Phosphonate conjugates, preferably, bisphosphonate conjugates; methods of inhibiting Ron receptor tyrosine kinase and methods of treatment of bone destruction due to cancer or other conditions utilizing the provided phosphonate conjugates.

The present disclosure provides methods of synthesizing a compound of Formula (P)-I. The method proceeds through several different pathways including several novel chiral separations, a Sonogashira coupling, a zinc mediated reductive cyanation, as well as through various halide containing intermediates. Also disclosed is the multi-kilogram preparation of several novel intermediates.

The present invention provides an effective production method for a pyridone compound. More specifically, the present invention provides a production method comprising: a step of reacting the compound represented by formula (1) (in the formula, X.sup.1 and X.sup.2 each independently represent a halogen atom, R.sup.1 represents a hydrogen atom, an amino group, or a group represented by NHCOR.sup.2, and R.sup.2 represents a C1-C5 alkyl group) with 4 to 10 times by mass, with respect to the compound represented by formula (1), of the compound represented by formula (2) (in the formula, R.sup.2 represents the same as described previously), in the presence of at least one of a tri(C1-C8 alkyl)amine and an alkali metal acetate, at a temperature of 100° C. or higher to obtain the compound represented by formula (3) (in the formula, X.sup.1, X.sup.2 and R.sup.2 represent the same as described previously, R.sup.6 represents a hydrogen atom or an NHCOR.sup.2 group); and a step of hydrolyzing the compound represented by formula (3), to obtain the pyridone compound represented by formula (4) (in the formula, X.sup.1, X.sup.2 and R.sup.1 represent the same as described previously). ##STR00001##

The present invention provides an effective production method for a pyridone compound. More specifically, the present invention provides a production method comprising: a step of reacting the compound represented by formula (1) (in the formula, X.sup.1 and X.sup.2 each independently represent a halogen atom, R.sup.1 represents a hydrogen atom, an amino group, or a group represented by NHCOR.sup.2, and R.sup.2 represents a C1-C5 alkyl group) with 4 to 10 times by mass, with respect to the compound represented by formula (1), of the compound represented by formula (2) (in the formula, R.sup.2 represents the same as described previously), in the presence of at least one of a tri(C1-C8 alkyl)amine and an alkali metal acetate, at a temperature of 100° C. or higher to obtain the compound represented by formula (3) (in the formula, X.sup.1, X.sup.2 and R.sup.2 represent the same as described previously, R.sup.6 represents a hydrogen atom or an NHCOR.sup.2 group); and a step of hydrolyzing the compound represented by formula (3), to obtain the pyridone compound represented by formula (4) (in the formula, X.sup.1, X.sup.2 and R.sup.1 represent the same as described previously). ##STR00001##

The present invention relates to crystal forms of an oxypyridine amide derivative and a preparation method therefor. In particular, the present invention relates to crystal forms A, B, C, D, E and F of a compound represented by formula (I) and a preparation method therefor. The crystal forms of the compound represented by formula (I) as described in the present invention have good crystal form stability and may be better for clinical use.

Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

The invention provides novel pyridylpyridone compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for using such compounds in treatment of diseases including cancer, type II diabetes, inflammatory disease, autoimmune diseases, neurodegenerative disorders, cardiovascular disorders and viral infections; wherein R.sup.1, R.sup.2, R.sup.3 and X are as defined in the specification. ##STR00001##

The invention provides novel pyridylpyridone compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for using such compounds in treatment of diseases including cancer, type II diabetes, inflammatory disease, autoimmune diseases, neurodegenerative disorders, cardiovascular disorders and viral infections; wherein R.sup.1, R.sup.2, R.sup.3 and X are as defined in the specification. ##STR00001##

Disclosed are chelating co-polymer compositions that are soluble in aqueous media and chelate essential metals, methods of preparation and uses thereof. The chelating compositions are comprised of two or more different monomers, at least one of which possesses metal binding or metal chelating activity. The chelating compositions are synthesized by reversible addition-fragmentation transfer (RAFT) polymerization with the aid of a suitable RAFT-mediating agent. Also described are chelating compositions that comprise hydroxypyridinone chelating groups. The ability of the chelating compositions to bind metals affects the activity of a living cells and organisms, which require the metals for cellular functions.