CAS: 741713-40-6; (4-Amino-2-((1-(Methylsulfonyl)Piperidin-4-yl)Amino)Pyrimidin-5-yl)(2,3-Difluoro-6-Methoxyphenyl)Methanone

上下游产品

CAS号402927-97-3 1-甲砜基-4-氨基哌啶 | CAS号741713-37-1 (4-氨基-2-(乙硫基)嘧啶... | CAS号741712-36-7 4-氨基-2-(乙基硫代)-N... | CAS号287953-38-2 1-MS-4-B°C-氨基哌啶 | CAS号89853-87-2 2-乙基巯基-4-氨基嘧啶-5-羧酸 | CAS号73874-95-0 4-B°C-氨基哌啶

📜1-Ms-4-Boc-氨基哌啶置于间氯过氧苯甲酸,三氟乙酸体系中,用 二氯甲烷,氯仿 作为反应溶剂,化学反应 6.0H,反应生成 [4-氨基-2-[(1-甲磺酰基哌啶-4-基)氨基]嘧啶-5-基](2,3-二氟-6-甲氧基苯基)甲酮
参考文献:Discovery Of [4-Amino-2-(1-Methanesulfonylpiperidin-4-Ylamino)Pyrimidin-5-Yl](2,3-Difluoro-6-Methoxyphenyl)Methanone (R547),A Potent And Selective Cyclin-Dependent Kinase Inhibitor With Significant In Vivo Antitumor Activity
标题:Discovery Of [4-Amino-2-(1-Methanesulfonylpiperidin-4-Ylamino)Pyrimidin-5-Yl](2,3-Difluoro-6-Methoxyphenyl)Methanone (R547),A Potent And Selective Cyclin-Dependent Kinase Inhibitor With Significant In Vivo Antitumor Activity
摘要:The Cyclin-Dependent Kinases (Cdks) And Their Cyclin Partners Are Key Regulators Of The Cell Cycle. Since Deregulation Of Cdks Is Found With High Frequency In Many Human Cancer Cells,Pharmacological Inhibition Of Cdks With Small Molecules Has The Potential To Provide An Effective Strategy For The Treatment Of Cancer. The 2,4-Diamino-5-Ketopyrimidines 6 Reported Here Represent A Novel Class Of Potent And Atp-Competitive Inhibitors That Selectively Target The Cyclin-Dependent Kinase Family. This Diaminopyrimidine Core With A Substituted 4-Piperidine Moiety On The C2-Amino Position And 2-Methoxybenzoyl At The C5 Position Has Been Identified As The Critical Structure Responsible For The Cdk Inhibitory Activity. Further Optimization Has Led To A Good Number Of Analogues That Show Potent Inhibitory Activities Against Cdk1,Cdk2,And Cdk4 But Are Inactive Against A Large Panel Of Serine/threonine And Tyrosine Kinases (K-I > 10 Am). As One Of These Representative Analogues,Compound 39 (R547) Has The Best Cdk Inhibitory Activities (K-I = 0.001,0.003,And 0.001 Am For Cdk1,Cdk2,And Cdk4,Respectively) And Excellent In Vitro Cellular Potency,Inhibiting The Growth Of Various Human Tumor Cell Lines Including An Hct116 Cell Line (Ic50 = 0.08 Mu M). An X-Ray Crystal Structure Of 39 Bound To Cdk2 Has Been Determined In This Study,Revealing A Binding Mode That Is Consistent With Our Sar. Compound 39 Demonstrates Significant In Vivo Efficacy In The Hct116 Human Colorectal Tumor Xenograft Model In Nude Mice With Up To 95% Tumor Growth Inhibition. On The Basis Of Its Superior Overall Profile,39 Was Chosen For Further Evaluation And Has Progressed Into Phase I Clinical Trial For The Treatment Of Cancer.
DOI:10.1021/jm0606138

专利信息

专利号:US-7615634-B2
优先权日:2003-02-10
标题:4-aminopyrimidine-5-one derivatives
发明人：BARTKOVITZ DAVID JOSEPH; CHU XIN-JIE; DING QINGJIE; JIANG NAN; LOVEY ALLEN JOHN; MOLITERNI JOHN ANTHONY; MULLIN JR JOHN GUILFOYLE; VU BINH THANH; WOVKULICH PETER MICHAEL
权利人:HOFFMANN LA ROCHE
摘要:Novel intermediate compounds are disclosed. These compounds are useful in the synthesis of 4-aminopyrimidine-5-one derivatives that inhibit cyclin-dependent kinases, in particular cyclin-dependent kinase 4 (Cdk4). The 4-aminopyrimidine-5-one derivatives and their pharmaceutically acceptable salts have antiproliferative activity and are useful in the treatment or control of cancer, in particular solid tumors.

专利号:US-8816095-B2
优先权日:2008-08-15
标题:Na channels, disease, and related assays and compositions
发明人：BROWN MILTON L; GRINDROD SCOTT; WALLS THOMAS H; HANSEN TODD; SUY SIMENG; PAIGE MIKELL A
权利人:BROWN MILTON L; GRINDROD SCOTT; WALLS THOMAS H; HANSEN TODD; SUY SIMENG; PAIGE MIKELL A; UNIV GEORGETOWN
摘要:Disclosed are molecules and their synthesis, for use in blocking gated ion channels such as voltage-gated sodium channels (VGSCs) and prostate voltage sodium channels (PVSCs). These inhibitors have superior blocking efficacy, for instance in displacing the radioligand [ 3 H]-Batrachotoxin-B ([ 3 H]-BTX-B) that binds to site 2 of a VGSC. The molecules of the invention comprise a moiety which increases the binding affinity of molecules for the protein binding site in prostate cancer cells (PCs), and which is also fluorescent. In one embodiment the invention molecules are an inhibition system that can be used to target over-abundant or hyperactive VGSCs selectively in pain, epilepsy or prostate cancer, inhibiting the proliferation of PCs. The fluorescent moiety also facilitates screening, tracking, and pharmacodynamic studies of the drug in a biological system both in vitro and in vivo.