disease. Specifically, methods and compositions are provided for the diagnostic evaluation and prognosis of conditions involving a disease, specifically cardiac, kidney or inflammatory disease, for the identification of subjects exhibiting a predisposition to such conditions, for modulating the effect of these differentially expressed genes, for monitoring patients undergoing clinical evaluation for the prevention and treatment of a disease, specifically cardiac, kidney or inflammatory disease, and its disorders, and for monitoring the efficacy of compounds used in clinical trials.

    摘要翻译： 本发明涉及用于检测，诊断，预防和治疗疾病，特别是心脏，肾脏或炎症性疾病以及相关疾病的方法和组合物。 本发明还涉及用于诊断，预防和治疗疾病，特别是心脏，肾脏或炎性疾病的组合物和方法。 具体地，提供方法和组合物用于诊断评估和预后涉及疾病，特别是心脏，肾脏或炎性疾病的疾病，用于鉴定表现出对这些病症倾向的受试者，用于调节这些差异表达基因的作用，用于 监测接受临床评估的患者，用于预防和治疗疾病，特别是心脏，肾脏或炎症疾病及其疾病，并监测临床试验中使用的化合物的功效。

    Agonists and antagonists of peripheral-type benzodiazepine receptors
    6.
    发明授权
    Agonists and antagonists of peripheral-type benzodiazepine receptors 有权
    外周型苯二氮类受体的激动剂和拮抗剂

    公开(公告)号：US06686354B2

    公开(公告)日：2004-02-03

    申请号：US10033189

    申请日：2001-12-27

    申请人： Alison Joly ,  George F. Schreiner ,  Lawrence W. Stanton ,  R. Tyler White

    发明人： Alison Joly ,  George F. Schreiner ,  Lawrence W. Stanton ,  R. Tyler White

    IPC分类号： A61K3155

    CPC分类号： C12Q1/6883 ,  C12Q2600/158

    摘要： The invention concerns the use of agonists and antagonists of peripheral-type benzodiazepine receptors (PTBR) in the diagnosis and treatment of cardiac hypertrophy and other circulatory conditions. The invention specifically concerns the use of PTBR antagonists in the prevention or treatment of decompensated cardiac hypertrophy and, eventually, heart failure. The invention also concerns the use of PTBR agonists in the management of conditions calling for increased blood flow or cardiac output, including injury or functional compromise of the heart, increased demand for physical exercise, or an acquired or inherited predisposition to cardiac contractile disfunction. Pharmaceutical compositions for the treatment of such conditions and screening methods to identify PTBR agonists and antagonists are also included.

    摘要翻译： 本发明涉及外周型苯二氮卓受体（PTBR）的激动剂和拮抗剂在心脏肥大和其他循环状况的诊断和治疗中的应用。 本发明具体涉及使用PTBR拮抗剂来预防或治疗失代偿性心脏肥大，最终导致心力衰竭。 本发明还涉及PTBR激动剂在管理呼吸增加的血流量或心输出量的情况下的应用，包括对心脏的损伤或功能损害，对体育运动的增加的需求，或心脏收缩功能障碍的获得或遗传倾向。 还包括用于治疗这些病症的药物组合物和鉴定PTBR激动剂和拮抗剂的筛选方法。

    Alpha-ketoamide inhibitors of 20S proteasome
    8.
    发明授权
    Alpha-ketoamide inhibitors of 20S proteasome 失效
    20S蛋白酶体的α-酮酰胺抑制剂

    公开(公告)号：US06781000B1

    公开(公告)日：2004-08-24

    申请号：US09356842

    申请日：1999-07-19

    申请人： Lisa Wang ,  Robert T. Lum ,  Steven R. Schow ,  Alison Joly ,  Suresh Kerwar ,  Michael M Wick

    发明人： Lisa Wang ,  Robert T. Lum ,  Steven R. Schow ,  Alison Joly ,  Suresh Kerwar ,  Michael M Wick

