Substituted phenoxypropylaminoethoxyphenoxyacetamides

Claim 2

A compound of the general formula (I) or a pharmaceutically acceptable salt thereof, in which R represents a hydroxy group or an in vivo hydrolysable ester thereof, R l represents a hydroxy group in the 2-, 3-, or 4-position, or an ester thereof, R 2 represents a hydrogen atom or a lower alkyl group, R 3 and R 4 , which may be the same or different, each represents a hydrogen atom; an alkyl radical; or an unsubstituted or substituted aryl, arylalkyl or diarylalkyl radical ; or R 3 and R 4 , together with the nitrogen atom to which they are attached, form a 5-, 6- or 7-membered saturated or unsaturated heterocyclic radical.

Claim 3

A compound as claimed in claim l, wherein R 3 represents a hydrogen atom and R 4 represents a methyl group.

Claim 4

A compound as claimed in claim 1 or claim 2 wherein R and R 1 each represents a free hydroxyl group.

Claim 5

A compound as claimed in any one of claims 1 to 3, wherein R 1 is in the 4-position. _

Claim 6

A compound as claimed in claim 1, wherein: R represents a hydroxy group, R 1 represents a hydroxy group in the 4-position, R 2 represents a hydrogen atom or a methyl group R 3 represents a hydrogen atom, and R 4 represents a methyl group.

Claim 7

A compound as claimed in claim 1, selected from the group consisting of: N-Methyl 4-[2-[3-(4-hydroxyphenoxy) -2-hydroxypropylamino]-2-methylethoxy]phenoxyacetamide; and N-methyl 4-[2-[3-(4-hydroxyphenoxy)-2-hydroxy- propylamino]ethoxy]phenoxyacetamide; or a pharmaceutically acceptable salt thereof.

Claim 8

A process for the preparation of a compound of the general formula (I) or a pharmaceutically acceptable salt thereof, which comprises: A. reacting a compound of the general formula (II): with a. compound of the general formula (III): wherein Y represents a hydroxy group or a protected hydroxy group, Z represents the radical CH 2 CONR 3 R 4 or a radical convertible to CH 2 CONR 3 R 4 , Q represents a group of the formula (a) or (b): in which R is as defined in relation to formula (I) and X represents a leaving group, and Q 1 represents a group of formula (A): in which R 2 is as defined in relation to formula (I) or Q represents a group of the formula (c): in which R has the meaning given above, and Q 1 represents a group of the formula (B): in which R 2 and X have the meanings given above, and, if required, converting any protected hydroxy group represented by Y into a free hydroxy group and/or converting a group represented by Z into the radical CH 2 CON R 3 R 4 ; or

Claim 9

A process for the preparation of a compound of the general formula (I) or a pharmaceutically acceptable salt thereof, which comprises: A. reacting a compound of the general formula (II): with a. compound of the general formula (III): wherein Y represents a hydroxy group or a protected hydroxy group, Z represents the radical CH 2 CONR 3 R 4 or a radical convertible to CH 2 CONR 3 R 4 , Q represents a group of the formula (a) or (b): in which R is as defined in relation to formula (I) and X represents a leaving group, and Q 1 represents a group of formula (A): in which R 2 is as defined in relation to formula (I) or Q represents a group of the formula (c): in which R has the meaning given above, and Q 1 represents a group of the formula (B): in which R 2 and X have the meanings given above, and, if required, converting any protected hydroxy group represented by Y into a free hydroxy group and/or converting a group represented by Z into the radical CH 2 CON R 3 R 4 ; or

