The present disclosure is directed toward alkynyl nucleoside analogs, compositions comprising these compounds, and their use for treating hepatitis E infections.

Provided is a new therapeutic agent for a malignant tumor, which is highly safe, sustains an antitumor effect, and can improve the means for administration and the number of times of administration. Disclosed is a compound of Formula (1), or a salt thereof:

C[CH.sub.2O(CH.sub.2CH.sub.2O).sub.nCH.sub.2CO—R.sup.1—R.sup.2].sub.4   (1) wherein R.sup.1 represents a single bond, —N(R.sup.3)(CH.sub.2).sub.n1CO—, or —N(R.sup.4)(CH.sub.2).sub.n2N (R.sup.5)CO(CH.sub.2).sub.n3CO—; R.sup.2 represents a group of Formula (a), (b), (c), (d), (e), or (f):

##STR00001## ##STR00002## m represents a number of from 10 to 1,000; and an arrow represents a bonding site.

Embodiments for the synthesis of sensitive oligonucleotides as well as insensitive oligonucleotides are provided. Sulfur-based groups are used for the protection of exo-amino groups of nucleobases, phosphate groups and 2′-OH groups, and as cleavable linker for linking oligonucleotides to a support. Oligonucleotide syntheses are achieved under typical conditions using phosphoramidite chemistry with important modifications. To prevent replacing sulfur-based protecting groups by acyl groups via cap-exchange, special capping agents are used. To retain hydrophobic tag to assist RP HPLC purification, special phosphoramidites are used in the last synthetic cycle. With the sulfur-based groups for protection and linking, oligonucleotide deprotection and cleavage are achieved via oxidation followed by beta-elimination under mild conditions. Therefore, besides for insensitive oligonucleotide synthesis, the embodiments of the invention are capable for the synthesis of oligonucleotide analogs containing sensitive functional groups that cannot survive the harsh conditions used in prior art oligonucleotide synthesis technologies.

Provided herein are novel synthetic routes to amines through an oxime intermediate, e.g., 3′-N nucleosides and novel and intermediate compounds produced during these synthetic procedures.

Modified oligonucleotides that contain one or more of the phosphate groups substituted at phosphorus and methods for their synthesis are disclosed.

Certain anti-viral compounds, pharmaceutical compositions, and methods related thereto are disclosed.

A drug combination against acid-fast bacillus, including: an inhibitor for WecA or an ortholog thereof; and at least one of an inhibitor for MurX or an ortholog thereof and an RNA synthesis inhibitor, wherein the inhibitor for WecA or an ortholog thereof is used in combination with the at least one of an inhibitor for MurX or an ortholog thereof and an RNA synthesis inhibitor; a screening method for a drug against acid-fast bacillus; and an inhibitor for WecA or an ortholog thereof.

A drug combination against acid-fast bacillus, including: an inhibitor for WecA or an ortholog thereof; and at least one of an inhibitor for MurX or an ortholog thereof and an RNA synthesis inhibitor, wherein the inhibitor for WecA or an ortholog thereof is used in combination with the at least one of an inhibitor for MurX or an ortholog thereof and an RNA synthesis inhibitor; a screening method for a drug against acid-fast bacillus; and an inhibitor for WecA or an ortholog thereof.

The present invention aims to provide a method of producing, more efficiently at a high purity, a phosphoramidite preferable for the production (synthesis) of a nucleic acid. Using a coupling reaction of an ether represented by the following chemical formula (105), an enantiomer, tautomer or stereoisomer thereof, or a salt thereof, and a glycoside compound, phosphoramidite that enables efficient synthesis of nucleic acid can be obtained:

##STR00001##

wherein n is a positive integer, and R and R′ are the same or different and each is a hydrogen atom or a hydroxyl-protecting group.

The present invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the Patatin-Like Phospholipase Domain Containing 3 (PNPLA3) gene, and methods of using such RNAi agents to inhibit expression of a PNPLA3 gene and methods of treating subjects having Nonalcoholic Fatty Liver Disease (NAFLD) and/or a PNPLA3-associated disorder.