Patent EA-003742-B1 (EA)
Title: O-demethyltramadol ester derivatives, process for obtaining thereof and use for preparing a medicament
Inventor: DEL CASTILLO NIETO JUAN CARLOS
IPC: C07B53/00
Filed: 1999-11-04
Abstract: 1. Compound of general formula (I): where R1 is:     or   R2 is OH; R3 is H; or R2 and R3 together form a double bond; R4 is H or C1-C3 alkyl; R5 is H, NH2, NH-R11 or O-R11; R6 is H, CO-R11, O-R11 or halogen; R7 is H, C1-C5 alkyl, C2-C5 O-alkenyl, phenyl; or R6 and R7 are -CH=CR12-CR13=CH-, forming an optionally substituted condensed aromatic ring; R8 is OH, -O-CO-N(CH3)2 or NH-R11 ; R9 and R10 are H or C1-C4 alkyl, whether equal or different; or form a -CH2- CH2- bond; R11 is phenyl; phenyl optionally substituted by 1 or more of the following substituents: halogen (Cl, Br, I), NO2, C1-C6 alkyl, C2-C6 alkenyl, OH, or NH2; R12 and R13 are H, or C1-C3 O-alkyl, whether equal or different; its salts and optical isomers. 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)2. 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. 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):    where: R2 = OH, R3 = H, or R2 and R3 together form a double bond; X = OH, halogen, , O-R14, R14 = C1-6 alkyl, phenyl, optionally substituted phenyl, and R1 is      R4 is H or C1-C3 alkyl; R5 is H, NH2, NH-R11 or O-R11; R6 is H, CO-R11, O-R11 or halogen; R7 is H, C1-C5 alkyl, C2-C5 O-alkenyl, phenyl, or R6 and R7 are -CH=CR12-CR13=CH-, forming an optionally substituted condensed aromatic ring; R8 is OH, -O-CO-N(CH3)2 or NH-R11; R9 and R10 are H or C1-C4 alkyl, whether equal or different, or form a -CH2- CH2- bond; R11 is: phenyl, phenyl optionally substituted by 1 or more of the following substituents: halogen (Cl, Br, I), NO2, C1-C6 alkyl, C2-C6 alkenyl, OH, or NH2; R12 and R13 are H, or C1-C3 O-alkyl, whether equal or different; in an inert solvent, in a temperature range of -20 degree to 120 degree C, in the presence or absence of a condensation promoting agent. 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 degree to 35 degree C. 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.