City University of New York

Other

University of British Columbia

Children's Hospital Research Center at Oakland

Mayo Foundation for Medical Education and Research

Albert Einstein College of Medicine

The University of Manitoba

The Liposome Company, Inc.

Robert Bittman

Hassan Salari

Gilbert Arthur

Eric G Mayhew

Zaiguo Li

Julie D Saba

Henrik Fyrst

Ravi K Erukulla

Hoe-Sup Byun

Andrew C Peters

William R Jacobs, Jr

John S Blanchard

Hirohito Kita

James Sacchettini

Richard W Frank

Lawrence Leung

David L Marks

Ramandeep S Takhter

Antonio Gomez Munoz

Richard E Pagano

The invention relates to novel caged ceramide 1-phosphate (C1P), caged ceramide 1-phosphate derivatives(C1P), and the method of using them for delivering C1P intracellularly in vitro and in vivo, for research and therapeutic purposes. Therapeutic purposes include treatment of diseases associated with cell death, such as neurodegerative diseases, including Alzheimer's disease. The disclosed compositions may also be used for wound healing.

Caged ceramide-1-phosphate derivatives

The present invention is directed to unsaturated sphingosine compounds which are useful as therapeutic agents for the treatment of cancer and for the treatment of other diseases including diabetes and infection with intracellular bacteria. The invention is also directed to methods of using the compounds and pharmaceutical compositions comprising the compounds in treating these diseases.

Use of unsaturated sphingosine compounds as chemotherapeutic agents for the treatment of cancer

The present invention is directed to unsaturated sphingosine compounds which are useful as therapeutic agents for the treatment of cancer and for the treatment of other diseases including diabetes and infection with intracellular bacteria. This invention is also directed to methods of using the compounds and pharmaceutical compositions comprising the compounds in treating these diseases.

The present invention relates to FTY720 analogs bearing a boron dipyrromethene difluoro (BODIPY) fluorophore in the alkyl side chain and methods of preparation. The compounds of the present invention can be used in fluorescence spectroscopy and fluorescence microscopy and in chromatography using fluorescence detection.

Boron dipyrromethene difluoro (BODIPY) conjugates

This disclosure provides a composition useful for inhibiting caveolar endocytosis, plasma membrane microdomain formation, virus binding and infection, transmembrane signaling, and integrin function in cells. The composition is composed of non-natural analogs of sphingolipids, and may have applications in the treatment or amelioration of diseases associated with caveolar endocytosis, plasma membrane microdomain formation, transmembrane signaling, and integrin function. Methods for making and using the described composition are also provided.

Non-natural sphingolipid analogs and uses thereof

The syntheses and in vitro antitumor properties of carbamate-containing, dicarbamate-containing, and ureido-containing phospholipid compounds that have an ether linkage at the C-1 position of a glycerol backbone, a carbamate, dicarbamate, or ureido moiety at the C-2 position of the glycerol backbone, and a phosphocholine, phosphonocholine, or glycoside moiety at the C-3 position of the glycerol backbone are described. The synthesis and antiproliferative activity of ether lipids with a naphthol moiety at the C-1 position are also described. These compounds were shown to be potent inhibitors of cancer cell growth. These compounds are useful for killing cancer cells and treating cancer.

Synthesis of glycerolipid carbamates and dicarbamates and their use as an antitumor compounds

The present invention relates to free cholesterol analogs bearing a boron dipyrromethene difluoro (BODIPY) fluorophore in the side chain and methods of preparation. The compounds of the present invention can be used in fluorescence spectroscopy and fluorescence microscopy to visualize the exchange, distribution, and trafficking of free cholesterol between living cells and to monitor the movement of free cholesterol between ordered and disordered lipid domains in membranes.

Free cholesterol analogs bearing a boron dipyrromethene difluoro (BODIPY) fluorophore in the side chain and method of preparation and use thereof

Unsaturated alkyllysophosphonocholines compounds of formula (I) or (II): or pharmaceutically-acceptable salts, prodrugs or isomers thereof. The compounds of the invention have anti-neoplastic activity, and accordingly have utility in treating cancer and related diseases. The invention also provides enantiomers of these compounds, as well as synthetic methods for producing an enantiomer, substantially free of the other enantiomer. Also disclosed are pharmaceutical compositions, as well methods for treating cancer with the pharmaceutical compositions.

