# US 12,213,987 B2 · Prodrug salts

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- Number: US 12,213,987 B2
- Document ID: US12213987B2
- Status: Granted
- Kind: B2
- Application number: 17/304,201
- Filed: 2021-06-16
- Published: 2022-05-12
- Granted: 2025-02-04
- Earliest claimed: 2013-11-06
- Assignees: Aeromics, Inc.
- Applicants: Aeromics, Inc.
- Inventors: Marc F. Pelletier; Paul Robert McGuirk; George William Farr; Robert Zamboni; John Colucci; Helmi Zaghdane
- Web page: https://patentgrep.com/patent/US12213987B2

## CPC

- A61K 31/661: Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion {or mevinphos}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
- A61K 31/222: with compounds having aromatic groups, e.g. dipivefrine, ibopamine
- A61K 31/5375: 1,4-Oxazines, e.g. morpholine
- A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/08: Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock (artificial tears A61P27/04)
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/06: Antimigraine agents
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 27/02: Ophthalmic agents
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07F 9/09: Esters of phosphoric acids
- 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
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

Provided are novel prodrug salts of selective aquaporin inhibitors, their use as pharmaceuticals, and pharmaceutical compositions comprising them, and novel processes for their synthesis and novel intermediates for use in their synthesis. Also provided is use of a compound for the prophylaxis, treatment, and control of aquaporin-mediated conditions. Aquaporin inhibitors, e.g., inhibitors of AQP4 and/or AQP2, may be of utility in the treatment or control of diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord), hyponatremia, and excess fluid retention, as well as diseases such as epilepsy, retinal ischemia and other diseases of the eye, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines.

## Claims

### Claim 1

A process for synthesizing:
wherein the process comprises deprotecting:
with a deprotecting agent and wherein the process further comprises isolating:

### Claim 2 (depends on 1)

The process of claim 1, wherein the deprotecting agent comprises F.

### Claim 3 (depends on 2)

The process of claim 2, wherein the deprotecting agent is tetra-n-butylammonium fluoride.

### Claim 4 (depends on 1)

The process of claim 1, wherein the deprotecting agent is an acid.

### Claim 5 (depends on 4)

The process of claim 4, wherein the acid is CF3COOH (TFA).

### Claim 6 (depends on 1)

The process of claim 1, wherein the deprotection reaction is stirred at room temperature.

### Claim 7 (depends on 2)

The process of claim 2, wherein the deprotection reaction is stirred at room temperature.

### Claim 8 (depends on 3)

The process of claim 3, wherein the deprotection reaction is stirred at room temperature.

### Claim 9 (depends on 4)

The process of claim 4, wherein the deprotection reaction is stirred at room temperature.

### Claim 10 (depends on 5)

The process of claim 5, wherein the deprotection reaction is stirred at room temperature.