    IPC分类号： C07D20912

    CPC分类号： C07K5/0202 ,  A61K38/00 ,  C07K5/0205 ,  C07K5/0207 ,  C07K5/06043 ,  C07K5/0808

    摘要： &agr;-ketoamide compounds useful for treating disorders mediated by 20S proteasome in mammals having the following formula: wherein X2 is Ar or Ar—X3 wherein X3 is is —C═O, or —CH2CO—, and wherein Ar is phenyl, substituted phenyl, indole, substituted indoles, and any other heteroaryls; R1, and R2 are each individually selected from the side chains of the known natural &agr;-amino acids and unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear, branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle substituted heterocycle, heteroaryl and substituted heteroaryl; X1 is selected from hydroxide, monoalkylamino, dialkylamino, alkoxide, arylkoxide and wherein X4 is hydroxide, arylamino, monoalkylamino, dialkylamino, alkoxide, or arylalkoxide; and R3 is selected from the known natural &agr;-amino acids, unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear and branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle, substituted heterocycle, heteroaryl and substituted heteroaryl.

    摘要翻译： 用于治疗由20S蛋白酶体介导的疾病的α-酮酰胺化合物，其具有下式：其中X 2是Ar或Ar-X 3，其中X 3是-C = O或-CH 2 CO-，并且其中Ar是苯基，取代的苯基， 吲哚，取代的吲哚和任何其它杂芳基; R1和R2分别选自已知天然α-氨基酸和非天然氨基酸的侧链，氢，1-10碳直链和支链烷基，1-10碳直链和支链取代的烷基，芳基，取代芳基 ，1-10碳直链，支链取代的芳基，烷氧基芳基，3-8碳环烷基，杂环取代的杂环，杂芳基和取代的杂芳基; X1选自氢氧化物，一烷基氨基，二烷基氨基，醇盐，芳基氧化物，其中X4为氢氧化物，芳基氨基，单烷基氨基，二烷基氨基，醇盐或芳基醇盐; R 3选自已知的天然α-氨基酸，非天然氨基酸，氢，1-10碳直链和支链烷基，1-10碳直链和支链取代的烷基，芳基，取代的芳基，1-10碳直链和支链 取代的芳基，烷氧基芳基，3-8碳环烷基，杂环，取代的杂环，杂芳基和取代的杂芳基。

    Agonists and antagonists of peripheral-type benzodiazepine receptors
    9.
    发明授权
    Agonists and antagonists of peripheral-type benzodiazepine receptors 有权
    外周型苯二氮类受体的激动剂和拮抗剂

    公开(公告)号：US06342495B1

    公开(公告)日：2002-01-29

    申请号：US09461780

    申请日：1999-12-15

    申请人： Alison Joly ,  George F. Schreiner ,  Lawrence W. Stanton ,  R. Tyler White

    发明人： Alison Joly ,  George F. Schreiner ,  Lawrence W. Stanton ,  R. Tyler White

    IPC分类号： A61K3155

    CPC分类号： C12Q1/6883 ,  C12Q2600/158

    摘要： The invention concerns the use of agonists and antagonists of peripheral-type benzodiazcpine receptors (PTBR) in the diagnosis and treatment of cardiac hypertrophy and other circulatory conditions. The invention specifically concerns the use of PTBR antagonists in the prevention or treatment of decompensated cardiac hypertrophy and, eventually, heart failure. The invention also concerns the use of PTBR agonists in the management of conditions calling for increased blood flow or cardiac output, including injury or functional compromise of the heart, increased demand for physical exercise, or an acquired or inherited predisposition to cardiac contractile disfunction. Pharmaceutical compositions for the treatment of such conditions and screening methods to identify PTBR agonists and antagonists are also included.

