1445853-75-7

Upstream product

• 1445854-49-8 methyl 7-(4-(3-(4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl)pentan-3-yl)-2-methylbenzamido)heptanoate 
• 700818-36-6 4-(1-{4-[2-(hydroxy)-3,3-dimethyl-butoxy]-3-methylphenyl}-1-ethylpropyl)-2-methylbenzoic acid 
• 17994-94-4 methyl 7-aminoheptanoate hydrochloride 

Relevant academic research and scientific papers

Optimization of histone deacetylase inhibitor activity in non-secosteroidal vitamin D-receptor agonist hybrids

The combination of (1α,25)-dihydroxyvitamin D3 (1,25D) and histone deacetylase inhibitor (HDACi) trichostatin A is highly antiproliferative in numerous cancer cell lines. We have previously prepared novel non-secosteroidal hybrid molecules which simultaneously act as both vitamin D receptor (VDR) agonists and HDACi. These molecules function as cytostatic and cytotoxic agents in 1,25D-resistant SCC4 squamous carcinoma cells. Here we have extended the scope of the hybrids by making several modifications to the diarylpentane core and to the aliphatic spacer unit to develop molecules with increased potency towards HDACs while maintaining VDR agonist activity. Notably, hybrid DK-366 (33a), a direct analog of first-generation hybrids but lacking a methyl group on one aryl ring possesses low micromolar potency for HDAC3 and HDAC6 and is a highly effective antiproliferative agent in SCC4 cells. Chain extended hybrids such as DK-367 (33c) possess even greater HDAC potency and are also highly antiproliferative. These results show that we can optimize HDACi potency in hybrid molecules without sacrificing VDR agonism.

BIS-(ARYL/HETEROARYL)-METHYLENE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND THEIR USE FOR TREATING CANCER

The present disclosure relates to novel bis-(aryl/heteroaryl)-methylene compounds of formula (I) having vitamin D receptor agonist and histone deacetylase (HDAC) inhibitory efficacy as well as to methods for reducing or inhibiting the proliferation of can