241127-66-2

Upstream product

• 62-23-7 4-nitro-benzoic acid 
• 122-04-3 4-nitro-benzoyl chloride 
• 768-95-6 1-adamanthanol 
• 968-84-3 1-adamantanol p-nitrobenzoate 

Downstream Products

• 241127-58-2 Adaphostin 

Relevant academic research and scientific papers

Synthesis and biological evaluation of platensic alcohol as an adamantane surrogate in antitumor drug lead adaphostin

Adamantane has been widely used as a “lipophilic bullet” in drug discovery and development, due to its unique diamond-like architecture with benign pharmacological/ pharmaceutical properties. Platensimycin is a natural product isolated from a soil streptomycete, which contains an adamantane-like moiety extensively modified from a diterpenoid precursor. In the current study, platensic alcohol was semisynthesized from platensimycin and used as an adamantane surrogate in anticancer drug lead adaphostin. The resulting hybrid platensic alcohol/adaphostin compounds, eg. 4a and 4b, exhibited similar cytotoxic activity with adaphostin against the tested cancer cell lines. In particular, 4b generates significantly more reactive oxygen species (ROS) and shows stronger synergy with the clinically used histone deacetylase inhibitor vorinostat than adaphostin, probably due to the presence of two hydroquinone groups. Density functional theory calculation supports that there could be certain π-π stacking interaction in 4b in aqueous solution, which might explain that 4b has similar serum stability with adaphostin. Our study not only leads to the identification of 4b as a potent ROS generating agent, but showcases a simple scaffold hopping strategy to harvest lipophilic scaffolds from natural products.

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.

Disubstituted lavendustin a analogs and pharmaceutical compositions comprising the analogs

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.