# US 2019/0167685 A1 · Selective calcium channel antagonists

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- Number: US 2019/0167685 A1
- Document ID: US20190167685A1
- Status: Published application
- Kind: A1
- Application number: 16/167,055
- Filed: 2018-10-22
- Published: 2019-06-06
- Earliest claimed: 2011-01-19
- Assignees: Northwestern University
- Applicants: Northwestern University
- Inventors: Dalton J. Surmeier, JR.; Richard B. Silverman; Soo Sung Kang; Garry Cooper
- Web page: https://patentgrep.com/patent/US20190167685A1

## CPC

- A61K 31/515: Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C07D 239/62: Barbituric 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to compositions and methods for the treatment and/or prevention of neurodegenerative disorders, e.g., Parkinson's disease (PD). In particular, the present invention provides compositions comprising selective antagonists of calcium ion channels (e.g., Cav1.3-type ion channels), and methods of use thereof to treat or prevent neurodegenerative disorders.

## Claims

### Claim 1

A method of selectively inhibiting a Cav1.3-calcium ion channel, comprising contacting said Cav1.3-calcium ion channel with a compound of the formula:
wherein R1 comprises a cycloalkane or bicycloalkane, and R2 comprises a substituted aryl ring group.

### Claim 2 (depends on 1)

The method of claim 1, wherein R1 comprises cyclohexane, cyclopentane, or bicyclo[2.2.1]heptanes (norbornane).

### Claim 3 (depends on 1)

The method of claim 1, wherein R2 comprises a substituted phenyl group.

### Claim 4 (depends on 4)

The method of claim 4, wherein said phenyl group comprises a single non-hydrogen substituent selected from the group consisting of: F, Cl, Br, CF3, CO2H, CN, NO2, MeO, and Me.

### Claim 5 (depends on 1)

The method of claim 1, wherein said compound has formula:
or derivatives thereof.

### Claim 6 (depends on 1)

The method of claim 1, wherein said compound has the formula:
or derivatives thereof.

### Claim 7 (depends on 1)

The method of claim 1, wherein said compound has the formula:
or derivatives thereof.

### Claim 8 (depends on 1)

The method of claim 1, wherein said compound has the formula:
or derivatives thereof.

### Claim 9 (depends on 1)

The method of claim 1, wherein said compound has the formula:
or derivatives thereof.

### Claim 10 (depends on 1)

The method of claim 1, wherein said compound has the formula:
or derivatives thereof.

### Claim 11 (depends on 1)

The method of claim 1, wherein said compound has the formula:
or derivatives thereof.

### Claim 12

A method of treating and/or preventing a neurodegenerative disorder comprising administering to a subject a Cav1.3-selective calcium ion channel antagonist of the formula:
wherein R1 comprises a cycloalkane or bicycloalkane, and R2 comprises a substituted aryl ring group.

### Claim 13 (depends on 12)

The method of claim 12, wherein said neurodegenerative disorder comprises Parkinson's disease.

### Claim 14 (depends on 12)

The method of claim 12, wherein said neurodegenerative disorder comprises Alzheimer's disease.

### Claim 15 (depends on 12)

The method of claim 12, wherein said subject suffers from a neurodegenerative disorder.

### Claim 16 (depends on 12)

The method of claim 12, wherein said subject has one or more risk factors for a neurodegenerative disorder.

### Claim 17 (depends on 16)

The method of claim 16, wherein said risk factors for a neurodegenerative disorder comprise: increased age, genetic polymorphisms linked to neurodegenerative disorders, environmental factors, gender, education, endocrine conditions, oxidative stress, inflammation, stroke, hypertension, diabetes, smoking, head trauma, depression, infection, tumors, vitamin deficiencies, immune and metabolic conditions, and chemical exposure.

### Claim 18 (depends on 12)

The method of claim 12, wherein R1 comprises cyclohexane, cyclopentane, or bicyclo[2.2.1]heptanes (norbornane).

### Claim 19 (depends on 12)

The method of claim 12, wherein R2 comprises a substituted phenyl group.

### Claim 20

A pharmaceutical composition comprising a Cav1.3-selective calcium ion channel antagonist of the formula:
wherein R1 comprises a cycloalkane or bicycloalkane, and R2 comprises a substituted aryl ring group. In some embodiments, R1 comprises cyclohexane, cyclopentane, or bicyclo[2.2.1]heptanes (norbornane). In some embodiments, R2 comprises a substituted phenyl group. In some embodiments, the phenyl group comprises a single non-hydrogen substituent selected from the group consisting of: F, Cl, Br, CF3, CO2H, CN, NO2, MeO, and Me.