CAS: 1454846-35-5; (R)-26-Amino-55-Fluoro-11,4,7-Trimethyl-6-Oxo-11H-3-Oxa-7-Aza-2(3,5)-Pyridina-1(4,3)-Pyrazola-5(1,2)-Benzenacyclooctaphane-15-Carbonitrile

上下游产品

((4-bromo-5-cyano-1-methyl-1H-pyrazol-3-yl)methyl)(methyl)carbamic acid tert-butyl ester 1-(5-fluoro-2-iodophenyl)ethan-1-one (S)-1-(5-fluoro-2-iodophenyl)-ethan-1-ol 2-amino-3-hydroxypyridine

2-氨基-3-羟基吡啶置于盐酸,(1,1'-Bis(Diphenylphosphino)Ferrocene)Palladium(II) Dichloride,N-溴代丁二酰亚胺(Nbs),Catacxium A,Palladium Diacetate,Caesium Carbonate,三乙胺,N,N-二异丙基乙胺,Cesium Fluoride,联硼酸频那醇酯,N-[(Dimethylamino)-3-Oxo-1H-1,2,3-Triazolo[4,5-B]Pyridin-1-Yl-Methylene]-N-Methylmethanaminium Hexafluorophosphate,Sodium Hydroxide体系中,用 四氢呋喃,2-甲基四氢呋喃,1,4-二氧六环,甲醇,水,N,N-二甲基甲酰胺,丙酮,甲苯,乙腈 用作溶剂,100.0 °C,700.01 Kpa 条件下,反应 50.75H,反应生成劳拉替尼
参考文献:发现(10 R)-7-氨基-12-氟-2,10,16-三甲基-15-氧代-10,15,16,17-四氢-2H-8,4-(甲基)吡唑并[4,3-H ] [2,5,11]-苯并恶二氮杂环十四烷-3-甲腈(pf-06463922),具有临床前脑暴露和广谱性的间变性淋巴瘤激酶(alk)和c-Ros癌基因1(ros1)的大环抑制剂抗alk突变的效力
标题:发现(10 R)-7-氨基-12-氟-2,10,16-三甲基-15-氧代-10,15,16,17-四氢-2H-8,4-(甲基)吡唑并[4,3-H ] [2,5,11]-苯并恶二氮杂环十四烷-3-甲腈(pf-06463922),具有临床前脑暴露和广谱性的间变性淋巴瘤激酶(alk)和c-Ros癌基因1(ros1)的大环抑制剂抗alk突变的效力
摘要:尽管克唑替尼在间变性淋巴瘤激酶(alk)阳性的非小细胞肺癌患者中显示出强大的疗效,但最终仍会在治疗过程中发展.抗药性患者样品显示alk激酶结构域中存在多种点突变,包括l1196M网守突变.另外,一些患者由于脑癌转移而进展.使用基于结构的药物设计,亲脂性效率和基于物理性质的优化,制备了具有强吸收,分布,代谢和排泄(adme),P-糖蛋白1介导外排倾向低的高效大环alk抑制剂,以及非常好的被动渗透性.这些结构异常的大环抑制剂对野生型alk和临床报道的alk激酶结构域突变有效.克服了重大的合成挑战,利用新颖的转化方法使这些大环化合物能够用于药物发现范例中.这项工作导致发现8K(pf-06463922),结合了广谱效能,中枢神经系统adme和高度的激酶选择性.
Doi:10.1021/jm500261Q

专利信息

专利号:WO-2024199465-A1
优先权日:2023-03-30
标 题:Unnatural amino acid in cellulo synthesis for site-specific protein modification
发明人：CHAN MICHAEL KENNETH; LEE MARIANNE; CHENG JIAHUI
权利人:UNIV HONG KONG CHINESE
摘要:Provided are genetically modified host cells containing engineered enzymes that support the synthesis of unnatural amino acids, such as D-Cys-ε-Lys, and the incorporation of such unnatural amino acids into a newly synthesized protein. These cells are therefore capable of in vivo or in cellulo synthesis of a protein containing one or more unnatural amino acids strategically placed at pre-determined locations for site-specific modification of the protein. Also provided are the corresponding methods for in vivo synthesis of modified proteins as well as the modified proteins produced by the method.

专利号:US-2025289827-A1
优先权日:2022-12-02
标 题:Morphic forms of a mutant braf degrader and methods of manufacture thereof
发明人：YU ROBERT T; HE MINSHENG; SCHNADERBECK MATTHEW J; KREGER BRIDGET; POLLOCK ROY MACFARLANE; JIANG SIYI; LI MEIQI; CHEN BOLU; LU JIANNAN
权利人:C4 THERAPEUTICS INC
摘要:Advantageous isolated morphic forms of (3R)-3-[6-[2-cyano-3-[[ethyl(methyl)sulfamoyl]amino]-6-fluorophenoxy]-4-oxoquinazolin-3-yl]-8-[2-[1-[3-(2,4-dioxo-1,3-diazinan-1-yl)-5-fluoro-1-methylindazol-6-yl]-4-hydroxypiperidin-4-yl]acetyl]-1-oxa-8-azaspiro[4.5]decane (Compound 1), which is a mutant BRAF degrader, and methods to prepare Compound 1 morphic forms for therapeutic applications are provided in the invention. The invention also provides improved methods for the synthesis of Compound 1, new pharmaceutical compositions comprising Compound 1, and new uses of Compound 1.

专利号:US-12390420-B1
优先权日:2024-10-22
标题 :Compositions for targeted delivery of therapeutic agents and methods for the synthesis and use thereof
发明人：EGUCHI MASAKATSU
权利人:BRYET US INC
摘要:The present disclosure provides compositions and methods for delivering therapeutic agents to particular tissues or cells in a subject. The composition disclosed herein combines unique properties of porous micro- or nano-particles with host-guest chemistry provided by functionalized silicon particle, offering a versatile approach to addressing the challenges associated with delivering therapeutic agents to target tissues or sites within the body. The present disclosure also provides a method for synthesizing a composition capable of delivering therapeutic agents to particular tissues or cells in a subject.

专利号:CN-113336703-B
优先权日:2021-05-17
标 题:Synthesis of 1,3,4,5-tetrasubstituted 1H-pyrazole derivatives

专利号:US-2024208898-A1
优先权日:2021-03-25
标 题 :Enamine n-oxides: synthesis and application to hypoxia-responsive prodrugs and imaging agents
发明人：KIM JUSTIN; KANG DAHYE; CHEUNG SHELDON T
权利人:DANA FARBER CANCER INST INC
摘要:Disclosed are compounds and pharmaceutically acceptable salts and stereoisomers thereof that are suitable for diagnosis and the treatment of diseases and disorders characterized by, associate with or which exhibit tissue hypoxia, such as, for example, solid tumors. Also disclosed are pharmaceutical compositions containing same, and methods of making and using the compounds.

专利号:WO-2025137620-A1
优先权日:2023-12-21
标题:Methods for high quality and high accuracy methylation sequencing
发明人：KENNEDY ANDREW
权利人:GUARDANT HEALTH INC
摘要:Provided herein are methods and compositions for calibrating one or more base calling metrics in a sequencing by synthesis reaction, and for calling at least a portion of nucleobases in a converted region of a DNA molecule using the one or more calibrated base calling metrics. Provided herein are also methods for determining the likelihood that a subject has a disease or condition, such as cancer.