536974-74-0Relevant academic research and scientific papers
Design and synthesis of carbon-11-labeled dual aromatase-steroid sulfatase inhibitors as new potential PET agents for imaging of aromatase and steroid sulfatase expression in breast cancer
Wang, Min,Mickens, Jarrett,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Hutchins, Gary D.,Zheng, Qi-Huang
experimental part, p. 896 - 905 (2009/12/01)
Aromatase and steroid sulfatase (STS) are particularly attractive targets in the treatment of estrogen-receptor-positive breast cancer and the development of enzyme-based cancer imaging agents for the biomedical imaging technique positron emission tomography (PET). New carbon-11-labeled sulfamate derivatives were first designed and synthesized as potential PET dual aromatase-steroid sulfatase inhibitor (DASSI) radiotracers for imaging of aromatase and STS expression in breast cancer. The target tracers 5-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-[11C]methoxyphenyl sulfamate ([11C]8a) and 4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-[11C]methoxyphenyl sulfamate ([11C]8b) were prepared from their corresponding precursors 5-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-hydroxyphenyl sulfamate (16) and 4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-hydroxyphenyl sulfamate (21) with [11C]CH3OTf under basic conditions through the O-[11C]methylation and isolated by the reversed-phase high pressure liquid chromatography (HPLC) method in 30-45% radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The specific activity at end of synthesis (EOS) was 111-185 GBq/μmol.
Dual aromatase-steroid sulfatase inhibitors
Woo, L. W. Lawrence,Bubert, Christian,Sutcliffe, Oliver-B.,Smith, Andrew,Chander, Surinder K.,Mahon, Mary F.,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
, p. 3540 - 3560 (2008/02/09)
By introducting the steroid sulfatase inhibitory pharmacophore into aromatase inhibitor 1 (YM511), two series of single agent dual aromatase-sulfatase inhibitors (DASIs) were generated. The best DASIs in'vitro (JEG-3 cells) are 5, (IC50(aromatase) = 0.82 nM; IC 50(sulfatase) = 39 nM), and 14, (IC50(aromatase) = 0.77 nM; IC50(sulfatase) = 590 nM). X-ray crystallography of 5, and docking studies of selected compounds into an aromatase homology model and the steroid sulfatase crystal structure are presented. Both 5 and 14 inhibit aromatase and sulfatase in PMSG pretreated adult female Wistar rats potently 3 h after a single oral 10 mg/kg dose. Almost complete dual inhibition is observed for 5 but the levels were reduced to 85% (aromatase) and 72% (sulfatase) after 24 h. DASI 5 did not inhibit aldosterone synthesis. The development of a potent and selective DASI should allow the therapeutic potential of dual aromatase-sulfatase inhibition in hormone-dependent breast cancer to be assessed.
SULFAMIC ACID ESTER COMPOUNDS USEFUL IN THE INHIBITION OF SEROID SULPHATASE ACTIVITY AND AROMATASE ACTIVITY
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Page/Page column 71, (2010/02/14)
There is provided a compound of Formula (III) or Formula (IV), wherein A is selected from H, OH, halogen and hydrocarbyl D, E and F are each independently of each other an optional linker group; P, Q and R are independently of each other a ring system, wherein R4 and R5 are independently selected from H, alkyl, cycloalkyl, alkenyl, acyl and aryl, or combinations thereof, or together represent alkylene, wherein the or each alkyl or cycloalkyl or alkenyl or optionally contain one or more hetero atoms or groups