Enanitomers of unsaturated alkyllysophosphonocholines and use as anti-neoplastics

C-glucosyl ether lipids

This invention provides lipids having: 1) a glycerol backbone; 2) a hydrocarbon chain, preferably saturated and containing 16 or 18 carbon atoms, attached to C-1 of the backbone by an ether linkage, 3) a methyl group attached to C-2 of the backbone, preferably by an ether linkage; and, 4) a sugar attached to C-3 of the glycerol backbone in either the alpha or beta anomeric configuration, the sugar being altered by modification of, or substitution for, one or more of its hydroxyl groups. Also provided herein are ether-lipid-containing compositions, as well as methods of administering such compositions to animals, for example, those afflicted with cancers, as well as various other diseases and disorders.

Modified ether glyceroglycolipids

This invention provides lipids having: 1) a glycerol backbone; 2) a hydrocarbon chain, preferably saturated and containing 16 or 18 carbon atoms, attached to C-1 of the backbone by an ether linkage; 3) a methyl group attached to C-2 of the backbone, preferably by an ether linkage; and, 4) a sugar attached to C-3 of the glycerol backbone in either the alpha or beta anomeric configuration, the sugar being altered by modification of, or substitution for, one or more of its hydroxyl groups. Also provided herein are ether-lipid-containing compositions, as well as methods of administering such compositions to animals, for example, those afflicted with cancers, as well as various other diseases and disorders.

The present invention provides a compound having the structure: ##STR1## wherein R is a branched or unbranched C1-C30 alkyl, alkenyl or alkynl; or a branched or unbranched C1-C30 alkyl, alkenyl or alkynl substituted with S, O, N, P, SO.sub.2, F, Cl, Br, or I, wherein S, O, N, P, or SO.sub.2 replaces at least one --CH.sub.2 --, and F, Cl, Br, or I replaces at least one H. The present invention also provides a pharmaceutical composition comprising the compound above, as well as a method for treating a mycobacterial disease or infection in a subject in need of such treatment by administering to the subject an effective amount of the compound above.

Antimycobacterial compounds and method of using same

Provided herein are novel syntheses of the phosphate-based inositol derivatives 1-O-�(+)-menthoxycarbonyl!-6-O-benzyl-2,3:4,5-di-O-isopropylidene-myo-inos itol (D4P), D-myo-inositol 1,4,5-trisphosphate (D-IP.sub.3), 6-O-benzyl-2,3:4,5-di-O-isopropylidene-myo-inositol H-phosphonate ((-)-3-HP) and L-myo-inositol 1,4,5-trisphosphate (L-IP.sub.3). These syntheses employ fewer column chromatography steps for the isolation of intermediates than do prior art syntheses, and hence, are more convenient, economical and efficient than are the previously known synthetic methods.

Synthesis of myo-inositol phosphates

This invention pertains to the synthesis and usc as anti-cancer therapeutic agents of a group of substances with a glycerol backbone linked to phosphonocholinc, or other phosphorus-containing head groups, of the following formula: ##STR1## wherein n is 0 to 14 and R.sub.1 is an alkyl group containing 12 to 20 carbon atoms, R.sub.2 is a methyl group, n=0 to 14 and m=2 to 10, or enantiomer thereof, or mixture of stereoisomers. This invention also pertains to the following formula: ##STR2## wherein n is 15 to 17; R1 is an alkyl group: m is 0 to 2; T is an oxygen atom or a methylene; and R.sub.2 is a choline group and therapeutically effective pharmaceutically acceptable salts thereof. These thiophosphonolipids are useful for treating cancer in a mammal in need of cancer treatment.

Phosphonates as anti-cancer agents

This invention pertains to the synthesis and use as therapeutic agents of a group of substances with a glycerol backbone or aliphatic chain structure linked to a phosphorus atom and a polar head group. Depending on the polar head group, the substance has anti-cancer, anti-inflammatory, anti-allergy or anti-cardiovascular disease properties. Compounds of the formula: ##STR1## wherein n is 0 to 14 and R.sub.1 is an alkyl group of C.sub.12 -C.sub.20, R.sub.2 is a methyl group, and wherein R.sub.3 is an inositol analog head group, a (CH.sub.2).sub.m N.sup.+ (CH.sub.3).sub.3 group with m=2 to 10, a serine head group, or an ethanolamine head group, or of the formula ##STR2## wherein R.sub.1 and R.sub.2 are as described above, n=0 or 1, and R.sub.3 is (CH.sub.2).sub.m N.sup.+ (CH.sub.3).sub.3 (m=2-10 ) are claimed. This invention also pertains to the synthesis and use as therapeutic agents of a group of substances that have no glycerol backbone but have an aliphatic chain structure linked directly to a phosphorus atom of the general formula R--P(O)(O-)OR' wherein R is a long-chain alkyl group such as hexadecyl or octadecyl and R' is a head group such as choline, glycerol, inositol, ethanolamine, or serine.

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Roslyn Heights, NY, United States of America

Robert Bittman