The invention relates to novel camptothecin derivatives and their applications, tumor cell growth inhibitors, ternary complexes, and a method for improving the solubility of the camptothecin derivatives. The camptothecin derivatives are prepared by modifying the substance shown as Formula I with glycosylated triazole at position R.sup.3. In the structure shown as Formula I, R.sup.1 represents H, C.sub.1-10 alkyl, C.sub.1-10 alkyl-D or C.sub.1-10 haloalkyl; R.sup.2 represents H, CH.sub.2N(CH.sub.3).sub.2 or CH.sub.2N(CD.sub.3).sub.2; and R.sup.4 represents ##STR00001##
or H, wherein X represents N, O or S; and L represents polypeptide, C.sub.1-20 linear alkyl or derivatives thereof, C.sub.1-20 linear or branched acyl derivatives, C.sub.2-100 ethylene glycol or derivatives thereof. The camptothecin derivatives have high solubility, the anticancer drugs prepared from them have the advantages of wide anticancer spectrum and high safety, and have in vivo anticancer activity higher than irinotecan hydrochloride.

Embodiments of the present application relate to functionalized N-acetylgalactosamine-analogs, methods of making, and uses of the same. In particular, mono or trivalent N-acetylgalactosamine analogs may be prepared by utilizing a wide variety of linkers containing functional groups. These functionalized N-acetylgalactosamine-analogs may be used in the preparation of targeted delivery of oligonucleotide-based therapeutics.

Embodiments of the present application relate to functionalized N-acetylgalactosamine-analogs, methods of making, and uses of the same. In particular, mono or trivalent N-acetylgalactosamine analogs may be prepared by utilizing a wide variety of linkers containing functional groups. These functionalized N-acetylgalactosamine-analogs may be used in the preparation of targeted delivery of oligonucleotide-based therapeutics.

Embodiments of the present application relate to N-acetylgalactosamine-conjugated nucleosides. In particular, the N-acetylgalactosamine is installed on the nucleobase of the nucleosides through a wide variety of linkers. Methods of making N-acetylgalactosamine-conjugated nucleosides are also disclosed herein. N-acetylgalactosamine is a well-defined liver-targeted moiety and N-acetylgalactosamine-conjugated nucleosides may be used in the preparation of targeted delivery of oligonucleotide-based therapeutics.

Embodiments of the present application relate to N-acetylgalactosamine-conjugated nucleosides. In particular, the N-acetylgalactosamine is installed on the nucleobase of the nucleosides through a wide variety of linkers. Methods of making N-acetylgalactosamine-conjugated nucleosides are also disclosed herein. N-acetylgalactosamine is a well-defined liver-targeted moiety and N-acetylgalactosamine-conjugated nucleosides may be used in the preparation of targeted delivery of oligonucleotide-based therapeutics.

The present disclosure generally describes methods of preparing 1′-cyano nucleosides, such as a compound of Formula (I). For example, the compound of Formula (I) can be prepared from a compound of Formula (II-a) in a flow reactor.

The present disclosure generally describes methods of preparing 1′-cyano nucleosides, such as a compound of Formula (I). For example, the compound of Formula (I) can be prepared from a compound of Formula (II-a) in a flow reactor.

The present disclosure falls within the field of biomedical technology, and in particular relates to modified oligonucleotides and a compound that can be used for synthesizing same and a method for modifying oligonucleotides. The present disclosure also relates to the use of the modified oligonucleotides for preventing and/or treating diseases associated with the liver in a subject.

The present disclosure describes a convergent liquid phase process for manufacturing oligonucleotides by coupling two or more oligonucleotide fragments, each of which have two or more nucleotides. Also provided by the present disclosure are reaction steps involved the convergent liquid phase process.

The invention describes compositions that include a stevia sweetener and a salt of a steviol glycoside, wherein the concentration of the components provide an improved taste profile where bitterness, after taste and/or lingering of the stevia sweetener is decreased or eliminated.