# US 12,178,827 B2 · Nicotinyl riboside compounds and their uses

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- Number: US 12,178,827 B2
- Document ID: US12178827B2
- Status: Granted
- Kind: B2
- Application number: 18/377,979
- Filed: 2023-10-09
- Published: 2024-02-15
- Granted: 2024-12-31
- Earliest claimed: 2018-12-17
- Assignees: MitoPower LLC
- Applicants: MitoPower LLC
- Inventors: Gangadhara Ganapati; Atignal Shankara Rao Arvind
- Web page: https://patentgrep.com/patent/US12178827B2

## CPC

- A61K 31/706: containing six-membered rings with nitrogen as a ring hetero atom
- A61K 31/502: ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- C07H 19/048: Pyridine radicals
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)

## Abstract

The disclosure provides nicotinamide riboside (NR), the reduced form of NR (NRH), nicotinic acid riboside (NAR), the reduced form of NAR (NARH), derivatives thereof, compositions thereof and uses thereof. The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR. NR, NRH, NAR, NARH, and derivatives thereof can increase intracellular NAD+ levels, and can enhance mitochondrial and cellular function and cell viability. Therefore, NR, NRH, NAR, NARH, and derivatives thereof, whether alone or in combination with one or more additional therapeutic agents (e.g., a PARP inhibitor), are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, and other disorders and conditions.

## Claims

### Claim 1

A method of increasing cytoprotection in a peripheral blood mononuclear, kidney or liver cells or tissue of a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of Formula (V) or Formula (VI):
or pharmaceutically acceptable salts and a therapeutically effective amount of a poly(ADP-ribose) polymerase (PARP) inhibitor or pharmaceutically acceptable salts thereof, wherein:
Y and Z are —OH or —NH2;
X− is fluoride, chloride, bromide, iodide, nitrate, sulfate, sulfite, phosphate, bicarbonate, carbonate, thiocyanate, formate, acetate, trifluoroacetate, glycolate, lactate, gluconate, ascorbate, benzoate, oxalate, malonate, succinate, citrate, methanesulfonate, ethanesulfonate, propanesulfonate, benzenesulfonate, p-toluenesulfonate or trifluoromethanesulfonate; and the therapeutically effective amount of the poly(ADP-ribose) polymerase (PARP) inhibitor is not more than 10% of the therapeutically effective amount of the poly(ADP-ribose) polymerase (PARP) inhibitor used in chemotherapy.

### Claim 2 (depends on 1)

The compound of claim 1, wherein the poly(ADP-ribose) polymerase (PARP) inhibitor is niraparib, rucaparib, talazoparib, veliparib, 4-amino-1,8-naphthalimide, BGB290, CEP9722 or E7016.

### Claim 3 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount of the PARP inhibitor is no more than about 10%, about 5%, about 1%, about 0.5% or about 0.1% of the therapeutically effective amount of the poly(ADP-ribose) polymerase (PARP) inhibitor used in chemotherapy.

### Claim 4 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount of the PARP inhibitor is no more than 10 mg, about 5 mg, about 1 mg, about 0.5 mg or about 0.1 mg.

### Claim 5 (depends on 4)

The method of claim 4, wherein the therapeutically effective amount of the compound is about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 900 mg or about 1000 mg.

### Claim 6 (depends on 1)

The method of claim 1, wherein the compound is

### Claim 7 (depends on 6)

The method of claim 6, wherein the therapeutically effective amount of the PARP inhibitor is no more than about 10 mg, about 5 mg, about 1 mg, about 0.5 mg or about 0.1 mg.

### Claim 8 (depends on 7)

The method of claim 7, wherein the therapeutically effective amount of the compound is about 50 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 900 mg or about 1000 mg.