Georgetown University

U.S. Bioscience, Inc.

Medimmune Oncology, Inc.

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Philip S Schein

Abdolhossen Talebian

Dianna C Green

Martin Stogniew

Charles F Hammer

Eugene McPherson

Aquilur Rahman

James R Piper

Robert R Clarke

Alem Ghiorghis

Thea Kalebic

The present invention provides methods of administering aminoalkyl phosphorothioate and/or aminoalkyl thiol compounds to patients in a manner that significantly reduces or decreases the adverse or undesirable side-effects of the compounds as compared with conventional intravenous administration.

Methods for the administration of amifostine and related compounds

Method for the administration of amifostine and related compounds

Chronic HIV infection is treated by administering to a subject an organic thiophosphate alone or in combination with another anti-HIV or anti-AIDS drug. The organic thiophosphate is preferably WR 151327, a compound with antioxidant and free radical scavenging activities, or a functional derivative or analogue thereof. WR 151327 suppresses induction of HIV expression in chronically infected cells mediated by cytokines such as TNF.alpha. and GM-CSF. Pharmaceutical compositions comprising at least one organic thiophosphate in combination with one or more anti-HIV or anti-AIDS drugs are also disclosed.

Suppression of HIV expression by organic thiophosphate

S-.omega.(.omega.-aminoalkylamino)alkyl dihydrogen phosphorothioates or pharmaceutically acceptable derivatives thereof are useful in protecting a patient undergoing AZT treatment for AIDS and AIDS-related complex from the harmful side effects or reactions and toxicity of the AZT.

Method for protection from AZT side effects and toxicity

A method of decreasing the toxicity of chemical therapeutic agents administered in cancer chemotherapy including adminstration to a patient undergoing chemotherapy. This reduction in toxicity can be accomplished by administering an effective amount of S-3-(3-methylaminopropylamino)propyl dihydrogen phosphorothioate. Methods of inducing mucolytic activity and reducing toxicity of acetominophen overdose are also discussed. Such activities are induced through the administration of S-3-(3-methylaminopropylamino)propyl dihydrogen phosphorothioate.

Method of reducing chemotherapy toxicity using

The invention relates to certain derivatives of mitomycins A and C and the use thereof to treat bacterial infections and to supress the growth of cancer cells. The invention also relates to processes for the preparation of the mitomycin derivatives of the invention.

Mitomycin derivatives having reduced bone marrow toxicity, processes for

Compounds of the formula: ##STR1## wherein each of R.sub.1 and R.sub.2 is independently selected from the group consisting of halogen, hydroxy, or mono carboxylic acid or R.sub.1 and R.sub.2 together is a multifunctional carboxylic acid residue which forms a ring with the platinum atom through two oxygens of said multifunctional carboxylic acid; R.sub.3 is a deoxy mono or disaccharide or a derivative thereof; and R.sub.4 is selected from the group consisting of hydrogen, C.sub.1-4 -alkyl, phenyl, benzyl, substituted phenyl or substituted benzyl, wherein substituents are selected from the group consisting of halogen, nitro, C.sub.1-2 -alkoxy, carboxy, carbony ester or phenyl or a pharmaceutically acceptable salt thereof are disclosed. Compositions containing these compounds and methods using these compounds are also discussed.

Platinum compounds suitable for use as pharmaceuticals

Platinum compounds useful in the treatment of cancer are disclosed. Compositions containing these compounds and methods of using the same are also discussed. Compounds having the formula ##STR1## wherein n is 0 or 1 and when n is 1 R.sub.1 is H or C.sub.1 -C.sub.4 alkyl, R is non-substituted higher alkyl or mono or disaccharide or a derivative of a mono or disaccharide,

Platinum pharmaceutical agents

Platinum compounds of the formulae: ##STR1## are disclosed. Compositions containing these compounds and methods of using the same in the treatment of tumors are also discussed.

Platinum pharmaceuticals

Platinum compounds useful in the treatment of cancer are disclosed. Compositions containing these compounds and methods of using the same are also discussed. The compound have the formula: ##STR1## wherein n is 0 or 1, R.sub.1 is selected from the group consisting of hydrogen, a mono or disaccharide or a derivative thereof linked to the nitrogen atom by a --NHCO-amide moiety, an --NHCS-- thioamide moeity or a --CO-- carbonylmoiety, R' is selected from the group consisting of hydrogen and C.sub.1-4 alkyl, and R.sub.2 and R.sub.3 are selected from the group consisting of hydrogen, C.sub.1-4 alkyl or R.sub.2 and R.sub.3 or R.sub.2 and R.sub.3 together are linked to adjacent carbon atoms on a four, five or six membered ring structure, or R.sub.2 and R.sub.3 together form a fused or bicyclic ring with adjacent carbon atoms; with the proviso that R' and R.sub.1 cannot both be hydrogen when n=o, or a pharmaceutically acceptable salt thereof.

This invention discloses 1a- and 7-substituted derivatives of mitosanes containing thiocarbamoyl and glycosyl residues. The compounds possess antibacterial and antitumor activity, with a concomitant reduction in bone marrow toxicity as compared to the parent compounds.

1a-7-substituted derivatives of mitomycin and uses thereof

Compounds of the formula ##STR1## wherein X is halogen; each R independently represents H, a C.sub.1 -C.sub.4 alkyl group, a C.sub.2 -C.sub.4 alkanoyl group, a phosphate group, or a sulfate, sulfonate, or benzoate group with the proviso that no more than one sulfate, sulfonate, or benzoate group is present in said compound; and R' represents R or a carbohydrate residue derived from a carbohydrate having the formula R'OH with the proviso that R' and the R on C-2 or both R groups on C-3 and C-4 together can represent an isopropylidene group; or a pharmaceutically acceptable salt thereof, are disclosed along with methods of synthesizing and using these compounds.

Galactose-C-6 nitrogen mustard compounds and their uses

Anthracycline glycoside antibiotics are complexed with cardiolipin and then encapsulated in liposomes to reduce mammalian cardiac tissue uptake of the anthracycline glycoside and to thereby reduce the deleterious effect of such cardiac tissue uptake. The invention is directed to the composition, preparation and use of the encapsulated complex of anthracycline glycoside.

Growing community of inventors

Bryn Mawr, PA, United States of America

Philip S Schein