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 compositions and methods related to activating alpha-kinase 1 (ALPK1) for modulating an immune response and treating or preventing cancer, infection, inflammation and related diseases and disorders as well as potentiating an immune response to a target antigen. The disclosure also provides heterocyclic compounds of formula (I) as agonists of alpha protein kinase 1 (ALPK1) and their use in activating ALPK1, modulating an immune response and treating diseases such as cancer, wherein A.sup.1, A.sup.2, L.sup.1, L.sup.2, L.sup.3, Z.sup.1, Z.sup.2, W.sup.1, W.sup.2, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are defined herein. ##STR00001##

Disclosed are halogen containing nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of viral infections. Such viral infections can include tongaviridae, bunyaviridae, arenaviridae, coronaviridae, flaviviridae, picornaviridae, Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, RSV, and Zika virus infections.

To provide a chiral reagent or a salt thereof. The chiral reagent has following chemical formula (I). In the formula (I), G.sup.1 and G.sup.2 are independently a hydrogen atom, a nitro group (—NO.sub.2), a halogen atom, a cyano group (—CN), a group of formula (II) or (III), or both G.sup.1 and G.sup.2 taken together to form a group of formula (IV). ##STR00001##

To provide a chiral reagent or a salt thereof. The chiral reagent has following chemical formula (I). In the formula (I), G.sup.1 and G.sup.2 are independently a hydrogen atom, a nitro group (—NO.sub.2), a halogen atom, a cyano group (—CN), a group of formula (II) or (III), or both G.sup.1 and G.sup.2 taken together to form a group of formula (IV). ##STR00001##

The present invention is directed to methods for the use of 5′-adenosine diphosphate ribose (ADPR), and compositions thereof, for treating, managing, or preventing adenovirus-related diseases or conditions, eye disorders, cancer, or diseases or conditions caused by infection, inflammation, or physical, chemical, thermal, or radiation injuries.

The present invention is directed to methods for the use of 5′-adenosine diphosphate ribose (ADPR), and compositions thereof, for treating, managing, or preventing adenovirus-related diseases or conditions, eye disorders, cancer, or diseases or conditions caused by infection, inflammation, or physical, chemical, thermal, or radiation injuries.

A β-modified phosphoric acid compound precursor having a partial structure represented by

##STR00001##

where A.sub.1 represents —SR.sub.1, —S—S—R.sub.1, —SeR.sub.1, or —X, where X is a halogen selected from fluorine, chlorine, bromine, and iodine; R.sub.1 represents hydrogen, an alkyl group having 1 to 20 carbon atoms, or the like; L.sub.1 represents hydrogen, an alkyl group having 1 to 20 carbon atoms, or the like; L.sub.2 represents an alkyl group having 1 to 20 carbon atoms, or the like; L.sub.1 and L.sub.2 may be linked to each other to form a 4 to 6-membered ring structure; L.sub.1 and L.sub.2 may each have a substituent; and the symbol * represents a bond to be bonded to a phosphate group by phosphorylation. Further, provided are a reaction inhibitor and a medicine, each of which includes the β-modified phosphoric acid compound precursor.

Disclosed are compounds, compositions and methods for treating of diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I), wherein R.sub.1, R.sub.1′, X.sub.1, B.sub.1, R.sub.2, R.sub.2′, B.sub.2, X.sub.2, R.sub.3, Z-M-Y, and Y.sub.1-M.sub.1-Z.sub.1 are as defined herein.

##STR00001##

Disclosed are compounds, compositions and methods for treating of diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I), wherein R.sub.1, R.sub.1′, X.sub.1, B.sub.1, R.sub.2, R.sub.2′, B.sub.2, X.sub.2, R.sub.3, Z-M-Y, and Y.sub.1-M.sub.1-Z.sub.1 are as defined herein.

##STR00001##