公开(公告)号：US20100190777A1

公开(公告)日：2010-07-29

申请号：US12669450

申请日：2008-07-16

申请人： Guoxian Wu ,  Jiazhong Zhang ,  Yong-Liang Zhu ,  Chao Zhang ,  Prabha N. Ibrahim ,  Songyuan Shi ,  Wayne Spevak ,  Dean R. Artis ,  James Tsai

发明人： Guoxian Wu ,  Jiazhong Zhang ,  Yong-Liang Zhu ,  Chao Zhang ,  Prabha N. Ibrahim ,  Songyuan Shi ,  Wayne Spevak ,  Dean R. Artis ,  James Tsai

IPC分类号： C07D213/75 ,  A61K31/54 ,  A61K31/5377 ,  A61K31/505 ,  A61K31/47 ,  A61K31/437 ,  A61K31/44 ,  A61K31/41 ,  A61K31/42 ,  A61K31/415 ,  A61K31/165 ,  C07D471/02 ,  C07D413/02 ,  C07D403/00 ,  A61K31/444 ,  C07D215/38 ,  A61P35/00 ,  C07D417/02 ,  C07D213/02 ,  C07D285/12 ,  C07D261/14 ,  C07D231/02 ,  C07C233/64

CPC分类号： A61K31/44 ,  A61K31/415 ,  A61K31/42 ,  A61K31/433 ,  A61K31/437 ,  A61K31/4436 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/549 ,  A61K45/06 ,  C07D213/74 ,  C07D213/75 ,  C07D213/76 ,  C07D213/82 ,  C07D215/12 ,  C07D215/14 ,  C07D215/20 ,  C07D215/38 ,  C07D231/40 ,  C07D239/48 ,  C07D239/49 ,  C07D261/14 ,  C07D263/48 ,  C07D285/135 ,  C07D285/16 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  A61K31/4427 ,  A61K2300/00

摘要： Compounds of formula I active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases. Formula (I) wherein Ar is optionally substituted heteroaryl; R2 is hydrogen, lower alkyl or halogen; U is selected from the group consisting of —S(O)2—, —C(X)—, —C(X)—N(R10)—, and —S(O)2—N(R10)—; R3 is optionally substituted lower alkyl, optionally substituted C3.6 cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl; and wherein R1, R3, R4, m, L1, X R10 are as described herein.

摘要翻译： 描述了对蛋白激酶有活性的式I化合物，以及使用这些化合物治疗与蛋白激酶异常活性相关的疾病和病症的方法。 式（I）其中Ar是任选取代的杂芳基; R2是氢，低级烷基或卤素; U选自-S（O）2 - ， - C（X） - ， - C（X）-N（R 10） - 和-S（O）2 -N（R 10） - ; R 3是任选取代的低级烷基，任选取代的C 3-6环烷基，任选取代的杂环烷基，任选取代的芳基或任选取代的杂芳基; 并且其中R 1，R 3，R 4，m，L 1，X R 10如本文所述。

公开(公告)号：US20090286782A1

公开(公告)日：2009-11-19

申请号：US12467194

申请日：2009-05-15

申请人： Prabha N. Ibrahim ,  Ryan Bremer ,  Jiazhong Zhang ,  Marika Nespi ,  Hanna Cho

发明人： Prabha N. Ibrahim ,  Ryan Bremer ,  Jiazhong Zhang ,  Marika Nespi ,  Hanna Cho

IPC分类号： A61K31/5377 ,  C07D487/04 ,  A61K31/519 ,  A61P19/02 ,  A61P35/00

CPC分类号： C07D487/04 ,  A61K31/519

摘要： Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one of Fms protein kinase or Kit protein kinase. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of Fms protein kinases and/or Kit protein kinases, including rheumatoid arthritis, osteoarthritis, osteoporosis, peri-prosthetic osteolysis, systemic sclerosis, demyelinating disorders, multiple sclerosis, Charcot Marie Tooth syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, myelopreparation for autologous transplantation, transplant rejection, nephritis, nephropathy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastomas, neurofibromatosis, osteolytic bone metastases, and giant cell tumors.

