Enantiomerically pure basic N-heterocyclic arylcycloalkylhydroxycarboxylic esters, processes for their preparation and their use in medicaments
AssigneesChristian Noe, Ernst Mutschler
InventorsChristian Noe, Ernst Mutschler, Günter Lambrecht, Michael Elgert, Sittah Czeche, Magali Waelbroeck
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Abstract
Disclosed are enantiomerically pure cyclic aminoalcohol esters of arylcycloalkylhydroxycarboxylic acids with at least 90% enantiomeric excess of the (3R,2′R), (3S,2′R), (3R,2′S), or (3S,2′S) configured enantiomer.
Claims20
An enantiomerically pure ester with enantiomeric purity of 90% minimum enantiomeric excess (ee) selected from the group consisting of the (3R,2′R)-, and (3S,2′R)-configured enantiomers of the formula I
- in which
- R1 is a cyclopentyl, a cyclohexyl or a norbornyl radical;
- R2 is a methyl radical;
- R3 is a methyl radical;
- AR is a phenyl radical or thienyl radical;
- n is 1, or 2
- A is an anion of a pharmacologically acceptable acid and in which OH, AR, and R1 are arranged clockwise when viewed looking toward the carboxyl group.
A process for preparing an enantiomerically pure ester with enantiomeric purity of 90% minimum enantiomeric excess (ee) selected from the group consisting of the (3R,2′R)-, (3S,2′R)-, (3R,2′S)- and (3S,2,S)-configured enantiomers of the formula I
- in which
- R1 is a cyclopentyl, a cyclohexyl or a norbornyl radical;
- R2 is a methyl radical;
- R3 is a methyl radical;
- AR is a phenyl radical or thienyl radical;
- n is 1, or 2 and
- A is an anion of a pharmacologically acceptable acid in which the R or S enantiomer of an enantiomerically pure-hydroxycarboxylic acid of the formula II
- in which R1 and AR are each as defined above, or a lower alkyl ester, acid anhydride or acid halide thereof, is reacted with the R or S enantiomer of an enantiomerically pure amino alcohol of the formula III
- in which R2 and n are each as defined above, and the resulting enantiomerically pure ester of the formula IV
- is reacted with an alkylating agent of the formula V
- R3—X (V)
- in which R3 is as defined above and X is an alkylating agent leaving group, and the resulting salt is isolated or, if not a salt of pharmaceutically acceptable anion A, converted to such salt by anion exchange.
A process for preparing an enantiomerically pure ester with enantiomeric purity of 90% minimum enantiomeric excess (ee) selected from the group consisting of the (3R,2′R)-, (3S,2′R)-, (3R,2′S)- and (3S,2′S)-configured enantiomers of the formula I
- in which
- R1 is a cyclopentyl, a cyclohexyl or a norbornyl radical;
- R2 is a methyl radical;
- R3 is a methyl radical;
- AR is a phenyl radical or thienyl radical;
- n is 1, or 2 and
- A is an anion of a pharmacologically acceptable acid.
- in which the racemic form of an -a-hydroxycarboxylic acid of the formula II
- in which R1 and AR are each as defined above, or a lower alkyl ester acid anhydride or acid halide thereof, is reacted with the R or S enantiomer of an enantiomerically pure amino alcohol of the formula III
- in which R2 and n are each as defined above, the resulting mixture of diastereomeric esters of the formula IV
- is separated, the desired diastereomer is reacted with an alkylating agent of the formula V
- R3—(V)
- in which R3 ais as defined above and X is an alkylating agent leaving group, and the resulting salt is isolated or, if not a salt of pharmaceutically acceptable anion A, converted to such salt by anion exchange.
Dependencies are inferred from the claim text.