Estramustine Phosphate Sodium

Treatment of castration-resistant prostate cancer is and has been a challenge. In 1957, the chemist Imre Könyves came to Sweden as a refugee from Hungary and started to work at AB Leo, a pharmaceutical company in Helsingborg. In 1961, he started to synthesize compounds where the oestrogens were linked to a mustard group by a carbamate. This resulted in estramustine phosphate, which was initially tested against mammary cancer with disappointing results. He then started a cooperation with urology professor Gösta Jönsson, Head of the Department of Urology at the Lund University Hospital, to test estramustine phosphate against prostate cancer. Jönsson started clinical estramustine phosphate tests in 1966. His studies were one-armed and consecutive, with a “favourable response” in 83% of previously untreated patients. These favourable results could not be reproduced in later randomized controlled studies suggesting that estramustine phosphate as primary treatment was not better than conventional estrogenic treatment. Conclusions: Even if the results of Gösta Jönsson's studies could not be confirmed, the subsequent randomized studies of estramustine phosphate may hide the desired action of estramustine phosphate in a subgroup of patients. It has still not been elucidated whether estramustine phosphate has effects in this subgroup of patients with ostrogen-resistant prostate cancer.

Abraham solvation equation (Absolv) is a popular and well-established approach for modeling solute partitioning between phases of different polarity, which finds its applications in both organic chemistry and biomedical fields. Parameters constituting this equation are good quantitative descriptors of solute hydrogen bonding potential that are useful for QSAR modeling of more complex chemical and biological phenomena. Numerous studies dealing with fast determination of Abraham descriptors using HPLC can be found in the literature, but these mostly focus on small un-ionizable industrial and environmental chemicals, whereas experimental data for pharmaceutical molecules are clearly lacking. In the current study we build upon a previously published chromatographic approach, aiming to adapt the method to ionizable drug-like compounds, and optimize it by reducing the number of required HPLC columns. The analysis involves determination of the overall H-bond acidity (A), H-bond basicity (B) and polarity/polarizability (S) descriptors for 62 pharmaceutical molecules with previously unpublished parameter values.