Ly reduced yield. Rdern replacing the coupling reagent for bromo tris-pyrrolidino phosphate phosphoniumhexafluoro known to the formation of amide difficult to f Lead again to moderate, w Rmt during LY2109761 the performance of microwave radiation mentioned. The lower yield in No. 2 and 3 was obtained was, surprisingly, that microwave radiation is often touted for its F Ability to transform difficult to f Wheels, both efficiently and cleanly. Access via an intermediate compound 4a, a Lipo The acyl chloride by treatment with thionyl chloride, gave a good performance, but was still lower than our initial conditions of the reaction. Although these protocols produced different yields of the desired products 4a, best CONFIRMS their collective success in providing the desired N phenylamide each set of conditions that the street s of valid request when it removed to the electrons is problematic anilines. Attention is now turned on to the synthesis of amide-N-lipo The other aryl bearing a series of electron-withdrawing functional groups, normally used for the design of the androgen survivin receptor antagonist. Our focus on electron-withdrawing substituents on the aryl ring is on the literature shows that these priorit Other groups will critically affect binding to AR. 5b chloroaniline coupling with S Acid lipo 3 before that has indicated under the reaction conditions in Method A a low yield of 27% under microwave irradiation for a period much shorter ensures optimum performance and acceptable. Surprisingly, the formation of 4c, Method A is an h higher yield than 4b under the same conditions, despite the presence of a trifluoromethyl disable the meta position of aniline reagent. In view of the m Cent yield of 44%, we performed the same coupling with methods B and C with the h Chsten yield of 5c is obtained for Method B, the synthesis of compound 4d
above mentioned Above, an a good yield by method D, but in our H ends this protocol was not optimal. Tats was Chlich the synthesis 4d problematic and very complex mixtures were isolated from the crude reaction mixture analyzed for all methods. The analysis of these crude products by 1 H NMR showed C only method to have a significant amount of 4d, but still a satisfactory yield t lower than 36%. Close Lich, using the fifth cyanoaniline trifluoromethyl, cyano, despite wearing Acadesine very disabling the para position, a better performance than 5d has a nitro group at this position. Ligands in our H We have ascertained that the method B or C is optimal, although moderate yields were fourth. With a range of these compounds in the hands of our attention to the study of their interaction properties of AR. The data in FIG. 1 show the rate of cell proliferation after 6 days of culture with the target links and normalized with respect to dihydrotestosterone in the use bicalutamide 2 as contr Positive. In this study, a significant anti-proliferative observed when these compounds and several new lipo, Were incubated in the presence of androgen sensitive prostate cancer cell lines. Development of proliferative behavior of compounds Which display thwart LNCaP cells is important that they serve as potential Ren Ans Tze for the treatment of prostate tumors in humans prime. As mentioned above HNT, Hu et al. judged 4a, 4b and fourth to this hormone.