公开(公告)号：US08030305B2

公开(公告)日：2011-10-04

申请号：US11612020

申请日：2006-12-18

申请人： Tianbao Lu ,  Richard Alexander ,  Richard W. Connors ,  Maxwell D. Cummings ,  Robert A. Galemmo ,  Heather Rae Hufnagel ,  Dana L. Johnson ,  Ehab Khalil ,  Kristi A. Leonard ,  Thomas P. Markotan ,  Anna C. Maroney ,  Jan L. Sechler ,  Jeremy M. Travins ,  Robert W. Tuman

发明人： Tianbao Lu ,  Richard Alexander ,  Richard W. Connors ,  Maxwell D. Cummings ,  Robert A. Galemmo ,  Heather Rae Hufnagel ,  Dana L. Johnson ,  Ehab Khalil ,  Kristi A. Leonard ,  Thomas P. Markotan ,  Anna C. Maroney ,  Jan L. Sechler ,  Jeremy M. Travins ,  Robert W. Tuman

IPC分类号： C07D487/04 ,  A61K31/5025 ,  A61P35/00

CPC分类号： C07D487/04 ,  C07D519/00

摘要： The invention is directed to triazolopyridazine compounds of Formula I: where R1, R5, R6, R7, R8, and A are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

摘要翻译： 本发明涉及式I的三唑并哒嗪化合物：其中R 1，R 5，R 6，R 7，R 8和A如本文所定义，使用这些化合物作为蛋白质酪氨酸激酶调节剂，特别是c-Met的抑制剂，以及使用 的这样的化合物以减少或抑制细胞或受试者中c-Met的激酶活性，并调节细胞或受试者中的c-Met表达，以及这些化合物在受试者中用于预防或治疗细胞增殖性病症和 /或与c-Met有关的障碍。 本发明进一步涉及包含本发明化合物的药物组合物和治疗诸如癌症和其它细胞增殖性疾病的病症的方法。

公开(公告)号：US08173654B2

公开(公告)日：2012-05-08

申请号：US12187524

申请日：2008-08-07

申请人： Tianbao Lu ,  Richard Alexander ,  Richard W. Connors ,  Maxwell D. Cummings ,  Robert A. Galemmo ,  Heather Rae Hufnagel ,  Dana L. Johnson ,  Ehab Khalil ,  Kristi A. Leonard ,  Thomas P. Markotan ,  Anna C. Maroney ,  Jan L. Sechler ,  Jeremy M. Travins ,  Robert W. Tuman

发明人： Tianbao Lu ,  Richard Alexander ,  Richard W. Connors ,  Maxwell D. Cummings ,  Robert A. Galemmo ,  Heather Rae Hufnagel ,  Dana L. Johnson ,  Ehab Khalil ,  Kristi A. Leonard ,  Thomas P. Markotan ,  Anna C. Maroney ,  Jan L. Sechler ,  Jeremy M. Travins ,  Robert W. Tuman

IPC分类号： A61K31/4985 ,  C07D487/04 ,  A61P3/10 ,  A61P17/06 ,  A61P25/18 ,  A61P19/02 ,  A61P9/10 ,  A61P9/00 ,  A61P35/00

CPC分类号： C07D487/04 ,  C07D519/00

摘要： The invention is directed to triazolopyridazine compounds of Formula I: where R1, R5, R6, R7, R8, and A are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

摘要翻译： 本发明涉及式I的三唑并哒嗪化合物：其中R 1，R 5，R 6，R 7，R 8和A如本文所定义，使用这些化合物作为蛋白质酪氨酸激酶调节剂，特别是c-Met的抑制剂，以及使用 的这样的化合物以减少或抑制细胞或受试者中c-Met的激酶活性，并调节细胞或受试者中的c-Met表达，以及这些化合物在受试者中预防或治疗细胞增殖性病症和 /或与c-Met有关的障碍。 本发明进一步涉及包含本发明化合物的药物组合物和治疗诸如癌症和其它细胞增殖性疾病的病症的方法。

