948903-64-8

Upstream product

• 383-63-1 ethyl trifluoroacetate, 
• 34231-22-6 [3-(aminomethyl)phenyl]methanol 
• 407-25-0 trifluoroacetic anhydride 
• 96-63-9 trifluoroacetic anhydride 
• 34403-46-8 [4-(amino-methyl)phenyl]methanol hydrochloride 

Downstream Products

• 1055972-09-2 N-(3-(((2-amino-9H-purin-6-yl)oxy)methyl)benzyl)-2,2,2-trifluoroacetamide 
• 948903-72-8 O⁶-[3-(Aminomethyl)benzyl]guanine 

Relevant academic research and scientific papers

Synthesis and antitumor activity evaluation of a novel combi-nitrosourea prodrug: Designed to release a DNA cross-linking agent and an inhibitor of O6-alkylguanine-DNA alkyltransferase

The drug resistance of CENUs induced by O6-alkylguanine-DNA alkyltransferase (AGT), which repairs the O6-alkylated guanine and subsequently inhibits the formation of dG-dC cross-links, hinders the application of CENU chemotherapies. Therefore, the discovery of CENU analogs with AGT inhibiting activity is a promising approach leading to novel CENU chemotherapies with high therapeutic index. In this study, a new combi-nitrosourea prodrug 3-(3-(((2-amino-9H-purin-6-yl)oxy)methyl)benzyl)-1-(2-chloroethyl)-1-nitrosourea (6), designed to release a DNA cross-linking agent and an inhibitor of AGT, was synthesized and evaluated for its antitumor activity and ability to induce DNA interstrand cross-links (ICLs). The results indicated that 6 exhibited higher cytotoxicity against mer+ glioma cells compared with ACNU, BCNU, and their respective combinations with O6-benzylguanine (O6-BG). Quantifications of dG-dC cross-links induced by 6 were performed using HPLC-ESI-MS/MS. Higher levels of dG-dC cross-link were observed in 6-treated human glioma SF763 cells (mer+), whereas lower levels of dG-dC cross-link were observed in 6-treated calf thymus DNA, when compared with the groups treated with BCNU and ACNU. The results suggested that the superiority of 6 might result from the AGT inhibitory moiety, which specifically functions in cells with AGT activity. Molecular docking studies indicated that five hydrogen bonds were formed between the O6-BG analogs released from 6 and the five residues in the active pocket of AGT, which provided a reasonable explanation for the higher AGT-inhibitory activity of 6 than O6-BG.

Inhibitor of low-oxygen targeted tumor cell DNA repair enzyme methylguanine methyl transferase (MGMT), and preparation method and application of inhibitor

The invention discloses an inhibitor of low-oxygen targeted tumor cell DNA repair enzyme methylguanine methyl transferase (MGMT), and a preparation method and application of the inhibitor. The structural formula of the compound disclosed by the invention

Hypoxia-activated O6-benzyl-2-nitropurine derivative as well as preparation method and application thereof

The invention provides a hypoxia-activated O6-benzyl-2-nitropurine derivative as well as a preparation method and application thereof. The hypoxia-activated O6-benzyl-2-nitropurine derivative is a hypoxia-activated AGT protein inhibitor and contains a compound represented by a structure of a general formula (I) (shown in the description), wherein R represents a substituent group containing primary amine, secondary amine or quaternary amine. The compound can be selectively activated by reductase in solid tumor cells in a hypoxia environment and has good hypoxia activation property and tumor cell targeting property, so that the sensitivity of a chemotherapy drug is increased. The compound shows an obvious inhibition effect to multiple tumor cells when being combined with CCNU in use, is capable of obviously increasing the sensitivity of tumor cells to anti-cancer drugs when being combined with alkylating agent anti-cancer drugs and can be applied to targeted combined chemotherapy of malignant tumors.

A β-chloro ethylnitrosourea compound and its synthetic method and use

The invention relates to novel beta-chloroethylnitrosourea compounds, and a synthesis method and application thereof. The structure of the beta-chloroethylnitrosourea compounds is disclosed as general formula (II). The in-vitro antitumor screening test on the compounds disclosed as general formula II proves that the compounds disclosed as general formula I have obvious inhibiting action on human cerebral nerve glioma cells SF763, SF767, SF126 and SF188, human colon cancer cell HT29, mouse leukaemia cell L1210 and many other tumor cell lines and have higher tumor inhibiting activity than the existing CENU and CENU/O6-benzylguanine combined medicine.