You're using a free limited version of DrugPatentWatch: Upgrade for Complete Access

Last Updated: December 22, 2024

Claims for Patent: 5,236,952


✉ Email this page to a colleague

« Back to Dashboard


Summary for Patent: 5,236,952
Title: Catechol derivatives
Abstract:Catechol derivatives of the formula ##STR1## wherein Ra, Rb and Rc have the significance given herein, the ester and ether derivatives thereof which are hydrolyzable under physiological conditions and the pharmaceutically acceptable salts thereof are described and possess valuable pharmacological properties. In particular, they inhibit the enzyme catechol-O-methyltransferase (COMT), a soluble, magnesium-dependent enzyme which catalyses the transference of the methyl group of S-adensoylmethionine to a catechol substrate, whereby the corresponding methyl ethers are formed. Suitable substrates which can be O-methylated by COMT and which can thus be deactivated are, for example, extraneuornal catecholamines and exogeneously-administered therapeutically active substances having a catechol structure. Formula Ia above embraces not only compounds which form part of the invention, but also known compounds; the compounds which form part of the invention can be prepared according to known methods.
Inventor(s): Bernauer; Karl (Oberwil, CH), Borgulya; Janos (Basel, CH), Bruderer; Hans (Biel-Benken, CH), DaPrada; Mose (Riehen, CH), Zurcher; Gerhard (Basel, CH)
Assignee: Hoffmann-La Roche Inc. (Nutley, NJ)
Application Number:07/686,210
Patent Claims: 1. A compound of the formula ##STR24## wherein Ra is nitro or cyano, Rb is hydrogen or halogen, Rc' is the group CO--R.sup.11 wherein R.sup.11 is a phenyl group optionally mono- or disubstituted by halogen, cyano, hydroxy or lower alkyl, or an ester or ether derivative thereof which is hydrolyzable under physiological conditions or a pharmaceutically acceptable salt thereof.

2. A compound, according to claim 1, wherein Rb is situated in the p-position to Ra.

3. A compound, according to claim 2, wherein Ra is nitro.

4. A compound, according to claim 3, wherein Rb is hydrogen, chlorine or fluorine.

5. A compound, according to claim 4, wherein Rb is hydrogen.

6. A compound, according to claim 1, 3,4-Dihydroxy-5-nitrobenzophenone.

7. A compound, according to claim 1, 2'-Fluoro-3,4-dihydroxy-5-nitrobenzophenone.

8. A pharmaceutical composition comprising a compound of the formula ##STR25## wherein Ra is nitro or cyano, Rb is hydrogen or halogen, Rc is CO--R.sup.1 wherein R.sup.1 is a phenyl group optionally mono- or disubstituted by halogen, cyano, hydroxy or lower alkyl or an ester or ether derivative thereof which if hydrolyzable under physiological conditions or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier material.

9. A pharmaceutical composition, according to claim 8, wherein the compound of formula Ia is 3,4-dihydroxy-5-nitrobenzophenone.

10. A pharmaceutical composition, according to claim 8, wherein the compound of formula Ia is 2'-fluoro-3,4-dihydroxy-5-nitrobenzophenone.

11. A pharmaceutical composition comprising L-dopa, peripheral decarboxylase inhibitor, a compound of the formula ##STR26## wherein Ra is nitro or cyano, Rb is hydrogen or halogen, Rc is the group CO--R.sup.1 wherein R.sup.1 is a phenyl group optionally mono- or disubstituted by halogen, cyano, hydroxy or lower alkyl or an ester or ether derivative thereof which is hydrolyzable under physiological conditions or a pharmaceutically acceptable salt thereof and a therapeutically inert carrier material.

12. A pharmaceutical composition, according to claim 11, wherein the compound of formula Ia is 3,4-dihydroxy-5-nitrobenzophenone.

13. A pharmaceutical composition, according to claim 11, wherein the compound of formula Ia is 2'-fluoro-3,4-dihydroxy-5-nitrobenzophenone.

14. A compound according to claim 1, wherein said compound is 4-dihydroxy-5'-methyl-5-nitrobenzophenone.

15. A pharmaceutical composition according to claim 8, wherein the compound of formula Ia is 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone.

16. A pharmaceutical composition according to claim 11, wherein the compound of formula Ia is 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone.

17. A pharmaceutical composition for treating depression comprising an effective amount of a compound of the formula ##STR27## wherein Ra is nitro or cyano, Rb is hydrogen or halogen, Rc is CO--R.sup.1 wherein R.sup.1 is a phenyl group optionally mono- or disubstituted by halogen, cyano, hydroxy or lower alkyl or an ester or ether derivative thereof which if hydrolyzable under physiological conditions or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier material.

18. A pharmaceutical composition according to claim 17, wherein the compound of formula Ia is 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone.

19. A pharmaceutical composition for treating Parkinson's disease comprising L-dopa, a peripheral decarboxylase inhibitor, a compound of the formula ##STR28## wherein Ra is nitro or cyano, Rb is hydrogen or halogen, Rc is CO--R.sup.1 wherein R.sup.1 is a phenyl group optionally mono- or disubstituted by halogen, cyano, hydroxy or lower alkyl or an ester or ether derivative thereof which if hydrolyzable under physiological conditions or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier material.

20. A pharmaceutical composition according to claim 19, wherein the compound of formula Ia is 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone.

21. A pharmaceutical composition for inhibiting catechol-O-methyl-transferase, said composition comprising a catechol-O-methyl transferase inhibiting amount of a compound of the formula ##STR29## wherein Ra is nitro or cyano, Rb is hydrogen or halogen, Rc is CO--R.sup.1 wherein R.sup.1 is a phenyl group optionally mono- or disubstituted by halogen, cyano, hydroxy or lower alkyl or an ester or ether derivative thereof which if hydrolyzable under physiological conditions or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier material.

22. A pharmaceutical composition according to claim 8, wherein the compound of formula Ia is 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone.

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.