公开(公告)号：US20090098181A1

公开(公告)日：2009-04-16

申请号：US12187524

申请日：2008-08-07

申请人： Tianbao Lu ,  Richard Alexander ,  Richard W. Connors ,  Maxwell D. Cummings ,  Robert A. Galemmo ,  Heather Rae Hufnagel ,  Dana L. Johnson ,  Ehab Khalil ,  Kristi A. Leonard ,  Thomas P. Markotan ,  Anna C. Maroney ,  Jan L. Sechler ,  Jeremy M. Travins ,  Robert W. Tuman

发明人： Tianbao Lu ,  Richard Alexander ,  Richard W. Connors ,  Maxwell D. Cummings ,  Robert A. Galemmo ,  Heather Rae Hufnagel ,  Dana L. Johnson ,  Ehab Khalil ,  Kristi A. Leonard ,  Thomas P. Markotan ,  Anna C. Maroney ,  Jan L. Sechler ,  Jeremy M. Travins ,  Robert W. Tuman

IPC分类号： A61F2/04 ,  C07D487/04 ,  A61K31/5025 ,  C12N9/99 ,  A61K31/541

CPC分类号： C07D487/04 ,  C07D519/00

摘要： The invention is directed to triazolopyridazine compounds of Formula I: where R1, R5, R6, R7, R8, and A are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

摘要翻译： 本发明涉及式I的三唑并哒嗪化合物：其中R 1，R 5，R 6，R 7，R 8和A如本文所定义，使用这些化合物作为蛋白质酪氨酸激酶调节剂，特别是c-Met的抑制剂，以及使用 的这样的化合物以减少或抑制细胞或受试者中c-Met的激酶活性，并调节细胞或受试者中的c-Met表达，以及这些化合物在受试者中预防或治疗细胞增殖性病症和 /或与c-Met有关的障碍。 本发明进一步涉及包含本发明化合物的药物组合物和治疗诸如癌症和其它细胞增殖性疾病的病症的方法。

公开(公告)号：US07662824B2

公开(公告)日：2010-02-16

申请号：US11377077

申请日：2006-03-16

申请人： Kristi Leonard ,  Tianbao Lu ,  Robert W. Tuman ,  Dana L. Johnson ,  Anna C. Maroney ,  Jan L. Sechler ,  Richard W. Connors ,  Richard S. Alexander ,  Maxwell D. Cummings ,  Robert A. Galemmo ,  Thomas P. Markotan

发明人： Kristi Leonard ,  Tianbao Lu ,  Robert W. Tuman ,  Dana L. Johnson ,  Anna C. Maroney ,  Jan L. Sechler ,  Richard W. Connors ,  Richard S. Alexander ,  Maxwell D. Cummings ,  Robert A. Galemmo ,  Thomas P. Markotan

IPC分类号： A61K31/496 ,  A61K31/404 ,  C07D405/14 ,  C07D405/12 ,  C07D407/14

CPC分类号： C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12

摘要： The invention is directed to acylhydrazones compounds of Formula I: where R1, R2 and A are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

摘要翻译： 本发明涉及式I的酰腙化合物：其中R 1，R 2和A如本文所定义，使用这些化合物作为蛋白质酪氨酸激酶调节剂，特别是c-Met的抑制剂，以及使用这些化合物来减少或抑制 c-Met在细胞或受试者中的激酶活性和调节细胞或受试者中的c-Met表达，以及这些化合物用于预防或治疗受试者的细胞增殖性病症和/或与c- 遇见 本发明进一步涉及包含本发明化合物的药物组合物和治疗诸如癌症和其它细胞增殖性疾病的病症的方法。

公开(公告)号：US07563781B2

公开(公告)日：2009-07-21

申请号：US11329642

申请日：2006-01-11

申请人： Donald W. Ludovici ,  Richard W. Connors ,  Steven J. Coats ,  Li Liu ,  Bart L. De Corte ,  Dana L. Johnson ,  Mark J. Schulz

