Novel esters derived from (rr,ss)-2-hydroxybenzoate of 3-(2-dimethylaminomethyl-1-hydroxycyclohexyl)phenyl

• US 20030100598A1
• Filed: 06/27/2002
• Published: 05/29/2003
• Est. Priority Date: 12/30/1999
• Status: Active Grant

• Current Assignee: Laboratorios Vita, S.A.
• Original Assignee: Laboratorios Vita, S.A.
• Inventors: Huguet Clotet, Juan, Mourelle Mancini, Marisabel, De Ramon Amat, Elisabet
• Granted Patent: US 6,894,076 B2
• Time in Patent Office: Days
• US Class Current: 514/423
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07C 219/28 having amino groups bound to acyclic carbon atoms of the carbon skeleton
• CPC Class Codes: C07C 2601/14 The ring being saturated

Abstract

New esters derived from substituted phenyl-cyclohexyl compounds, which are derived from Tramadol, process for obtaining them and their use for preparing a drug with analgesic properties. These new compounds of general formula (I) have a higher analgesic activity, a lower toxicity and a longer effective time period than Tramadol.

Claims

1. Compound of general formula (I):

2. Compound as claimed in claim 1, characterised in that R₁ is A, and R₄ is methyl or H, R₅ is NH₂, 2,5-dichlorophenylamino, or H, R₆ is substituted CO-phenyl or H, R₇ is isobutyl or H, or R₆ and R₇ form a substituted condensed aromatic ring.

3. Compound as claimed in claim 1, characterised in that R₁ is B, and R₈ is OH or —

O—

CO—

N(CH₃).

4. Compound as claimed in claim 1, characterised in that R₁ is C, and R₉ is methyl or H, or forms a —

CH₂—

CH₂—

bond with R₁₀, and R₁₁ is phenyl or tolyl.

5. Compound as claimed in claim 2, characterised in that it is selected from one of the following:

3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl 2-(4-isobutyl-phenyl)-propionate;

3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl 2-(6-methoxy-naphthalen-2-yl)-propionate;

3-(2-dimethylaminomethyl-cyclohex-1-enyl)-phenyl 2-(4-isobutyl-phenyl)-propionate;

3-(2-dimethylaminomethyl-cyclohex-1-enyl)-phenyl 2-(6-methoxy-naphthalen-2-yl)-propionate;

6. Compound as claimed in claim 3, characterised in that it is selected from one of the following:

3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl 2-hydroxybenzoate;

3-(2-dimethylaminomethyl-cyclohex-1-enyl)-phenyl 2-hydroxybenzoate;

3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl 2-dimethylcarbamoyloxy-benzoate;

3-(2-dimethylaminomethyl-cyclohex-1-enyl)-phenyl 2-dimethylcarbamoyloxy-benzoate.

7. Compound as claimed in claim 4, characterised in that it is selected from one of the following:

3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)phenyl 5-benzoyl-2, 3-dihydro-1H-pyrrolizine-1-carboxylate.

8.rocess. Process for obtaining a compound as claimed in claim 1, characterised in that a compound of formula (II) is reacted with a compound of formula (III):

12. Use of a compound of general formula (I) as claimed in any of claims 1 to 7 for preparing a drug for the treatment of pain.

9. Process as claimed in claim 8, characterised in that said inert solvent is dichloromethane or tetrahydrofuran.

10. Process as claimed in claim 8, characterised in that said condensation promoting agent is carbonyldiimidazol or dicyclohexylcarbo-diimida.

11. Process as claimed in claim 8, characterised in that said temperature range is from 0°

to 35°

C.