摘要翻译： 其化合物及其盐，其制剂，其缀合物，其衍生物，其形式及用途。 在某些方面和实施方案中，所述的化合物或其盐，其制剂，其缀合物，其衍生物，其形式在Fms蛋白激酶或Kit蛋白激酶中的至少一种上是有活性的。 还描述了其用于治疗疾病和病症的方法，包括与Fms蛋白激酶和/或Kit蛋白激酶（包括类风湿性关节炎，骨关节炎，骨质疏松症，骨质疏松症，系统性硬化症，脱髓鞘疾病， 多发性硬化症，Charcot玛丽牙综合征，肌萎缩性侧索硬化，阿尔茨海默病，帕金森病，溃疡性结肠炎，克罗恩病，免疫性血小板减少性紫癜，自体移植用骨髓制剂，移植排斥，肾炎，肾病，I型糖尿病，急性疼痛， 神经性疼痛，乳腺癌，前列腺癌，胰腺癌，肺癌，卵巢癌，神经胶质瘤，成胶质细胞瘤，神经纤维瘤病，溶骨性骨转移和巨细胞肿瘤。

公开(公告)号：US07504509B2

公开(公告)日：2009-03-17

申请号：US11016350

申请日：2004-12-17

申请人： Prabha Ibrahim ,  Dean Richard Artis ,  Ryan Bremer ,  Gaston Habets ,  Clarence R. Hurt ,  Shumeye Mamo ,  Marika Nespi ,  Chao Zhang ,  Jiazhong Zhang ,  Yong Zhu ,  Rebecca Zuckerman ,  Heike Krupka ,  Abhinav Kumar ,  Brian West

发明人： Prabha Ibrahim ,  Dean Richard Artis ,  Ryan Bremer ,  Gaston Habets ,  Clarence R. Hurt ,  Shumeye Mamo ,  Marika Nespi ,  Chao Zhang ,  Jiazhong Zhang ,  Yong Zhu ,  Rebecca Zuckerman ,  Heike Krupka ,  Abhinav Kumar ,  Brian West

IPC分类号： C07D471/02

CPC分类号： C07D471/04

摘要： Compounds active on Ret are described, as well as methods of using such compounds. Also described are crystal structures of Ret surrogates that were determined using X-ray crystallography. The use of such Ret surrogate crystals and structural information can, for example, be used for identifying molecular scaffolds and for developing ligands that bind to and modulate Ret and for identifying improved ligands based on known ligands.

摘要翻译： 描述了在Ret上活性的化合物，以及使用这些化合物的方法。 还描述了使用X射线晶体学测定的Ret替代物的晶体结构。 使用这种Ret替代晶体和结构信息可以例如用于鉴定分子支架和开发结合并调节Ret的配体，并用于基于已知配体鉴定改良的配体。

公开(公告)号：US20080221148A1

公开(公告)日：2008-09-11

申请号：US11962044

申请日：2007-12-20

申请人： Prabha N. Ibrahim ,  Ryan Bremer ,  Chao Zhang ,  Jiazhong Zhang ,  Klaus-Peter Hirth ,  Guoxian Wu ,  Hongyao Zhu

发明人： Prabha N. Ibrahim ,  Ryan Bremer ,  Chao Zhang ,  Jiazhong Zhang ,  Klaus-Peter Hirth ,  Guoxian Wu ,  Hongyao Zhu

IPC分类号： A61K31/454 ,  A61P35/00 ,  C07D471/04

CPC分类号： C07D471/04

摘要： Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

公开(公告)号：US09624213B2

公开(公告)日：2017-04-18

申请号：US13820734

申请日：2012-02-01

申请人： Prabha Ibrahim ,  Chao Zhang ,  Wayne Spevak ,  Jiazhong Zhang ,  Guoxian Wu ,  Jack Lin ,  Hanna Cho ,  Marika Nespi ,  Songyuan Shi ,  Todd Ewing ,  Ying Zhang

发明人： Prabha Ibrahim ,  Chao Zhang ,  Wayne Spevak ,  Jiazhong Zhang ,  Guoxian Wu ,  Jack Lin ,  Hanna Cho ,  Marika Nespi ,  Songyuan Shi ,  Todd Ewing ,  Ying Zhang

IPC分类号： C07D471/04 ,  A61K31/506 ,  A61K31/437 ,  A61K31/5377

CPC分类号： A61K31/506 ,  A61K31/437 ,  A61K31/5377 ,  C07D471/04

摘要： Compounds active on protein kinases are described, as well as methods of making and using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

公开(公告)号：US20150166547A1

公开(公告)日：2015-06-18

申请号：US14571186

申请日：2014-12-15

申请人： Prabha N. Ibrahim ,  Ryan Bremer ,  Jiazhong Zhang ,  Marika Nespi ,  Hanna Cho

发明人： Prabha N. Ibrahim ,  Ryan Bremer ,  Jiazhong Zhang ,  Marika Nespi ,  Hanna Cho

IPC分类号： C07D487/04

CPC分类号： C07D487/04 ,  A61K31/519

摘要： Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one of Fms protein kinase or Kit protein kinase. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of Fms protein kinases and/or Kit protein kinases, including rheumatoid arthritis, osteoarthritis, osteoporosis, peri-prosthetic osteolysis, systemic sclerosis, demyelinating disorders, multiple sclerosis, Charcot Marie Tooth syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, myelopreparation for autologous transplantation, transplant rejection, nephritis, nephropathy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastomas, neurofibromatosis, osteolytic bone metastases, and giant cell tumors.