发明人： Donald W. Ludovici ,  Richard W. Connors ,  Steven J. Coats ,  Li Liu ,  Bart L. De Corte ,  Dana L. Johnson ,  Mark J. Schulz

IPC分类号： C07D487/04 ,  C07F9/40 ,  A61K31/5355 ,  A61K31/519 ,  C07D239/30 ,  A61P35/00 ,  G01N33/53 ,  C07H21/04 ,  C12P21/06 ,  C12N5/06 ,  C07K16/40 ,  C12N9/12

CPC分类号： C07K14/4738 ,  C07D487/04 ,  C12N9/1205 ,  C12Q1/485 ,  G01N2500/02

摘要： The invention relates to the discovery of triazolopyrimidine derivatives of formula (I), which have been found to exhibit inhibitory activity against the serine-tyrosine and tyrosine kinases.

摘要翻译： 本发明涉及已发现对丝氨酸 - 酪氨酸和酪氨酸激酶具有抑制活性的式（I）三唑并嘧啶衍生物的发现。

公开(公告)号：US5218090A

公开(公告)日：1993-06-08

申请号：US604728

申请日：1990-10-26

申请人： Richard W. Connors

发明人： Richard W. Connors

IPC分类号： C07K14/71 ,  C12N15/12

CPC分类号： C07K14/71

摘要： The present invention is for EGF receptor truncates which retain the activity of ligand binding for the EGF receptor. The specific truncates include LD.sub.1 D.sub.2 D.sub.3.Apa L encompassing amino acids Met.sub.-24 to Val.sub.505 of the EGF receptor; for LD.sub.2 D.sub.3 D.sub.4 which melds the EGF receptor leader peptide (amino acids Met.sub.-24 to Ala.sub.-1), 9 amino acids of the mature amino terminus of the receptor (Leu.sub.1 to Gly.sub.9) and receptor sequences Ser.sub.150 to Gly.sub.625 ; for LD.sub.3 D.sub.4 which is the leader peptide (Met.sub.-24 to Ala.sub.-1), Leu.sub.1 to Gln.sub.8 of the mature amino terminus and the receptor sequence Asp.sub.297 to Gly.sub.625.

摘要翻译： 本发明涉及保留EGF受体配体结合活性的EGF受体截短物。 特异性截短物包括包含EGF受体的氨基酸Met-24至Val505的LD1D2D3.Apa L; 对于将EGF受体前导肽（氨基酸Met-24至Ala-1），受体的成熟氨基末端的9个氨基酸（Leu1至Gly9）和受体序列Ser150与Gly625融合的LD2D3D4; 对于作为成熟氨基末端的前导肽（Met-24至Ala-1），Leu1至Gln8的LD3D4和受体序列Asp297至Gly625的LD3D4。

公开(公告)号：US20110151470A1

公开(公告)日：2011-06-23

申请号：US12972085

申请日：2010-12-17

申请人： Richard W. Connors

发明人： Richard W. Connors

IPC分类号： C12Q1/68 ,  C07K14/475 ,  C07K14/46 ,  C07K14/705 ,  C12N9/64 ,  C12Q1/37 ,  C12Q1/02

CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/136 ,  G01N33/5011 ,  G01N33/57484 ,  G01N2333/52 ,  G01N2333/70585 ,  G01N2800/52

摘要： Biomarkers that correlate to treatment with drugs that inhibit c-met are disclosed. These biomarkers have been shown to have utility in assessing response to the compounds. The expression level of the biomarkers is reduced upon treatment with c-met inhibitor compounds, thus indicating that these biomarkers are involved in c-met activity.

摘要翻译： 公开了与抑制c-met的药物治疗相关的生物标志物。 这些生物标志物已被证明可用于评估对化合物的反应。 在用c-met抑制剂化合物治疗时，生物标志物的表达水平降低，从而表明这些生物标志物参与c-met活性。