Phosphine Oxides (-Pome2) For Medicinal Chemistry: Synthesis, Properties, And Applications

A general practical approach to hetero(aromatic) and aliphatic P(O)Me-2-substituted derivatives is elaborated. The key synthetic step was a [Pd]-mediated C-P coupling of (hetero)aryl bromides/iodides with HP(O)Me-2. The P(O)Me-2 substituent was shown to dramatically increase solubility and decrease Iipophilicity of organic compounds. This tactic was used to improve the solubility of the antihypertensive drug prazosin without affecting its biological profile.