# US 12,213,957 B2 · Use of aminoacetonitrile compounds for the treatment of infection and disease

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- Number: US 12,213,957 B2
- Document ID: US12213957B2
- Status: Granted
- Kind: B2
- Application number: 17/924,537
- Filed: 2021-05-11
- Published: 2023-06-15
- Granted: 2025-02-04
- Earliest claimed: 2020-05-11
- Assignees: Pitney Pharmaceuticals Pty Limited
- Applicants: Pitney Pharmaceuticals Pty Limited
- Inventors: Roger Aston; Richard Mollard
- Web page: https://patentgrep.com/patent/US12213957B2

## CPC

- A61K 31/277: having a ring, e.g. verapamil
- A61P 25/00: Drugs for disorders of the nervous system
- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- A61P 31/14: for RNA viruses
- A61P 35/00: Antineoplastic agents
- 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 the use of aminoacetonitrile derivatives (AADs) in the treatment of cancer and mTOR (mammalian Target of Rapamycin) pathway related diseases. In particular it relates to the use of AADs administered at particular dose amounts in order to achieve therapeutic effects.

## Claims

### Claim 1

A method for the treatment of cancer, or one or more mTOR pathway related diseases, the method comprising administering to a patient in need thereof an amount of a compound of formula (I):
or a pharmaceutically acceptable salt or solvate thereof, sufficient to achieve a plasma concentration of said compound and/or a metabolite thereof of about 0.005 μM, about 0.01 μM, about 0.05 μM, about 0.1 μM, about 0.2 μM, about 0.3 μM, about 0.4 μM, about 0.5 μM, about 0.6 μM, about 0.7 UM, about 0.8 μM, or about 0.9 μM,
wherein
R1, R2 and R3 and R5 are each independently selected from H, alkyl, halogen, —CF3 or —CN;
R4 and R6 are each independently selected from H, alkyl, halogen, alkoxy, —CF3, —OCF3, —SO2CF3, —SOCF3 or —SCF3;
X is heteroatom, N(alkyl) or NH; and
n is 1 to 20;
and
wherein the cancer is selected from bladder cancer, kidney cancer, liver cancer, lung cancer, esophageal cancer, gall bladder cancer, pancreatic cancer, stomach cancer, thyroid cancer, B-cell lymphoma, T-cell lymphoma, Hodgkins lymphoma, non-Hodgkins lymphoma, hairy cell lymphoma, mantle cell lymphoma, myeloma, Burkett's lymphoma, myelodysplastic syndrome, rhabdomyosarcoma, astrocytoma, neuroblastoma, schwannoma, seminoma, teratocarcinoma, osteosarcoma, or Kaposi's sarcoma, and
wherein the mTOR pathway related disease is selected from Alzheimer's disease, Huntington's disease, motor neurone disease/amyotrophic lateral sclerosis, Parkinson's disease, age-related diseases, diseases related to transplant rejection, chronic inflammatory diseases, diseases related to glycogen storage, systemic lupus, diseases related to inflammation and immune activation, anaemia, leucopenia, thrombocytopenia, diseases related to stent coatings, renal insufficiency, obesity, diabetes/insulin resistance, diseases related to non-alcoholic fatty liver, polycystic kidney, fibrosis, or vial infection.

### Claim 2 (depends on 1)

The method of claim 1, wherein:
R1 is —CN, H or halogen;
R2 is H or halogen;
R3 is —CF3 or halogen;
R4 is —SCF3, —SOCF3, —SO2CF3, —OCF3, or —CF3;
R5 is H;
R6 is alkyl;
X is O; and
n is 1 to 5.

### Claim 3 (depends on 2)

The method of claim 2, wherein the compound of formula (I) is MPL (N-[(1R)-1-cyano-2-(5-cyano-2-trifluoromethyl-phenoxy)-1-methyl-ethyl]-4-trifluoromethylsulfanyl-benzamide):
or a pharmaceutically acceptable salt or solvate thereof.

### Claim 4 (depends on 2)

The method of claim 2, wherein the compound of formula (I) is MPL (N-[(1S)-1-cyano-2-(5-cyano-2-trifluoromethyl-phenoxy)-1-methyl-ethyl]-4-trifluoromethylsulfanyl-benzamide):
or a pharmaceutically acceptable salt or solvate thereof.

### Claim 5 (depends on 2)

The method of claim 2, wherein the compound of formula (I) is monepantel sulfone (MPL-SO2):
or a pharmaceutically acceptable salt or solvate thereof.

### Claim 6 (depends on 1)

The method of claim 1, wherein the compound according to formula (I) is MPL, and is administered in an amount sufficient to achieve a plasma concentration of MPL-SO2 of about 0.5 μM.

### Claim 7 (depends on 1)

The method of claim 1, wherein the compound according to formula (I) is MPL, and is administered in an amount sufficient to achieve a plasma concentration of MPL-SO2 of about 0.2 μM.

### Claim 8 (depends on 1)

The method of claim 1, wherein the compound is to be administered according to a regimen of i) once daily; or ii) twice daily.

### Claim 9 (depends on 1)

The method of claim 1, wherein the subject is a human.

### Claim 10 (depends on 1)

The method of claim 1, wherein the subject is a non-human animal.

### Claim 11 (depends on 10)

The method of claim 10, wherein the non-human animal is a canine.

### Claim 12 (depends on 1)

The method of claim 1, wherein the compound is administered orally.