CAS: 89-38-3; Pteropterin

📜芴甲氧羰基-L-谷氨酸 1-叔丁酯置于哌啶,N-甲基吗啉,盐酸,4-二甲氨基吡啶,Sodium Hydroxide,Kh Polyamide Resin,N,N'-二环己基碳二亚胺,三氟乙酸体系中,用 四氢呋喃,二氯甲烷 作为反应溶剂,化学反应 18.25H,反应生成 蝶酰三谷氨
参考文献:Folate Analogs. 33. Synthesis Of Folate And Antifolate Poly-.Gamma.-Glutamates By [(9-Fluorenylmethoxy)Oxy]Carbonyl Chemistry And Biological Evaluation Of Certain Methotrexate Polyglutamate Polylysine Conjugates As Inhibitors Of The Growth Of H35 Hepatoma Cells
标题:Folate Analogs. 33. Synthesis Of Folate And Antifolate Poly-.Gamma.-Glutamates By [(9-Fluorenylmethoxy)Oxy]Carbonyl Chemistry And Biological Evaluation Of Certain Methotrexate Polyglutamate Polylysine Conjugates As Inhibitors Of The Growth Of H35 Hepatoma Cells
摘要:Representative Examples Of Folate And Antifolate Poly-Gamma-Glutamyl Metabolites Were Synthesized Via The [(9-Fluorenylmethoxy)Oxy]Carbonyl (Fmoc) Chemistry Using The Kh Polyamide Resin. Polyglutamate Yields Were Consistently Better In All Cases Compared To The Previous Merrifield Method,And The Crude Products Were Obtained In Greater Than 85% Purity. The Symmetrical Anhydride (7) Derived From Alpha-Tert-Butyl N-Fmoc-L-Glutamate (6) Was Used For The Initial Coupling Of The First Glutamate Residue To The Kh Resin And Also For Subsequent Chain Elongation. The Alpha-Tert-Butyl Protective Groups Were Not Labile Under The Conditions Used For The Cleavage Of The Finished Peptide From The Resin. A Series Of Poly-Gamma-Glutamyl Metabolites Of Methotrexate (Mtx) With A Chain Length Ranging From Two To Five Glutamyl Residues Were Synthesized And Coupled With Poly(L-Lysine) Having An Average Molecular Weight Of 27,000 And 52,000. Each Conjugate Was Tested For Its Ability To Inhibit The Growth Of Wild Type (H35) And Mtx Transport Resistant (H35R) Strains Of Hepatoma Cells In Culture,The Latter Having A 100-Fold Reduced Sensitivity To Mtx. 4-Amino-4-Deoxy-N10-Methylpteroylglutamyl-Gamma-Glutamylpoly (L-Lysine) Conjugate [mtx(G2)-Poly-L-Lys-52000] And Mtx(G4)-Poly-L-Lys-52000 Were Among The Most Active (I50 = 8.0 And 10 Nm Against H35 Cells) Mtx-Polylysines Synthesized To Date,And They Were Somewhat More Inhibitory To The Transport Resistant Cells. Mtx(G5)-Poly-L-Lys-52000 Was Approximately 1000 Times More Effective Than Mtx(G5)-Poly-D-Lys-52000 In Inhibiting The Growth Of H35R Hepatoma Cells In Culture,Indicating That Internal Cleavage Of The Gamma-Glutamate Chain Of The Conjugate With Subsequent Release Of Mtx Or Shorter Chain Polyglutamates Of Mtx Is Unlikely To Be An Important Determinant Of Mtx-Polyglutamate Polylysine Cytotoxicity. The Results Indicate That Mtx-Polyglutamate Poly(L-Lysine) Conjugates Are Taken Up By The Cells Independently Of Mtx And Probably Via Endocytosis.
DOI:10.1021/jm00164A038

