19916-73-5
19916-73-5 結(jié)構(gòu)式
基本信息
O-6-芐基鳥嘌呤
6-芐基鳥嘌呤
2-amino-6-(phenylmethoxy)-9h-purine
6-BENZYLOXY-9H-PURIN-2-AMINE
6-BENZYLOXY GUANINE
6-O-BENZYLGUANINE
O6-BENZYLGUANINE
4 6-Benzyloxyguanine
6-BENZYLOXY GUANINE2-AMINO-6-BENZYLOXYPURINE
O(sup 6)benzylguanidine
2-Amino-6-(benzyloxy)-9H-purine
6-(Benzyloxy)-1H-purin-2-amine
物理化學(xué)性質(zhì)
安全數(shù)據(jù)
制備方法
10310-21-1
100-51-6
19916-73-5
一般步驟：將苯甲醇（37.5 g，0.347 mol）與氫氧化鈉（2.96 g，0.074 mol）混合，加熱至氫氧化鈉完全溶解。待反應(yīng)混合物冷卻后，加入2-氨基-6-氯嘌呤（6.00 g，0.035 mol），于80-90℃下攪拌反應(yīng)5小時(shí)。反應(yīng)完成后，向反應(yīng)混合物中加入甲基叔丁基醚（120 mL），用氫氧化鈉溶液（70 mL）進(jìn)行兩次萃取。合并堿水層，用甲苯洗滌，隨后蒸發(fā)除去甲苯。用35%鹽酸將溶液中和至pH 6-8，過濾收集析出的晶體。將所得粗產(chǎn)物2-氨基-6-(芐氧基)嘌呤（7.60 g，0.032 mol，收率92%）在減壓下干燥。
參考文獻(xiàn)：
[1] Patent: WO2003/84957, 2003, A1. Location in patent: Page/Page column 9-10
[2] Nucleosides and Nucleotides, 1999, vol. 18, # 10, p. 2219 - 2231
[3] Helvetica Chimica Acta, 2012, vol. 95, # 12, p. 2621 - 2634
[4] Tetrahedron, 2007, vol. 63, # 24, p. 5323 - 5327
[5] Synthetic Communications, 2003, vol. 33, # 6, p. 941 - 952
常見問題列表
O6-Benzylguanine 是鳥嘌呤類似物，是 DNA 修復(fù)酶 O6 烷基鳥嘌呤DNA烷基轉(zhuǎn)移酶 (MGMT/AGT) 抑制劑。
| Target | Value |
|
AGT
() |
The L3.6pl cells are relatively sensitive to O6-Benzylguanine (24-72 hours) in a dose- and time-dependent manner. The IC
50
is 50 μg (at 48 hours).
O6-Benzylguanine (50 μg; 48 hours) modulates p53 downstream target protein expression, induces apoptosis, and decreases cell proliferation.
O6-Benzylguanine (50 μg; 48 hours) significantly decreases the MGMT transcriptional activity in L3.6pl.
Western Blot Analysis
| Cell Line: | L3.6pl and PANC1 cells |
| Concentration: | 50 μg |
| Incubation Time: | 48 hours |
| Result: | Expressions of O6 methyl guanine DNA methyl transferase (MGMT), cyclin B1, cyclin B2, cyclin A, p53, and ki-67 were decreased, whereas p21 was increased. The levels of cyto C and caspase 9 were increased, whereas the levels of PARP1 protein were decreased. |
RT-PCR
| Cell Line: | L3.6pl cells |
| Concentration: | 50 μg |
| Incubation Time: | 48 hours |
| Result: | Decreased the MGMT transcriptional activity in L3.6pl. |
O6-Benzylguanine (100 μg; i.p.; daily for 35 days) inhibits pancreatic cancer cell growth and increases pancreatic cell sensitivity to Gemcitabine (100 mg/kg).
O6-Benzylguanine inhibits pancreatic cancer cell proliferation and induces tumor cell apoptosis in vivo.
| Animal Model: | Male athymic nude mice (NCI-nu) (bearing human pancreatic cancer L3.6pl cells) |
| Dosage: | 100 μg |
| Administration: | i.p; daily for 35 days |
| Result: | Significantly decreased median tumor volume and weight. |