Substituted 2-phenyl-1-(3,4-dihydroxy-5-nitrophenyl)-1-ethanones, their use in the treatment of some central and peripheral nervous system disorders and pharmaceutical compositions containing them

• US 6,512,136 B1
• Filed: 12/17/1999
• Issued: 01/28/2003
• Est. Priority Date: 12/18/1998
• Status: Expired due to Fees

• Current Assignee: Henkel KGaA (Henkel AG & Co KGaA), Portela & Ca SA
• Original Assignee: Portela & Ca SA
• Inventors: Da Silva, Patricio Manuel Viera Araujo Soares, Benes, Jan, Learmonth, David Alexander
• Primary Examiner(s): Killos, Paul J.
• Application Number:
  US09/464,813
• Time in Patent Office: 1,138 Days
• Field of Search: 568/337, 560/108, 560/136, 564/299, 564/300
• US Class Current: 560/108
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07C 205/43 to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
• CPC Class Codes: C07C 205/45 the carbon skeleton being further substituted by at least one doubly—bound oxygen atom, not being part of a —CHO group
• CPC Class Codes: C07C 205/59 the carbon skeleton being further substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 255/56 containing cyano groups and doubly-bound oxygen atoms bound to the carbon skeleton
• CPC Class Codes: C07C 309/73 to carbon atoms of non-condensed six-membered aromatic rings
• CPC Class Codes: C07C 45/292 with chromium derivatives
• CPC Class Codes: C07C 45/46 Friedel-Crafts reactions
• CPC Class Codes: C07C 45/673 by change of size of the carbon skeleton
• CPC Class Codes: C07C 49/84 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07D 317/54 Radicals substituted by oxygen atoms

Abstract

New compounds of formula I are described

The compounds have potentially valuable pharmaceutical properties in the treatment of some central and peripheral nervous system disorders, where a reduction in the O-methylation of catecholamines may be of therapeutical benefit, such as Parkinson'"'"'s disease and parkinsonian disorders, gastrointestinal disturbances, edema formation states and hypertension.

Claims

1. A compound of formula I:

where R₁ and R₂ are the same or different and signify hydrogens, optionally substituted lower alkanoyl or aroyl groups, or optionally substituted lower alkylcarbamoyl groups;

R₃, R₄ and R₅ are the same or different and signify hydrogens, optionally substituted saturated or partially unsaturated lower hydrocarbon residues, hydroxyls, optionally substituted lower alkoxy or aryloxy groups, optionally substituted aryl, optionally substituted alkanoyl or aroyl groups, lower alkanoylamino groups, lower dialkanoylamino groups, optionally substituted lower alkyloxycarbonyl or aryloxycarbonyl groups, optionally substituted carbamoyl, halogen, amino, lower alkylamino or lower dialkylamino groups, or taken together signify aliphatic or heteroaliphatic rings or aromatic or heteroaromatic rings, and pharmaceutically acceptable salts thereof.

2. A compound according to claim 1 comprising:

1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-1-ethanone;

1-(3,4-dihydroxy-5-nitrophenyl)-2-(2-methylphenyl)-1-ethanone;

1 -(3,4-dihydroxy-5-nitrophenyl)-2-(4-chlorophenyl)- 1-ethanone;

1-(3,4-dihydroxy-5-nitrophenyl)-2-(1-naphthyl)-1-ethanone;

1-(3,4-dihydroxy-5-nitrophenyl)-2-(2-naphthyl)-1-ethanone or 1-(3,4-dihydroxy-5-nitrophenyl)-2-(4-biphenyl)-1-ethanone.

3. A method of treating a subject afflicted by some central and peripheral nervous system disorders, where a reduction in the O-methylation of catecholamines may be of therapeutical benefit, such as Parkinson'"'"'s disease and parkinsonian disorders, gastrointestinal disturbances, edema formation states and hypertension, which comprises administering to the subject an amount of a compound according to claim 1 effective to treat said diseases in the subject.

4. A method of treating a subject afflicted by some central and peripheral nervous system disorders, where a reduction in the O-methylation of catecholamines may be of therapeutical benefit, such as Parkinson'"'"'s disease and parkinsonian disorders, gastrointestinal disturbances, edema formation states and hypertension, which comprises administering to the subject an amount of a compound according to claim 2 effective to treat said diseases in the subject.

5. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 in combination with a pharmaceutically acceptable carrier.

6. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 2 in combination with a pharmaceutically acceptable carrier.

7. A method of manufacturing a medication for treating a subject afflicted by central or peripheral nervous system disorders comprising combining a compound according to claim 1 with a pharmaceutically acceptable carrier.

8. A method of manufacturing a medication for treating a subject afflicted by central or peripheral nervous system disorders comprising combining a compound according to claim 2 with a pharmaceutically acceptable carrier.

9. A method of manufacturing a medication for treating Parkinson'"'"'s Disease and parkinsonian disorders, gastrointestinal disturbances, edema formation states and hypertension comprising combining a compound according to claim 1 with a pharmaceutically acceptable carrier.

10. A method of manufacturing a medication for treating Parkinson'"'"'s Disease and parkinsonian disorders, gastrointestinal disturbances, edema formation states and hypertension comprising combining a compound according to claim 2 with a pharmaceutically acceptable carrier.

11. A pharmaceutical composition according to claim 5, further comprising L-DOPA and a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor.

12. A pharmaceutical composition according to claim 6, further comprising L-DOPA and a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor.