公开(公告)号：US06369086B1

公开(公告)日：2002-04-09

申请号：US09262351

申请日：1999-03-04

申请人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

发明人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

IPC分类号： A61K314439

CPC分类号： C07D231/12 ,  C07D209/34 ,  C07D209/40 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D413/04 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D513/04

摘要： The present invention relates generally to novel substituted oxindole compounds and compositions. Such compounds and compositions have utility as pharmacological agents in treating diseases or conditions alleviated by the inhibition or antagonism of protein kinase activated signalling pathways. In particular, the present invention relates to a series of substituted oxindole compounds, which exhibit protein tyrosine kinase and protein serine/threonine kinase inhibition, and which are useful in inhibiting tumor growth via inhibition of such kinases as well as protecting a patient undergoing chemotherapy from chemotherapy induced alopecia.

摘要翻译： 本发明一般涉及新型取代的羟基吲哚化合物和组合物。 这样的化合物和组合物可用作治疗通过抑制或拮抗蛋白激酶激活的信号通路而减轻的疾病或病症的药理学作用。 特别地，本发明涉及一系列取代的羟吲哚化合物，其表现出蛋白质酪氨酸激酶和蛋白质丝氨酸/苏氨酸激酶抑制，并且其可用于通过抑制这种激酶抑制肿瘤生长以及保护接受化疗的患者 化疗引起秃发。

公开(公告)号：US06815439B2

公开(公告)日：2004-11-09

申请号：US10669400

申请日：2003-09-23

申请人： Philip Anthony Harris ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  James Marvin Veal

发明人： Philip Anthony Harris ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  James Marvin Veal

IPC分类号： A61K3133

CPC分类号： C07D471/04 ,  C07D471/14 ,  C07D513/04 ,  C07D513/14 ,  C40B40/00

摘要： Substituted aza-oxindole derivatives useful as cyclin dependent kinase II inhibitors, for preventing/reducing the severity of epithelial cytotoxicity side-effects (e.g., alopecia, plantar-palmar syndrome, mucositis) induced by chemoptherapy and/or radiation therapy in a patient receiving such therapy.

摘要翻译： 用作细胞周期蛋白依赖性激酶II抑制剂的取代的氮杂 - 羟吲哚衍生物，用于预防/降低接受这种治疗的患者中化学疗法和/或放射治疗引起的上皮细胞毒性副作用（例如，脱发，足底 - 手掌综合征，粘膜炎）的严重性 治疗。

公开(公告)号：US07105529B2

公开(公告)日：2006-09-12

申请号：US09999331

申请日：2001-11-30

申请人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Stephen Vernon Frye ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

发明人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Stephen Vernon Frye ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

IPC分类号： A61K31/505 ,  A61K31/44 ,  A61K31/425

CPC分类号： C07D231/12 ,  C07D209/34 ,  C07D209/40 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D413/04 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D513/04

摘要： Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7 sulfonyl-C1-12 aliphatic, R7-aminosulfonyl, R7-aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by cancer chemotherapy or radiotherapy.

公开(公告)号：US06624171B1

公开(公告)日：2003-09-23

申请号：US09914393

申请日：2001-08-28

申请人： Philip Anthony Harris ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  James Marvin Veal

发明人： Philip Anthony Harris ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  James Marvin Veal

IPC分类号： A61K31407

CPC分类号： C07D471/04 ,  C07D471/14 ,  C07D513/04 ,  C07D513/14 ,  C40B40/00

摘要： Substituted aza-oxindole derivatives useful as cyclin dependent kinase 11 inhibitors, for preventing/reducing the severity of epithelial cytotoxicity side-effects (e.g., alopecia, plantar-palmar syndrome, mucositis) induced by chemoptherapy and/or radiation therapy in a patient receiving such therapy.

摘要翻译： 用作细胞周期蛋白依赖性激酶11抑制剂的取代的氮杂 - 羟吲哚衍生物，用于预防/减轻接受这种治疗的患者中由化学疗法和/或放射治疗引起的上皮细胞毒性副作用（例如，脱发，足底 - 手掌综合征，粘膜炎）的严重性 治疗。

公开(公告)号：US06541503B2

公开(公告)日：2003-04-01

申请号：US09924431

申请日：2001-08-08

申请人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Stephen Vernon Frye ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

发明人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Stephen Vernon Frye ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

IPC分类号： A61K31429

CPC分类号： C07D231/12 ,  C07D209/34 ,  C07D209/40 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D413/04 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D513/04

摘要： Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7 sulfonyl-C1-12 aliphatic, R7-aminosulfonyl, R7-aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by cancer chemotherapy or radiotherapy.

