143621-35-6
143621-35-6 結(jié)構(gòu)式
基本信息
M2亞基抑制劑(TRIAPINE)
2-[(3-氨基吡啶-2-基)亞甲基]氨基硫脲
PAN-811)是核糖核苷酸還原酶抑制劑,已進(jìn)入各種臨床實(shí)驗(yàn)。
3-Apct
Pan-811
Pan 811
C078157
OCX 191
CS-2006
Triapine
OCX 0191
NSC 663249
物理化學(xué)性質(zhì)
安全數(shù)據(jù)
常見問題列表
79-19-6
143621-33-4
143621-35-6
以氨基硫脲和2-(1,3-二氧戊環(huán)基)-3-氨基吡啶（CAS:143621-33-4）為原料合成[(3-氨基吡啶-2-基)亞甲基氨基]硫脲的一般步驟： 實(shí)施例VII：向2-(1,3-二氧戊環(huán)基)-3-氨基吡啶（0.80 g，4.8 mmol）溶于10 mL乙醇、8 mL水和2 mL濃鹽酸的溶液中加入氨基硫脲（0.48 g，5.3 mmol）。將反應(yīng)混合物于室溫?cái)嚢柽^夜，隨后回流1小時(shí)。冷卻后過濾，得到粗制的黃色鹽酸鹽。將該鹽酸鹽溶于50 mL熱水中，過濾。向熱的濾液中加入10 mL 5%碳酸氫鈉溶液?；旌衔镉谑覝?cái)嚢?小時(shí)，過濾，依次用水和乙醇洗滌，得到3-氨基-2-甲?；拎たs氨基硫脲。產(chǎn)量：0.72 g（77%）；熔點(diǎn)：240-241°C。質(zhì)譜（MS）m/e 194（M+）；1H NMR（90 MHz，DMSO-d6）δ 6.48（br s，2H，3-NH2，可交換于D2O），7.12（m，2H，4-H和6-H），7.83（dd，1H，5-H），8.10（br s，2H，CSNH2，可交換于D2O），8.10（s，1H，2-CH），10.95（s，1H，NNH，可交換于D2O）。元素分析（C7H9N5S）符合C、H、N的理論值。
參考文獻(xiàn)：
[1] Journal of Medicinal Chemistry, 1992, vol. 35, # 20, p. 3672 - 3677
[2] Patent: US5281715, 1994, A
Ribonucleotide reductase (RR)
3-AP (Triapine) is a potent derivative of α-heterocyclic carboxaldehyde thiosemicarbazone (HCT) that inhibits hRRM2 and p53R2 isoforms of the M2 subunit. 3-AP (Triapine) is thought to inhibit ribonucleotide reductase through its preformed iron chelate, rather than directly by removing iron from the active site. In cells containing less topoisomerase IIα fewer DNA strand breaks will be produced, and thus topoisomerase II poisons will be less inhibitory in the K/VP.5 cell line. The IC 50 s for Dp44mT growth inhibition are 48±9 nM and 60±12 nM, for K562 and K/VP.5 cells, respectively. The IC 50 s for 3-AP growth inhibition are 476±39 nM and 661±69 nM for K562 and K/VP.5 cells, respectively. PKIH and DpT Fe chelators show high antiproliferative activity against a range of tumor cell lines. Dp44mT shows the greatest antitumor efficacy with an IC 50 that ranged from 0.005 to 0.4 μM. The average IC 50 of Dp44mT over 28 cell types is 0.03±0.01 μM, which is significantly lower than that of 3-AP (Triapine; average IC 50 : 1.41±0.37 μM).
3-AP (Triapine) causes a significant increase (1.7-fold) in splenic weight when expressed as a percentage of total body weight (1.02±0.06%; n=25) compared with control mice (0.6±0.03%; n=27). In the long-term group, a significant increase in heart weight is observed after Dp44mT (0.4 mg/kg per day) (0.8±0.06%; n=4) compared with control mice (0.5±0.01%; n=6). A significant decrease in the expression of Ndrg1, TfR1, and VEGF1 in the liver is noted for Dp44mT- and 3-AP (12 mg/kg per day)-treated animals. The decreased expression could be related to the increased liver Fe in both Dp44mT- and 3-AP-treated mice.