CAS: 854001-07-3; N-(2-Chloro-6-Methylphenyl)-2-((6-(4-(2-Hydroxyethyl)Piperazin-1-yl)-2-Methylpyrimidin-4-yl)Amino)Thiazole-5-Carboxamide Hydrochloride

该化合物是一种小分子气旋状体酶抑制剂,主要针对BCR-ABL,SRC家族血动脉和其他蛋白质动脉,广泛用于治疗慢性流状白血病(CML)和费城红血球阳性急性淋巴菌白血病(Ph+AL),盐状会提高溶性性和生物利用率,确保药用动力性能的一致性.Dasatinib表现出高能性和选择性,能够有效抑制低浓度的畸变动脉动脉活性,其穿透血液脑屏障的能力进一步扩大了其治疗用途.该化合物的纯度和稳定性很高,符合临床和研究应用的严格药品标准.

英文名称N-(2-Chloro-6-Methylphenyl)-2-((6-(4-(2-Hydroxyethyl)Piperazin-1-yl)-2-Methylpyrimidin-4-yl)Amino)Thiazole-5-Carboxamide Hydrochloride
中文名称达沙替尼盐酸盐
IUPAC名称N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrochloride
CAS编号854001-07-3
MFCD编号:MFCD26960525
分子式:C22H27Cl2N7O2S分子量:524.48
产品CID: 1850018
产品分类Protein Tyrosine Kinase/RTK → Src | Protein Tyrosine Kinase/RTK → c-Kit

相似结构搜索
InChIKey: MSCGWICDJYLQOJ-UHFFFAOYSA-N
InChI=1S/C22H26ClN7O2S.ClH/c1-14-4-3-5-16(23)20(14)28-21(32)17-13-24-22(33-17)27-18-12-19(26-15(2)25-18)30-8-6-29(7-9-30)10-11-31;/h3-5,12-13,31H,6-11H2,1-2H3,(H,28,32)(H
计算化学: 氢键受体数9.0氢键供体数3.0可旋转键数8.0

物理性质

熔点279-280 °C
溶解性DMSO: 15 mg/mL (28.60 Mm; Need Ultrasonic And Warming)H2O: 10 mg/mL (19.07 Mm; Need Ultrasonic)
外观形态白色至类白色粉末
储存条件在惰性气体(氮气或氩气)下 2-8°C

合成工艺路线路线简述

824-94-2 + 302964-11-0 = 854001-07-3
反应条件:1.1 Reagents: Sodium Hydride Solvents: Dimethylformamide; 30 Min,Rt1.2 Reagents: Tetrabutylammonium Iodide; 16 H,Rt2.1 Reagents: Sodium Hydride Solvents: Tetrahydrofuran; 30 Min,0 °C2.2 4 H,Reflux; Reflux -> Rt2.3 Reagents: Hydrochloric Acid Solvents: Water; Acidified,Rt3.1 Reagents: Trifluoroacetic Acid,Trifluoromethanesulfonic Acid Solvents: Dichloromethane; 3 H,Rt4.1 Reagents: Diisopropylethylamine Solvents: 1,4-Dioxane; 12 H,Reflux4.2 Reagents: Hydrochloric Acid Solvents: Diethyl Ether,Methanol,Water; 30 Min,Rt
标题:Discovery Of N-(2-Chloro-6-Methyl-Phenyl)-2-(6-(4-(2-Hydroxyethyl)-Piperazin-1-Yl)-2-Methylpyrimidin-4-Ylamino)Thiazole-5-Carboxamide (Bms-354825),A Dual Src/abl Kinase Inhibitor With Potent Antitumor Activity In Preclinical Assays
作者:Lombardo,Louis J.; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2004 卷标:47(27) 页码:6658-6661]

3034-52-4 + 40398-01-4 = 854001-07-3
反应条件:1.1 Solvents: Tetrahydrofuran; Rt -> -78 °C1.2 Reagents: Butyllithium Solvents: Hexane; 20 Min,< -75 °C; 15 Min,-78 °C1.3 Solvents: Tetrahydrofuran; 2 H,-78 °C1.4 Reagents: Ammonium Chloride Solvents: Water2.1 Reagents: Sodium Hydride Solvents: Dimethylformamide; 30 Min,Rt2.2 Reagents: Tetrabutylammonium Iodide; 16 H,Rt3.1 Reagents: Sodium Hydride Solvents: Tetrahydrofuran; 30 Min,0 °C3.2 4 H,Reflux; Reflux -> Rt3.3 Reagents: Hydrochloric Acid Solvents: Water; Acidified,Rt4.1 Reagents: Trifluoroacetic Acid,Trifluoromethanesulfonic Acid Solvents: Dichloromethane; 3 H,Rt5.1 Reagents: Diisopropylethylamine Solvents: 1,4-Dioxane; 12 H,Reflux5.2 Reagents: Hydrochloric Acid Solvents: Diethyl Ether,Methanol,Water; 30 Min,Rt
标题:Discovery Of N-(2-Chloro-6-Methyl-Phenyl)-2-(6-(4-(2-Hydroxyethyl)-Piperazin-1-Yl)-2-Methylpyrimidin-4-Ylamino)Thiazole-5-Carboxamide (Bms-354825),A Dual Src/abl Kinase Inhibitor With Potent Antitumor Activity In Preclinical Assays
作者:Lombardo,Louis J.; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2004 卷标:47(27) 页码:6658-6661]