专利信息

专利号:US-10925977-B2
优先权日:2006-10-05
标 题 :Efficient synthesis of chelators for nuclear imaging and radiotherapy: compositions and applications
发明人：YANG DAVID J; YU DONGFANG; THOMPSON ANDREW S
权利人:YANG DAVID J; YU DONGFANG; THOMPSON ANDREW S; CEIL POINT LLC; UNIV TEXAS
摘要:Novel methods of synthesis of chelator-targeting ligand conjugates, compositions comprising such conjugates, and therapeutic and diagnostic applications of such conjugates are disclosed. The compositions include chelator-targeting ligand conjugates optionally chelated to one or more metal ions. Methods of synthesizing these compositions in high purity are also presented. Also disclosed are methods of imaging, treating and diagnosing disease in a subject using these novel compositions, such as methods of imaging a tumor within a subject and methods of diagnosing myocardial ischemia.

专利号:US-12391691-B2
优先权日:2018-11-16
标题:Synthesis of key intermediate of KRAS G12C inhibitor compound
发明人：PARSONS ANDREW THOMAS; COCHRAN BRIAN MCNEIL; POWAZINIK IV WILLIAM; CAPORINI MARC ANTHONY
权利人:AMGEN INC
摘要:The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure n nuseful for the synthesis of compounds that target KRAS G12C mutations, such as

专利号:US-2025206736-A1
优先权日:2019-11-14
标题 :Synthesis of kras g12c inhibitor compound
发明人：CORBETT MICHAEL THOMAS; CAILLE SEBASTIEN
权利人:AMGEN INC
摘要:The present disclosure relates to an improved, efficient, scalable process to prepare intermediate compounds, such as 2-isopropyl-4-methylpyridin-3-amine, useful for the synthesis of compounds, such as Compound 9, for the treatment of KRAS G12C mutated cancers.

专利号:WO-2017100796-A1
优先权日:2015-12-11
标 题 :Modulation of globoseries glycosphingolipid synthesis and cancer biomarkers
发明人：WONG CHI-HUEY; HSU TSUI-LING; WU CHUNG-YI; CHEUNG SARAH K C; CHUANG PO-KAI
权利人:SINACA ACAD; WONG CHI-HUEY; HSU TSUI-LING
摘要:The present disclosure relates to methods and compositions which can modulate the globoseries glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globoseries glycosphingolipid SSEA-3/SSEA-4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta- 4GalNAcT-I; or beta-3GalT-V enzymes in the globoseries synthetic pathway. Additionally, the present disclosure is also directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA-3/SSEA-4/GLOBO H associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globoseries glycosphingolipid synthesis. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions. Furthermore, the instant disclosure also relates to cancer stem cell biomarkers for disgnostic and therapeutic uses.

专利号:US-2017283878-A1
优先权日:2015-12-11
标题:Modulation of globoseries glycosphingolipid synthesis and cancer biomarkers
发明人：WONG CHI-HUEY; WU CHUNG-YI; CHEUNG SARAH K C; CHUANG PO-KAI; HSU TSUI-LING
权利人:ACADEMIA SINICA
摘要:The present disclosure relates to methods and compositions which can modulate the globoseries glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globoseries glycosphingolipid SSEA-3/SSEA-4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globoseries synthetic pathway. Additionally, the present disclosure is also directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA-3/SSEA-4/GLOBO H associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globoseries glycosphingolipid synthesis. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions. Furthermore, the instant disclosure also relates to cancer stem cell biomarkers for diagnostic and therapeutic uses.

专利号:US-10342858-B2
优先权日:2015-01-24
标题 :Glycan conjugates and methods of use thereof
发明人：WONG CHI-HUEY; WU CHUNG-YI
权利人:ACADEMIA SINICA
摘要:The present disclosure is directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA3/SSEA4/GloboH associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globo-series glycosphingolipid synthesis. The present disclosure relates to methods and compositions which can modulate the globo-series glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globo-series glycosphingolipid SSEA3/SSEA4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globo-series synthetic pathway. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions.