Polyamine conjugates as selective NMDA inhibitors and...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...

Reexamination Certificate

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C514S654000, C564S367000

Reexamination Certificate

active

07728040

ABSTRACT:
Polyamine compounds, method of synthesis and method of use for anti-cancer purposes, for enhancing the activity of existing anti-cancer drugs, as well as, for inhibiting N-Methyl-D-Aspartate (NMDA) receptors found in neurotransmission systems are provided. Certain polyamine motifs have been identified that can be attached to toxic agents to facilitate their access to cancer cells as well as polyamine compounds of surprising cytotoxicity with selectivity in killing cancer cells, and surprising utility in the treatment of Alzheimer's disease and brain stroke. It includes an illustrative conjugate system with examples of a triamine or a tetraamine appended to a cytotoxic agent. Included is a general strategy to enhance cell uptake by attaching a polyamine vectoring system with an example of a triamine vector attached to an existing anti-cancer drug to improve its chemotherapeutic potency. There is an illustration of tetraamine derivatives which have surprising enhanced selectivity in inhibiting N-methyl-D-aspartate (NMDA) receptors involved in neurotransmission. Several ligands can affect the activity of this receptor, which has been shown to initiate cell death under stroke conditions (lack of oxygen). Tetraamine derivatives which bind or inhibit the action of the NMDA receptor provide new therapy for NMDA-associated human diseases, such as Alzheimer's disease and stroke.

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