# US 10,245,326 B2 · Amantadine, memantine, and rimantadine conjugates and a pharmaceutical composition for treatment of neuronal disorders

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- Number: US 10,245,326 B2
- Document ID: US10245326B2
- Status: Granted
- Kind: B2
- Application number: 14/819,959
- Filed: 2015-08-06
- Published: 2017-02-09
- Granted: 2019-04-02
- Earliest claimed: 2015-08-06
- Applicants: Landon C. G. Miller
- Inventors: Landon C. G. Miller
- Web page: https://patentgrep.com/patent/US10245326B2

## CPC

- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- 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)

## Abstract

A compound is provided that has the formula (II): where R1 in each occurrence is independently H, or C1-C4 alkyl; R2 is a nullity or CH—CH3, R3 is a nullity or C(O)—R6—NH; R6 is C2-C6 alkyl, (CH2CH2—O)n, or (CH(OH)CH2)n; n is an integer of between 1 and 4; R4 is a nullity or NH—R6—C(O); and R5 is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine, blood brain barrier (BBB) peptide, membrane translocating peptide, TAT peptides, endocannabinoids 1 & 2, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosyl ester, lactic acid, leucine, tryptophan, glutamic acid.

## Claims

### Claim 1

A method of treating Parkinson's disease, the method comprising:
administration to subject having Parkinson's disease, a therapeutically effective amount of an amantadine analog conjugate compound having the formula (II):
where R1 in each occurrence is independently H, or C1-C4 alkyl; R2 is a nullity or CH—CH3, R3 is a nullity or C(O)—R6—NH; R6 is C2-C6 alkyl, (CH2CH2—O)n, or (CH(OH)CH2)n; n is an integer of between 1 and 4; R4 is a nullity or NH—R6—C(O); and R5 is a moiety capable of crossing the blood brain barrier and is as a free compound is one of: serotonin, dopamine, blood brain barrier (BBB) peptide, membrane translocating peptide, TAT peptides, endocannabinoids, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosyl ester, lactic acid, leucine, tryptophan, glutamic acid.

### Claim 2 (depends on 1)

The method of claim 1, wherein R5 is serotonin as the free compound and has a carboxyl group that forms an amide bond.

### Claim 3 (depends on 1)

The method of claim 1, wherein R5 is glucosyl, R3 is a nullity and R4 is a nullity.

### Claim 4 (depends on 1)

The method of claim 1, wherein R5 is transferrin as the free compound and has a carboxyl group that forms an amide bond.

### Claim 5 (depends on 1)

The method of claim 1, wherein R5 is lactic acid as the free compound and has a carboxyl group that forms an amide bond.

### Claim 6 (depends on 1)

The method of claim 1, wherein at least one of R3 and R4 is C(O)—R6—NH, where R6 is C2-C6 alkyl, (CH2CH2—O)n, or (CH(OH)CH2)n and n is an integer of between 1 and 4.

### Claim 7 (depends on 6)

The method of claim 6, wherein R6 is (CH2CH2—O)n, and n is an integer of between 1 and 4.

### Claim 8 (depends on 6)

The method of claim 6, wherein R6 is (CH(OH)CH2)n and n is an integer of between 1 and 4.

### Claim 9 (depends on 6)

The method of claim 6, further comprising at least one of a radioactive atom, a spectroscopically active marker, and an organic dye.

### Claim 10 (depends on 1)

The method of claim 1, wherein the administration is by a route selected from the group consisting of: parenteral, intraventricular, and intrathecal.