103766-25-2
103766-25-2 结构式
基本信息
吉莫斯特
吉莫斯特(CDHP)
5-氯-4-羟基-2(1H)-吡啶酮
吉美嘧啶
GIMERACIL
gimestat
5-Chloro-2,4-dihydroxypyridine
5-Chloro-4-hydroxy-2(1H)-pyridinone
5-Chloro-4-hydroxy-2-pyridone
2(1H)-Pyridinone,5-chloro-4-hydroxy-(9CI)
2(1H)-Pyridinone, 5-chloro-4-hydroxy-
Gimeracil,(CDHP)
CDHP
5-Chloro-2,4-pyridinediol
（CDHP）Gimeracil
物理化学性质
灼烧残渣 ≤0.1%
有关物质 ≤1.0％
重金属 ≤20ppm
含量 ≥98.5%
制备方法
103792-80-9
103766-25-2
以化合物6（8.0g，44mmol）为原料，将其与乙腈（100mL）、乙酸（3mL）及碘化钠（13.2g，88mmol）混合，于60℃下加热反应8小时。反应完成后，将混合物冷却至室温，并倒入10%硫代硫酸钠溶液（200mL）中，以沉淀出无色固体。通过水重结晶纯化，得到目标产物5-氯-4-羟基吡啶-2(1H)-酮（化合物2），产量5.6g，收率86%。产物表征数据如下：熔点272-273℃（文献值273-274℃）；1H NMR（400MHz，DMSO-d6）δ 5.70（s，1H），7.51（s，1H），11.29（br，2H）；13C NMR（100MHz，DMSO-d6）δ 163.5, 163.2, 134.6, 105.6, 98.7；LRMS（ESI）m/z（百分比）：146（100）[M（35Cl）+H]+，148（30）[M（37Cl）+H]+；HRMS（ESI）m/z计算值C5H535ClNO2：[M+H]+：146.0003，实测值：146.0012；C5H537ClNO2：[M+H]+：147.9975，实测值：147.9975。
参考文献：
[1] Journal of Chemical Research, 2018, vol. 42, # 1, p. 33 - 34
[2] Recueil des Travaux Chimiques des Pays-Bas, 73<1954<704,708,
常见问题列表
| Target | Value |
| Dihydropyrimidine dehydrogenase |
Gimeracil reduces the frequency of neo-positive clones. Additionally, it sensitized the cells in S-phase more than in G0/G1.
Gimeracil may enhance the efficacy of radiotherapy through the suppression of HR-mediated DNA repair pathways.
Gimeracil pretreatment significantly restrains the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of Nbs1, Mre11, Rad50, and FancD2.
Cell Viability Assay
| Cell Line: | DLD-1, HeLa, and LC-11 cell lines. |
| Concentration: | 1 mM. |
| Incubation Time: | 48 h. |
| Result: |
Inhibits the repair of irradiation-induced DNA double strand breaks.
Did not increase the c-H2AX foci residual at 24 h in unirradiated cells. |
Gimeracil (2.5-25 mg/kg, orally) may inhibit the rapid repair of X-ray-induced DNA damage in tumors.
| Animal Model: |
Nude mice (Lu-99, LC-11, KB/C3 and PAN-4 tumors were xenografted).
|
| Dosage: | 2.5-25 mg/kg. |
| Administration: | Orally. |
| Result: | Exhibited anti-tumor activity. |