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1. 发明申请

WO2008033999A2 KINASE INHIBITORS USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISEASES 审中-公开
标题翻译：激酶抑制剂用于治疗增殖性疾病
公开(公告)号：WO2008033999A2
公开(公告)日：2008-03-20
申请号：PCT/US2007/078394
申请日：2007-09-13
申请人： DECIPHERA PHARMACEUTICALS, LLC , FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D. , PATT, William, C.
发明人： FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D. , PATT, William, C.
IPC分类号： A61K31/4375 , A61K31/519 , A61P1/00 , A61P11/00 , A61P17/06 , A61P19/02 , A61P35/00 , A61P37/00
CPC分类号： C07D471/04 , C07D487/04
摘要： The present invention relates to novel kinase inhibitors and modulator compounds useful for the treatment of various diseases. More particularly, the invention is concerned with such compounds, kinase/compound adducts, methods of treating diseases, and methods of synthesis of the compounds. Preferrably, the compounds are useful for the modulation of kinase activity of Raf kinases and disease polymorphs thereof. Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant melanoma, colorectal cancer, ovarian cancer, papillary thyroid carcinoma, non small cell lung cancer, and mesothelioma. Compounds of the present invention also find utility in the treatment of rheumatoid arthritis and retinopathies including diabetic retinal neuropathy and macular degeneration.
摘要翻译：本发明涉及用于治疗各种疾病的新型激酶抑制剂和调节剂化合物。更具体地说，本发明涉及这样的化合物，激酶/化合物加合物，治疗疾病的方法以及合成该化合物的方法。优选地，所述化合物可用于调节Raf激酶及其疾病多晶型物的激酶活性。本发明化合物可用于治疗哺乳动物癌症，特别是人类癌症，包括但不限于恶性黑素瘤，结肠直肠癌，卵巢癌，乳头状甲状腺癌，非小细胞肺癌和间皮瘤。本发明的化合物还可用于治疗类风湿性关节炎和视网膜病，包括糖尿病性视网膜神经病和黄斑变性。

2. 发明申请

WO2008140895A1 KINASE INHIBITORS USEFUL FOR THE TREATMENT OF MYLEOPROLIFERATIVE DISEASES AND OTHER PROLIFERATIVE DISEASES 审中-公开
标题翻译：激酶抑制剂用于治疗增生性疾病和其他增殖性疾病
公开(公告)号：WO2008140895A1
公开(公告)日：2008-11-20
申请号：PCT/US2008/060855
申请日：2008-04-18
申请人： DECIPHERA PHARMACEUTICALS, LLC , FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D.
发明人： FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D.
IPC分类号： A61K31/506 , A61K31/517 , A61K31/426 , A61K31/433 , A61P35/00 , C07D401/14 , C07D403/14
CPC分类号： C07D401/14 , C07D413/14 , C07D417/14
摘要： Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant, melanomas, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, leukemias, papillary thyroid carcinoma, non small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, a disease caused by c-Abl kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, or a disease caused by c-Kit kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof.
摘要翻译：本发明的化合物可用于治疗哺乳动物癌症，特别是人类癌症，包括但不限于恶性肿瘤，黑素瘤，成胶质细胞瘤，卵巢癌，胰腺癌，前列腺癌，肺癌，乳腺癌，肾癌，宫颈癌，原发性肿瘤部位转移，骨髓增殖性疾病，白血病，乳头状甲状腺癌，非小细胞肺癌，间皮瘤，嗜酸性粒细胞增多症，胃肠道间质瘤，结肠癌，以过度增殖为特征的导致失明的眼部疾病，视网膜病，类风湿性关节炎，哮喘，慢性阻塞性肺病，肥大细胞增多症，肥大细胞白血病，由c-Abl激酶引起的疾病，其致癌形式，其异常融合蛋白及其多形体，或由c-Kit激酶引起的疾病，致癌其形式，其异常融合蛋白及其多晶型物。

3. 发明申请

WO2008046003A3 KINASE INHIBITORS USEFUL FOR THE TREATMENT OF MYLEOPROLIFERATIVE DISEASES AND OTHER PROLIFERATIVE DISEASES 审中-公开
公开(公告)号：WO2008046003A3
公开(公告)日：2008-04-17
申请号：PCT/US2007/081098
申请日：2007-10-11
申请人： DECIPHERA PHARMACEUTICALS, LLC , PETILLO, Peter, A. , KAUFMAN, Michael, D. , FLYNN, Daniel, L.
发明人： PETILLO, Peter, A. , KAUFMAN, Michael, D. , FLYNN, Daniel, L.
IPC分类号： A61K31/54 , A61K39/395
摘要： The present invention is concerned with novel compounds useful in the treatment of hyperproliferative diseases and mammalian cancers, especially human cancers. The invention also pertains to methods of modulating kinase activities, pharmaceutical compositions, and methods of treating individuals, incorporating or using the compounds. The preferred compounds are active small molecules set forth in formulae Ia-Iww.

