Hormone-responsive rat and human mammary tumor, unlike normal epithelium, actively sulfoconjugates estrogens. The title compounds (9-11) were synthesized in search of specific inhibitors of estrogen sulfotransferase as a possible means of developing effective chemotherapeutic agents for treatment of hormone-dependent human mammary cancer. 4-Nitroestrone 3-triflate (7a) was converted to the corresponding estradiol derivative (8a) in 93% yield by reduction with NaBH4 under phase-transfer conditions. Catalytic reduction (10% Pd/C) of the latter gave 4-aminoestra-1,3,5(10)-trien-17 beta-ol (9a) in 77% yield. These same reactions were applied consecutively to 4-nitroestrone 3-nonaflate (7b) to give 9a in 56% overall yield. The amino steroid (9a) was converted to 4-fluoroestra-1,3,5(10)-trien-17 beta-ol (10a) via a Balz-Schiemann reaction, in 17% overall yield. Successive NaBH4 and (10% Pd/C) catalytic reductions of 4-fluoroestrone 3-O-(1-phenyl-1H-tetrazol-5-yl) ether (2b) provided a less satisfactory route to 10a. MCPBA oxidation of 9a gave 4-nitroestra-1,3,5(10)-trien-17 beta-ol (11a) in 56% yield. The same series of reactions were applied to 2-nitroestrone 3-triflate (7c) to give 2-amino- (9b), 2-fluoro- (10b), and 2-nitro- (11b) estra-1,3,5(10)-trien-17-ols in comparable yields. Substitution in the A ring results in improved inhibition of porcine endometrial sulfotransferase sulfoconjugation of estradiol relative to estra-1,3,5(10)-trien-17 beta-ol (4a). Moreover, electronegative substitution at C-4 of 4a is more effective than at C-2. In particular, the Ki (2.43 +/- 0.16 microM) of 11a is sixfold smaller than that of the unsubstituted steroid (4a).
of cyclohexane in a quartz tube, and argon was bubbled through the suspension for 30 min. The mixture was then irradiated for 15 h at 300 nm in a Rayonet RPR-100 chamber reactor. Filtration, concentration of the filtrate under reduced pressure and filtration through a short column of Celite gave 0.19 g (90%) of benoxaprofen methyl ester, mp 91-93 °C, identical in all respects with an authentic sample.13Benoxaprofen (3). Benoxaprofen methyl ester (180 mg) was dissolved in 10 mL of 5% methanolic potassium hydroxide and the mixture was heated under reflux for 30 min. The solvent was then removed under reduced pressure, and the remaining solid was dissolved in water. Addition of HC1 led to the separation of a heavy white precipitate which was collected by filtration and recrystallized from ethanol to give 152 mg (75%) of benoxaprofen, mp 188.5-190 °C, identical in all respects with an authentic sample.13
The present study therefore, indicated that it was better to do an echocardiographic screening of asymptomatic subjects who had even a marginal increase in blood pressure and BMI, to diagnose potential cardiac dysfunction.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.