103766-25-2
103766-25-2 結(jié)構(gòu)式
基本信息
吉莫斯特
吉莫斯特(CDHP)
5-氯-4-羥基-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
物理化學(xué)性質(zhì)
灼燒殘渣 ≤0.1%
有關(guān)物質(zhì) ≤1.0％
重金屬 ≤20ppm
含量 ≥98.5%
安全數(shù)據(jù)
制備方法
103792-80-9
103766-25-2
以化合物6（8.0g，44mmol）為原料，將其與乙腈（100mL）、乙酸（3mL）及碘化鈉（13.2g，88mmol）混合，于60℃下加熱反應(yīng)8小時。反應(yīng)完成后，將混合物冷卻至室溫，并倒入10%硫代硫酸鈉溶液（200mL）中，以沉淀出無色固體。通過水重結(jié)晶純化，得到目標(biāo)產(chǎn)物5-氯-4-羥基吡啶-2(1H)-酮（化合物2），產(chǎn)量5.6g，收率86%。產(chǎn)物表征數(shù)據(jù)如下：熔點272-273℃（文獻值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計算值C5H535ClNO2：[M+H]+：146.0003，實測值：146.0012；C5H537ClNO2：[M+H]+：147.9975，實測值：147.9975。
參考文獻：
[1] Journal of Chemical Research, 2018, vol. 42, # 1, p. 33 - 34
[2] Recueil des Travaux Chimiques des Pays-Bas, 73<1954<704,708,
常見問題列表
| 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. |