3-Aminopropoxyphenyl derivatives, their preparation and pharmaceutical compositions containing them

Claim 2

A compound of formula I wherein R is alkyl, alkenyl, cycloalkyl, cycloalkylalkyl or optionally substituted aryl, aralkyl or aralkenyl, R 1 is hydrogen or a substituent, R 2 is hydrogen or has the significance indicated above for R, A is alkylene, X is a bond or imino, Y is an oxygen or a sulfur atom and either Z is an oxygen atom and n is 2 or 3 or Z is a bond and n is 1, 2 or 3, with the proviso that when R 2 is cycloalkylalkyl, R is alkyl and X is a bond then R 1 is other than hydrogen, or aphysiologically acceptable hydrolyzable derivative thereof having the hydroxy group in the 2 position of the 3-aminopropoxy side chain in esterified form, in free form or in salt form.

Claim 3

A compound of claim 1 of formula Ia, wherein X, Y, Z and n are as defined in claim 1 R is alkyl of 1 to 4 carbon atoms, alkenyl of 3 to 5 carbon atoms wherein the double bond is not attached to the carbon atom adjacent to X, cycloalkyl of 5 to 7 carbon atoms, cycloalkylalkyl of 3 to 7 carbon atoms in the cycloalkyl moiety and of 1 to 4 carbon atoms in the alkyl moiety thereof, or phenyl, phenylalkyl of 7 to 10 carbon atoms or phenylalkenyl of 8 to 11 carbon atoms, wherein the double bond is not attached to the carbon atom adjacent to X, the last three substituents optionally being i) monosubstituted in the phenyl ring by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, halogen of atomic number of from 9 to 35, hydroxy, cyano, trifluoromethyl, hydroxymethyl, carbamoyl, alkoxyalkoxy of 1 to 4 carbon atoms in each of the alkoxy moieties thereof, amino or alkanoylamino of 1 to 5 carbon atoms, or ii) independently disubstituted in the phenyl ring by alkyl of 1 to 4 carbon atoms, hydroxymethyl, carbamoyl, cyano, alkoxy of 1 to 4 carbon atoms, halogen of atomic number of from 9 to 35 or hydroxy, or i i i) independently trisubstituted in the phenyl ring by alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms, is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, halogen of atomic number of from 9 to 53, trifluoromethyl, pyrrol-1-yl, cyano, carbamoyl, alkenyl of 2 to 5 carbon atoms, alkenyloxy of 3 to 5 carbon atoms wherein the double bond is not attached to the carbon atom adjacent to the oxygen atom, alkanoyl of 2. to 5 carbon atoms, nitro, amino, alkanoylamino of 1 to 5 carbon atoms or alkoxycarbonylamino of 1 to 4 carbon atoms in the alkoxy moiety thereof, is hydrogen, alkyl of 1 to 5. carbon atoms, alkenyl of 3 to 5 carbon atoms wherein the double bond is not attached to the carbon atom adjacent to Y, cycloalkyl of 5 to 7 carbon atoms, - cycloalkylalkyl of 3 to 7 carbon atoms in the cycloalkyl moiety and of 1 to 4 carbon atoms in the alkyl moiety thereof, or phenyl, phenylalkyl of 7 to 10 carbon atoms or phenylalkenyl of 8 to 11 carbon atoms wherein the double bond is not attached to the carbon atom adjacent to Y, the . last three substituents optionally being mono-or independently di- or independently trisubstituted in the phenyl ring by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35 and A is alkylene of 2 to 5 carbon atoms, with the proviso that when is cycloalkylalkyl, a R is alkyl and X is a bond, then is other than hydrogen, or a physiologically acceptable hydrolyzable derivative. thereof having the hydroxy group in the 2 position of the 3-aminopropoxy side chain in esterified form, in free form or in salt form.

Claim 4

A compound of claim 1 of formula I wherein A is ethylene, X is imino, either R is phenyl, p-hydroxyphenyl or p-carbamoylphenyl, R 1 is cyano and R 2 is methyl, or R is phenyl, R 1 is bromine and R 2 is cyclopropylmethyl, or R is p-OH-phenyl, R 1 is cyano and R 2 is cyclopropyimethyl, Z and Y are oxygen and n is 2, whereby R 1 is in the position on the phenyl ring ortho to the 3-aminopropoxy side chain, in free form or in salt form.

Claim 5

A process for the production of a compound of claim 1, which includes the step of appropriately 3-amino-2-oxypropylating a corresponding compound of formula IV, wherein R 1 , R 2 , Z, Y and n are as defined in claim 1, or a precursor form thereof, and recovering the resultant compound in free form or in salt form.

Claim 6

A process according to claim 4 for the production of a compound of claim 1, which comprises reacting a corresponding compound of formula II, wherein R 1 , R 2 , Z, Y and n are as defined in claim 1 and R is a group capable of reacting with a primary amine to give a 2-amino-l-hydroxyethyl group, with a corresponding compound of formula III, wherein A, X and R are as defined in claim 1, and, where required, appropriately esterifying the 2 position of the 3-aminopropoxy side chain in the resultant compound of formula I, and recovering the resultant compound in free form or in salt form.

Claim 7

A pharmaceutical composition which comprises a compound of any one of claims 1 to 3 in free form or in pharmaceutically acceptable salt form in association with a pharmaceutical carrier or diluent.

Claim 8

A compound of any one of claims 1 to 3 in free form or in pharmaceutically acceptable salt form, for use in a method for the treatment of the human or animal body by surgery or therapy, or in a diagnostic method practised on the human or animal body.

Claim 9

A compound of any one of claims 1 to 3 in free form or in pharmaceutically acceptable salt form, for use as a cardioselective β-adrenoceptor blocking agent.