4. 发明申请

WO2010051373A1 CYCLOPROPANE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES 审中-公开
标题翻译：环丙沙星和类似物展示抗癌和抗增生活性
公开(公告)号：WO2010051373A1
公开(公告)日：2010-05-06
申请号：PCT/US2009/062575
申请日：2009-10-29
申请人： DECIPHERA PHARMACEUTICALS, LLC , FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D.
发明人： FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D.
IPC分类号： A01N43/90 , A01N55/02 , A61K31/555
CPC分类号： C07D413/04 , A61K31/555 , C07D401/04 , C07D401/14 , C07D403/04
摘要： Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including, but not limited to, malignant melanomas, solid tumors, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, hepatic cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, chronic myelogenous leukemia, leukemias, papillary thyroid carcinoma, non-small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, diabetic retinopathy, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, and diseases caused by PDGFR-α kinase, PDGFR-β kinase, c-KIT kinase, cFMS kinase, c-MET kinase, and oncogenic forms, aberrant fusion proteins and polymorphs of any of the foregoing kinases.
摘要翻译：本发明的化合物可用于治疗哺乳动物癌症，特别是人类癌症，包括但不限于恶性黑素瘤，实体瘤，成胶质细胞瘤，卵巢癌，胰腺癌，前列腺癌，肺癌，乳腺癌，肾癌，肝癌，宫颈癌，原发性肿瘤部位转移，骨髓增生性疾病，慢性骨髓性白血病，白血病，甲状腺乳头状癌，非小细胞肺癌，间皮瘤，嗜酸性粒细胞综合征，胃肠道间质瘤，结肠癌，以过度增生为特征的眼部疾病包括各种视网膜病变，糖尿病性视网膜病变，类风湿性关节炎，哮喘，慢性阻塞性肺病，肥大细胞增多症，肥大细胞白血病和由PDGFR-α激酶，PDGFR-β激酶，c-KIT激酶，cFMS激酶，c-MET引起的疾病激酶和致癌形式，异常融合蛋白和任何上述k的多态性 inases。

5. 发明申请

WO2008131276A1 KINASE INHIBITORS USEFUL FOR THE TREATMENT OF MYLEOPROLIFERATIVE DISEASES AND OTHER PROLIFERATIVE DISEASES 审中-公开
标题翻译：用于治疗单发性增生性疾病和其他增殖性疾病的激素抑制剂
公开(公告)号：WO2008131276A1
公开(公告)日：2008-10-30
申请号：PCT/US2008/060896
申请日：2008-04-18
申请人： DECIPHERA PHARMACEUTICALS, LLC , FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D.
发明人： FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D.
IPC分类号： A61K31/519 , A61K31/444 , C07D239/70 , C07D401/12
CPC分类号： C07D401/14 , C07D413/14 , C07D417/14
摘要： Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant melanomas, solid tumors, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers. breast cancers, kidney cancers, hepatic cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, chronic myelogenous leukemia, leukemias, papillary thyroid carcinoma, non-small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, diabetic retinopathy, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, a disease caused by c-Abl kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, a disease caused by c-Kit kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, a disease caused by c-Met kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, or a disease caused by a Raf kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof.
摘要翻译：本发明的化合物可用于治疗哺乳动物癌症，特别是人类癌症，包括但不限于恶性黑素瘤，实体瘤，成胶质细胞瘤，卵巢癌，胰腺癌，前列腺癌，肺癌。乳腺癌，肾癌，肝癌，宫颈癌，原发性肿瘤部位转移，骨髓增生性疾病，慢性骨髓性白血病，白血病，甲状腺乳头状癌，非小细胞肺癌，间皮瘤，嗜酸性粒细胞综合征，胃肠道间质瘤，结肠癌，特征在于过度增生导致失明的眼部疾病，包括各种视网膜病变，糖尿病性视网膜病变，类风湿性关节炎，哮喘，慢性阻塞性肺病，肥大细胞增多症，肥大细胞白血病，由c-Abl激酶引起的疾病，其致癌形式，异常融合蛋白和多晶型物由c-Kit激酶，其致癌形式，异常融合蛋白和其多态性引起的疾病，由c-Met激酶引起的疾病，其致癌形式，异常融合蛋白及其多态性，或由 Raf激酶，其致癌形式，异常融合蛋白a d多晶型。

