The present disclosure provides methods of making nicotinoyl riboside compounds or derivatives of formula (I): ##STR00001##
wherein X.sup.−, Z.sup.1, Z.sup.2, n, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are described herein, reduced analogs thereof, modified derivatives thereof, phosphorylated analogs thereof, and adenylyl dinucleotide conjugates thereof, or salts, solvates, or prodrugs thereof; and novel crystalline forms thereof.

The disclosure provides derivatives of both the oxidized form and the reduced form of nicotinamide riboside (NR) and nicotinic acid riboside (NAR). The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR, and can increase cellular NAD.sup.+ levels and improve mitochondrial function. Therefore, the NR and NAR derivatives are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, and other disorders and conditions.

The disclosure provides derivatives of both the oxidized form and the reduced form of nicotinamide riboside (NR) and nicotinic acid riboside (NAR). The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR, and can increase cellular NAD.sup.+ levels and improve mitochondrial function. Therefore, the NR and NAR derivatives are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, and other disorders and conditions.

Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of an E-selectin, galectin-3, or E-selectin and galectin-3 to ligands are disclosed. For example, heterobifunctional inhibitors of E-selectin and galectin-3 are described and pharmaceutical compositions comprising at least one such agent is described.

There are provided, inter alia, methods and reagents for labeling nucleic acids.

There are provided, inter alia, methods and reagents for labeling nucleic acids.

The present disclosure provides methods of making nicotinoyl riboside compounds or derivatives of formula (I):

##STR00001##

wherein X.sup.−, Z.sup.1, Z.sup.2, n, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are described herein, reduced analogs thereof, modified derivatives thereof, phosphorylated analogs thereof, and adenylyl dinucleotide conjugates thereof, or salts, solvates, or prodrugs thereof, and novel crystalline forms thereof.

The present application relates to a salt of a pyranose-substituted heterocyclic compound, a preparation method therefor, and use thereof, and in particular, to an acid addition salt of a compound of formula (I) or a prodrug thereof, and further relates to D-glucuronate of a crystalline compound of formula (I) or a prodrug thereof. D-glucuronate of a crystalline compound of formula (II) has particular advantages in terms of crystallizability, subsequent purification, stability, formulation medicinal properties or quality control, and is most applicable for improving the formulation pharmaceutical properties, purity and quality control, as well as large-scale process development of such drugs.

The present invention provides a compound of Formula (I) or the pharmaceutically acceptable salts thereof, which are PRMT5 inhibitors.

##STR00001##

The invention describes novel conjugates of formula (I) of a pharmaceutical agent and a moiety capable of binding to a glucose sensing protein allowing a reversible release of the pharmaceutical agent depending on the glucose concentration.