150258-61-0Relevant academic research and scientific papers
Disubstituted lavendustin a analogs and pharmaceutical compositions comprising the analogs
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Page 12, (2010/02/05)
Disubstituted lavendustin A analogs that are PTK inhibitors having antiproliferative activity are described. Preferred compounds of the present invention, without limitation, satisfy either Formula 1 or Formula 2. Currently preferred compounds ,based on in vivo biological activity, are 4'-adamantylbenzoate-1'-N-1,4-dihydroxybenzylamine and 4'-adamantylmethylbenzoate-1'-N-1,4-dihydroxybenzylamine. The present invention also provides pharmaceutical compositions comprising effective amounts of disubstituted lavendustin A analogs. Such compositions also may comprise other active ingredients, other materials conventionally used in the formulation of pharmaceutical composition, and mixtures thereof. The compounds and compositions of the present invention can be used for treating subjects to, for example, inhibit the proliferation of living cells in the treatment of proliferative diseases.
Non-Amine Based Analogues of Lavendustin A as Protein-Tyrosine Kinase Inhibitors
Smyth, Mark S.,Stefanova, Irena,Hartmann, Frank,Horak, Ivan D.,Osherov, Nir,et al.
, p. 3010 - 3014 (2007/10/02)
The fermentation product lavendustin A (1) is a protein-tyrosine kinase (PTK) inhibitor whose active pharmacophore has previously been shown to reside in the more simplified salicyl-containing benzylamine 2.Amine 2 bears some structural resemblance to two other natural product PTK inhibitors, erbstatin (3) and piceatannol (4).Non-amine containing analogues of 2 were therefore synthesized which incorporated additional aspects of either erbstatin or piceatannol.Examination of these inhibitors in immunoprecipitated p56lck, epidermal growth factor receptor (EGFR), and c-erb B-2/HER 2/neu PTK preparation showed that compound 12 (IC50=60 nM)was one of the most potent p56lek inhibitors reported to date.These results demonstrate that nitrogen is not an essential component of the lavendustin A pharmacophore 2 and that 1,2-diarylethanes and ethenes bearing a salicyl moiety appear to be valuable structural motifs for the constuction of extremely potent PTK inhibitors.