公开(公告)号：US06268391B1

公开(公告)日：2001-07-31

申请号：US09446586

申请日：2000-04-07

申请人： Scott Howard Dickerson ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  David Kendall Jung ,  Karen Elizabeth Lackey ,  Robert Walton McNutt, Jr. ,  Michael Robert Peel ,  James Marvin Veal

发明人： Scott Howard Dickerson ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  David Kendall Jung ,  Karen Elizabeth Lackey ,  Robert Walton McNutt, Jr. ,  Michael Robert Peel ,  James Marvin Veal

IPC分类号： A61K31404

CPC分类号： C07D249/08 ,  C07D209/34 ,  C07D231/12 ,  C07D233/56 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D405/06 ,  C07D413/04 ,  C07D413/06 ,  C07D417/04 ,  C07D417/06 ,  C07D471/04

摘要： Compounds of general formula (I) wherein: R1 is H or optionally joined with R2 to form a fused ring selected from the group consisting of five to ten membered aryl, heteroaryl or heterocyclyl rings, R2 and R3 are independently H, HET, aryl, C1-12 aliphatic, CN, NO2, halogen, R10, —OR10, —SR10, —S(O)R10, —SO2R10, —NR10R11, —NR11R12, —NR12COR11, —NR12CO2R11, —NR12CONR11R12, —NO12SO2R11, —NR12C(NR 12)NHR11, —COR11, —CO2R11, —CONR12R11, —SO2NR12R11, —OCONR12R11, C(NR12)NR12R11, R6 and R7 are independently halogen, CN, NO2, —CONR10R11, —SO2NR10R11, —NR10R11, or —OR11, where R10 and R11 are as defined below; R8 is OH, NHSO2R12 or NHCOCF3; and their use in therapy, especially in the treatment of disorders mediated by cRaf1 kinase.

摘要翻译： 通式（I）的化合物，其中：R 1为H或任选地与R 2连接形成选自5至10元芳基，杂芳基或杂环基环的稠环，R 2和R 3独立地为H，HET，芳基， C 12-12脂族基，CN，NO 2，卤素，R 10，-OR 10，-SR 10，-S（O）R 10，-SO 2 R 10，-NR 10 R 11，-NR 11 R 12，-NR 12 COR 11，-NR 12 CO 2 R 11，-NR 12 CONR 11 R 12，-NO 12 SO 2 R 11， NR 12）NHR 11，-COR 11，-CO 2 R 11，-CONR 12 R 11，-SO 2 NR 12 R 11，-OCONR 12 R 11，C（NR 12）NR 12 R 11，R 6和R 7独立地为卤素，CN，NO 2，-CONR 10 R 11，-SO 2 NR 10 R 11，-NR 10 R 11或-OR 11， 其中R 10和R 11如下所定义; R8是OH，NHSO2R12或NHCOCF3; 及其在治疗中的应用，特别是治疗由cRaf1激酶介导的疾病。

公开(公告)号：US06964977B2

公开(公告)日：2005-11-15

申请号：US10362739

申请日：2001-08-23

申请人： Philip Anthony Harris ,  Robert N Hunter ,  Robert Walton McNutt, Jr. ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Robert Peel ,  Edgar Raymond Wood, III

发明人： Philip Anthony Harris ,  Robert N Hunter ,  Robert Walton McNutt, Jr. ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Robert Peel ,  Edgar Raymond Wood, III

IPC分类号： A61K31/404 ,  A61K31/4045 ,  A61K31/405 ,  A61K31/4184 ,  A61K31/4196 ,  A61K31/4245 ,  A61K31/454 ,  A61K31/53 ,  A61P7/02 ,  A61P9/10 ,  A61P29/00 ,  A61P29/02 ,  A61P35/00 ,  A61P43/00 ,  C07D209/14 ,  C07D209/34 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D487/04 ,  A61K31/415

CPC分类号： C07D401/12 ,  A61K31/4045 ,  A61K31/405 ,  A61K31/4184 ,  A61K31/4196 ,  A61K31/4245 ,  A61K31/454 ,  A61K31/53 ,  C07D209/14 ,  C07D209/34 ,  C07D403/12 ,  C07D405/12 ,  C07D487/04

摘要： The present invention is related to oxindole derivatives of structure (I), compositions containing the same, and methods of use and manufacture of the same. Such compounds generally are useful pharmacologically as agents in those disease states alleviated by the alteration of mitogen activated signaling pathways in general, and in particular in the inhibition or antagonism of protein kinases, which pathologically involve aberrant cellular proliferation. Such disease states include tumor growth, restenosis, atherosclerosis, pain and thrombosis. In particular, the present invention relates to a series of substituted oxindole compounds, which exhibit Trk family protein tyrosine kinase inhibition, and which are useful in cancer therapy and chronic pain indications.

