Hypoxia-selective, weakly basic 2-nitroimidazole delivery agents and methods of use thereof
AssigneeNatural Pharmacia International, Inc.
InventorsDavid Y-W Lee, Xiao-Shen Ji, James A. Raleigh
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Abstract
The invention features a class of 2-nitroimidazole compounds with a secondary basic nitrogen atom and a linker bearing one or more therapeutic agents, cytotoxic agents, detectable labels, or chelating groups. In particular, the invention provides 2-nitroimidazole compounds containing a cluster of boron atoms for use in boron neutron capture therapy (BNCT). The 2-nitroimidazole compounds can be used to treat hypoxic conditions, including, e.g., cancer, inflammation, and ischemia. The weakly basic 2-nitroimidazole compounds target to hypoxic tissue and provide increased tissue concentration overall.
Claims38
A compound having the structure of formula I and pharmaceutically acceptable salts thereof
- wherein:
- R1 is a halogen, positron emitting radionuclide, non-metal, lower alkyl substituted to contain a halogen, lower alkyl substituted to contain a positron emitting radionuclide, lower alkyl substituted to contain a non-metal, tosylate, mesylate, tryflate, hydrogen, or hydroxyl;
- and
- R2 and R3 are independently selected from a lower alkyl, allyl, alkenyl, alkynyl, hydroxyalkyl, heteroalkyl, polyether, and polyether with a terminal heteroatom and wherein at least one of R2 or R3 comprises a boron cluster and, optionally, a therapeutic agent, cytotoxic agent, detectable label, or chelating group.
A compound having the structure of formula I and pharmaceutically acceptable salts thereof
- wherein:
- R1 is a halogen, positron emitting radionuclide, non-metal, lower alkyl substituted to contain a halogen, lower alkyl substituted to contain a positron emitting radionuclide, lower alkyl substituted to contain a non-metal, tosylate, mesylate, tryflate, hydrogen, or hydroxyl;
- and
- R2 and R3 are independently selected from a hydrogen, lower alkyl, allyl, alkenyl, alkynyl, hydroxyalkyl, heteroalkyl, polyether, and polyether with a terminal heteroatom and wherein at least one of R2 or R3 comprises a boron cluster and, optionally, a therapeutic agent, cytotoxic agent, detectable label, or chelating group.
Dependencies are inferred from the claim text.