The invention relates to intermediates useful in the preparation of halichondrin compounds, methods for preparing the same and use thereof, such as halichondrins, eribulin, or their analogs. The intermediates, the methods and use thereof are used for the synthesis of the C20-C26 fragment of halichondrin compounds. The raw materials in the synthetic route of the invention are cheap and easily obtained, the sources and the qualities of the raw materials are reliable. The choice of the methods useful in the synthesis of chiral central structures are based on the structural characteristics of the reactants, thus effectively improving the synthesis efficiency, reducing the difficulties and risks of product quality control, and avoiding the use of highly toxic and expensive organotin catalysts to significantly decrease costs and improve environmental friendliness.

The invention relates to intermediates useful in the preparation of halichondrin compounds, methods for preparing the same and use thereof, such as halichondrins, eribulin, or their analogs. The intermediates, the methods and use thereof are used for the synthesis of the C20-C26 fragment of halichondrin compounds. The raw materials in the synthetic route of the invention are cheap and easily obtained, the sources and the qualities of the raw materials are reliable. The choice of the methods useful in the synthesis of chiral central structures are based on the structural characteristics of the reactants, thus effectively improving the synthesis efficiency, reducing the difficulties and risks of product quality control, and avoiding the use of highly toxic and expensive organotin catalysts to significantly decrease costs and improve environmental friendliness.

Nanoparticles having a plurality of PVP chains covalently bonded to a surface of the nanoparticle are provided, along with their methods of formation and the RAFT agents for the polymerization of the PVP chains. RAFT agents are generally provided, along with their methods of formation and use. Methods are also generally provided for grafting a PVP polymer onto a nanoparticle. In one embodiment, the method includes polymerizing a plurality of monomers in the presence of a RAFT agent to form a polymeric chain covalently bonded to the nanoparticle.

Nanoparticles having a plurality of PVP chains covalently bonded to a surface of the nanoparticle are provided, along with their methods of formation and the RAFT agents for the polymerization of the PVP chains. RAFT agents are generally provided, along with their methods of formation and use. Methods are also generally provided for grafting a PVP polymer onto a nanoparticle. In one embodiment, the method includes polymerizing a plurality of monomers in the presence of a RAFT agent to form a polymeric chain covalently bonded to the nanoparticle.

The use of an N-heterocyclic compound of the general formula (a) or (b) with the following definitions: X.sup.1 being S or X.sup.2 being S or O and at least one of X.sup.1 and X.sup.2 being S R.sup.2 H or C.sub.1-4-alkyl, R.sup.3 H or C.sub.1-4-alkyl R.sup.6 and R.sup.7 are hydrogen or together form a covalent carbon-carbon bond in general formula (a) R.sup.1 being H, C.sub.1-12-alkyl or CH.sub.2NR.sup.4R.sub.5 with R.sup.4 hydrogen or C.sub.1-4-alkyl, R.sup.5 C.sub.1-12-hydrocarbon residue which can contain one to three halogen atoms and/or one to four heteroatoms, selected from the group consisting of nitro-gen, oxygen and sulfur, it also being possible for R.sup.4 and R.sup.5, together with the nitrogen atom joining them, to form a 5- or 6-membered saturated or unsaturated heterocyclic radical, which optionally may also contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, in general formula (b) R.sup.1 being H or C.sub.1-17-hydrocarbon, preferably H, or CH.sub.2R.sup.5 with R.sup.5 being H or C.sub.1-16-hydrocarbon residue, which hydrocarbon can contain one to three halogen atoms and/or one to six heteroatoms, selected from the group consisting of nitrogen, oxygen and sulfur, and preferably in general formula (a) and (b) X.sup.1 and X.sup.2 being S, as nitrification inhibitor.

##STR00001##

The use of an N-heterocyclic compound of the general formula (a) or (b) with the following definitions: X.sup.1 being S or X.sup.2 being S or O and at least one of X.sup.1 and X.sup.2 being S R.sup.2 H or C.sub.1-4-alkyl, R.sup.3 H or C.sub.1-4-alkyl R.sup.6 and R.sup.7 are hydrogen or together form a covalent carbon-carbon bond in general formula (a) R.sup.1 being H, C.sub.1-12-alkyl or CH.sub.2NR.sup.4R.sub.5 with R.sup.4 hydrogen or C.sub.1-4-alkyl, R.sup.5 C.sub.1-12-hydrocarbon residue which can contain one to three halogen atoms and/or one to four heteroatoms, selected from the group consisting of nitro-gen, oxygen and sulfur, it also being possible for R.sup.4 and R.sup.5, together with the nitrogen atom joining them, to form a 5- or 6-membered saturated or unsaturated heterocyclic radical, which optionally may also contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, in general formula (b) R.sup.1 being H or C.sub.1-17-hydrocarbon, preferably H, or CH.sub.2R.sup.5 with R.sup.5 being H or C.sub.1-16-hydrocarbon residue, which hydrocarbon can contain one to three halogen atoms and/or one to six heteroatoms, selected from the group consisting of nitrogen, oxygen and sulfur, and preferably in general formula (a) and (b) X.sup.1 and X.sup.2 being S, as nitrification inhibitor.

##STR00001##

The present invention relates to bumetanide derivatives of formula (I) as well as pharmaceutical compositions comprising these compounds for use in the treatment or prevention of diseases/disorders involving Na.sup.+K.sup.+2Cl.sup.-cotransporters (NKCCs), and particularly for use in the treatment or prevention of hyperhidrosis.

##STR00001##

The present invention relates to bumetanide derivatives of formula (I) as well as pharmaceutical compositions comprising these compounds for use in the treatment or prevention of diseases/disorders involving Na.sup.+K.sup.+2Cl.sup.-cotransporters (NKCCs), and particularly for use in the treatment or prevention of hyperhidrosis.

##STR00001##

Provided is a process for synthesizing a functionalized cyclic dithiocarbamate.

Compounds having General Formula (I) or General Formula (II): ##STR00001##
in which R.sup.1 is chosen from C.sub.1 to C.sub.10 aliphatic or heteroaliphatic groups, optionally substituted with one or more aryl groups, substituted aryl groups, heteroaryl groups, substituted heteroaryl groups, or combination thereof, R.sup.2 is chosen from aromatic moieties, substituted aromatic moieties, heteroaromatic moieties, substituted heteroaromatic moieties, and coumarin; R.sup.3 is chosen from H, C.sub.1 to C.sub.10 aliphatic or heteroaliphatic groups, phenyl, or substituted phenyl, wherein the aliphatic or heteroaliphatic groups are optionally substituted with one or more phenyl groups, aryl groups, heteroaryl groups, substituted heteroaryl groups, or combination thereof, and wherein the aliphatic or heteroaliphatic groups are optionally bonded to R.sup.2 to form a ring; X is S or O; and Y is S or NH, may be used in pharmaceutical compositions that modify of biological signaling processes or as reagents for biological assays.