Abstract:
A method is provided for enhancing the solubility of an ionizable compound i n a lipophilic medium by admixing the compound with an effective solubility- enhancing amount of an N,N-dinitramide salt. The ionizable compound, upon ionization, gives rise to a biologically active cationic species that ionically associates with the N,N-dinitramide anion N(NO2)2 following admixture with the N,N-dinitramide salt. The biologically active cationic species may be a pharmacologically active cation, in which case the method i s useful for enhancing the penetration of the blood-brain barrier by the pharmacologically active cation. In other embodiments, the ionizable compoun ds are medical imaging or diagnostic agents, or agricultural agents such as pesticides. Salts of biologically active cations and N,N-dinitramide ion are also provided as novel compositions of matter.
Abstract:
Novel compounds are provided in the form of nucleoside pyrophosphate and triphosphate analogs. In these analogs, the pyrophosphate or triphosphate group is replaced with a moiety that is isosterically and electronically identical thereto, but is hydrolytically and enzymatically more stable. The compounds are useful as therapeutic agents, e.g., as antiviral agents, anticancer agents, metabolic moderators and the like. The invention also provides pharmaceutical compositions containing a compound of the invention as an active agent, and in addition provides methods of treating disease, including viral infections, cancer, bacterial infections, inflammatory and/or autoimmune diseases, and the like, by administering a compound of the invention to a patient in need of such treatment.