Nemzeti Gyógyszerkutatási és Fejlesztési Laboratórium (PharmaLab)(RRF-2.3.1-21-2022-00015)
Támogató: NKFIH
beta-Aminophosphonates obtained by the Michael addition of primary amines to the double
bond of diethyl vinylphosphonate proved to be suitable starting materials (amine components)
in the Kabachnik-Fields reaction with formaldehyde and dialkyl phosphites or secondary
phosphine oxides to afford N-phosphonylmethyl- and N-phosphinoylmethyl-beta-aminophosphonates.
On the other hand, the starting aminophosphonates were modified by N-acylation using
acid chlorides. The N-acyl products were found to exist in a dynamic equilibrium of
two conformers as suggested by the broad NMR signals. At 26 degrees C, there may be
rotation around the N-C axis of the acylamide function. At the same time, low-temperature
NMR measurements at -5 degrees C revealed the presence of two distinct rotamers that
could be characterized by P-31, C-13 and H-1 NMR data. The modified beta-aminophosphonic
derivatives were subjected to a comparative structure-activity analysis on MDA-MB-231,
PC-3, A431 and Ebc-1 tumor cell lines, and in a few cases, significant activity was
detected.