公开(公告)号：US08901118B2

公开(公告)日：2014-12-02

申请号：US13090969

申请日：2011-04-20

申请人： Jiazhong Zhang ,  Prabha N. Ibrahim ,  Wayne Spevak ,  Jianming Tsai ,  Todd Ewing ,  Ying Zhang ,  Chao Zhang

发明人： Jiazhong Zhang ,  Prabha N. Ibrahim ,  Wayne Spevak ,  Jianming Tsai ,  Todd Ewing ,  Ying Zhang ,  Chao Zhang

IPC分类号： C07D487/04 ,  A61K31/519 ,  C07D471/04 ,  A61P19/02 ,  A61P19/10 ,  A61P25/28 ,  A61P29/00 ,  A61K31/437

CPC分类号： C07D487/04 ,  C07D471/04

摘要： Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described, wherein the compounds have formula I: In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC kinase protein. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC, including rheumatoid arthiritis, osteoarthritis, osteoporosis, peri-prosthetic osteolysis, systemic sclerosis, demyelinating disorders, multiple sclerosis, Charcot Marie Tooth syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, global ischemia, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, atherosclerosis, systemic lupus erythematosis, myelopreparation for autologous transplantation, transplant rejection, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, acute myeloid leukemia, melanoma, multiple myeloma, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastoma, neurofibromatosis, osteolytic bone metastases, brain metasteses, gastrointestinal stromal tumors, and giant cell tumors.

摘要翻译： 描述了其化合物和盐，其制剂，其缀合物，其衍生物，其形式及其用途，其中所述化合物具有式I：在某些方面和实施方案中，所述的化合物或其盐，其制剂，其缀合物，其衍生物 其形式在Fms，Kit，Flt3，TrkA，TrkB和TrkC激酶蛋白中的一种或多种上是有活性的。 还描述了其用于治疗疾病和病症的方法，包括与Fms，Kit，Flt3，TrkA，TrkB和TrkC中的一种或多种的活性相关的疾病和病症，包括类风湿性关节炎，骨关节炎，骨质疏松症，假体周围骨质溶解， 系统性硬化症，脱髓鞘疾病，多发性硬化症，Charcot玛丽牙综合征，肌萎缩性侧索硬化症，阿尔茨海默氏病，帕金森病，全球缺血，溃疡性结肠炎，克罗恩病，免疫性血小板减少性紫癜，动脉粥样硬化，系统性红斑狼疮，自体移植骨髓移植，移植排斥 肾小球肾炎，间质性肾炎，狼疮性肾炎，肾小管坏死，糖尿病性肾病，肾肥大，I型糖尿病，急性疼痛，炎性疼痛，神经性疼痛，急性骨髓性白血病，黑素瘤，多发性骨髓瘤，乳腺癌，前列腺癌，胰腺癌，肺癌 癌症，卵巢癌，神经胶质瘤，成胶质细胞瘤，神经 纤维瘤病，溶骨性骨转移，脑转移，胃肠道间质瘤和巨细胞瘤。

公开(公告)号：US20140045840A1

公开(公告)日：2014-02-13

申请号：US14033291

申请日：2013-09-20

申请人： Jiazhong Zhang ,  Prabha N. Ibrahim ,  Ryan Bremer ,  Wayne Spevak ,  Hanna Cho

发明人： Jiazhong Zhang ,  Prabha N. Ibrahim ,  Ryan Bremer ,  Wayne Spevak ,  Hanna Cho

IPC分类号： C07D471/04

CPC分类号： C07D471/04 ,  A61K31/437 ,  A61K31/4427 ,  A61K31/506 ,  C07D401/04 ,  C07D401/14

摘要： Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, or forms thereof are active on Fms protein kinase, or on Fms and Kit protein kinase, or on Fms and Flt-3 protein kinase. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of Fms protein kinase, Kit protein kinase, or Flt-3 protein kinase including rheumatoid arthritis, osteoarthritis, multiple sclerosis, Alzheimer's disease, Parkinson's disease, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, acute myeloid leukemia, melanoma, multiple myeloma, metastatic breast cancer, prostate cancer, pancreatic cancer, neurofibromatosis, brain metastases, and gastrointestinal stromal tumors.

