Gemcitabine ProTide hypoxia-activated prodrug and application thereof
View Patent ↗A gemcitabine ProTide hypoxic-activated prodrug and a use thereof in the preparation of a medicament for treating tumors. The general structural formula thereof is formula (A), wherein: one of R1 and R2 is a hypoxic-activated group of —C(R3R4)ArNO2, and the other is an alkyl group of 1 to 6 carbon atoms, a phenyl group or —CH2Ar, wherein R3 and R4 are —H or a methyl group, and —Ar is an aromatic ring compound. The gemcitabine ProTide hypoxic-activated prodrug described in the present invention has a stronger cytotoxicity under a hypoxic condition, has excellent anti-tumor effects and is very safe; the present invention can be used along with other anti-tumor drugs to exert a better anti-tumor activity, and can be used in the preparation of a medicament for treating tumors.
1. A gemcitabine ProTide hypoxic-activated prodrug, wherein the chemical structural formula of the gemcitabine ProTide hypoxic-activated prodrug is:
wherein one of R 1 and R 2 is a hypoxic-activated group of —C(R 3 R 4 )ArNO 2 , the other of R 1 and R 2 is an alkyl group of 1 to 6 carbon atoms, a phenyl group or —CH 2 Ar, R 3 and R 4 are —H or a methyl group, and —Ar is an aromatic ring compound.
2. The gemcitabine ProTide hypoxic-activated prodrug according to claim 1 , wherein the structure of R 1 is:
R 2 is an alkyl or benzyl group of 1 to 6 carbon atoms, R 3 is —H or a methyl group, and R 4 is a methyl group.
3. The gemcitabine ProTide hypoxic-activated prodrug according to claim 1 , wherein R 1 is a phenyl group, the structure of R 2 is:
R 3 is —H or a methyl group, and R 4 is a methyl group.
4. The gemcitabine ProTide hypoxic-activated prodrug according to claim 1 , wherein the structure of R 1 is:
R 2 is an alkyl or benzyl group of 1 to 6 carbon atoms, and R 3 and R 4 are —H.
5. The gemcitabine ProTide hypoxic-activated prodrug according to claim 1 , wherein R 1 is —CH 2 Ar, —Ar is a benzene ring with an electron donating group, the structure of R 2 is:
R 3 is —H or a methyl group, and R 4 is a methyl group.
6. The gemcitabine ProTide hypoxic-activated prodrug according to claim 1 , wherein the chemical structural formula of the gemcitabine ProTide hypoxic-activated prodrug is one selected from the group consisting of chemical structural formulas as follows:
7. The gemcitabine ProTide hypoxic-activated prodrug according to claim 1 , wherein the chemical structural formula of the gemcitabine ProTide hypoxic-activated prodrug is one selected from the group consisting of chemical structural formulas as follows:
8. A medicament for treating tumors, wherein an effective component of the medicament for treating tumors is the gemcitabine ProTide hypoxic-activated prodrug according to claim 1 or pharmaceutically acceptable salt of the gemcitabine ProTide hypoxic-activated prodrug.
9. The medicament according to claim 8 , wherein the structure of R 1 is:
R 2 is an alkyl or benzyl group of 1 to 6 carbon atoms, R 3 is —H or a methyl group, and R 4 is a methyl group.
10. The medicament according to claim 8 , wherein R 1 is a phenyl group, the structure of R 2 is:
R 3 is —H or a methyl group, and R 4 is a methyl group.
11. The medicament according to claim 8 , wherein the structure of R 1 is:
R 2 is an alkyl or benzyl group of 1 to 6 carbon atoms, and R 3 and R 4 are —H.
12. The medicament according to claim 8 , wherein R 1 is —CH 2 Ar, —Ar is a benzene ring with an electron donating group, the structure of R 2 is:
R 3 is —H or a methyl group, and R 4 is a methyl group.
13. The medicament according to claim 8 , wherein the chemical structural formula of the gemcitabine ProTide hypoxic-activated prodrug is one selected from the group consisting of chemical structural formulas as follows:
14. The medicament according to claim 8 , wherein the chemical structural formula of the gemcitabine ProTide hypoxic-activated prodrug is one selected from the group consisting of chemical structural formulas as follows: