151391-92-3

Upstream product

• 65-49-6 4-Aminosalicylic acid 
• 36387-22-1 2-hydroxy-4-aminobenzoyl chloride 
• 4136-97-4 methyl 4-aminosalicylate 
• 39614-82-9 2-hydroxy-4-nitrobenzoyl chloride 
• 13684-28-1 2-hydroxy-4-nitro-benzoic acid methyl ester 
• 151391-81-0 4-{[1-(2,5-Dihydroxy-phenyl)-meth-(E)-ylidene]-amino}-2-hydroxy-benzoic acid methyl ester 

Relevant academic research and scientific papers

Synthesis, structure-activity relationship, and p210bcr-abl protein tyrosine kinase activity of novel AG 957 analogs

A series of novel, sterically hindered lipophilic analogs of AG 957 was designed and synthesized as potential protein tyrosine kinase (PTK) inhibitors. The in vitro activity, in vivo anti-leukemia activity, and pharmacology of these PTK inhibitors were studied. Some aspects of the structure-activity relationship associated with the carboxylic acid, phenol ring, and linker modifications are discussed. We have demonstrated that the 1,4-hydroquinone moiety is essential for activity and that sterically hindered esters contribute to enhanced in vivo efficacy. Adaphostin (NSC 680410) has emerged as the improved compound with the maximum in vivo anti-leukemia hollow fiber activity, concordant with the original lead compound AG 957. Currently, adaphostin is undergoing preclinical toxicology studies.

Synthesis and Structure-Activity Studies of a Series of salicylates as Inhibitors of EGF Receptor-Associated Tyrosine Kinase Activity

The synthesis and structure-activity relationships of a series of salicylates and a series of salicylates as inhibitors of EGF receptor-associated tyrosine kinase activity are described.Their inhibitory potency was evaluated in vitro using ER 22 cell membranes (CCL 39 cells transfected with EGF receptor) as an enzyme source and the tridecapeptide RRSrc (RRLIEDAEYAARG) as substrate.Their cellular activity was measured by inhibition of the EGF-stimulated DNA synthesis of ER 22 cells.Chemical modifications were made to analyze the role of the different substituents.The amino series was found to be more active than the imino series.The hydroquinone moiety appears to be essential for tyrosine kinase inhibitory activity in the series of 5-salicylates.Comparison of the imino and amino series by molecular modeling techniques provides further evidence in support of the hypothesis that the important reduced linking chain, CH2NH allows the correct positioning of the 2,5-dihydroxybenzyl ring, possibly in a cis-like conformational arrangement.