Abstract: The present invention relates to pharmaceutical compositions and methods for controlling tumor growth in cancer patients. These compounds and pharmaceutical compositions modulate the P-glycoprotein multidrug transporter system and inhibit the activated PI3K/Akt/mTOR/p70S6K signaling pathway. The compounds and pharmaceutical compounds of the present invention are particularly useful for treating metastatic and drug-resistant tumors.

Abstract: The present invention relates to pharmaceutical compositions containing tumor-selective targeted inhibitor glycoconjugates. These bioconjugates are ALK5 inhibitors covalently bound to biocompatible carrier molecules which selectively target and specifically bind to Muc4 that is overexpressed on a variety of tumor cell types. The ALK5 inhibitors are conjugated to tumor targetable glycans through a covalent linker. Preferably the acid-labile linker is designed to be stable in plasma and releases pharmacologically active inhibitors through acid-catalyzed hydrolysis in the acidic environment of the target tumor where the inhibitor activity is restored. Because the glycoconjugates are stable at physiological pH and in plasma, they advantageously reduce undesirable systemic ALK5 inhibitor activity; however, the preferable glycoconjugates are acid-labile conjugates that can be hydrolyzed upon reaching the more acid environment of the tumor.

Abstract: The present invention relates to pharmaceutical compositions containing targetable bioconjugates of hydralazine, a direct vasodilating agent previously shown to decrease tumor blood flow, oxygenation and interstitial fluid pressure in solid tumors. These bioconjugates are hydralazine prodrugs that contain hydralazine conjugated to biocompatible carrier molecules which specifically bind to sites that are expressed on a diverse variety of tumor cell types. These hydralazine prodrugs are preferably conjugated through an acid-labile hydrazone link that is designed to be stable in plasma and release hydralazine through acid-catalyzed hydrolysis in the acidic environment of the target tumor. Because these prodrugs are stable at physiological pH and in plasma, they are devoid of systemic vasoactive activity; however, they are acid-labile conjugates that can be hydrolyzed upon reaching the more acid environment of the tumor where the vasoactive activity of hydralazine is restored.

Abstract: The present invention relates to improved fluorescently labeled monosaccharide and low molecular weight oligosaccharide conjugates for immunofluorescent staining, confocal microscopic imaging and flow cytometry/fluorescence activated cell sorting (FACS). These fluorophore conjugates target cells, components of cell surfaces and extracellular components; and are useful as probes for tumor targeting and cellular uptake.

Abstract: The present invention relates to pharmaceutical compositions containing tumor-selective targeted inhibitor glycoconjugates. These bioconjugates are ALK5 inhibitors covalently bound to biocompatible carrier molecules which selectively target and specifically bind to Muc4 that is overexpressed on a variety of tumor cell types. The ALK5 inhibitors are conjugated to tumor targetable glycans through a covalent linker. Preferably the acid-labile linker is designed to be stable in plasma and releases pharmacologically active inhibitors through acid-catalyzed hydrolysis in the acidic environment of the target tumor where the inhibitor activity is restored. Because the glycoconjugates are stable at physiological pH and in plasma, they advantageously reduce undesirable systemic ALK5 inhibitor activity; however, the preferable glycoconjugates are acid-labile conjugates that can be hydrolyzed upon reaching the more acid environment of the tumor.

Abstract: The present invention relates to novel noncardiotoxic compounds and pharmaceutical compositions useful in the treatment of a variety of disorders including the treatment of depression, allergies, psychoses, cancer and gastrointestinal disorders. In particular, the present invention describes pharmaceutical compositions that mitigate life-threatening arrhythmias such as torsade de pointes. Torsade de pointes is a particular cardiac problem associated with many therapeutic agents and has been implicated as a possible cause of sudden death, particularly in those individuals with a past history of disturbances of cardiac rhythm, myocardial infarction, congenital repolarization abnormalities and cardiac risk factors such as hyperlipidemia and age. This arrhythmia is a variant of paroxysmal ventricular tachycardia associated with a prolonged QTc interval or prominent U waves on the ECG.

Abstract: The present invention relates to improved fluorescently labeled monosaccharide and low molecular weight oligosaccharide conjugates for immunofluorescent staining, confocal microscopic imaging and flow cytometry/fluorescence activated cell sorting (FACS). These fluorophore conjugates target cells, components of cell surfaces and extracellular components; and are useful as probes for tumor targeting and cellular uptake.

