US 6,313,132 B1Granted

Therapeutically active diarylpropylamines; their pharmaceutically acceptable salts; a method for their preparation and method for their use

AssigneePharmacia Corporation

InventorsRolf Johansson, Martin Haraldsson, Erik Ringberg, Ian Vagberg, Katarina Beierlein, Rikard Emond, Birger Sjoberg

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Abstract

The invention relates to novel compounds of Formula (I) wherein R1, R2, R3, R4, R5, R6, R7 and Ar are as defined in claim 1, their salts with physiologically acceptable acids and, when the compounds can be in the form of optical isomers, the racemic mixture and the individual enantiomers. The compounds have anticholinergic activity, and the invention also relates to the compounds of Formula (I), the use of the compounds of Formula (I) for preparing anticholinergic drugs, the use of the compounds of Formula (I) for treating urinary tract incontinence, and methods for preparing the compounds of Formula (I).

A compound of Formula (I):

wherein:
R1 is hydrogen, hydroxy, alkyl, alkoxy, hydroxyalkyl, trifluoromethyl, amino, alkylcarbonylamino, alkylcarbonyloxy, halogen,
R2 and R3 independently are hydrogen, hydroxy, alkyl, alkoxy, hydroxyalkyl, halogen, alkoxycarbonylalkyl, carbamoyl, sulphamoyl,
R4 is ω-hydroxyalkoxy, ω-aminoalkoxy, ω-aminoalkylamino, alkoxyalkyl, hydroxyalkoxyalkylaminoalkyl, alkoxycarbonylalkyl, dihydroxyalkyl, formyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylaminoalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, carboxyalkyl, carbamoylalkyl, carboxamidoalkyl, carboxyl, amino, nitro, cyano, nitrilo, cyanoalkyl, azido, alkyl having two or more carbon atoms, alkoxy having two or more carbon atoms, hydroxyalkyl having two or more carbon atoms,
R5 is hydrogen, halogen, alkyl,
Ar is aryl or heteroaryl wherein said aryl or heteroaryl are unsubstituted or independently substituted with one or two alkyl, alkoxy, hydroxy, hydroxyalkyl, halogen, alkoxycarbonylalkyl, carbamoyl, or sulphamoyl, and
R6 and R7 are hydrocarbyl groups which are the same or different, together having three or more carbon atoms, and unsubstituted or substituted by one or more hydroxy groups, and wherein carbon atoms are or are not interconnected by oxygen atoms, and wherein R6 and R7 may or may not together form a ring with the amine nitrogen;
with the provisions that (a) when:
(i) two or more of R2, R3, and R5 are other than hydrogen, or
(ii) R1 is other than hydroxy or methoxy, and Ar is other than phenyl that is ortho-substituted by hydroxy or methoxy, or
(iii) Ar is heteroaryl, or
(iv) one or more of R6 and R7 is aromatic hydrocarbyl or cycloalkyl, then
R4 must be hydrogen, methyl, methoxy, hydroxymethyl, hydroxy, halogen, carbamoyl, or sulphamoyl;
and (b), when Ar is unsubstituted phenyl, then R1, R2, R3, R4 and R5 can not all be hydrogen;
and
physiologically acceptable salts thereof, or the racemic mixture or the enantiomers thereof.

13 more elements

Abstract

Claims33