776-00-1Relevant academic research and scientific papers
Phosphine Oxides from a Medicinal Chemist's Perspective: Physicochemical and in Vitro Parameters Relevant for Drug Discovery
Finkbeiner, Peter,Hehn, J?rg P.,Gnamm, Christian
, p. 7081 - 7107 (2020)
Phosphine oxides and related phosphorus-containing functional groups such as phosphonates and phosphinates are established structural motifs that are still underrepresented in today's drug discovery projects, and only few examples can be found among approved drugs. In this account, the physicochemical and in vitro properties of phosphine oxides and related phosphorus-containing functional groups are reported and compared to more commonly used structural motifs in drug discovery. Furthermore, the impact on the physicochemical properties of a real drug scaffold is exemplified by a series of phosphorus-containing analogs of imatinib. We demonstrate that phosphine oxides are highly polar functional groups leading to high solubility and metabolic stability but occasionally at the cost of reduced permeability. We conclude that phosphine oxides and related phosphorus-containing functional groups are valuable polar structural elements and that they deserve to be considered as a routine part of every medicinal chemist's toolbox.
SYNTHESIS OF PHOSPHONIC DICHLORIDES AND CORRELATION OF THEIR P-31 CHEMICAL SHIFTS
Grabiak, Raymond C.,Miles, James A.,Schwenzer, Gretchen M.
, p. 197 - 202 (2007/10/02)
Various mono-substituted diethyl arylphosphonates were prepared in good yield by treatment of aryl bromides or iodides with triethyl phosphite in the presence of NiCl2 or alternatively, addition of the aryl grignard reagent to diethyl phosphorochloridate.