103-76-4 + 302964-08-5 = 854001-07-3
反应条件:1.1 Reagents: Diisopropylethylamine Solvents: 1,4-Dioxane; 12 H,Reflux1.2 Reagents: Hydrochloric Acid Solvents: Diethyl Ether,Methanol,Water; 30 Min,Rt
标题:2-Aminothiazole As A Novel Kinase Inhibitor Template. Structure-Activity Relationship Studies Toward The Discovery Of N-(2-Chloro-6-Methylphenyl)-2-[[6-[4-(2-Hydroxyethyl)-1-Piperazinyl)]-2-Methyl-4-Pyrimidinyl]Amino)]-1,3-Thiazole-5-Carboxamide (Dasatinib,Bms-354825) As A Potent Pan-Src Kinase Inhibitor
作者:Das,Jagabandhu; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2006 卷标:49(23) 页码:6819-6832]

103-76-4 + 302964-08-5 = 854001-07-3
反应条件:1.1 Reagents: Diisopropylethylamine Solvents: 1,4-Dioxane; 12 H,Reflux1.2 Reagents: Hydrochloric Acid Solvents: Diethyl Ether,Methanol,Water; 30 Min,Rt
标题:Discovery Of N-(2-Chloro-6-Methyl-Phenyl)-2-(6-(4-(2-Hydroxyethyl)-Piperazin-1-Yl)-2-Methylpyrimidin-4-Ylamino)Thiazole-5-Carboxamide (Bms-354825),A Dual Src/abl Kinase Inhibitor With Potent Antitumor Activity In Preclinical Assays
作者:Lombardo,Louis J.; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2004 卷标:47(27) 页码:6658-6661]

834888-64-1 = 854001-07-3
反应条件:1.1 Reagents: Trifluoromethanesulfonic Acid Solvents: Dichloromethane,Trifluoroacetic Acid; 3 H,Rt2.1 Reagents: Diisopropylethylamine Solvents: 1,4-Dioxane; 12 H,Reflux2.2 Reagents: Hydrochloric Acid Solvents: Diethyl Ether,Methanol,Water; 30 Min,Rt
标题:2-Aminothiazole As A Novel Kinase Inhibitor Template. Structure-Activity Relationship Studies Toward The Discovery Of N-(2-Chloro-6-Methylphenyl)-2-[[6-[4-(2-Hydroxyethyl)-1-Piperazinyl)]-2-Methyl-4-Pyrimidinyl]Amino)]-1,3-Thiazole-5-Carboxamide (Dasatinib,Bms-354825) As A Potent Pan-Src Kinase Inhibitor
作者:Das,Jagabandhu; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2006 卷标:49(23) 页码:6819-6832]

834888-64-1 = 854001-07-3
反应条件:1.1 Reagents: Trifluoroacetic Acid,Trifluoromethanesulfonic Acid Solvents: Dichloromethane; 3 H,Rt2.1 Reagents: Diisopropylethylamine Solvents: 1,4-Dioxane; 12 H,Reflux2.2 Reagents: Hydrochloric Acid Solvents: Diethyl Ether,Methanol,Water; 30 Min,Rt
标题:Discovery Of N-(2-Chloro-6-Methyl-Phenyl)-2-(6-(4-(2-Hydroxyethyl)-Piperazin-1-Yl)-2-Methylpyrimidin-4-Ylamino)Thiazole-5-Carboxamide (Bms-354825),A Dual Src/abl Kinase Inhibitor With Potent Antitumor Activity In Preclinical Assays
作者:Lombardo,Louis J.; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2004 卷标:47(27) 页码:6658-6661]

1749-68-4 + 834888-63-0 = 854001-07-3
反应条件:1.1 Reagents: Sodium Hydride Solvents: Tetrahydrofuran; 0 °C; 30 Min,0 °C1.2 0 °C; 4 H,Reflux; Reflux -> Rt1.3 Reagents: Hydrochloric Acid Solvents: Water; Acidified,Rt2.1 Reagents: Trifluoromethanesulfonic Acid Solvents: Dichloromethane,Trifluoroacetic Acid; 3 H,Rt3.1 Reagents: Diisopropylethylamine Solvents: 1,4-Dioxane; 12 H,Reflux3.2 Reagents: Hydrochloric Acid Solvents: Diethyl Ether,Methanol,Water; 30 Min,Rt
标题:2-Aminothiazole As A Novel Kinase Inhibitor Template. Structure-Activity Relationship Studies Toward The Discovery Of N-(2-Chloro-6-Methylphenyl)-2-[[6-[4-(2-Hydroxyethyl)-1-Piperazinyl)]-2-Methyl-4-Pyrimidinyl]Amino)]-1,3-Thiazole-5-Carboxamide (Dasatinib,Bms-354825) As A Potent Pan-Src Kinase Inhibitor
作者:Das,Jagabandhu; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2006 卷标:49(23) 页码:6819-6832]