6. 发明申请

WO2008131253A1 KINASE INHIBITORS USEFUL FOR THE TREATMENT OF MYLEOPROLIFERATIVE DISEASES AND OTHER PROLIFERATIVE DISEASES 审中-公开
标题翻译：用于治疗单发性增生性疾病和其他增殖性疾病的激素抑制剂
公开(公告)号：WO2008131253A1
公开(公告)日：2008-10-30
申请号：PCT/US2008/060867
申请日：2008-04-18
申请人： DECIPHERA PHARMACEUTICALS, LLC , FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D.
发明人： FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D.
IPC分类号： A61K31/506 , A61K31/517 , A61K31/426 , A61K31/433 , A61P35/00 , C07D401/14 , C07D403/14
CPC分类号： C07D401/14 , C07D413/14 , C07D417/14
摘要： Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant, melanomas, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, leukemias, papillary thyroid carcinoma, non small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocyctosis, mast cell leukemia, a disease caused by c-Abl kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, or a disease caused by c-Kit kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof.
摘要翻译：本发明的化合物可用于治疗哺乳动物癌症，特别是人类癌症，包括但不限于恶性，黑素瘤，成胶质细胞瘤，卵巢癌，胰腺癌，前列腺癌，肺癌，乳腺癌，肾癌，宫颈癌，转移原发性肿瘤部位，骨髓增生性疾病，白血病，甲状腺乳头状癌，非小细胞肺癌，间皮瘤，嗜酸性粒细胞综合征，胃肠道间质瘤，结肠癌，以过度增生为特征的眼部疾病导致失明，包括各种视网膜病变，类风湿关节炎，哮喘，慢性阻塞性肺疾病，肥大细胞增多症，肥大细胞白血病，由c-Abl激酶引起的疾病，其致癌形式，异常融合蛋白及其多形体，或由c-Kit激酶，其致癌形式，异常融合蛋白引起的疾病和其多晶型。

7. 发明申请

WO2008131227A1 KINASE INHIBITORS USEFUL FOR THE TREATMENT OF MYLEOPROLIFERATIVE DISEASES AND OTHER PROLIFERATIVE DISEASES 审中-公开
标题翻译：用于治疗单发性增生性疾病和其他增殖性疾病的激素抑制剂
公开(公告)号：WO2008131227A1
公开(公告)日：2008-10-30
申请号：PCT/US2008/060833
申请日：2008-04-18
申请人： DECIPHERA PHARMACEUTICALS, LLC , FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D.
发明人： FLYNN, Daniel, L. , PETILLO, Peter, A. , KAUFMAN, Michael, D.
IPC分类号： A61K31/506 , A61K31/517 , A61K31/426 , A61K31/433 , A61P35/00 , C07D401/14 , C07D403/14
CPC分类号： C07D401/14 , C07D413/14 , C07D417/14
摘要： Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant, melanomas, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, leukemias, papillary thyroid carcinoma, non small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, a disease caused by c-Abl kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, or a disease caused by c-Kit kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof.
摘要翻译：本发明的化合物可用于治疗哺乳动物癌症，特别是人类癌症，包括但不限于恶性，黑素瘤，成胶质细胞瘤，卵巢癌，胰腺癌，前列腺癌，肺癌，乳腺癌，肾癌，宫颈癌，转移原发性肿瘤部位，骨髓增生性疾病，白血病，甲状腺乳头状癌，非小细胞肺癌，间皮瘤，嗜酸性粒细胞综合征，胃肠道间质瘤，结肠癌，以过度增生为特征的眼部疾病导致失明，包括各种视网膜病变，类风湿关节炎，哮喘，慢性阻塞性肺疾病，肥大细胞增多症，肥大细胞白血病，由c-Abl激酶引起的疾病，其致癌形式，其异常融合蛋白及其多形体，或由c-Kit激酶，其致癌形式，异常融合蛋白引起的疾病和其多晶型。

8. 发明申请

WO2008034008A2 KINASE INHIBITORS USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISEASES 审中-公开
公开(公告)号：WO2008034008A2
公开(公告)日：2008-03-20
申请号：PCT/US2007/078408
申请日：2007-09-13
申请人： DECIPHERA PHARMACEUTICALS, LLC. , FLYNN, Daniel, L. , KAUFMAN, Michael, D. , PATT, William, C. , PETILLO, Peter, A.
发明人： FLYNN, Daniel, L. , KAUFMAN, Michael, D. , PATT, William, C. , PETILLO, Peter, A.
IPC分类号： A61K31/4375 , A61K31/519 , A61P1/00 , A61P11/00 , A61P17/06 , A61P19/02 , A61P35/00 , A61P37/00
CPC分类号： A61K31/4375 , A61K31/519 , C07D471/04
摘要： The present invention relates to novel kinase inhibitors and modulator compounds useful for the treatment of various diseases. More particularly, the invention is concerned with such compounds, kinase/compound adducts, methods of treating diseases, and methods of synthesis of the compounds. Preferrably, the compounds are useful for the modulation of kinase activity of Raf kinases and disease polymorphs thereof. Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant melanoma, colorectal cancer, ovarian cancer, papillary thyroid carcinoma, non small cell lung cancer, and mesothelioma. Compounds of the present invention also find utility in the treatment of rheumatoid arthritis and retinopathies including diabetic retinal neuropathy and macular degeneration.

