Abstract: Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphosphoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.

Abstract: A method for the synthesis of N-protected 3,6-aminoalkyl-2,5-diketopiperazines is provided. The method includes obtaining a cyclic ?-N protected active amino ester and adding it to a mixture of an amine catalyst in an organic solvent.

Abstract: Several aromatic hydrocarbons di-substituted with a polyamine are described according to formulas selected from compounds 4, 7, 10, 15 and pharmaceutically acceptable salts thereof. The novel dimeric polyamines of the present invention demonstrate enhanced penetration into cells having an upregulated polyamine transport system, such as various types of cancer cells. The disclosed aromatic polyamine dimers provide highly efficient drugs for targeting cancer cells with active polyamine transporters.

Abstract: A method for the synthesis of N-protected 3,6-aminoalkyl-2,5-diketopiperazines is provided. The method includes obtaining a cyclic ?-N protected active amino ester and adding it to a mixture of an amine catalyst in an organic solvent.

Abstract: The present invention relates to novel compounds for modulating US28 receptor activity and methods for their use in preventing or treating US28 receptor-mediated disorders or conditions.

Abstract: Disclosed herein are novel motuporamine compounds that act as anti-metastatic agents with low toxicity and high anti-migration activity. The non-toxic, anti-metastatic agents may be given to patients with potential or actual metastatic cancers, such as pancreatic cancers, alone in combination with known and/or new therapies to help block the growth and spread of tumor(s).

Abstract: A method for the synthesis of N-protected 3,6-aminoalkyl-2,5-diketopiperazines is provided. The method includes obtaining a cyclic ?-N protected active amino ester and adding it to a mixture of an amine catalyst in an organic solvent.

Abstract: Disclosed herein are di-substituted aryl polyamine compounds and methods of making and using the same. The di-substituted polyamine compounds act as PTS targeting agents, which selectively target the polyamine transport system (PTS) with high efficacy and have improved stability in the presence of amine oxidases.

Abstract: A method for the synthesis of N-protected 3,6-aminoalkyl-2,5-diketopiperazines is provided. The method includes obtaining a cyclic ?-N protected active amino ester and adding it to a mixture of an amine catalyst in an organic solvent.

Abstract: Several aromatic hydrocarbons di-substituted with a polyamine are described according to formulas selected from compounds 4, 7, 10, 15 and pharmaceutically acceptable salts thereof. The novel dimeric polyamines of the present invention demonstrate enhanced penetration into cells having an upregulated polyamine transport system, such as various types of cancer cells. The disclosed aromatic polyamine dimers provide highly efficient drugs for targeting cancer cells with active polyamine transporters.

Abstract: Cyano-substituted anthracene containing polyamines were synthesized and shown to be efficient polyamine transporter ligands. Moreover, these compounds (3 and 4) had improved fluorescence properties over previously known anthryl-polyamine conjugates, which facilitated their intracellular trafficking by confocal microscopy and fluorescence methods. These cytotoxic fluorescent agents may find use as molecular probes which traffic into cells via the polyamine transport system and may also be viable anticancer drugs which are readily quantified in human tissues due to their excellent fluorescence properties: (excitation: ?405 nm) and emission (420 nm) occurs in the visible light range. The ability to excite and emit in the visible range provides an advantage to these probes as these wavelengths are considered non-toxic to human cells (versus ultraviolet mediated excitations, ?<400 nm) and visible light lasers are less costly to purchase and operate than UV laser sources.

Abstract: Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphosphoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.

Abstract: Several aromatic hydrocarbons di-substituted with a polyamine are described according to formulas selected from compounds 4, 7, 10, 15 and pharmaceutically acceptable salts thereof. The novel dimeric polyamines of the present invention demonstrate enhanced penetration into cells having an upregulated polyamine transport system, such as various types of cancer cells. The disclosed aromatic polyamine dimers provide highly efficient drugs for targeting cancer cells with active polyamine transporters.

Abstract: Cyano-substituted anthracene containing polyamines were synthesized and shown to be efficient polyamine transporter ligands. Moreover, these compounds (3 and 4) had improved fluorescence properties over previously known anthryl-polyamine conjugates, which facilitated their intracellular trafficking by confocal microscopy. These cytotoxic fluorescent agents may find use as molecular probes which traffic into cells via the polyamine transport system and may also be viable anticancer drugs which are readily quantified in human tissues due to their excellent fluorescence properties: (excitation: ? 405 nm) and emission (420 nm) occurs in the visible light range. The ability to excite and emit in the visible range provides an advantage to these probes as these wavelengths are not toxic to human cells (versus ultraviolet mediated excitations, ?<400 nm) and visible light lasers are less costly to purchase and operate than UV laser sources.

Abstract: Novel polyamine transport inhibitors have been synthesized and demonstrated to block the uptake of native polyamines into human cancer cells. A combination therapy of the transport inhibitor and DFMO (a drug which blocks polyamine biosynthesis) provided synergistic activity against a metastatic human colon cancer cell line. The strategy uses polyamine depletion and polyamine metabolism to generate reactive oxygen species within cells as a novel way to treat cancers. This approach may be implemented for widespread use in the treatment of diseases which rely upon polyamine transport activity for proliferation.

Abstract: Disclosed are diagnostic tests helpful in indicating presence of an inflammatory bowel disease (IBD) in a human patient. In one embodiment, the test comprises obtaining a sample of mucosal tissue from the ileum or sigmoid colon of the patient; evaluating sample quality by testing for cadaverine and continuing the diagnostic test if the sample has no detectable cadaverine; testing the cadaverine negative sample for N-acetylated spermine; and correlating a detectable level of N-acetylated spermine in the sample with presence of IBD in the patient. Another, less invasive, method disclosed includes a diagnostic test comprising isolating mononuclear leukocytes from the patient's blood; testing the isolated mononuclear leukocytes for level of spermidine; and correlating a level of spermidine higher than that in mononuclear leukocytes of normal subjects as indicative of an inflammatory bowel disease in the patient.

Abstract: Polyamine cationic lipids have been synthesized that have the ability to be transported into cells having an active polyamine transport system. Accordingly, these lipids may be conjugated with various agents and, thereby, act as vectors for transporting the agent into the cell aided by the cell's own polyamine transport system. A method of delivering an agent into a cell includes associating the agent with a polyamine cationic lipid selected from compounds 25, 26, 27, 28, their pharmaceutically acceptable salts and combinations thereof and contacting the cell therewith.

Abstract: Disclosed herein are motuporamine mimic agents and methods of making and using same. Particularly exemplified are motuporamine mimic agents comprising cytotoxic activity and/or anti-metaplastic activity.

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.

Abstract: Disclosed herein are motuporamine mimic agents and methods of making and using same. Particularly exemplified are motuporamine mimic agents comprising cytotoxic activity and/or anti-metaplastic activity.