Acylamino acid antihypertensives in the treatment of congestive heart failure

Claim 1

A method of treating congestive heart failure comprising administering an effective amount of a compound having the structural formula ##STR61## wherein R 1a is Y--C 6 H 4 --, Y--C 6 H 4 S--, Y--C 6 H 4 O--, ##STR62## α-naphthyl, β-naphthyl, furyl, benzofuryl, benzothienyl, H 2 N(CH 2 ) m --, diphenylmethyl or ##STR63## R 2 is alkyl, alkyl--S(O) 0-2 (CH 2 ) k S(O) 0-2 (CH 2 ) q --, alkyl-O(CH 2 ) q --, R 5 (CH 2 ) k --O(CH 2 ) q --, R 5 (CH 2 ) q --, H 2 N(CH 2 ) q --, cycloalkyl(CH 2 ) k --, R 13 CONH(CH 2 ) q --, R 13 NHCO(CH 2 ) q -- or R 6 OCO(CH 2 ) q --; R 3 is --OR 7 , --NR 7 R 8 , ##STR64## R 4 and R 13 are independently hydrogen, alkyl or Y 1 --C 6 H 4 --; R 5 is Y 2 --C 6 H 4 13 , Y 2 --C 6 H 4 S--, Y 2 --C 6 H 4 O--, naphthyl, furyl, thienyl, benzofuryl, benzothienyl, indolyl or ##STR65## provided that when R 5 is Y 2 --C 6 H 4 S-- or Y 2 C 6 H 4 O--, k is 2 or 3; R 14 is R 5 , mono-unsaturated lower alkyl, hydroxy, alkoxy or alkylthio, provided that when R 14 is hydroxy or alkoxy, k is 2 or 3 and when R 14 is mono-unsaturated alkyl or alkylthio, k is 1, 2 or 3; R 6 , R 7 and R 8 are independently H, alkyl, hydroxyalkyl, dihydroxyalkyl, alkoxyalkyl, dialkoxyalkyl, alkoxyalkoxyalkyl, haloalkyl, (haloalkoxy)alkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylalkyl or alkyl substituted with a 5-6 membered saturated ring comprising 1-2 oxygen atoms as ring members wherein the ring carbon atoms may be substituted with 0-2 alkyl substituents, or R 7 and R 8 together with the nitrogen to which they are attached complete a 5-7 membered ring, wherein one of the 4-6 ring members comprising R 7 and R 8 may be a nitrogen atom, an alkyl-substituted nitrogen atom or an oxygen atom, and wherein the ring may be substituted on the ring carbon atoms with substituents chosen from alkyl and hydroxy groups; R 9 is hydrogen, alkyl, carboxyalkyl, mercaptoalkyl, alkylthioalkyl, aminoalkyl, hydroxyalkyl, phenylalkyl, hydroxyphenylalkyl, guanidinoalkyl, imidazolyalkyl, indolylalkyl, or carbamoylalkyl; n is 0-2; m and k are independently 0-3; q is 1-4; X and X 1 are independently a bond, --O--, --S--, or --CH 2 --; Q is hydrogen or R 10 CO--; R 10 is alkyl, hydroxyalkyl, alkoxyalkyl, alkylaminoalkyl, dialkylaminoalkyl, Y 3 --C 6 H 4 -alkyl, alkoxy, Y 3 --C 6 H 4 --, naphthyl, furyl, thienyl or pyridyl; Y, Y 1 , Y 2 and Y 3 independently represent one or more substituents selected from H, alkyl, cycloalkyl, alkoxy, OH, F, Cl, Br, CN, --CH 2 NH 2 , --CO 2 H, --CO 2 alkyl, --CONH 2 and phenyl; or a pharmaceutically acceptable addition salt thereof.

Claim 2

A method of treating congestive heart failure comprising administering an effective amount of a compound having the structural formula ##STR61## wherein R 1a is Y--C 6 H 4 --, Y--C 6 H 4 S--, Y--C 6 H 4 O--, ##STR62## α-naphthyl, β-naphthyl, furyl, benzofuryl, benzothienyl, H 2 N(CH 2 ) m --, diphenylmethyl or ##STR63## R 2 is alkyl, alkyl--S(O) 0-2 (CH 2 ) k S(O) 0-2 (CH 2 ) q --, alkyl-O(CH 2 ) q --, R 5 (CH 2 ) k --O(CH 2 ) q --, R 5 (CH 2 ) q --, H 2 N(CH 2 ) q --, cycloalkyl(CH 2 ) k --, R 13 CONH(CH 2 ) q --, R 13 NHCO(CH 2 ) q -- or R 6 OCO(CH 2 ) q --; R 3 is --OR 7 , --NR 7 R 8 , ##STR64## R 4 and R 13 are independently hydrogen, alkyl or Y 1 --C 6 H 4 --; R 5 is Y 2 --C 6 H 4 13 , Y 2 --C 6 H 4 S--, Y 2 --C 6 H 4 O--, naphthyl, furyl, thienyl, benzofuryl, benzothienyl, indolyl or ##STR65## provided that when R 5 is Y 2 --C 6 H 4 S-- or Y 2 C 6 H 4 O--, k is 2 or 3; R 14 is R 5 , mono-unsaturated lower alkyl, hydroxy, alkoxy or alkylthio, provided that when R 14 is hydroxy or alkoxy, k is 2 or 3 and when R 14 is mono-unsaturated alkyl or alkylthio, k is 1, 2 or 3; R 6 , R 7 and R 8 are independently H, alkyl, hydroxyalkyl, dihydroxyalkyl, alkoxyalkyl, dialkoxyalkyl, alkoxyalkoxyalkyl, haloalkyl, (haloalkoxy)alkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylalkyl or alkyl substituted with a 5-6 membered saturated ring comprising 1-2 oxygen atoms as ring members wherein the ring carbon atoms may be substituted with 0-2 alkyl substituents, or R 7 and R 8 together with the nitrogen to which they are attached complete a 5-7 membered ring, wherein one of the 4-6 ring members comprising R 7 and R 8 may be a nitrogen atom, an alkyl-substituted nitrogen atom or an oxygen atom, and wherein the ring may be substituted on the ring carbon atoms with substituents chosen from alkyl and hydroxy groups; R 9 is hydrogen, alkyl, carboxyalkyl, mercaptoalkyl, alkylthioalkyl, aminoalkyl, hydroxyalkyl, phenylalkyl, hydroxyphenylalkyl, guanidinoalkyl, imidazolyalkyl, indolylalkyl, or carbamoylalkyl; n is 0-2; m and k are independently 0-3; q is 1-4; X and X 1 are independently a bond, --O--, --S--, or --CH 2 --; Q is hydrogen or R 10 CO--; R 10 is alkyl, hydroxyalkyl, alkoxyalkyl, alkylaminoalkyl, dialkylaminoalkyl, Y 3 --C 6 H 4 -alkyl, alkoxy, Y 3 --C 6 H 4 --, naphthyl, furyl, thienyl or pyridyl; Y, Y 1 , Y 2 and Y 3 independently represent one or more substituents selected from H, alkyl, cycloalkyl, alkoxy, OH, F, Cl, Br, CN, --CH 2 NH 2 , --CO 2 H, --CO 2 alkyl, --CONH 2 and phenyl; or a pharmaceutically acceptable addition salt thereof.