Abstract: Pharmaceutical compounds having the general formula: or compounds having the formula: where R1 and R2 are independently H, branched or straight chain alkyl having from 1 to about 7 carbon atoms, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted alkylcycloalkyl, lower alkenyl or R1 and R2 together form part of a substituted or unsubstituted cycloalkyl having from about 4 of about 7 carbon atoms; where R3 is a branched or straight chain alkyl having from 1 to about 7 carbon atoms, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted cycloalkyl, aralkyl, substituted or unsubstituted alkylcycloalkyl or a group having the formula (CH2)nCOOH where n is from 1 to about 7.

Abstract: The present invention relates to pharmaceutical compositions containing targetable bioconjugates of hydralazine, a direct vasodilating agent previously shown to decrease tumor blood flow, oxygenation and interstitial fluid pressure in solid tumors. These bioconjugates are hydralazine prodrugs that contain hydralazine conjugated to biocompatible carrier molecules which specifically bind to sites that are expressed on a diverse variety of tumor cell types. These hydralazine prodrugs are preferably conjugated through an acid-labile hydrazone link that is designed to be stable in plasma and release hydralazine through acid-catalyzed hydrolysis in the acidic environment of the target tumor. Because these prodrugs are stable at physiological pH and in plasma, they are devoid of systemic vasoactive activity; however, they are acid-labile conjugates that can be hydrolyzed upon reaching the more acid environment of the tumor where the vasoactive activity of hydralazine is restored.

Abstract: The present invention relates to pharmaceutical compositions containing sulpiride compounds having the general formula: where R1 is branched or straight chain alkyl having from 1 to about 7 carbon atoms, a substituted or unsubstituted aryl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted aralkyl, a substituted or unsubstituted alkylcycloalkyl, or a group having the formula (CH2)n R2 where R2 is a substituted or unsubstituted aryl or a substituted or unsubstituted cycloalkyl, and n is an alkyl group having from 0 to about 6 carbon atoms and pharmaceutically acceptable salts or diluents.

Abstract: Disclosed are compounds having the formula wherein R2 is hydrogen, a monomeric glycoside or an oligomeric glycoside, R3 is hydrogen, a monomeric glycoside, an oligomeric glycoside, or a group having the formula R is a lower alkylene, R? is selected from the group consisting of moieties having the formula where X=0 or 1, Y=0 or 1, R1 is hydrogen or a pharmacologically active drug residue, R8 a pharmacologically active drug residue, R4, R5, and R6 are independently hydrogen, alkyl, aryl, aralkyl, and cycloalkyl or together form a nitrogen-containing ring, and R7 is hydroxyl or hydroxyalkyl.

Abstract: A method of improving the stability of a hydralazine composition during manufacturing or storage comprising coupling an N-protecting group with hydralazine to produce the compound having the formula: or a compound having the formula: where R1 and R2 are independently H, branched or straight chain alkyl having from 1 to about 7 carbon atoms, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted alkylcycloalkyl, lower alkenyl or R1 and R2 together form part of a substituted or unsubstituted cycloalkyl having from about 4 of about 7 carbon atoms; where R3 is a branched or straight chain alkyl having from 1 to about 7 carbon atoms, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted cycloalkyl, aralkyl, substituted or unsubstituted alkylcycloalkyl or a group having the formula (CH2)nCOOH where n is from 1 to about 7.

Abstract: Pharmaceutical compounds having the general formula: or compounds having the formula: where R1 and R2 are independently H, branched or straight chain alkyl having from 1 to about 7 carbon atoms, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted alkylcycloalkyl, lower alkenyl or R1 and R2 together form part of a substituted or unsubstituted cycloalkyl having from about 4 of about 7 carbon atoms; where R3 is a branched or straight chain alkyl having from 1 to about 7 carbon atoms, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted cycloalkyl, aralkyl, substituted or unsubstituted alkylcycloalkyl or a group having the formula (CH2)nCOOH where n is from 1 to about 7.

Abstract: Disclosed are compounds having the formula 1

Abstract: Disclosed are compounds having the formula wherein R2 is hydrogen, a monomeric glycoside or an oligomeric glycoside, R3 is hydrogen, a monomeric glycoside, an oligomeric glycoside, or a group having the formula R is a lower alkylene, R′ is selected from the group consisting of moieties having the formula where X=0 or 1, Y=0 or 1, R1 is hydrogen or a pharmacologically active drug residue, R8 a pharmacologically active drug residue, R4, R5, and R6 are independently hydrogen, alkyl, aryl, aralkyl, and cycloalkyl or together form a nitrogen-containing ring, and R7 is hydroxyl or hydroxyalkyl.

Abstract: Pharmaceutical compounds having the general formula: 1

Abstract: A method of improving the stability of a hydralazine composition during manufacturing or storage comprising coupling an N-protecting group with hydralazine to produce the compound having the formula: 1