The present invention generally relates to artemisinin/dihydroartemisinin (DHA) derivatives, and their use for therapy, in particular cancer therapy. These tumor-homing artemisinin derivatives (THAD) comprise three moieties: an artemisinin/DHA or a derivative thereof, a heptamethine carbocyanine dye (HMCD) residue, and a linker that conjugates the HMCD dye residue to the artemisinin residue. The THAD include compounds wherein the linker is linked to one or two DHA residue(s) via one or more ether bonds, and wherein the linker is linked to two DHA residues via two bonds independently selected from ester, carbamate and thiocarbamate. The THAD of the invention provide improved growth inhibition of cancer cells. The present invention also relates to improved methods of cancer therapy wherein a THAD is administered to a cancer patient. In embodiments, one or more THAD may be co-administered in a coordinated administration schedule. Advantages of the THAD and their use include, among others, improved dose-response and/or efficacy. The invention also relates to new dyes, their drug conjugates, and processes of making them.

The present disclosure relates to the field of epoxide synthesis, and particularly to a safe, environmentally friendly and controllable method for preparing cycloaliphatic diepoxides. The method comprises the steps of: mixing a diene compound, a carboxylic acid, an alkaline salt, and a solvent, and cooling; dropwise adding a hydrogen peroxide solution thereto over 1-12 h; standing for layering to obtain an underlayer of an organic phase 1, washing the organic phase 1 with a washing liquid, and standing for layering to obtain an underlayer of an organic phase 2; and purifying the organic phase 2. The reaction system of the present disclosure is simple, environmentally friendly, safe and controllable, and the production cost is low, which can meet the technical and economic requirements. The obtained cycloaliphatic diepoxides have high purity, high yield, low solvent content, low chroma and low halogen content, which are suitable for large-scale industrial production.

The invention relates to compounds constituting C20-N-acyl derivatives of salinomycin with the general formula (2):

##STR00001##

and their salts, where X denotes R, O—R or NH—R, and R is as defined in the claims and in the description. The invention also relates to a composition comprising the compound defined above and at least one pharmaceutically acceptable excipient. The invention also relates to a method for obtaining salinomycin derivatives with the general formula (2), as well as an intermediate product for obtaining these compounds. The invention also relates to compounds constituting C20-N-acyl derivatives of salinomycin with the general formula (2) for use as a medicament, particularly as anti-cancer agents.

The invention relates to compounds constituting C20-N-acyl derivatives of salinomycin with the general formula (2):

##STR00001##

and their salts, where X denotes R, O—R or NH—R, and R is as defined in the claims and in the description. The invention also relates to a composition comprising the compound defined above and at least one pharmaceutically acceptable excipient. The invention also relates to a method for obtaining salinomycin derivatives with the general formula (2), as well as an intermediate product for obtaining these compounds. The invention also relates to compounds constituting C20-N-acyl derivatives of salinomycin with the general formula (2) for use as a medicament, particularly as anti-cancer agents.

The present invention relates to an organic light emitting diode comprising: a first electrode; a second electrode facing the first electrode; a hole injecting layer or a hole transport layer, which is interposed between the first electrode and the second electrode; and a light emitting layer, wherein the hole injecting layer or the hole transport layer comprises at least one type of amine compound represented by chemical formula A or chemical formula B, and the chemical formula A and the chemical formula B are the same as those included in the description of the invention.

The invention relates to a method for the preparation of a 4,5-dihydroxyisoleucine derivative comprising the steps of asymmetric Claisen rearrangement of a Z-aminocrotyl-glycin ester and subsequent kinetic resolution of the product diastereomer mix by acylase, and subsequent Sharpless dihydroxylation of the resulting 2-amino-3-methylpent-4-enoic acid derivative.

The invention relates to a method for the preparation of a 4,5-dihydroxyisoleucine derivative comprising the steps of asymmetric Claisen rearrangement of a Z-aminocrotyl-glycin ester and subsequent kinetic resolution of the product diastereomer mix by acylase, and subsequent Sharpless dihydroxylation of the resulting 2-amino-3-methylpent-4-enoic acid derivative.

The present invention generally relates to tumor homing statin derivatives (THSD) and their use for therapy, in particular cancer therapy. These THSD comprise three moieties: a statin moiety which comprises a dihydroxyheptanoic acid unit (DHHA) fixated by linkage into its open chain form, a heptamethine carbocyanine dye (HMCD) moiety, and a linker that conjugates the DHHA of the statin to the dye moiety. The linker is linked to the DHHA via an ester bond (ester-linked statin derivative or ELSD), or via an amide bond (amide-linked statin derivative or ALSD). Thus linked to the DHHA, the linker provides a relatively stable link either for essentially no hydrolysis/statin release after administration, or preferably for very slow hydrolysis and statin release, as is the case for the ELSD. Embodiments include methods to provide the desired THSD, in particular the ELSD, with the DHHA in its open chain form. The invention also relates to methods wherein one or more ELSD is administered to a patient in a therapeutically effective amount, and methods wherein an ELSD and an ALSD are co-administered in a coordinated administration schedule. Advantages of the THSD and their use include, among others, improved efficacy and dose-response, and decreased statin-associated side effects.

A salt having a group represented by the formula (aa):

##STR00001##

wherein X.sup.a and X.sup.b independently each represent an oxygen atom or a sulfur atom,
the ring W represents a C3-C36 heterocyclic ring which has an ester bond or a thioester bond, said heterocyclic ring optionally further having an oxygen atom, a sulfur atom, a carbonyl group or a sulfonyl group each by which a methylene group has been replaced, and said heterocycilic ring optionally having a hydroxyl group, a cyano group, a carboxyl group, a C1-C12 alkyl group, a C1-C12 alkoxy group, a C2-C13 alkoxycarbonyl group, a C2-C13 acyl group, a C2-C13 acyloxy group, a C3-C12 alicyclic hydrocarbon group, a C6-C10 aromatic hydrocarbon group or any combination of these groups each by which a hydrogen atom has been replaced, and
* represents a binding position.

A salt having a group represented by the formula (aa):

##STR00001##

wherein X.sup.a and X.sup.b independently each represent an oxygen atom or a sulfur atom,
the ring W represents a C3-C36 heterocyclic ring which has an ester bond or a thioester bond, said heterocyclic ring optionally further having an oxygen atom, a sulfur atom, a carbonyl group or a sulfonyl group each by which a methylene group has been replaced, and said heterocycilic ring optionally having a hydroxyl group, a cyano group, a carboxyl group, a C1-C12 alkyl group, a C1-C12 alkoxy group, a C2-C13 alkoxycarbonyl group, a C2-C13 acyl group, a C2-C13 acyloxy group, a C3-C12 alicyclic hydrocarbon group, a C6-C10 aromatic hydrocarbon group or any combination of these groups each by which a hydrogen atom has been replaced, and
* represents a binding position.