868962-66-7

Upstream product

• 54824-17-8 mitonafide 
• 3027-38-1 3-nitro-1,8-naphthalic anhydride 
• 618-65-5 helicin 
• 14581-83-0 helicin acetate 
• 69408-81-7 amonafide 

Downstream Products

• 937261-90-0 C₃₅H₃₉N₃O₁₁ 
• 868962-59-8 5-{[(2-(2-phenoxy)-6-hydroxymethyltetrahydropyran-3,4,5-triol)-5-ylmethyl]amino}-N-(2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinolin-1,3(2H)-dione) 

Relevant academic research and scientific papers

2,2,2-Trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2, 3-dihydro-1H-benzo[de]isoquinolin-5-yl}carbamoyl)acetamide (UNBS3157), a novel nonhematotoxic naphthalimide derivative with potent antitumor activity

Amonafide (1), a naphthalimide which binds to DNA by intercalation and poisons topoisomerase IIα, has demonstrated activity in phase II breast cancer trials, but has failed thus far to enter clinical phase III because of dose-limiting bone marrow toxicity. Compound 17 (one of 41 new compounds synthesized) is a novel anticancer naphthalimide with a distinct mechanism of action, notably inducing autophagy and senescence in cancer cells. Compound 17 (2,2,2-trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H- benzo[de]isoquinolin-5-yl}carbamoyl)acetamide (UNBS3157)) was found to have a 3-4-fold higher maximum tolerated dose compared to amonafide and not to provoke hematotoxicity in mice at doses that display significant antitumor effects. Furthermore, 17 has shown itself to be superior to amonafide in vivo in models of (i) L1210 murine leukemia, (ii) MXT-HI murine mammary adenocarcinoma, and (iii) orthotopic models of human A549 NSCLC and BxPC3 pancreatic cancer. Compound 17, therefore, merits further investigation as a potential anticancer agent.

NAPHTHALIMIDE DERIVATIVES, METHODS FOR THEIR PRODUCTION AND PHARMACEUTICAL COMPOSITIONS THEREFROM

Novel substituted naphthalimide derivatives, pharmaceutically acceptable salts thereof and solvates thereof, are useful for making pharmaceutical compositions for the treatment of cell proliferative diseases such as cancer. The invention also provides methods for making such derivatives.