MDV3100: Tritium labeling at high specific activity

Tritium NMR: A compilation of data and a practical guide

“…It is also indicated by the doublet at δ 7.8 ppm that a second tritium had been installed at the oposition to the amide of the "eastern" aromatic ring with splitting caused by fluorine in the m-position; it followed that tritium and proton NMR spectra were essentially identical except for the aromatic ring regions, where tritium had been added. [91] Egan et al [92] reported the direct tritiation at high specific activity of dihydroergotamine belonging to an important class of medicinally useful ergot alkaloids, arising from the fungal colonization of grain crops. A proton decoupled tritium NMR spectrum of dihydroergocryptine shown in Figure 63 contains several tritium resonances F I G U R E 5 6 The 1 H and 3 H spectra of 3 H-labeled natural product (shown in figure) in the CD 3 OD solution obtained with and without heteronuclear decoupling.…”

“…Reproduced with minor editing privilege from Orphanos and Filer [90] with the permission of Elsevier F I G U R E 6 2 Tritium proton decoupled (top) and proton with expanded aromatic region (bottom) NMR spectra of MDV3100 recorded in DMSO-d 6 at 320 MHz. Reproduced with minor editing privilege from Byon et al [91] with the permission of Elsevier Recently Filer and coauthors [97] reported the tritium NMR study of the tritium labeled spiperone. While spiperone itself had not been widely used clinically, its extreme antagonist potency at the common receptor systems had been widely utilized as a powerful research tool to explore important binding sites.…”

“…As such, it constitutes a major advance in prostate cancer treatment. Byon et al [ 91 ] reported the technical details for the tritiation and characterization of MDV3100 at high specific activity.…”

“…Tritium proton decoupled (top) and proton with expanded aromatic region (bottom) NMR spectra of MDV3100 recorded in DMSO‐ d 6 at 320 MHz. Reproduced with minor editing privilege from Byon et al [ 91 ] with the permission of Elsevier…”

“…It is also indicated by the doublet at δ 7.8 ppm that a second tritium had been installed at the o ‐position to the amide of the “eastern” aromatic ring with splitting caused by fluorine in the m ‐position; it followed that tritium and proton NMR spectra were essentially identical except for the aromatic ring regions, where tritium had been added. [ 91 ]…”