9. 发明申请

WO2007008917A2 MODULATION OF PROTEIN FUNCTIONALITIES 审中-公开
标题翻译：蛋白质功能调节
公开(公告)号：WO2007008917A2
公开(公告)日：2007-01-18
申请号：PCT/US2006/026920
申请日：2006-07-10
申请人： DECIPHERA PHARMACEUTICALS, LLC , FLYNN, Daniel, L. , PETILLO, Peter, A.
发明人： FLYNN, Daniel, L. , PETILLO, Peter, A.
IPC分类号： C07K1/00
CPC分类号： C07K14/4702 , C12N9/1205
摘要： New methods for the rational identification of molecules capable of interacting with specific naturally occurring proteins are provided, in order to yield new pharmacologically important compounds and treatment modalities. Broadly, the method comprises the steps of identifying a switch control ligand forming a part of a particular protein of interest, and also identifying a complemental switch control pocket forming a part of the protein and which interacts with said switch control ligand. The ligand interacts in vivo with Hie pocket to regulate the conformation and biological activity of the protein such that the protein assumes a first conformation and a first biological activity, upon the ligand-pocket interaction, and assumes a second, different conformation and biological activity in the absence of the ligand-pocket interaction. Next, respective samples of said protein in the first and second conformations are provided, and these are screened against one or more candidate molecules by contacting the molecules and the samples. Thereupon, small molecules which bind with the protein at the region of the pocket maybe identified. Novel protein-modulator adducts and methods of altering protein activity are also provided.
摘要翻译：提供了用于合理鉴定能够与特定天然存在的蛋白质相互作用的分子的新方法，以产生新的药理学上重要的化合物和治疗方式。广泛地，该方法包括鉴定形成特定目的蛋白质的一部分的开关控制配体，以及鉴定形成蛋白质的一部分并与所述开关对照配体相互作用的互补开关控制袋。配体与Hie口袋相互作用以调节蛋白质的构象和生物活性，使得蛋白质在配体 - 口袋相互作用时呈现第一构象和第一生物学活性，并呈现第二种不同的构象和生物学活性没有配体 - 口袋相互作用。接下来，提供第一和第二构象中的所述蛋白质的各个样品，并且通过使分子和样品接触将它们与一种或多种候选分子进行筛选。因此，可以鉴定在口袋区域与蛋白质结合的小分子。还提供了新的蛋白质调节剂加合物和改变蛋白质活性的方法。

10. 发明申请

WO2005024755A2 MEDICAMENTS FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS OR DIABETES 审中-公开
标题翻译：治疗神经损伤性疾病或糖尿病的药物
公开(公告)号：WO2005024755A2
公开(公告)日：2005-03-17
申请号：PCT/US2004/011922
申请日：2004-04-15
申请人： DECIPHERA PHARMACEUTICALS, LLC. , FLYNN, Daniel, L. , PETILLO, Peter, A.
发明人： FLYNN, Daniel, L. , PETILLO, Peter, A.
IPC分类号： G09B1/00
CPC分类号： G09B1/00 , G09B19/02
摘要： Novel compounds and methods are provided for the treatment of human neurodegenerative diseases, diabetes, mental conditions, inflammatory diseases, strokes and cancers. The compounds are small molecule inhibitors of glycogen synthease kinase-3 proteins. GSK-3 kinase protein/small molecule inhibitor compound adducts are also described wherein the compounds are bonded to the kinase proteins at the region of a protein switch control pocket in order to alter the conformation and/or protein activity of the kinases.
摘要翻译：提供新的化合物和方法用于治疗人神经变性疾病，糖尿病，精神状况，炎性疾病，中风和癌症。这些化合物是糖原合成酶激酶-3蛋白的小分子抑制剂。还描述了GSK-3激酶蛋白/小分子抑制剂化合物加合物，其中化合物与蛋白质切换对照口袋区域的激酶蛋白结合，以改变激酶的构象和/或蛋白质活性。

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