# US 9,434,704 B2 · Compositions and methods for the treatment of neurological degenerative disorders

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- Number: US 9,434,704 B2
- Document ID: US9434704B2
- Status: Granted
- Kind: B2
- Application number: 14/399,528
- Filed: 2013-02-02
- Published: 2015-04-23
- Granted: 2016-09-06
- Earliest claimed: 2012-05-08
- Assignees: Cellix Bio Private Limited
- Applicants: Mahesh Kandula
- Inventors: Mahesh Kandula
- Web page: https://patentgrep.com/patent/US9434704B2

## CPC

- C07D 277/82: Nitrogen atoms
- A61K 31/428: condensed with carbocyclic rings
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/24: Antidepressants
- 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 417/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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 invention relates to the compounds of formula I and formula II or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I or formula II; and methods for treating or preventing neurological degenerative disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of Parkinson's disease (PD), restless legs syndrome (RLS), cluster headache, depression, fibromyalgia, sexual dysfunction, amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease and depression.

## Claims

### Claim 1

A compound of Formula I:
or pharmaceutically acceptable salts, stereoisomers, enantiomers, hydrates, solvates, or mixtures thereof, wherein:
R1 represents
R2 represents H, D,
a is independently 2, 3 or 7;
each b is independently 3, 5 or 6;
e is independently 1, 2 or 6;
c and d are each independently H, D, —OH, —OD, C1-C6-alkyl, —NH2 or —COCH3;
R3 represents
R4 represents
a is independently 2, 3 or 7;
each b is independently 3, 5 or 6;
e is independently 1, 2 or 6; and
c and d are each independently H, D, —OH, —OD, C1-C6-alkyl, —NH2 or —COCH3;
and wherein when R2 is H, R1 may be NULL.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 2)

The pharmaceutical composition of claim 2, wherein said pharmaceutical composition is formulated to palliatively treat an underlying etiology with an effective amount administering the patient in need by oral administration, delayed release or sustained release, transmucosal administration, syrup, topical administration, parenteral administration, injection, subdermal administration, oral solution, rectal administration, buccal administration or transdermal administration.

### Claim 4 (depends on 3)

The pharmaceutical composition of claim 3, wherein said pharmaceutical composition is formulated for the treatment of Parkinson's disease, restless legs syndrome, cluster headache, depression, fibromyalgia, sexual dysfunction, amyotrophic lateral sclerosis, convulsions, partial seizures, or as an adjunctive therapy for partial, myoclonic, tonic-clonic seizures, mood-stabilizing agent, bipolar disorder, Tourette syndrome, Alzheimer's disease, autism, bipolar disorder, anxiety disorder, trigeminal neuralgia, attention-deficit hyperactivity disorder, schizophrenia, neuropathic pain, seizures, mania, phantom limb syndrome, complex regional pain syndrome, paroxysmal extreme pain disorder, neuromyotonia, intermittent explosive disorder, borderline personality disorder, myotonia congenita and post-traumatic stress disorder.

### Claim 5 (depends on 2)

The pharmaceutical composition of claim 2, further comprising a molecular conjugate of bioactive compounds selected from a group consisting of pramipexole, dexpramipexole and riluzole and carboxylic compounds selected from a group consisting of R-Lipoic acid, eicosapentaenoic acid, docosahexaenoic acid, fumaric acid, and salsalate.

### Claim 6 (depends on 5)

The molecular conjugate of claim 5, wherein the carboxylic acid compound is R-Lipoic acid.

### Claim 7 (depends on 5)

The molecular conjugate of claim 5, wherein the carboxylic acid compound is eicosapentaenoic acid.

### Claim 8 (depends on 5)

The molecular conjugate of claim 5, wherein the carboxylic acid compound is docosahexaenoic acid.

### Claim 9 (depends on 5)

The molecular conjugate of claim 5, wherein the carboxylic acid compound is salsalate.

### Claim 10 (depends on 5)

The molecular conjugate of claim 5, wherein the carboxylic acid compound is fumaric acid.

### Claim 11

A compound of Formula II:
or pharmaceutically acceptable salts, stereoisomers, enantiomers, hydrates, solvates, or mixtures thereof, wherein,
R1 represents
R2 represents
a is 2, 3 or 7;
each b is independently 3, 5 or 6;
e is 1, 2 or 6; and
c and d are each independently H, D, —OH, —OD, C1-C6-alkyl, —NH2 or —COCH3.

### Claim 12 (depends on 11)

A pharmaceutical composition comprising a compound of claim 11 and a pharmaceutically acceptable carrier.

### Claim 13 (depends on 12)

The pharmaceutical composition of claim 12, wherein said pharmaceutical composition is formulated to palliatively treat an underlying etiology with an effective amount administering the patient in need by oral administration, delayed release or sustained release, transmucosal administration, syrup, topical administration, parenteral administration, injection, subdermal administration, oral solution, rectal administration, buccal administration or transdermal administration.

### Claim 14 (depends on 13)

The pharmaceutical composition of claim 13, wherein said pharmaceutical composition is formulated for the treatment of Parkinson's disease, restless legs syndrome, cluster headache, depression, fibromyalgia, sexual dysfunction, amyotrophic lateral sclerosis, convulsions, partial seizures, or as an adjunctive therapy for partial, myoclonic, tonic-clonic seizures, mood-stabilizing agent, bipolar disorder, Tourette syndrome, Alzheimer's disease, autism, bipolar disorder, anxiety disorder, trigeminal neuralgia, attention-deficit hyperactivity disorder, schizophrenia, neuropathic pain, seizures, mania, phantom limb syndrome, complex regional pain syndrome, paroxysmal extreme pain disorder, neuromyotonia, intermittent explosive disorder, borderline personality disorder, myotonia congenita and post-traumatic stress disorder.

### Claim 15 (depends on 12)

The pharmaceutical composition of claim 12, further comprising a molecular conjugate of bioactive compounds selected from a group consisting of pramipexole, dexpramipexole and riluzole and carboxylic compounds selected from a group consisting of R-Lipoic acid, eicosapentaenoic acid, docosahexaenoic acid, fumaric acid, and salsalate.

### Claim 16 (depends on 15)

The molecular conjugate of claim 15, wherein the bioactive compound is riluzole.

### Claim 17 (depends on 15)

The molecular conjugate of claim 15, wherein the carboxylic acid compound is R-Lipoic acid.

### Claim 18 (depends on 15)

The molecular conjugate of claim 15, wherein the carboxylic acid compound is eicosapentaenoic acid.

### Claim 19 (depends on 15)

The molecular conjugate of claim 15, wherein the carboxylic acid compound is docosahexaenoic acid.

### Claim 20 (depends on 15)

The molecular conjugate of claim 15, wherein the carboxylic acid compound is salsalate.