网站主页>>>数据中心>>>工艺路线数据>>>Pelitrexol CAS# 446022-33-9 N-((5-(2-((6S)-2-氨基-1,4,5,6,7,8-六氢-4-氧代吡啶并[2,3-D]嘧啶-6-基)乙基)-4-甲基-2-噻吩)甲酰基)-L-谷氨酸
Pelitrexol CAS# 446022-33-9 N-((5-(2-((6S)-2-氨基-1,4,5,6,7,8-六氢-4-氧代吡啶并[2,3-D]嘧啶-6-基)乙基)-4-甲基-2-噻吩)甲酰基)-L-谷氨酸
Pelitrexol (AG2034) is a potent antifolate thymidylate synthase (TS) inhibitor with demonstrated antitumor activity in vitro and in vivo. In enzyme and cell-based assays, pelitrexol inhibits TS with low-nanomolar potency (Ki/IC50 typically ~1–5 nM) and suppresses proliferation of a broad range of human tumor cell lines, including colon, lung, breast, and ovarian cancer cells, often with sub-micromolar GI50 values. In murine xenograft models, pelitrexol produced significant tumor growth inhibition and, in some models, tumor regressions at tolerable doses, particularly in TS-dependent tumors; antitumor effects correlated with sustained TS inhibition and depletion of dTMP pools. Activity was schedule-dependent and enhanced under conditions favoring intracellular polyglutamation, supporting its mechanism as a classical cytotoxic antifolate.
📌 参考资料/链接：
1.1Reagents:Sulfuric acid;18 h, reflux; reflux → rt1.2Reagents:Sodium bicarbonate;pH 82.1Reagents:TriethylamineCatalysts:Cuprous iodide,Tetrakis(triphenylphosphine)palladiumSolvents:Acetonitrile;18 h, rt → 82 °C3.1Reagents:HydrogenCatalysts:PalladiumSolvents:Ethanol;10 d, 65 °C4.1Reagents:Lithium hydroxideSolvents:Tetrahydrofuran,Water;19 h, rt → 45 °C4.2Reagents:Hydrochloric acidSolvents:Water;pH 15.1Reagents:Potassium carbonateSolvents:Dimethylformamide;rt → 15 °C; overnight, 15 °C → rt6.1Reagents:Dipyridinium dichromateSolvents:Dimethylformamide;23 - 24 °C; overnight, 24 °C → rt6.2Reagents:Water6.3Reagents:Hydrochloric acidSolvents:Water;pH 3 - 47.1Reagents:TriethylamineSolvents:tert-Butyl methyl ether;rt → -16 °C7.2Reagents:Pivaloyl chloride;-16 °C → rt7.3Reagents:ButyllithiumSolvents:Tetrahydrofuran,Hexane;rt; 1 h, rt → -70 °C7.41 h, -70 °C7.5Reagents:Potassium bisulfateSolvents:Water8.1Reagents:Titanium tetrachlorideSolvents:Dichloromethane;1.25 h, 3 - 7 °C; 1 h, 3 - 7 °C8.2Reagents:Diisopropylethylamine;3 - 7 °C; 1 h, 3 - 7 °C; 7 °C → -70 °C8.3Solvents:Dichloromethane;30 min, -70 °C8.4Reagents:Titanium tetrachlorideSolvents:Dichloromethane;1.5 h, -70 °C; 1 h, -70 °C; 16 h, 4 °C8.5Reagents:Ammonium chlorideSolvents:Water8.1Reagents:Titanium tetrachlorideSolvents:Dichloromethane;1.25 h, 3 - 7 °C; 1 h, 3 - 7 °C8.2Reagents:Diisopropylethylamine;3 - 7 °C; 1 h, 3 - 7 °C; 7 °C → -70 °C8.3Solvents:Dichloromethane;30 min, -70 °C8.4Reagents:Titanium tetrachlorideSolvents:Dichloromethane;1.5 h, -70 °C; 1 h, -70 °C; 16 h, 4 °C8.5Reagents:Ammonium chlorideSolvents:Water9.1Reagents:Lithium borohydrideSolvents:Tetrahydrofuran,Water;rt; 2.5 h, rt9.2Reagents:Hydrochloric acidSolvents:Water10.1Reagents:TriethylamineSolvents:Dichloromethane;rt → -10.3 °C10.2-10.3 °C; 2.25 h, -10.3 °C10.3Reagents:Hydrochloric acidSolvents:Water11.1Reagents:Sodium hydride,Sodium iodideSolvents:Tetrahydrofuran;62 °C11.2Reagents:Sodium bicarbonateSolvents:tert-Butyl methyl ether,Water12.1Reagents:Hydrogen bromideSolvents:Acetic acid;15 h, rt12.2Solvents:Water;pH 8 - 9; pH 113.1Reagents:Lawesson's reagentSolvents:Tetrahydrofuran;21.5 h, 35 °C13.2Reagents:Sodium chlorideSolvents:Dichloromethane,Water14.1110 °C14.2Reagents:Hydrochloric acidSolvents:Water;pH 5 - 615.1Reagents:Triethylamine,2-Chloro-4,6-dimethoxy-1,3,5-triazineSolvents:Dimethylformamide;1.5 h, rt15.224 h, rt16.1Reagents:Trifluoroacetic acidSolvents:Dichloromethane;10 - 16 h, 0 °C
