CAS: 717906-29-1; N-Methyl-N-(2-(((2-((2-Oxoindolin-5-yl)Amino)-5-(Trifluoromethyl)Pyrimidin-4-yl)Amino)Methyl)Phenyl)Methanesulfonamide

上下游产品

5-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-2,3-dihydro-1H-indol-2-one N-[2-(aminomethyl)phenyl]-N-methylmethanesulfonamide

5-{[4-Chloro-5-(Trifluoromethyl)Pyrimidin-2-Yl]Amino}-2,3-Dihydro-1H-Indol-2-One,N-[2-(氨基甲基)苯基]-N-甲基甲烷磺酰胺置于sodium Carbonate体系中,用 N,N-二甲基甲酰胺 作为反应溶剂,化学反应生成 N-甲基-N-[2-[[[2-[(2-氧代-2,3-二氢-1H-吲哚-5-基)氨基]-5-三氟甲基嘧啶-4-基]氨基]甲基]苯基]甲磺酰胺
参考文献:Trifluoromethylpyrimidine-Based Inhibitors Of Proline-Rich Tyrosine Kinase 2 (Pyk2): Structure-activity Relationships And Strategies For The Elimination Of Reactive Metabolite Formation
标题:Trifluoromethylpyrimidine-Based Inhibitors Of Proline-Rich Tyrosine Kinase 2 (Pyk2): Structure-activity Relationships And Strategies For The Elimination Of Reactive Metabolite Formation
摘要:The Synthesis And Sar For A Series Of Diaminopyrimidines As Pyk2 Inhibitors Are Described. Using A Combination Of Library And Traditional Medicinal Chemistry Techniques,A Fak-Selective Chemical Series Was Transformed Into Compounds Possessing Good Pyk2 Potency And 10-To 20-Fold Selectivity Against Fak. Subsequent Studies Found That The Majority Of The Compounds Were Positive In A Reactive Metabolite Assay,An Indicator For Potential Toxicological Liabilities. Based On The Proposed Mechanism For Bioactivation,As Well As A Combination Of Structure-Based Drug Design And Traditional Medicinal Chemistry Techniques,A Follow-Up Series Of Pyk2 Inhibitors Was Identified That Maintained Pyk2 Potency,Fak Selectivity And Hlm Stability,Yet Were Negative In The Rm Assay.
DOI:10.1016/j.Bmcl.2008.10.030

专利信息

专利号:US-11285169-B2
优先权日:2013-03-13
标题 :Methods for modulating chemotherapeutic cytotoxicity
发明人：ROBERTS DAVID D; SOTO PANTOJA DAVID R
权利人:US HEALTH
摘要:Methods of reducing cytotoxicity of a chemotherapeutic agent to non-cancer cells by administering to a subject with cancer an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent, such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are provided. Example disclosed methods reduce cardiotoxicity. In one example, the methods include administering to a subject with cancer an effective amount of a CD47 antisense morpholino oligonucleotide and an anthracycline such as doxorubicin. Methods of increasing cytotoxicity of a chemotherapeutic agent in cancer cells by administering to a subject with a tumor an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are also provided. In some embodiments, the inhibitor of CD47 signaling is administered to the subject before, during, or after the administration of the DNA damaging agent.