108761-48-4

Upstream product

• 99-28-5 2,6-dibromo-4-nitrophenol 
• 609-21-2 2,6-dibromo-4-aminophenol 
• 63558-07-6 N-(3,5-dibromo-4-hydroxyphenyl)acetamide 
• 74-88-4 methyl iodide 
• 31106-74-8 1,3-dibromo-2-methoxy-5-nitrobenzene 
• 41727-70-2 3,5-dibromo-4-methoxyaniline 
• 108-24-7 acetic anhydride 

Downstream Products

• 1363603-20-6 5-(1-(3,5-dibromo-4-methoxyphenyl)-1H-1,2,3-triazol-5-yl)-2-methoxyphenol 
• 1363603-26-2 2-(1-(3,5-dibromo-4-methoxyphenyl)-1H-1,2,3-triazol-5-yl)-5-methoxyphenol 
• 1363603-30-8 3-(1-(3,5-dibromo-4-methoxyphenyl)-1H-1,2,3-triazol-5-yl)-6-methoxybenzene-1,2-diol 
• 41727-70-2 3,5-dibromo-4-methoxyaniline 
• 1355597-71-5 3-((tert-butyldimethylsilyl)oxy)-N-(3,5-dibromo-4-methoxyphenyl)-4-methoxybenzamide 
• 1355597-78-2 3-((tert-butyldimethylsilyl)oxy)-N-(3,5-dibromo-4-methoxyphenyl)-4-methoxybenzothioamide 
• 1355597-84-0 5-(3-((tert-butyldimethylsilyl)oxy)-4-methoxyphenyl)-1-(3,5-dibromo-4-methoxyphenyl)-1H-tetrazole 
• 1355597-90-8 5-(1-(3,5-dibromo-4-methoxyphenyl)-1H-tetrazol-5-yl)-2-methoxyphenol 

Relevant academic research and scientific papers

Increased endothelial cell selectivity of triazole-bridged dihalogenated A-ring analogues of combretastatin A-1

The antiproliferative activity on ovarian cancer (SK-OV-3) cells of a series of triazole-bridged combretastatin analogues (37, 38, 40-43) containing dihalogenation of the A-ring is reported, and compared with their trimethoxy analogues (5, 15, 39). It was found that dihalogenation with either bromine or iodine was a tolerated modification when compared to the parent compound combretastatin (CA-4, 1) and had less effect than B-ring modification on potency. These compounds exhibited G2/M arrest, and maintained antitubulin activity. Further assays on human umbilical vein endothelial cells (HUVECs) demonstrated the potential antivascular effects of these triazoles. Of particular note was a 3,5-diiodo-4-methoxyaryl triazole (43) which had promising 7-fold selectivity for HUVECs over ovarian cancer cells.

A-ring dihalogenation increases the cellular activity of combretastatin-templated tetrazoles

The combretastatins have been investigated for their antimitotic and antivascular properties, and it is widely postulated that a 3,4,5-trimethoxyaryl A-ring is essential to maintain potent activity. We have synthesized new tetrazole analogues (32a€"34), demonstrating that 3,5-dihalogenation can consistently increase potency by up to 5-fold when compared to the equivalent trimethoxy compound on human umbilical vein endothelial cells (HUVECs) and a range of cancer cells. Moreover, this increased potency offsets that lost by installing the tetrazole bridge into combretastatin A-4 (1), giving crystalline, soluble compounds that have low nanomolar activity, arrest cells in G2/M phase, and retain microtubule inhibitory activity. Molecular modeling has shown that optimized packing within the binding site resulting in increased Coulombic interaction may be responsible for this improved activity.