Carbidopa and L-dopa prodrugs and methods of use

Patent metadata

Field	Value
Publication number	US-9446059-B2
Application number	US-201514919418-A
Country	US
Kind code	B2
Filing date	Oct 21, 2015
Priority date	Oct 21, 2014
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

Abstract

The present disclosure relates to (a) carbidopa prodrugs, (b) pharmaceutical combinations and compositions comprising a carbidopa prodrug and/or an L-dopa prodrug, and (c) methods of treating Parkinson's disease and associated conditions comprising administering a carbidopa prodrug and an L-dopa prodrug to a subject with Parkinson's disease.

First claim

What is claimed is:

1. A pharmaceutical combination comprising a first compound corresponding in structure to Formula (I):

or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are each independently selected from the group consisting of hydrogen, —P(O)(OH) 2 , and —R 5 —O—P(O)(OH) 2 ; R 5 is a C 1 -C 4 -alkyl; R 6 is hydrogen or a C 1 -C 4 -alkyl; and provided that at least one of R 1 and R 2 is —P(O)(OH) 2 or —R 5 —O—P(O)(OH) 2 ; and
a second compound corresponding in structure Formula (II):

or a pharmaceutically acceptable salt thereof, wherein R 3 and R 4 are each independently selected from the group consisting of hydrogen, —P(O)(OH) 2 , and —R 5 —O—P(O)(OH) 2 ; R 5 is a C 1 -C 4 -alkyl; R 6 is hydrogen or a C 1 -C 4 -alkyl; and provided that at least one of R 3 and R 4 is —P(O)(OH) 2 or —R 5 —O—P(O)(OH) 2 .

2. The pharmaceutical combination of claim 1 , wherein the first compound is selected from the group consisting of

and the second compound is selected from the group consisting of

3. The pharmaceutical combination of claim 1 , wherein the first compound is

and the second compound is

4. The pharmaceutical combination of claim 1 , wherein the first compound is

and the second compound is

5. The pharmaceutical combination of claim 1 , wherein the first compound is

and the second compound is

6. The pharmaceutical combination of claim 1 , wherein the first compound is

and the second compound is

7. The pharmaceutical combination of claim 1 , wherein a weight ratio of the first compound or pharmaceutically acceptable salt thereof to the second compound or pharmaceutically acceptable salt thereof is from about 1:4 to about 1:10.

8. The pharmaceutical combination of claim 1 , wherein the combination is an aqueous combination suitable for intragastric, subcutaneous, intramuscular, intrajejunum, oral, intranasal or intravenous administration.

9. The pharmaceutical combination of claim 1 , wherein the combination is an aqueous combination suitable for subcutaneous administration.

10. A compound corresponding in structure to Formula (I):

or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are each independently selected from the group consisting of hydrogen, —P(O)(OH) 2 , and —R 5 —O—P(O)(OH) 2 ; R 5 is a C 1 -C 4 -alkyl; R 6 is hydrogen or a C 1 -C 4 -alkyl; and provided that at least one of R 1 and R 2 is —P(O)(OH) 2 or —R 5 —O—P(O)(OH) 2 .

11. The compound or pharmaceutically acceptable salt of claim 10 , wherein R 1 and R 2 are each independently selected from the group consisting of hydrogen, —P(O)(OH) 2 , and —R 5 —O—P(O)(OH) 2 ; R 5 is a C 1 -C 2 -alkyl; R 6 is hydrogen; and provided that at least one of R 1 and R 2 is —P(O)(OH) 2 or —R 5 —O—P(O)(OH) 2 .

12. The compound or pharmaceutically acceptable salt of claim 10 , wherein R 1 and R 2 are each independently hydrogen or —P(O)(OH) 2 ; R 6 is hydrogen; and one of R 1 and R 2 is —P(O)(OH) 2 .

13. The compound or pharmaceutically acceptable salt of claim 10 , wherein R 1 and R 2 are each independently hydrogen or —R 5 —O—P(O)(OH) 2 ; R 5 is a C 1 -C 2 -alkyl; R 6 is hydrogen; and provided that one of R 1 and R 2 is —R 5 —O—P(O)(OH) 2 .

14. The compound or pharmaceutically acceptable salt of claim 10 , wherein R 1 and R 2 are each independently hydrogen, —P(O)(OH) 2 or —R 5 —O—P(O)(OH) 2 ; R 5 is a C 1 -C 2 -alkyl; R 6 is a C 1 -C 2 -alkyl; and provided that one of R 1 and R 2 is —P(O)(OH) 2 or —R 5 —O—P(O)(OH) 2 .

15. A compound corresponding in structure to Formula (II):

or a pharmaceutically acceptable salt thereof, wherein R 3 and R 4 are each independently hydrogen or —R 5 —O—P(O)(OH) 2 ; R 5 is a C 1 -C 2 -alkyl; R 6 is hydrogen; and provided that one of R 3 and R 4 is —R 5 —O—P(O)(OH) 2 .

16. A method of treating Parkinson's disease comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical combination according to claim 1 .

17. The method of claim 16 , wherein the first compound is selected from the group consisting of

and the second compound is selected from the group consisting of

18. The method of claim 16 , further comprising administering another anti-Parkinson's agent to the subject.

19. The method of claim 16 , wherein the pharmaceutical combination is an aqueous combination.

20. The method of claim 19 , wherein the aqueous pharmaceutical combination is administered by intragastric, subcutaneous, intramuscular, intranasal, intrajejunum, oral or intravenous administration.

21. The method of claim 20 , wherein the aqueous pharmaceutical combination is administered by subcutaneous administration.

22. The method of claim 21 , wherein the method comprises substantially continuous administration of the pharmaceutical combination over a period of at least about 12 hours.

23. A kit comprising the pharmaceutical combination of claim 1 .

24. A compound selected from the group consisting of

Assignees

• Abbvie Inc

Inventors

• Cardinal-David Benoit
• Chan Vincent S
• Dempah Kassibla E
• Enright Brian P
• Henry Rodger F
• Ho Raimundo
• Huang Ye
• Huters Alexander D
• Klix Russell C
• Krabbe Scott W
• Kym Philip R
• Lao Yanbin
• Lou Xiaochun
• Mackey Sean E
• Matulenko Mark A
• Mayer Peter T
• Miller Christopher P
• Stambuli James
• Voight Eric A
• Wang Zhi
• Zhang Geoff G
• Stella Valentino J

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07F9/06

  without P—C bonds · CPC title

• C07C309/24

  of a carbon skeleton containing six-membered aromatic rings · CPC title