Technetium And Three Carbonyl Technetium Tag Phenyl Methyl Synthesis And Biological Properties Of Sulfonamide Drugs Research

Breast cancer is the most common tumor in women, and its incidence and mortality rate are showing a gradual upward trend in the worldwide, while the incidence is growing at an annual rate of nearly4%in China. Approximately75%of postmenopausal breast cancers are hormone-dependent. Studies on breast cancer indicated that estrogen are known to be implicated in the breast cancer occurrence and development and different strategies have been devised to control or block the progression of strogen. Aromatase could convert androgens to estrogens and is a particularly attractive target in the treatment of estrogen receptor positive breast cancers. The aromatase inhibitors can effectively inhibit the enzyme activity and expression, to suppress estrogen levels.The phenyl methylsulfonyl compounds have a high sensitivity and specificity on inhibiting aromatase expresstion and activity in the breast cancer cells, and will be potential breast cancer treatments. The phenyl methylsulfonyl compounds (NSC) could be designed as the potential Single-Photon Emission Computed Tomography (SPECT) imaging agent to detect the estrogens level, which may be a important way for the diagnosis, treatment of breast cancerAccording to NSC-AIs QSAR studies, the phenyl methylsulfonyl derivatives as labeled precursor were designed and synthesied. Technetium labeled ligand:N-[2-cyclohexyl-methoxy-4(1-(2-(N-ethyl-N-mercaptocetyl-mercaptoethyl-)) amino) acetylamino] phenyl sulfonamide (NSC-N2S2) and tricarbonyl technetium labeled ligand:N-[2-cyclohexyl-methoxy-4-(1-(2,2’-pyridylmethyl)amino)acetylamino] phenyl sulfonamide (NSC-PA) were prepared by hydroxyl-alkylation, amino-methylsulfonyl ation, nitro-reduction, amino-bromideacetylation and N-alkylation from the raw material of2-amino-5-nitrophenol, and the structure of all the compounds was confirmed by1HNMR、IR、MS and elemental analysis.The rhenium complexes were synthesized with [Et4N]2[Re(CO)3Br3] and ReIO2(PPh3)2, respectively and were characterized by elemental analysis, IR, MS,1HNMR and13CNMR, then the radiolabeling technetium drugs99mTc(CO)3-PA-NSC and99mTc-N2S2-NSC were prepared. The labeling conditions were optimized to obtain the best labeling yield and radiochemical efficiency. The radiochemical yield of technetium(I)-99m and tricarbonyl technetium labeled complexes detected by by the high-performance liquid chromatography (HPLC) were over90%, which were suitable for the futural animal studies as potential breast cancer imaging agents.The in vitro stability, plasma protein binding ratios and partition coefficients, as well as pharmacokinetics and biodistribution studies in mice were also investigated to evaluate their biological properties in this study. The result indicated that the phenyl methylsulfonyl derivatives labeled by technetium(I)-99m and tricarbonyl technetium have the high in vitro stability, rapid blood clearance, significant selective uptake in target organs include thymus, ovarian and uterine. All these studies were to develop labeled phenylmethanesulfonamide derivatives as the new potential SPECT agents for imaging in breast cancer.The study provides a useful and processfull assessment of the stage for the breast cancer by imaging aromatase and COX-2inhibitors with SPECT imaging.