摘要翻译： 其化合物及其盐，其制剂，其缀合物，其衍生物，其形式及用途。 在某些方面和实施方案中，所述的化合物或其盐，其制剂，其缀合物，其衍生物或其形式在Fms蛋白激酶或Fms和Kit蛋白激酶或Fms和Flt-3蛋白激酶上具有活性。 还描述了其用于治疗疾病和病症的方法，包括与Fms蛋白激酶，Kit蛋白激酶或Flt-3蛋白激酶（包括类风湿性关节炎，骨关节炎，多发性硬化症，阿尔茨海默病，帕金森氏病， 肾小球性肾炎，间质性肾炎，狼疮性肾炎，肾小管坏死，糖尿病性肾病，肾肥大，急性骨髓性白血病，黑素瘤，多发性骨髓瘤，转移性乳腺癌，前列腺癌，胰腺癌，神经纤维瘤病，脑转移瘤和胃肠道间质瘤。

公开(公告)号：US08404700B2

公开(公告)日：2013-03-26

申请号：US13546923

申请日：2012-07-11

申请人： Prabha N. Ibrahim ,  Dean R. Artis ,  Ryan Bremer ,  Guoxian Wu ,  Hongyao Zhu ,  Marika Nespi ,  Chao Zhang ,  Jiazhong Zhang

发明人： Prabha N. Ibrahim ,  Dean R. Artis ,  Ryan Bremer ,  Guoxian Wu ,  Hongyao Zhu ,  Marika Nespi ,  Chao Zhang ,  Jiazhong Zhang

IPC分类号： A61K31/506 ,  A61K31/454 ,  A61P35/00 ,  C07D471/04 ,  C07D239/02

CPC分类号： C07D471/04 ,  A61K31/444 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06

摘要： Compounds active on the receptor protein tyrosine kinases c-kit and/or c-fms are provided herewith. Also provided herewith are compositions useful for treatment of c-kit mediated diseases or conditions and/or c-fms-mediated diseases or conditions, and methods for the use thereof.

公开(公告)号：US20110112127A1

公开(公告)日：2011-05-12

申请号：US12939998

申请日：2010-11-04

申请人： Jiazhong Zhang ,  Prabha N. Ibrahim ,  Ryan Bremer ,  Wayne Spevak ,  Hanna Cho

发明人： Jiazhong Zhang ,  Prabha N. Ibrahim ,  Ryan Bremer ,  Wayne Spevak ,  Hanna Cho

IPC分类号： A61K31/506 ,  C07D471/04 ,  C07D401/14 ,  A61K31/437 ,  A61P35/02 ,  A61P19/02 ,  A61P37/00

CPC分类号： C07D471/04 ,  A61K31/437 ,  A61K31/4427 ,  A61K31/506 ,  C07D401/04 ,  C07D401/14

摘要： Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, or forms thereof are active on Fms protein kinase, or on Fms and Kit protein kinase, or on Fms and Flt-3 protein kinase. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of Fms protein kinase, Kit protein kinase, or Flt-3 protein kinase including rheumatoid arthritis, osteoarthritis, multiple sclerosis, Alzheimer's disease, Parkinson's disease, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, acute myeloid leukemia, melanoma, multiple myeloma, metastatic breast cancer, prostate cancer, pancreatic cancer, neurofibromatosis, brain metastases, and gastrointestinal stromal tumors.

摘要翻译： 其化合物及其盐，其制剂，其缀合物，其衍生物，其形式及用途。 在某些方面和实施方案中，所述的化合物或其盐，其制剂，其缀合物，其衍生物或其形式在Fms蛋白激酶或Fms和Kit蛋白激酶或Fms和Flt-3蛋白激酶上具有活性。 还描述了其用于治疗疾病和病症的方法，包括与Fms蛋白激酶，Kit蛋白激酶或Flt-3蛋白激酶（包括类风湿性关节炎，骨关节炎，多发性硬化症，阿尔茨海默病，帕金森氏病， 肾小球性肾炎，间质性肾炎，狼疮性肾炎，肾小管坏死，糖尿病性肾病，肾肥大，急性骨髓性白血病，黑素瘤，多发性骨髓瘤，转移性乳腺癌，前列腺癌，胰腺癌，神经纤维瘤病，脑转移瘤和胃肠道间质瘤。