# US 10,307,389 B2 · Succinate prodrugs for use in the treatment of lactic acidosis or drug-induced side-effects due to Complex I-related impairment of mitochondrial oxidative phosphorylation

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- Number: US 10,307,389 B2
- Document ID: US10307389B2
- Status: Granted
- Kind: B2
- Application number: 15/128,496
- Filed: 2015-04-08
- Published: 2017-04-13
- Granted: 2019-06-04
- Earliest claimed: 2014-04-08
- Assignees: Neurovive Pharmaceutical AB
- Applicants: Neurovive Pharmaceutical AB
- Inventors: Eskil Elmer; Magnus Joakim Hansson; Karl Henrik Johannes Ehinger; Sarah Piel; Steven Moss
- Web page: https://patentgrep.com/patent/US10307389B2

## CPC

- A61K 31/225: Polycarboxylic acids
- A61K 31/155: Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/12: for electrolyte homeostasis
- A61P 39/02: Antidotes
- 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

## Abstract

The present invention relates to a succinate prodrug for use in the treatment or prevention of lactic acidosis.

## Claims

### Claim 1

A method for treating or preventing lactic acidosis, said method comprising administering an effective amount of a succinate prodrug to the subject,
wherein said succinate prodrug is a compound of Formula (I)
or a pharmaceutically acceptable salt thereof, wherein the dotted bond between A and B denotes an optional bond so as to form a ring closed structure, and wherein
Z is —CH2—CH2—,
A is —SR, and R is
B is selected from the group consisting of —O—R′, —SR′″ and —OH; and R′ is:
R′″ is:
R1 and R3 are independently different or identical and are selected from the group consisting of H, Me, Et, propyl, i-propyl, butyl, iso-butyl, and t-butyl,
X is selected from the group consisting of O, NH, and S,
p is an integer and is 1 or 2,
X5 is selected from the group consisting of —H, —COOH, —C(═O)XR6, and CONR1R3,
R6 is selected from the group consisting of H, Me, Et, propyl, i-propyl, butyl, iso-butyl, t-butyl, acetyl, acyl, propionyl, and benzoyl,
R13, R14 and R15 are independently different or identical and are selected from the group consisting of H, Me, Et, propyl, i-propyl, butyl, iso-butyl, t-butyl, —COOH, O-acyl, O-alkyl, N-acyl, N-alkyl, Xacyl, and CH2Xalkyl,
Rf, Rg and Rh are independently different or identical and are selected from the group consisting of Xacyl, —CH2Xalkyl, —CH2X-acyl and R9,
R9 is selected from the group consisting of H, Me, Et and O2CCH2CH2COXR8, wherein R8 is selected from the group consisting of H, alkyl, Me, Et, propyl, i-propyl, butyl, iso-butyl, t-butyl, acetyl, acyl, propionyl, and benzoyl,
alkyl is selected from the group consisting of Me, Et, propyl, i-propyl, butyl, iso-butyl, and t-butyl, and
acyl is selected from the group consisting of formyl, acetyl, propionyl, isopropionyl, butyryl, tert-butyryl, pentanoyl, and benzoyl.

### Claim 2 (depends on 1)

The method of claim 1, wherein said subject is suffering from a disease that is treated with a drug substance, which potentially induces lactic acidosis,
the method comprises administering an effective amount of said succinate prodrug to the subject before, during or after treatment with said drug substance.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the drug substance is an anti-diabetic substance.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the anti-diabetic substance is metformin.