摘要翻译： 本发明涉及结构（I）的羟吲哚衍生物，含有它们的组合物及其使用和制造方法。 这些化合物通常在药理学上作为通常通过改变促分裂原活化的信号通路而减轻的疾病状态中的药物有用，特别是在病理学上涉及异常细胞增殖的蛋白激酶的抑制或拮抗作用中。 这种疾病状态包括肿瘤生长，再狭窄，动脉粥样硬化，疼痛和血栓形成。 特别地，本发明涉及一系列取代的羟吲哚化合物，其表现出Trk家族蛋白酪氨酸激酶抑制，并且其可用于癌症治疗和慢性疼痛适应症。

公开(公告)号：US06350747B1

公开(公告)日：2002-02-26

申请号：US09514528

申请日：2000-02-28

申请人： Kimberley Caroline Glennon ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Robert Walton Mcnutt, Jr.

发明人： Kimberley Caroline Glennon ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Robert Walton Mcnutt, Jr.

IPC分类号： A61K314375

CPC分类号： C07D401/12 ,  C07D209/34 ,  C07D403/12 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04 ,  C07F9/6561

摘要： The present invention relates generally to novel amine substituted oxindole compounds and compositions. Such compounds and compositions have utility as pharmacological agents in treating diseases or conditions alleviated by the inhibition or antagonism of protein kinase activated signalling pathways in general, and in particular in the pathological processes which involve aberrant cellular proliferation, such as tumor growth. In particular, the present invention relates to a series of substituted oxindole compounds, which exhibit protein tyrosine kinase and protein serine/threonine kinase inhibition, and which are useful in inhibiting tumor growth via inhibition of tumor-related angiogenesis.

摘要翻译： 本发明一般涉及新的胺取代的羟基吲哚化合物和组合物。 这样的化合物和组合物通常用于治疗通过抑制或拮抗蛋白激酶激活的信号通路而减轻的疾病或病症，特别是涉及异常细胞增殖如肿瘤生长的病理过程中，作为药物学作用。 特别地，本发明涉及一系列取代的羟吲哚化合物，其表现出蛋白质酪氨酸激酶和蛋白质丝氨酸/苏氨酸激酶抑制，并且其可用于通过抑制肿瘤相关血管发生来抑制肿瘤生长。

公开(公告)号：US07129253B2

公开(公告)日：2006-10-31

申请号：US10742435

申请日：2003-12-19

申请人： Kimberley Caroline Glennon ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Robert Walton McNutt, Jr.

发明人： Kimberley Caroline Glennon ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Robert Walton McNutt, Jr.

IPC分类号： A61K31/4353 ,  C07D471/02

CPC分类号： C07D401/12 ,  C07D209/34 ,  C07D403/12 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04 ,  C07F9/6561

摘要： Compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, A, D, X, Y and Z have the meaning as defined in the claims exhibit protein tyrosine kinase and protein serin/threonine kinase inhibitory activity.

摘要翻译： 其中R 1，R 2，R 3，R 4，R 5，R 6，R 7，R 8，A，D，X，Y和Z具有如权利要求中所定义的含义的式（I）化合物显示蛋白酪氨酸激酶和蛋白丝氨酸/苏氨酸激酶 抑制活性。

公开(公告)号：US07071217B2

公开(公告)日：2006-07-04

申请号：US10362743

申请日：2001-08-23

申请人： Scott Howard Dickerson ,  Robert N Hunter ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael J. Luzzio ,  Edgar Raymond Wood, III

发明人： Scott Howard Dickerson ,  Robert N Hunter ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael J. Luzzio ,  Edgar Raymond Wood, III

IPC分类号： A61K31/44 ,  C07D401/02

CPC分类号： C07D401/12 ,  C07D209/34 ,  C07D209/40 ,  C07D417/12

摘要： The present invention is related to oxindole derivatives of structure (I), compositions containing the same, and methods of use and manufacture of the same. Such compounds generally are useful pharmacologically as agents in those disease states alleviated by the alteration of mitogen activated signaling pathways in general, and in particular in the inhibition or antagonism of protein kinases, which pathologically involve aberrant cellular proliferation. Such disease states include tumor growth, restenosis, atherosclerosis, pain and thrombosis, In particular, the present invention relates to a series of substituted oxindole compounds, which exhibit Trk family protein tyrosine kinase inhibition, and which are useful in cancer therapy and chronic pain indications.

摘要翻译： 本发明涉及结构（I）的羟吲哚衍生物，含有它们的组合物及其使用和制造方法。 这些化合物通常在药理学上作为通常通过改变促分裂原活化的信号通路而减轻的疾病状态中的药物有用，特别是在病理学上涉及异常细胞增殖的蛋白激酶的抑制或拮抗作用中。 这种疾病状态包括肿瘤生长，再狭窄，动脉粥样硬化，疼痛和血栓形成。特别地，本发明涉及一系列取代的羟吲哚化合物，其表现出Trk家族蛋白酪氨酸激酶抑制，并且其可用于癌症治疗和慢性疼痛适应症 。