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    • 4. 发明申请
    • COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR
    • 化合物及其调节方法及其适应症
    • WO2011079133A3
    • 2011-11-17
    • PCT/US2010061601
    • 2010-12-21
    • PLEXXIKON INCIBRAHIM PRABHA NWU GUOXIANLIN JACKSPEVAK WAYNECHO HANNAEWING TODDZHANG CHAO
    • IBRAHIM PRABHA NWU GUOXIANLIN JACKSPEVAK WAYNECHO HANNAEWING TODDZHANG CHAO
    • C07D471/04A61K31/437A61P35/00
    • C07D471/04A61K31/437A61K31/497A61K31/498A61K31/506A61K31/519C07D519/00
    • 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 each of B-Raf, B-Raf V600E and c-Raf-1 protein kinase. In certain aspects and embodiments, the described compounds are active in inhibiting proliferation of a Ras mutant cell line. Also described are methods of use thereof to treat diseases and conditions, including melanoma, glioma, glioblastoma, pilocytic astrocytoma, liver cancer, biliary tract cancer, cholangiocarcinoma, colorectal cancer, lung cancer, bladder cancer, gallbladder cancer, breast cancer, pancreatic cancer, thyroid cancer, kidney cancer, ovarian cancer, adrenocortical cancer, prostate cancer, gastrointestinal stromal tumors, medullary thyroid cancer, tumor angiogenesis, acute myeloid leukemia, chronic myelomonocytic leukemia, childhood acute lymphoblastic leukemia, plasma cell leukemia, and multiple myeloma.
    • 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B-Raf,B-Raf V600E和c-Raf-1蛋白激酶中的每一个上都是活性的。 在某些方面和实施方案中,所述化合物在抑制Ras突变细胞系的增殖中是有活性的。 还描述了其用于治疗疾病和病症的方法,包括黑素瘤,神经胶质瘤,成胶质细胞瘤,纤维细胞性星形细胞瘤,肝癌,胆道癌,胆管癌,结肠直肠癌,肺癌,膀胱癌,胆囊癌,乳腺癌,胰腺癌, 甲状腺癌,肾癌,卵巢癌,肾上腺皮质癌,前列腺癌,胃肠道间质瘤,甲状腺髓样癌,肿瘤血管生成,急性骨髓性白血病,慢性骨髓单核细胞白血病,儿童急性淋巴细胞性白血病,浆细胞白血病和多发性骨髓瘤。
    • 10. 发明申请
    • COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR
    • 化合物及其调节方法及其适应症
    • WO2011133637A3
    • 2012-02-09
    • PCT/US2011033192
    • 2011-04-20
    • PLEXXIKON INCZHANG JIAZHONGIBRAHIM PRABHA NSPEVAK WAYNETSAI JAMESEWING TODDZHANG YINGZHANG CHAO
    • ZHANG JIAZHONGIBRAHIM PRABHA NSPEVAK WAYNETSAI JAMESEWING TODDZHANG YINGZHANG CHAO
    • C07D471/04A61K31/437A61K31/506A61K31/519A61P19/00A61P25/00A61P35/00C07D487/04
    • C07D487/04C07D471/04
    • 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 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.
    • 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,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,自体移植骨髓造血,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。