The present invention relates to inorganic salts of nicotinic acid mononucleotides and compositions of Formula I, useful in the treatment of disorders and diseases associated with deficiencies in NAD.sup.+:

##STR00001##

wherein A, M.sup.1, M.sup.2, k, R.sup.1, R.sup.2, and R.sup.3 are as described herein.

The present invention relates to inorganic salts of nicotinic acid mononucleotides and compositions of Formula I, useful in the treatment of disorders and diseases associated with deficiencies in NAD.sup.+:

##STR00001##

wherein A, M.sup.1, M.sup.2, k, R.sup.1, R.sup.2, and R.sup.3 are as described herein.

The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treating or preventing cancer using the novel heterocyclic compounds of the invention.

The disclosure relates to in vivo and ex vivo uses of dihydronicotinamide riboside (NRH), dihydronicotinic acid riboside (NARH) and reduced derivatives thereof to treat immune-related disorders (e.g., systemic inflammatory response syndrome and sepsis), kidney disorders (e.g., acute kidney injury and hepatorenal syndrome [HRS]), liver disorders (e.g., acute liver failure and HRS), hemolytic disorders (e.g., hemolysis and hemolytic anemia), and disorders and conditions associated with oxidative stress, damage or injury (e.g., methemoglobinemia and anemia). NRH, NARH and reduced derivatives thereof can be used in vivo or ex vivo alone or in combination with one or more additional therapeutic agents, such as an anti-inflammatory agent or/and an antioxidant.

The present disclosure aims to solve the technical problems of larger content/weight difference and inconsistent quality of nicotinamide mononucleotide (NMN) medicines or health care products due to poor fluidity of existing nicotinamide mononucleotide crystals, and provides a nicotinamide mononucleotide-isonicotine cocrystal. Cu-Kαradiation is used for the cocrystal, and X-ray powder diffraction represented by an angle 2θ has diffraction peaks at 9.6±0.2°, 13.3±0.3°, 22.8±0.2° and 36.5±0.2°. The cocrystal has a higher bulk density than existing crystals, thereby significantly improving the fluidity of the nicotinamide mononucleotide. Therefore, the technical problems of larger content/weight difference and inconsistent quality of the NMN medicines or health care products in the production of enterprises may be well solved.

The present disclosure aims to solve the technical problems of larger content/weight difference and inconsistent quality of nicotinamide mononucleotide (NMN) medicines or health care products due to poor fluidity of existing nicotinamide mononucleotide crystals, and provides a nicotinamide mononucleotide-isonicotine cocrystal. Cu-Kαradiation is used for the cocrystal, and X-ray powder diffraction represented by an angle 2θ has diffraction peaks at 9.6±0.2°, 13.3±0.3°, 22.8±0.2° and 36.5±0.2°. The cocrystal has a higher bulk density than existing crystals, thereby significantly improving the fluidity of the nicotinamide mononucleotide. Therefore, the technical problems of larger content/weight difference and inconsistent quality of the NMN medicines or health care products in the production of enterprises may be well solved.

The invention provides a compound of formula (I): ##STR00001##
wherein R is as described herein. The invention also provides a process for the preparation of the compound.

The invention provides a compound of formula (I): ##STR00001##
wherein R is as described herein. The invention also provides a process for the preparation of the compound.

The invention relates to a method for preparing nicotinamide mononucleotide by using nicotinamide as a raw material, which comprises: in acetonitrile, dichloromethane, 1,2-dichloroethane or liquid sulfur dioxide as a solvent, allowing nicotinamide and tetraacetyl ribose to react as catalyzed by trimethylsilyl trifluoromethanesulfonate or tin tetrachloride, adjusting a pH value thereof to 3-5, adding a sodium methoxide solution thereto to react at −15° C. to 5° C., adjusting a pH value thereof to 3-5, and subjecting the reaction mixture to microfiltration and nanofiltration using a membrane concentrator, thereby obtain a nicotinamide ribose solution; allowing the nicotinamide ribose solution to react as catalyzed by nicotinamide ribokinase in the presence of Mg ions, ATP and a buffer, thereby obtaining nicotinamide mononucleotide. The method of the invention omits the step of refining nicotinamide ribose, and thus has simpler process, lower cost and less time consumption, and has the advantages of faster reaction speed and lower enzyme consumption compared with the enzyme catalytic process directly using refined nicotinamide ribose solid.

The invention relates to a method for preparing nicotinamide mononucleotide by using nicotinamide as a raw material, which comprises: in acetonitrile, dichloromethane, 1,2-dichloroethane or liquid sulfur dioxide as a solvent, allowing nicotinamide and tetraacetyl ribose to react as catalyzed by trimethylsilyl trifluoromethanesulfonate or tin tetrachloride, adjusting a pH value thereof to 3-5, adding a sodium methoxide solution thereto to react at −15° C. to 5° C., adjusting a pH value thereof to 3-5, and subjecting the reaction mixture to microfiltration and nanofiltration using a membrane concentrator, thereby obtain a nicotinamide ribose solution; allowing the nicotinamide ribose solution to react as catalyzed by nicotinamide ribokinase in the presence of Mg ions, ATP and a buffer, thereby obtaining nicotinamide mononucleotide. The method of the invention omits the step of refining nicotinamide ribose, and thus has simpler process, lower cost and less time consumption, and has the advantages of faster reaction speed and lower enzyme consumption compared with the enzyme catalytic process directly using refined nicotinamide ribose solid.