Description
Gimeracil (103766-25-2) is a dihydropyrimidine dehydrogenase (DPD) inhibitor. DPD is involved in the degradation of pyrimidine-based chemotherapeutic drugs such as 5-fluorouracil (5-FU). Gimeracil is used along with 5-FU or Tegafur to prolong circulating concentrations of the drugs.1,2 Gimeracil has also been shown to act as a radiosensitizer via inhibition of homologous recombination in the repair of DNA double strand breaks.3
Chemical Properties
Off-White Solid
Uses
Antitumor agent. A potent inhibitor of dihydropyrimidine dehydrogenase (DPD)
Uses
Gimeracil is an antitumor agent. Gimeracil is a potent inhibitor of dihydropyrimidine dehydrogenase (DPD).
Uses
Gimeracil is an inhibitor of dihydropyrimidine dehydrogenase, which inhibits the early step in homologous recombination for double strand breaks repair.
Definition
ChEBI: Gimeracil is an organic molecular entity.
Synthesis
Compound 6 (8.0 g, 44 mmol) was used as a raw material, which was mixed with acetonitrile (100 mL), acetic acid (3 mL) and sodium iodide (13.2 g, 88 mmol), and the reaction was heated at 60°C for 8 hours. Upon completion of the reaction, the mixture was cooled to room temperature and poured into 10% sodium thiosulfate solution (200 mL) to precipitate a colorless solid. Purification by aqueous recrystallization afforded the target product 5-chloro-4-hydroxypyridin-2(1H)-one (Compound 2) in a yield of 5.6 g in 86%. The product characterization data were as follows: melting point 272-273 °C (literature value 273-274 °C); 1H NMR (400 MHz, DMSO-d6) δ 5.70 (s, 1H), 7.51 (s, 1H), 11.29 (br, 2H); 13C NMR (100 MHz, DMSO-d6) δ 163.5, 163.2, 134.6 , 105.6, 98.7; LRMS (ESI) m/z (%): 146 (100) [M(35Cl)+H]+, 148 (30) [M(37Cl)+H]+; HRMS (ESI) m/z calculated value of C5H535ClNO2: [M+H]+: 146.0003, measured value: 146.0012; C5H537ClNO2: [M+H]+: 147.9975, measured value: 147.9975.
in vivo
Gimeracil (2.5-25 mg/kg, orally) may inhibit the rapid repair of X-ray-induced DNA damage in tumors[3].
| Animal Model: | Nude mice (Lu-99, LC-11, KB/C3 and PAN-4 tumors were xenografted)[3].
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| Dosage: | 2.5-25 mg/kg. |
| Administration: | Orally. |
| Result: | Exhibited anti-tumor activity. |
References
[1] DIASIO R B. Clinical implications of dihydropyrimidine dehydrogenase inhibition.[C]//13 7 Suppl 3. 1999: 17-21.
[2] MASAO KOBAYAKAWA Yasushi K. Tegafur/gimeracil/oteracil (S-1) approved for the treatment of advanced gastric cancer in adults when given in combination with cisplatin: a review comparing it with other fluoropyrimidine-based therapies.[J]. OncoTargets and therapy, 2011, 4: 193-201. DOI:
10.2147/ott.s19059[3] KOH-ICHI SAKATA. Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase, inhibits the early step in homologous recombination[J]. Cancer Science, 2011, 102 9: 1712-1716. DOI:
10.1111/j.1349-7006.2011.02004.x