Claim 10

B. reducing a compound of the general formula )IV): in which Y and Z have the meanings given above and R 0 represents a group of the formula or in which RP is hydrogen or a protecting group, preferably a benzyl group, R and R 2 are as defined in relation to formula (I) provided that R O does not represent a group of the formula (iii) when Z represents a group of the formula CH 2 CONR 3 R 4 , and, if required, removing any protecting group represented by RP,converting any protected hydroxy group represented by Y into a free hydroxy group and/or converting a group represented by Z into the radical CH 2 CONR 3 R 4 ;or C. treating a compound of the general formula (V): in which R and R 2 are as defined in relation to formula (I), and Y is as defined in relation to formula (II), and Z' represents a radical convertible to CH 2 CONR 3 R 4 , wherein R 3 and R 4 are as defined in relation to formula (I), or, when Y represents a protected hydroxy group, the radical CH 2 CONR 3 R 4 , or a salt thereof, to convert Y into a free hydroxy group and/or to convert a group represented by Z' into the radical CH 2 CONR 3 R 4 ; or D. reacting a compound of the formula (IIc'): in which Ph represents a phenyl group, with a compound of the general formula (IIIC), preferably a compound of the general formula (IIIc'): to form a compound of the general formula (IV) in which R O represents a group of the general formula (iv) which is then reduced with sodium cyanoborohydride, preferably in methanol, to give a compound of the general formula (V), in which Z' represents a group CH 2 COO-lower alkyl; this is then reacted with methylamine, preferably in ethanol, to give a compound of the general formula (V) in which Z' represents the group CH 2 CONHCH 3 and this is then subjected to hydrogenolysis, preferably with the use of a palladium-on-carbon catalyst, to prepare a compound of the general formula (I); and, if desired, converting a resulting compound of the general formula (I) into another such compound, and/or, if desired, converting a salt into a free compound of formula (I), or a compound of formula (I) into a pharmaceutically acceptable salt thereof.

Claim 11

B. reducing a compound of the general formula )IV): in which Y and Z have the meanings given above and R 0 represents a group of the formula or in which RP is hydrogen or a protecting group, preferably a benzyl group, R and R 2 are as defined in relation to formula (I) provided that R O does not represent a group of the formula (iii) when Z represents a group of the formula CH 2 CONR 3 R 4 , and, if required, removing any protecting group represented by RP,converting any protected hydroxy group represented by Y into a free hydroxy group and/or converting a group represented by Z into the radical CH 2 CONR 3 R 4 ;or C. treating a compound of the general formula (V): in which R and R 2 are as defined in relation to formula (I), and Y is as defined in relation to formula (II), and Z' represents a radical convertible to CH 2 CONR 3 R 4 , wherein R 3 and R 4 are as defined in relation to formula (I), or, when Y represents a protected hydroxy group, the radical CH 2 CONR 3 R 4 , or a salt thereof, to convert Y into a free hydroxy group and/or to convert a group represented by Z' into the radical CH 2 CONR 3 R 4 ; or D. reacting a compound of the formula (IIc'): in which Ph represents a phenyl group, with a compound of the general formula (IIIC), preferably a compound of the general formula (IIIc'): to form a compound of the general formula (IV) in which R O represents a group of the general formula (iv) which is then reduced with sodium cyanoborohydride, preferably in methanol, to give a compound of the general formula (V), in which Z' represents a group CH 2 COO-lower alkyl; this is then reacted with methylamine, preferably in ethanol, to give a compound of the general formula (V) in which Z' represents the group CH 2 CONHCH 3 and this is then subjected to hydrogenolysis, preferably with the use of a palladium-on-carbon catalyst, to prepare a compound of the general formula (I); and, if desired, converting a resulting compound of the general formula (I) into another such compound, and/or, if desired, converting a salt into a free compound of formula (I), or a compound of formula (I) into a pharmaceutically acceptable salt thereof.

Claim 12

A compound of formula (I) or a pharmaceutically acceptable salt thereof, for use as an active therapeutic substance.

Claim 13

A compound of formula (I) or a pharmaceutically acceptable salt thereof, for use as an active therapeutic substance.

Claim 14

A compound of the general formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment of congestive heart failure in the human or non-human animal body.

Claim 15

A compound of the general formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment of congestive heart failure in the human or non-human animal body.

Claim 16

A pharmaceutical composition comprising a compound of the general formula (I) or a pharmaceutically acceptable salt thereof, in admixture or conjunction with a pharmaceutically acceptable carrier therefore.

Claim 17

A pharmaceutical composition comprising a compound of the general formula (I) or a pharmaceutically acceptable salt thereof, in admixture or conjunction with a pharmaceutically acceptable carrier therefore.

Claim 18

ll. A compound of the general formula(I), or a pharmaceutically acceptable salt thereof, for use in the manufacture of a medicament for the treatment of congestive heart failure in the human or non-human animal body.

Claim 19

ll. A compound of the general formula(I), or a pharmaceutically acceptable salt thereof, for use in the manufacture of a medicament for the treatment of congestive heart failure in the human or non-human animal body.