1380432-32-5
1380432-32-5 結(jié)構(gòu)式
基本信息
N4-(9-乙基-9H-咔唑-3-基)-N2-[3-(4-嗎啉基)丙基]-2,4-嘧啶二胺
EHop-016, >=98%
EHOP 016
EHOP016
EHOP016
EHOP-016
EHOP 016
EHOP016
EHOP-016
EHOP 016.
4-N-(9-ethylcarbazol-3-yl)-2-N-(3-morpholin-4-ylpropyl)pyrimidine-2,4-diamine
N4-(9-Ethyl-9H-carbazol-3-yl)-N2-[3-(4-morpholinyl)propyl]-2,4-pyrimidinediamine
N4-(9-Ethyl-9H-carbazol-3-yl)-N2-(3-Morpholin-4-yl-propyl)-pyriMidine-2,4-diaMine
2,4-Pyrimidinediamine, N4-(9-ethyl-9H-carbazol-3-yl)-N2-[3-(4-morpholinyl)propyl]-
N4-(9-Ethyl-9H-carbazol-3-yl)-N2-[3-(4-morpholinyl)propyl]-2,4-pyrimidinediamine Ehop-016
EHOP-016
N4-(9-ETHYL-9H-CARBAZOL-3-YL)-N2-(3-MORPHOLIN-4-YL-PROPYL)-PYRIMIDINE-2,4-DIAMINE
物理化學(xué)性質(zhì)
常見問題列表
123-00-2
1380432-31-4
1380432-32-5
EHop-016的合成在Bruker 400MHz光譜儀上記錄1H和13C NMR光譜。在Hewlett Packard 6890N GC/MS光譜儀上獲得質(zhì)譜。所有化學(xué)品均購自Sigma Aldrich Chemical Company。根據(jù)圖1中提供的反應(yīng)方案，EHop-016（5）的合成分兩步進(jìn)行。如圖1（A）所示，進(jìn)行與文獻(xiàn)中描述的過程類似的過程。得到(2-氯-嘧啶-4-基)-(9-乙基-9H-咔唑-3-基)-胺3，為純化合物，收率為53%。通過TLC、NMR和GC/MS鑒定產(chǎn)物。Rf = 0.23（3:1，己烷-乙酸乙酯）；1H NMR（DMSO-d6, 400MHz）δ 1.32（t, J = 6.9Hz, 3H）, 4.45（q, J = 6.6Hz, 2H）, 6.72（s, 1H）, 7.20（t, J = 7.36Hz, 1H）, 7.47（t, J = 7.30Hz, 1H）, 7.56（s, 1H）, 7.62（t, J = 8.68Hz, 1H）, 8.11（t, J = 7.36Hz, 1H）, 8.27（s, 1H）, 10.1（s, 1H）；13C NMR（DMSO-d6, 100MHz）δ 13.7, 37.0, 109.2, 109.4, 115.0, 118.7, 120.3, 121.3, 121.9, 122.3, 125.9, 129.9, 136.9, 140.0, 156.9, 159.6, 162.4；LRGC-MS m/z（相對(duì)百分比）：[M]+ 276（100）, [M-Cl]+ 241（40）, [M-C5H5N3Cl]+ 134（26）。得到N4-(9-乙基-9H-咔唑-3-基)-N2-(3-嗎啉-4-基-丙基)-嘧啶-2,4-二胺5（EHop-016），為純化合物，收率為93%。通過TLC和NMR鑒定產(chǎn)物基本上是純的：Rf = 0.34（9:1，CH2Cl2-MeOH）；1H NMR（DMSO-d6, 400MHz）δ 1.31（t, J = 7.0Hz, 3H）, 1.73（m, 2H）, 2.32（m, 2H）, 2.34（t, J = 6.89Hz, 8H）, 3.52（m, 2H）, 4.42（q, J = 7.0Hz, 2H）, 5.98（d, J = 5.7Hz, 1H）, 6.69（t, J = 5.3Hz, 1H）, 7.16（t, J = 7.4Hz, 1H）, 7.43（t, J = 7.2Hz, 1H）, 7.53（t, J = 9.0Hz, 4H）, 7.81（d, J = 5.4Hz, 1H）, 8.10（s, 1H）, 8.66（s, 1H）, 9.1（s, 1H）；13C NMR（DMSO-d6, 100MHz）δ 13.7, 26.2, 36.9, 53.4, 56.3, 66.2, 108.9, 109.0, 118.2, 119.7, 120.2, 122.0, 122.2, 125.6, 132.5, 135.5, 139.9, 159.8, 160.9, 162.1。
參考文獻(xiàn)：
[1] Patent: US2013/172552, 2013, A1. Location in patent: Paragraph 0031
EHop-016 (1-10 μM; 24 hours; MDA-MB-435 cells) treatment inhibits Rac1 and Rac3 activity. At higher concentrations, EHop-016 inhibits the close homolog Cdc42. In MDA-MB-435 cells that demonstrate high active levels of the Rac GEF Vav2, EHop-016 inhibits the association of Vav2 with a nucleotide-free Rac1(G15A) .
EHop-016 also inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation in both cell lines. EHop-016 decreases Rac downstream effects of PAK1 (p21-activated kinase 1) activity and directed migration of metastatic cancer cells.
EHop-016 affectes cell viability by down-regulating Akt and Jun kinase activities and c-Myc and Cyclin D expression, as well as increasing caspase 3/7 activities in metastatic cancer cells.
Western Blot Analysis
| Cell Line: | MDA-MB-435 cells |
| Concentration: | 1 μM, 2 μM, 4 μM, 5 μM, 10 μM |
| Incubation Time: | 24 hours |
| Result: | The activity Rac3 was inhibited by 58%. |
EHop-016 (10-25 mg/kg; intraperitoneal injection; 3 times a week; for 55 days; nu/nu mice) treatment significantly reduces mammary fat pad tumor growth, metastasis, and angiogenesis.
| Animal Model: | Female athymic nu/nu mice (4-5 weeks old) injected with GFP-MDA-MB-435 cells |
| Dosage: | 10 mg/kg, 25 mg/kg |
| Administration: | Intraperitoneal injection; 3 times a week; for 55 days |
| Result: | Significantly reduced mammary fat pad tumor growth, metastasis, and angiogenesis. |