1.1Reagents:Sulfuric acid;18 h, reflux; reflux → rt1.2Reagents:Sodium bicarbonate;pH 82.1Reagents:TriethylamineCatalysts:Cuprous iodide,Tetrakis(triphenylphosphine)palladiumSolvents:Acetonitrile;18 h, rt → 82 °C3.1Reagents:HydrogenCatalysts:PalladiumSolvents:Ethanol;10 d, 65 °C4.1Reagents:Lithium hydroxideSolvents:Tetrahydrofuran,Water;19 h, rt → 45 °C4.2Reagents:Hydrochloric acidSolvents:Water;pH 15.1Reagents:Potassium carbonateSolvents:Dimethylformamide;rt → 15 °C; overnight, 15 °C → rt6.1Reagents:Dipyridinium dichromateSolvents:Dimethylformamide;23 - 24 °C; overnight, 24 °C → rt6.2Reagents:Water6.3Reagents:Hydrochloric acidSolvents:Water;pH 3 - 47.1Reagents:TriethylamineSolvents:tert-Butyl methyl ether;rt → -16 °C7.2Reagents:Pivaloyl chloride;-16 °C → rt7.3Reagents:ButyllithiumSolvents:Tetrahydrofuran,Hexane;rt; 1 h, rt → -70 °C7.41 h, -70 °C7.5Reagents:Potassium bisulfateSolvents:Water8.1Reagents:Titanium tetrachlorideSolvents:Dichloromethane;1.25 h, 3 - 7 °C; 1 h, 3 - 7 °C8.2Reagents:Diisopropylethylamine;3 - 7 °C; 1 h, 3 - 7 °C; 7 °C → -70 °C8.3Solvents:Dichloromethane;30 min, -70 °C8.4Reagents:Titanium tetrachlorideSolvents:Dichloromethane;1.5 h, -70 °C; 1 h, -70 °C; 16 h, 4 °C8.5Reagents:Ammonium chlorideSolvents:Water8.1Reagents:Titanium tetrachlorideSolvents:Dichloromethane;1.25 h, 3 - 7 °C; 1 h, 3 - 7 °C8.2Reagents:Diisopropylethylamine;3 - 7 °C; 1 h, 3 - 7 °C; 7 °C → -70 °C8.3Solvents:Dichloromethane;30 min, -70 °C8.4Reagents:Titanium tetrachlorideSolvents:Dichloromethane;1.5 h, -70 °C; 1 h, -70 °C; 16 h, 4 °C8.5Reagents:Ammonium chlorideSolvents:Water9.1Reagents:Lithium borohydrideSolvents:Tetrahydrofuran,Water;rt; 2.5 h, rt9.2Reagents:Hydrochloric acidSolvents:Water10.1Reagents:TriethylamineSolvents:Dichloromethane;rt → -10.3 °C10.2-10.3 °C; 2.25 h, -10.3 °C10.3Reagents:Hydrochloric acidSolvents:Water11.1Reagents:Sodium hydride,Sodium iodideSolvents:Tetrahydrofuran;62 °C11.2Reagents:Sodium bicarbonateSolvents:tert-Butyl methyl ether,Water12.1Reagents:Hydrogen bromideSolvents:Acetic acid;15 h, rt12.2Solvents:Water;pH 8 - 9; pH 113.1Reagents:Lawesson's reagentSolvents:Tetrahydrofuran;21.5 h, 35 °C13.2Reagents:Sodium chlorideSolvents:Dichloromethane,Water14.1110 °C14.2Reagents:Hydrochloric acidSolvents:Water;pH 5 - 615.1Reagents:Triethylamine,2-Chloro-4,6-dimethoxy-1,3,5-triazineSolvents:Dimethylformamide;1.5 h, rt15.224 h, rt16.1Reagents:Trifluoroacetic acidSolvents:Dichloromethane;10 - 16 h, 0 °C
📄 详细内容
CAS No. 446022-33-9 N-((5-(2-((6S)-2-氨基-1,4,5,6,7,8-六氢-4-氧代吡啶并[2,3-D]嘧啶-6-基)乙基)-4-甲基-2-噻吩)甲酰基)-L-谷氨酸Pelitrexol synthetic routes
Combination therapies for treating methylthioadenosine phosphorylase deficient cellsInventors: Bloom, Laura Anne; Boritzki, Theordore James; Kung, Pei-Pei; Ogden, Richard Charles; Skalitzky, Donald James; Zehnder, Luke Raymond; Kuhn, Leslie Ann; Meng, Jerry JialunWO2003074083 A1
产品链接: CAS No. 446022-33-9 ››
Combination therapies for treating methylthioadenosine phosphorylase deficient cellsInventors: Bloom, Laura Anne; Boritzki, Theordore James; Kung, Pei-Pei; Ogden, Richard Charles; Skalitzky, Donald James; Zehnder, Luke Raymond; Kuhn, Leslie Ann; Meng, Jerry JialunWO2003074083 A1
产品链接: CAS No. 446022-33-9 ››