The present disclosure is directed to novel methods of treating type-1 or type-2 diabetes by inactivating TLR2 and TLR4 genes together in cells capable of producing insulin and/or regenerating β cells, and providing the cells to a subject in need thereof.

Disclosed are compounds of Formula 1, ##STR00001##
stereoisomers thereof and pharmaceutically acceptable salts of the compounds and stereoisomers, wherein R.sup.1 and R.sup.2 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating obesity and related diseases, disorders, and conditions associated with MetAP2.

Phosphoramidate derivatives of 5-fluoro-2′-deoxyuridine are disclosed for use in the treatment of cancer, especially in the treatment of cancer where the patient shows resistance, for example, in a patient with cells with a lowered level of nucleoside transporter proteins and/or with nucleoside kinase-deficient cells and/or with mycoplasma-infected cells and/or with cells with a raised level of thymidylate synthase.

Provided is a method for the preparation of mono-amidated phosphates or phosphonates as well as mono-amidated phosphates and phosphonates prepared by such method.

In an embodiment, the invention is directed to prodrug compounds of L-BHDU according to the chemical structure I:

##STR00001##

Where R.sup.1 is a —(CH.sub.2).sub.n—O—R.sup.1a group or a —(CH.sub.2).sub.j—O—C(O)O.sub.k—R.sup.2a group; R.sup.2 is H, a —(CH.sub.2).sub.n—O—R.sup.1a group or a —(CH.sub.2).sub.j—O—C(O)O.sub.k—R.sup.2a group; R.sup.1a is independently a C.sub.6-C.sub.30 alkyl group, often a C.sub.12-C.sub.22 alkyl group, often a C.sub.14-C.sub.20 alkyl group or a C.sub.16-C.sub.18 alkyl group, often a C.sub.16 or C.sub.18 alkyl group; R.sup.2a is independently a C.sub.1-C.sub.12 alkyl group, often a C.sub.2-C.sub.6 alkyl group, a C.sub.3-C.sub.4 alkyl group, an isopropyl, t-butyl or sec-butyl group, or an isopropyl or t-butyl group; Each j is independently 1-6, 1-3, often 1 or 2; Each k is 0 or 1; Each n is independently 1-6, 1-4, 2-4 or 2 or 3; or A pharmaceutically acceptable salt, solute or polymorph thereof. Additional embodiments are directed to pharmaceutical compositions based upon the disclosed chemical compounds and methods of treating or reducing the likelihood of VZV, HSV-1 or HSV-2 infections. Methods of synthesizing compounds according to the present invention represent further embodiments of the invention.

The present invention is related to a biotransformation process, effected by means of an isolated polypeptide possessing benzopyrone phosphate synthetase activity, and also a microorganism comprising a nucleic acid sequence that encodes the polypeptide, for the preparation of phosphate-conjugated derivatives of benzopyrone compounds. The hydrophilic property of the benzopyrone compounds is enhanced after catalyzed by the benzopyrone phosphate synthetase of the present invention.

The present invention relates to novel immunostimulatory molecules which are derived from the intestinal protozoan Entamoeba histolytica. The compounds have been found to be useful for enhancing and/or inducing an immune response in a subject in need thereof. Specifically, the compounds have been found to be useful for the treatment of cancer diseases, such as breast cancer, and parasitic diseases, such as leishmaniasis. The invention also provides pharmaceutical compositions comprising the novel compounds.

Functionally-modified oligonucleotide analogs comprising modified intersubunit linkages and/or modified 3′ and/or 5′-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I):

##STR00001##

or a stereoisomer, tautomer or salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, L.sup.1, L.sup.2, L.sup.3, L.sup.4, M, m and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

A process of forming a flame retardant material from furan dicarboxylic methyl ester (FDME) includes converting an FDME molecule to a 2,5-furan dicarbonyl dichloride (FDCC) molecule and chemically reacting the FDCC molecule with a phosphorus-containing material to form an FDME-based flame retardant material that includes a phosphorus-based flame retardant moiety.