# US 2025/0145652 A1 · Inorganic salts of nicotinamide mononucleotide as anti-aging agents

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- Number: US 2025/0145652 A1
- Document ID: US20250145652A1
- Status: Published application
- Kind: A1
- Application number: 18/744,312
- Filed: 2024-06-14
- Published: 2025-05-08
- Earliest claimed: 2018-05-15
- Applicants: Life Biosciences Inc.; Jumpstart Fertility Pty Ltd
- Inventors: Sebastian Mario MARCUCCIO; Rohan David JOYCE; Michel WATHIER; Roland DOLLE; Simon TUCKER
- Web page: https://patentgrep.com/patent/US20250145652A1

## CPC

- C07H 19/048: Pyridine radicals
- A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- C07F 9/65586: {at least one of the hetero rings does not contain nitrogen as ring hetero atom}
- C12N 5/0603: {Embryonic cells (production of embryos, nuclear transfer A01K67/027); Embryoid bodies}
- C12N 5/0609: {Oocytes, oogonia (fertilised oocytes C12N5/0604)}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention relates to inorganic salts of nicotinamide mononucleotides and compositions of Formula I, useful in the treatment of disorders and diseases associated with deficiencies in NAD+: wherein A, M1, k, R1 and R2 are as described herein.

## Claims

### Claim 1

A salt of Formula (I):
or enantiomer, stereoisomer, or tautomer thereof,
wherein
A is NRaRb;
M1 is an inorganic cation;
R1 and R2 are independently H, C1-C6alkyl, C1-C6haloalkyl, (C0-C3alkylene)C(O)C1-C6alkyl, —C(O)ORa, —C(O)NRaRb, or —[CH2—CH2—O]n—Ra,
or R1 and R2, together with the atom to which they are attached, form a 5-membered heterocyclic ring optionally substituted with one or more substituents selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, (C0-C3alkylene)C3-C8cycloakyl, (C0-C3alkylene)heterocycloakyl, (C0-C3alkylene)C6-C14aryl, and (C0-C3alkylene)heteroaryl;
Ra and Rb are independently, at each occurrence, H, or C1-C6alkyl, wherein the alkyl is optionally substituted with one or more substituents selected from (C0-C3alkylene)C3-C8cycloakyl, (C0-C3alkylene)heterocycloakyl, (C0-C3alkylene)C6-C14aryl, and (C0-C3alkylene)heteroaryl;
k is 1 or 2; and
n is an integer from 1 to 8,
provided M1 is not Na.

### Claim 2 (depends on 1)

The salt of claim 1, wherein M1 is a cation selected from the group consisting of Li+, K+, Rb+, Cs+, Be2+, Mg2+, Ca2+, Sr2+, Zn2+, and Ba2+.

### Claim 3 (depends on 1)

The salt of claim 1, wherein M1 is K+.

### Claim 4 (depends on 1)

The salt of claim 1, wherein M1 is Li+.

### Claim 5 (depends on 1)

The salt of claim 1, wherein M1 is Rb+.

### Claim 6 (depends on 1)

The salt of claim 1, wherein R1 is H or C1-C3alkyl.

### Claim 7

(canceled)

### Claim 8 (depends on 1)

The salt of claim 1, wherein R2 is H or C1-C3alkyl.

### Claim 9

(canceled)

### Claim 10 (depends on 1)

The salt of claim 1, selected from the group consisting of:

### Claim 11 (depends on 1)

A pharmaceutical composition comprising a salt of claim 1, and a pharmaceutically acceptable carrier.

### Claim 12

A method of treating or preventing infertility comprising administering to a subject in need thereof, an effective amount of a salt of Formula I:
or enantiomer, stereoisomer, or tautomer thereof,
wherein
A is NRaRb;
M1 is an inorganic cation;
R1 and R2 are independently H, C1-C6alkyl, C1-C6haloalkyl, (C0-C3alkylene)C(O)C1-C6alkyl, —C(O)ORa, —C(O)NRaRb, or —[CH2—CH2—O]n—Ra,
or R1 and R2, together with the atom to which they are attached, form a 5-membered heterocyclic ring optionally substituted with one or more substituents selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, (C0-C3alkylene)C3-C8cycloakyl, (C0-C3alkylene)heterocycloakyl, (C0-C3alkylene)C6-C14aryl, and (C0-C3alkylene)heteroaryl;
Ra and Rb are independently, at each occurrence, H, or C1-C6alkyl, wherein the alkyl is optionally substituted with one or more substituents selected from (C0-C3alkylene)C3-C8cycloakyl, (C0-C3alkylene)heterocycloakyl, (C0-C3alkylene)C6-C14aryl, and (C0-C3alkylene)heteroaryl;
k is 1 or 2; and
n is an integer from 1 to 8.

### Claim 13

(canceled)

### Claim 14 (depends on 1)

A method of improving oocyte or blastocyst quality and maturation comprising contacting the oocyte or blastocyst with an effective amount of a salt of claim 1 prior to implantation into a subject in need of treatment of age-related infertility.

### Claim 15

(canceled)

### Claim 16 (depends on 14)

The method of claim 14 where the oocyte or blastocyst is cultured in an IVF media containing the salt.

### Claim at position 17

17-19. (canceled)

### Claim 20 (depends on 1)

A process for the preparation of the salt of claim 1 comprising contacting the compound of Formula II:
with a metal-alkali hydroxide under conditions effective to produce the product salt of claim 1.

### Claim 21 (depends on 20)

The process of claim 20, wherein the metal-alkali hydroxide is added dropwise into a solution of the compound of Formula II.

### Claim 22 (depends on 1)

A cell culture medium for in vitro fertilization comprising:
a salt of claim 1; and
culturing agents.

### Claim 23 (depends on 22)

The cell culture medium of claim 22, wherein the culturing agent is an inorganic salt, an energy substrate, an amino acid, a chelator, a pH indicator, an antibiotic, a serum, a vitamin, a growth factor, or any combination thereof.

### Claim at position 22

24-35. (canceled)

### Claim 36 (depends on 22)

The cell culture medium of claim 22, wherein the cell culture medium further comprises an oocyte, zygote, blastocyst, or any combination thereof.

### Claim at position 24

-38. (canceled)
