# US 11,077,129 B2 · Nicotinoyl riboside compositions and methods of use

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- Number: US 11,077,129 B2
- Document ID: US11077129B2
- Status: Granted
- Kind: B2
- Application number: 16/888,336
- Filed: 2020-05-29
- Published: 2020-09-17
- Granted: 2021-08-03
- Earliest claimed: 2005-11-18
- Assignees: Cornell University
- Applicants: Cornell University
- Inventors: Anthony A. Sauve; Tianle Yang Redanz
- Web page: https://patentgrep.com/patent/US11077129B2

## CPC

- A61K 31/706: containing six-membered rings with nitrogen as a ring hetero atom
- A61K 31/351: not condensed with another ring
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07H 1/00: Processes for the preparation of sugar derivatives
- 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)
- 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 invention relates to compositions of nicotinoyl ribosides and nicotinamide riboside derivatives and their methods of use. In some embodiments, the invention relates to methods of making nicotinoyl ribosides. In some embodiments, the invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinoyl riboside. In further embodiments, the invention relates to methods of using nicotinoyl ribosides and nicotinamide riboside derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival.

## Claims

### Claim 1

A method of reducing cell proliferation, which method comprises administering to proliferating cells a proliferation-reducing amount of a compound of formula (I):
and salt complexes thereof, wherein R is selected from the group consisting of alkylamino, substituted alkylamino, arylalkylamino, dialkylamino, substituted dialkylamino, hydroxylamino, substituted hydroxylamino, O-alkyloxyamino, substituted O-alkyloxyamino, aminooxy, substituted aminoxy, N-alkylaminooxy, substituted N-alkylaminoxy, hydrazino, substituted hydrazino, alkylhydrazino, and substituted alkylhydrazino,
whereby the cell proliferation is reduced.

### Claim 2 (depends on 1)

The method of claim 1, wherein the alkylamino or substituted alkylamino is
selected from —NHMe, —NHEt, —NHCH2CH2OH, —NHCH2CH═CH2, —NHCH(CH3)2, —NHCH2 CH2NH2, and NHcyclopropyl.

### Claim 3 (depends on 2)

The method of claim 2, wherein the alkylamino or substituted alkylamino is —NHCH2CH═CH2.

### Claim 4 (depends on 1)

The method of claim 1, wherein the dialkylamino is —N(CH3)2 or N-substituted pyrrolidinyl.

### Claim 5 (depends on 4)

The method of claim 4, wherein the dialkylamino is —N(CH3)2.

### Claim 6 (depends on 1)

The method of claim 1, wherein the cells are stem cells.

### Claim 7 (depends on 6)

The method of claim 6, wherein the stem cells are embryonic stem cells.

### Claim 8 (depends on 1)

The method of claim 1, wherein the proliferating cells are in a mammal, wherein the mammal is being treated with an agent selected from mechlorethamine, cyclophosphamide, melphalan, chlorambucil, hexamethylmelamine, thiotepa, busulfan, carmustine streptozocin, dacarbazinine, and methotrexate.

### Claim 9 (depends on 8)

The method of claim 8, wherein the mammal is afflicted with a cancer selected from brain cancer, kidney cancer, breast cancer, prostate cancer, testicular cancer, ovarian cancer, lymphoma, and leukemia.

### Claim 10 (depends on 8)

The method of claim 8, wherein the mammal is a human.

### Claim 11 (depends on 1)

The method of claim 1, wherein the cells are anaplastic cells.

### Claim 12

A method of treating cancer in a mammal in need thereof, wherein the cancer is a cancer responsive to treatment with an antiproliferative agent, comprising administering to the mammal an effective amount of a compound of formula (I):
and salt complexes thereof, wherein R is selected from the group consisting of alkylamino, substituted alkylamino, arylalkylamino, dialkylamino, substituted dialkylamino, hydroxylamino, substituted hydroxylamino, O-alkyloxyamino, substituted O-alkyloxyamino, aminooxy, substituted aminoxy, N-alkylaminooxy, substituted N-alkylaminoxy, hydrazino, substituted hydrazino, alkylhydrazino, and substituted alkylhydrazino in combination with an antiproliferative agent,
whereby the cancer is treated.

### Claim 13 (depends on 12)

The method of claim 12, wherein the alkylamino or substituted alkylamino is selected
from —NHMe, —NHEt, —NHCH2CH2OH, —NHCH2CH═CH2, —NHCH(CH3)2, —NHCH2CH2NH2, and —NHcyclopropyl.

### Claim 14 (depends on 13)

The method of claim 13, wherein the alkylamino or substituted alkylamino is —NHCH2CH═CH2.

### Claim 15 (depends on 12)

The method of claim 12, wherein the dialkylamino is —N(CH3)2 or N-substituted pyrrolidinyl.

### Claim 16 (depends on 15)

The method of claim 15, wherein the dialkylamino is —N(CH3)2.

### Claim 17 (depends on 12)

The method of claim 12, wherein the antiproliferative agent is selected from mechlorethamine, cyclophosphamide, melphalan, chlorambucil, hexamethylmelamine, thiotepa, busulfan, carmustine streptozocin, dacarbazinine, and methotrexate.

### Claim 18 (depends on 12)

The method of claim 12, wherein the mammal is afflicted with a cancer selected from brain cancer, kidney cancer, breast cancer, prostate cancer, testicular cancer, ovarian cancer, lymphoma, and leukemia.

### Claim 19 (depends on 12)

The method of claim 12, wherein the mammal is a human.