1749-68-4 + 834888-63-0 = 854001-07-3
反应条件:1.1 Reagents: Sodium Hydride Solvents: Tetrahydrofuran; 30 Min,0 °C1.2 4 H,Reflux; Reflux -> Rt1.3 Reagents: Hydrochloric Acid Solvents: Water; Acidified,Rt2.1 Reagents: Trifluoroacetic Acid,Trifluoromethanesulfonic Acid Solvents: Dichloromethane; 3 H,Rt3.1 Reagents: Diisopropylethylamine Solvents: 1,4-Dioxane; 12 H,Reflux3.2 Reagents: Hydrochloric Acid Solvents: Diethyl Ether,Methanol,Water; 30 Min,Rt
标题:Discovery Of N-(2-Chloro-6-Methyl-Phenyl)-2-(6-(4-(2-Hydroxyethyl)-Piperazin-1-Yl)-2-Methylpyrimidin-4-Ylamino)Thiazole-5-Carboxamide (Bms-354825),A Dual Src/abl Kinase Inhibitor With Potent Antitumor Activity In Preclinical Assays
作者:Lombardo,Louis J.; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2004 卷标:47(27) 页码:6658-6661]

824-94-2 + 302964-11-0 = 854001-07-3
反应条件:1.1 Reagents: Sodium Hydride Solvents: Dimethylformamide; 30 Min,Rt1.2 Catalysts: Tetrabutylammonium Iodide; 16 H,Rt2.1 Reagents: Sodium Hydride Solvents: Tetrahydrofuran; 0 °C; 30 Min,0 °C2.2 0 °C; 4 H,Reflux; Reflux -> Rt2.3 Reagents: Hydrochloric Acid Solvents: Water; Acidified,Rt3.1 Reagents: Trifluoromethanesulfonic Acid Solvents: Dichloromethane,Trifluoroacetic Acid; 3 H,Rt4.1 Reagents: Diisopropylethylamine Solvents: 1,4-Dioxane; 12 H,Reflux4.2 Reagents: Hydrochloric Acid Solvents: Diethyl Ether,Methanol,Water; 30 Min,Rt
标题:2-Aminothiazole As A Novel Kinase Inhibitor Template. Structure-Activity Relationship Studies Toward The Discovery Of N-(2-Chloro-6-Methylphenyl)-2-[[6-[4-(2-Hydroxyethyl)-1-Piperazinyl)]-2-Methyl-4-Pyrimidinyl]Amino)]-1,3-Thiazole-5-Carboxamide (Dasatinib,Bms-354825) As A Potent Pan-Src Kinase Inhibitor
作者:Das,Jagabandhu; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2006 卷标:49(23) 页码:6819-6832]

3034-52-4 + 40398-01-4 = 854001-07-3
反应条件:1.1 Reagents: Butyllithium Solvents: Tetrahydrofuran,Hexane; < -75 °C; 15 Min,-78 °C1.2 Solvents: Tetrahydrofuran; 2 H,-78 °C1.3 Reagents: Ammonium Chloride Solvents: Water2.1 Reagents: Sodium Hydride Solvents: Dimethylformamide; 30 Min,Rt2.2 Catalysts: Tetrabutylammonium Iodide; 16 H,Rt3.1 Reagents: Sodium Hydride Solvents: Tetrahydrofuran; 0 °C; 30 Min,0 °C3.2 0 °C; 4 H,Reflux; Reflux -> Rt3.3 Reagents: Hydrochloric Acid Solvents: Water; Acidified,Rt4.1 Reagents: Trifluoromethanesulfonic Acid Solvents: Dichloromethane,Trifluoroacetic Acid; 3 H,Rt5.1 Reagents: Diisopropylethylamine Solvents: 1,4-Dioxane; 12 H,Reflux5.2 Reagents: Hydrochloric Acid Solvents: Diethyl Ether,Methanol,Water; 30 Min,Rt
标题:2-Aminothiazole As A Novel Kinase Inhibitor Template. Structure-Activity Relationship Studies Toward The Discovery Of N-(2-Chloro-6-Methylphenyl)-2-[[6-[4-(2-Hydroxyethyl)-1-Piperazinyl)]-2-Methyl-4-Pyrimidinyl]Amino)]-1,3-Thiazole-5-Carboxamide (Dasatinib,Bms-354825) As A Potent Pan-Src Kinase Inhibitor
作者:Das,Jagabandhu; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2006 卷标:49(23) 页码:6819-6832