Studies on Aromatase Inhibitors. I. Synthesis and Biological Evaluation of 4-Amino-4H-1,2,4-triazole Derivatives.

11C-Cetrozole: An Improved C-11C-Methylated PET Probe for Aromatase Imaging in the Brain

“…To address these issues and explore a novel PET probe for aromatase imaging, we focused on YM511, an aminotriazole derivative developed as an aromatase inhibitor for breast cancer (25). Because this compound showed high inhibitory competence with a half maximal inhibitory concentration (IC 50 ) of 0.12 nM for human placental aromatase and had a simple structure that was easy to synthesize, we planned to modify and optimize this compound to obtain a more efficient PET probe.…”

Synthesis of Aromatase Inhibitors and Dual Aromatase Steroid Sulfatase Inhibitors by Linking an Arylsulfamate Motif to 4‐(4H‐1,2,4‐triazol‐4‐ylamino)benzonitrile: SAR, Crystal Structures, in vitro and in vivo Activities

“…[33] The 2-phenylethanol derivatives 16 a-d were converted into the alkyl bromides 17 a-d by using PBr 3 (for 17 a) [34] or Ph 3 PBr 2 (for 17 b and 17 c) or CBr 4 /Ph 3 P (for 17 d), which were then used to alkylate the anion of 4-(4H-1,2,4-triazol-4-ylamino)benzonitrile (7) to give the triazolyl derivatives 18 a-d in moderate yields. [26,29] The deprotection of 18 a-d by catalytic hydrogenation (for 18 a-c, R 2 = Bn) or acid-catalysed solvolysis in MeOH (for 18 d, R 2 = THP) gave the phenols 19 a-d, which were sulfamoylated according to the conditions described by Okada et al [35] with excess sulfamoyl chloride in N,N-dimethylacetamide (DMA) to give the sulfamates 20 a-d in good yields. The propylene linker series was prepared in a manner similar to that used for the ethylene linker series.…”

“…[24,[26][27][28] The initial strategy for designing DASIs led to the incorporation of a phenol sulfamate moiety, the pharmacophore required for irreversible STS inhibition, into the scaffold of YM511 (4, Figure 1), which is a potent and selective nonsteroidal investigative AI. [29] Several examples of YM511-based DASIs (6 a-d, Figure 1) were prepared and some of them exhibit desirable dual inhibition in vitro, displaying potent STS inhibition whilst preserving the high level of aromatase inhibition observed with 4. [24,26] In this work we further expand the series of YM511-based DASIs by preparing compounds that have the general structure 8 ( Figure 2).…”

“…The methylene linker group, which is present in YM511 and DASIs 6 a-d, is replaced by primarily linear linker systems in these new derivatives, although the 4-(4H-1,2,4-triazol-4-ylamino)benzonitrile moiety is retained. Four different series of compounds with alkyl-, ether-, thioether-, and sulfonamide-based linkers [A = (CH 2 ) n , OA C H T U N G T R E N N U N G (CH 2 ) n , SA C H T U N G T R E N N U N G (CH 2 ) n , CH 2 SA C H T U N G T R E N N U N G (CH 2 ) n , or SO 2 NCH 3 A C H T U N G T R E N N U N G (CH 2 ) 2 ] were prepared from 7 [29] and evaluated in a JEG-3 cell-based assay from which SAR information was derived. Several promising compounds were also investigated for dual inhibition in vivo.…”

Aspectos histopatológicos y receptores hormonales en mucosa endometrial de mujeres posmenopáusicas con terapia hormonal

“…Existen trabajos ( 33,36,41 ) sobre el uso de noretisterona combinada con beta estradiol. Al respecto, es conocido el mecanismo de acción de la noretisterona, la cual actúa provocando a nivel endometrial hiperplasia estromal, con el consiguiente deterioro de la irrigación endometrial y atrofia final en las fases avanzadas del tratamiento.…”