    摘要翻译： 本发明涉及外周型苯并二氮对受体（PTBR）的激动剂和拮抗剂在心脏肥大和其它循环状况的诊断和治疗中的应用。 本发明具体涉及使用PTBR拮抗剂来预防或治疗失代偿性心脏肥大，最终导致心力衰竭。 本发明还涉及PTBR激动剂在管理呼吸增加的血流量或心输出量的情况下的应用，包括对心脏的损伤或功能损害，对体育运动的增加的需求，或心脏收缩功能障碍的获得或遗传倾向。 还包括用于治疗这些病症的药物组合物和鉴定PTBR激动剂和拮抗剂的筛选方法。

    .alpha.-ketoamide inhibitors of 20S proteasome
    10.
    发明授权
    .alpha.-ketoamide inhibitors of 20S proteasome 失效
    20S蛋白酶体的α-酮酰胺抑制剂

    公开(公告)号：US6075150A

    公开(公告)日：2000-06-13

    申请号：US13365

    申请日：1998-01-26

    申请人： Lisa Wang ,  Robert T. Lum ,  Steven R. Schow ,  Alison Joly ,  Suresh Kerwar ,  Michael M Wick

    发明人： Lisa Wang ,  Robert T. Lum ,  Steven R. Schow ,  Alison Joly ,  Suresh Kerwar ,  Michael M Wick

    IPC分类号： A61K38/00 ,  A61K38/04 ,  A61P37/00 ,  C07K5/02 ,  C07K5/023 ,  C07K5/027 ,  C07K5/03 ,  C07K5/06 ,  C07K5/062 ,  C07K5/083 ,  C07D209/12 ,  A01N43/38

    CPC分类号： C07K5/0202 ,  C07K5/0205 ,  C07K5/0207 ,  C07K5/06043 ,  C07K5/0808 ,  A61K38/00

    摘要： .alpha.-ketoamide compounds useful for treating disorders mediated by 20S proteasome in mammals having the following formula: wherein X.sub.2 is Ar or Ar--X.sub.3 wherein X.sub.3 is --C.dbd.O, or --CH.sub.2 CO--, and wherein Ar is phenyl, substituted phenyl, indole, substituted indoles, and any other heteroaryls; R.sub.1, and R.sub.2 are each individually selected from the side chains of the known natural .alpha.-amino acids and unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear, branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle substituted heterocycle, heteroaryl and substituted heteroaryl; X.sub.1 is selected from hydroxide, monoalkylamino, dialkylamino, alkoxide, arylkoxide and ##STR1## wherein X.sub.4 is hydroxide, arylamino, monoalkylamino, dialkylamino, alkoxide, or arylalkoxide; and R.sub.3 is selected from the known natural .alpha.-amino acids, unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear and branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle, substituted heterocycle, heteroaryl and substituted heteroaryl.

    摘要翻译： 用于治疗由20S蛋白酶体介导的疾病的α-酮酰胺化合物，其具有下式：其中X2是Ar或Ar-X3，其中X3是-C = O或-CH2CO-，其中Ar是苯基，取代的苯基，吲哚 取代的吲哚和任何其它杂芳基; R1和R2分别选自已知天然α-氨基酸和非天然氨基酸的侧链，氢，1-10碳直链和支链烷基，1-10碳直链和支链取代的烷基，芳基，取代的芳基 ，1-10碳直链，支链取代的芳基，烷氧基芳基，3-8碳环烷基，杂环取代的杂环，杂芳基和取代的杂芳基; X1选自氢氧化物，单烷基氨基，二烷基氨基，醇盐，芳基醇盐，其中X4是氢氧根，芳基氨基，单烷基氨基，二烷基氨基，醇盐或芳基醇盐; R 3选自已知的天然α-氨基酸，非天然氨基酸，氢，1-10碳直链和支链烷基，1-10碳直链和支链取代的烷基，芳基，取代芳基，1-10碳直链和支链 取代的芳基，烷氧基芳基，3-8碳环烷基，杂环，取代的杂环，杂芳基和取代的杂芳基。