Derivatives of 3,3-diphenylpropylamines
AssigneeSchwarz Pharma AG
InventorsClaus Meese, Bengt Sparf
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Abstract
The invention concerns novel derivatives of 3,3-diphenylpropylamines, methods for their preparation, pharmaceutical compositions containing the novel compounds, and the use of the compounds for preparing drugs. More particularly, the invention relates to novel prodrugs of antimuscarinic agents with superior pharmacokinetic properties compared to existing drugs such as oxybutynin and tolterodine, methods for their preparation, pharmaceutical compositions containing them, a method of using said compounds and compositions for the treatment of urinary incontinence, gastrointestinal hyperactivity (irritable bowel syndrome) and other smooth muscle contractile conditions.
Claims26
A 3,3-Diphenylpropylamine of the general formula I:
- wherein R and R′ are independently
- a) hydrogen;
- or
- b) formyl, C1-C6 alkylcarbonyl, cycloalkylcarbonyl, substituted or unsubstitited arylcarbonyl;
- with the proviso that R′ is not hydrogen, methyl or benzyl when R is hydrogen, and R is not ethyl when R′ is hydrogen,
- X represents a tertiary amino group of formula Ia
- wherein R8 and R9 represent C1-C6 alkyl groups, which may be the same or different and which together contain at least three carbon atoms, or R8 and R9 may form a ring together with the amine nitrogen,
- A represents hydrogen (1H) or deuterium (2H), and
- their salts with physiologically acceptable acids, their free bases and, when the compounds are in the form of optical isomers, the racemic mixture and the individual enantiomers.
A 3,3-Diphenylpropylamine selected from
- (i) compounds of the formulae IX and IX′
- wherein o and p are the same or different and range from 0 to 6,
- (ii) Poly-co-DL-lactides of 2-(3-diisopropylamino-phenylpropyl)-4-hydroxymethylphenol and
- their salts with physiologically acceptable acids, their free bases and, when the compounds are in the form of optical isomers, the racemic mixture and the individual enantiomers.
A 3,3-Diphenylpropylamine of the general formula VII′:
- wherein R is
- a) hydrogen;
- or
- b) formyl, C1-C6 alkylcarbonyl, cycloalkylcarbonyl, substituted or unsubstituted arylcarbonyl;
- X represents a tertiary amino group of formula Ia
- wherein R8 and R9 represent non-aromatic hydrocarbyl groups, which may be the same or different and which together contain at least three carbon atoms, and wherein R8 and R9 may form a ring together with the amine nitrogen,
- Y and Z independently represent a single bond between the (CH2)n group and the carbonyl group, O, S or NH,
- A represents hydrogen (1H) or deuterium (2H),
- n is 0 to 12, and
- their salts with physiologically acceptable acids, their free bases and, when the compounds are in the form of optical isomers, the racemic mixture and the individual enantiomers.
A 3,3-Diphenylpropylamine selected from:
- (±)-malonic acid bis-[2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethylphenyl]ester,
- (±)-succinic acid bis-[2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethyl-phenyl]ester,
- (±)-pentanedioic acid bis-[2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethyl-phenyl]ester, and
- (±)-hexanedioic acid bis-[2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethylphenyl]ester.
Dependencies are inferred from the claim text.