203723-22-2

Upstream product

• 67022-39-3 2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoyl}-glutamic acid 5-methyl ester 
• 128139-42-4 methyl α-aminotetradecanoate hydrochloride 
• 59-05-2 N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid 

Relevant academic research and scientific papers

Lipophilic methotrexate conjugates with antitumor activity

Lipophilic methotrexate (MTX)-lipoamino acid conjugates coupled with amide or ester linkages (1a-1r) were synthesised. The inhibitory activity of the conjugates was evaluated on bovine liver DHFR. The in vitro growth inhibitory effect against MTX-sensitive human lymphoblastoid CCRF-CEM cells and an MTX-resistant sub-line (CEM/MTX), which displays defective intracellular transport of MTX, was determined under short-term and continuous (120-h incubation) exposure conditions. The α, γ, or α,γ amide conjugates showed different activity in inhibiting the growth of parent cells. CEM/MTX cells were much less susceptible than CCRF-CEM cells to inhibition by α or α,γ-substituted lipoamino acid conjugates, whereas both cell lines were almost equally sensitive to the MTX-γ conjugates. Although less potent than MTX, they could partially circumvent the impaired transport system. These findings confirm that lipophilic MTX conjugates may be good lead compounds on the drug development for the treatment of some MTX-resistant tumors. Ester-type conjugates displayed an interesting activity against parent CCRF-CEM cells, although they were less potent against the transport-resistant sub-line. Stability studies on these molecules indicated that they are not degraded into MTX in the culture medium, thus suggesting that they are not able to over-cross cell resistance despite of their lipophilicity. Copyright (C) 2000 Elsevier Science B.V.

Lipoamino acid conjugates of methotrexate with antitumor activity

The synthesis, characterization, and in vitro antitumor activity against a wild and a transport-resistant CCRF-CEM cell line is described for a series of α,γ-bisamide lipoamino acid and oligomer conjugates of methotrexate. The influence of the lipophilicity of the conjugates on the cytotoxicity and the dihydrofolate reductase inhibition was investigated. All compounds were more active than their fatty acid conjugate analogues. Compound 1e with a 12- carbon atom aliphatic side chain showed the highest in vitro activity.