3-Amino-(1)-benzazepin-2-one-1-alkanoic acids

Claim 2

A compound having the formula ##STR25## wherein the carbocyclic ring may also be hexahydro; R 1 is hydrogen, lower alkyl, amino(lower)alkyl, aryl, aryl(lower)alkyl, cycloalkyl or cycloalkyl(lower)alkyl; R 2 and R 5 represent hydrogen or lower alkyl; R 3 and R 4 represent hydrogen, lower alkyl, lower alkoxy, lower alkanoyloxy, hydroxy, halogen, trifluoromethyl; or R 3 and R 4 taken together represent lower alkylenedioxy; X represents one acylated hydroxy group and one hydrogen; R 6 and R 7 independently represent hydroxy, amino, mono- or di-(lower)alkylamino, lower alkoxy, aryl(lower)alkoxy, lower alkanoyloxymethoxy, (amino, mono- or di-lower alkylamino, carboxy, or lower alkoxycarbonyl)-lower alkoxy; and wherein within the above definitions acylated hydroxy represents lower alkanoyloxy, nicotinoyloxy, benzoyloxy or benzoyloxy substituted on the phenyl ring by lower alkyl, halogen or lower alkoxy; and wherein within the above definitions aryl represents phenyl unsubstituted or mono- or di-substituted by lower alkyl, lower alkoxy, lower alkylenedioxy, lower alkanoyloxy, hydroxy, halogen or trifluoromethyl; and cycloalkyl contains 3 to 8 carbons; or a pharmaceutically acceptable salt thereof.

Claim 3

A compound having the formula ##STR26## wherein the carbocyclic ring may also be hexahydro; R 1 is indolyl(lower)alkyl, mono- or di-(lower)alkylamino(lower)alkyl, lower alkylthio(lower)alkyl, hydroxy(lower)alkyl, aryloxy(lower)alkyl, arylthio(lower)alkyl, aryl-N-(lower)alkylamino(lower)alkyl or arylamino(lower)alkyl; or R 1 is etherified hydroxy(lower)alkyl in which etherified hydroxy represents lower alkoxy or benzyloxy; or R 1 is acylated hydroxy(lower)alkyl; or R 1 represents carboxy(lower)alkyl, esterified carboxy(lower)alkyl, carbamoyl(lower)alkyl, N-substituted carbamoyl (lower)alkyl wherein carboxy, esterified carboxy, carbamoyl and N-substituted carbamoyl are as represented by COR 6 and COR 7 ; or R 1 is acylamino(lower)alkyl in which acylamino represents lower alkanoylamino; lower alkoxycarbonylamino; aryl(lower)alkanoylamino; aryl(lower)alkoxycarbonylamino; or aroylamino in which aroyl represents benzoyl or benzoyl substituted by lower alkyl, lower alkoxy or halogen, or nicotinoyl; R 2 and R 5 represent hydrogen or lower alkyl; R 3 and R 4 represent hydrogen, lower alkyl, lower alkoxy, lower alkanoyloxy, hydroxy, halogen, trifluoromethyl; or R 3 and R 4 taken together represent lower alkylenedioxy; X represents oxo, two hydrogens, or one hydroxy or acylated hydroxy group and one hydrogen; R 6 and R 7 independently represent hydroxy, amino, mono- or di-(lower)alkylamino, lower alkoxy, aryl(lower)alkoxy, lower alkanoyloxymethoxy, (amino, mono- or di-lower alkylamino, carboxy or lower alkoxycarbonyl)-lower alkoxy; and wherein within the above definitions aryl represents phenyl unsubstituted or mono- or di-substituted by lower alkyl, lower alkoxy, lower alkylenedioxy, lower alkanoyloxy, hydroxy, halogen or trifluoromethyl; and wherein within the above definitions acylated hydroxy represents lower alkanoyloxy, nicotinoyloxy, benzoyloxy or benzoyloxy substituted on the phenyl ring by lower alkyl, halogen or lower alkoxy; or a pharmaceutically acceptable salt thereof.

Claim 4

A compound having the formula ##STR26## wherein the carbocyclic ring may also be hexahydro; R 1 is indolyl(lower)alkyl, mono- or di-(lower)alkylamino(lower)alkyl, lower alkylthio(lower)alkyl, hydroxy(lower)alkyl, aryloxy(lower)alkyl, arylthio(lower)alkyl, aryl-N-(lower)alkylamino(lower)alkyl or arylamino(lower)alkyl; or R 1 is etherified hydroxy(lower)alkyl in which etherified hydroxy represents lower alkoxy or benzyloxy; or R 1 is acylated hydroxy(lower)alkyl; or R 1 represents carboxy(lower)alkyl, esterified carboxy(lower)alkyl, carbamoyl(lower)alkyl, N-substituted carbamoyl (lower)alkyl wherein carboxy, esterified carboxy, carbamoyl and N-substituted carbamoyl are as represented by COR 6 and COR 7 ; or R 1 is acylamino(lower)alkyl in which acylamino represents lower alkanoylamino; lower alkoxycarbonylamino; aryl(lower)alkanoylamino; aryl(lower)alkoxycarbonylamino; or aroylamino in which aroyl represents benzoyl or benzoyl substituted by lower alkyl, lower alkoxy or halogen, or nicotinoyl; R 2 and R 5 represent hydrogen or lower alkyl; R 3 and R 4 represent hydrogen, lower alkyl, lower alkoxy, lower alkanoyloxy, hydroxy, halogen, trifluoromethyl; or R 3 and R 4 taken together represent lower alkylenedioxy; X represents oxo, two hydrogens, or one hydroxy or acylated hydroxy group and one hydrogen; R 6 and R 7 independently represent hydroxy, amino, mono- or di-(lower)alkylamino, lower alkoxy, aryl(lower)alkoxy, lower alkanoyloxymethoxy, (amino, mono- or di-lower alkylamino, carboxy or lower alkoxycarbonyl)-lower alkoxy; and wherein within the above definitions aryl represents phenyl unsubstituted or mono- or di-substituted by lower alkyl, lower alkoxy, lower alkylenedioxy, lower alkanoyloxy, hydroxy, halogen or trifluoromethyl; and wherein within the above definitions acylated hydroxy represents lower alkanoyloxy, nicotinoyloxy, benzoyloxy or benzoyloxy substituted on the phenyl ring by lower alkyl, halogen or lower alkoxy; or a pharmaceutically acceptable salt thereof.

Claim 5

A compound as claimed in claim 2 wherein R 1 is indolyl(lower)alkyl, carboxy(lower)alkyl, lower alkoxycarbonyl(lower)alkyl, hydroxy(lower)alkyl, lower alkylthio(lower)alkyl, acylamino(lower)alkyl, aryloxy(lower)alkyl or arylthio(lower)alkyl; and in which aryl, acylamino, X and R 2 to R 7 are as defined in said claim; or a pharmaceutically acceptable salt thereof; or any said compound wherein the carbocyclic ring is hexahydro.

Claim 6

A compound as claimed in claim 2 whrein R 1 is acylamino(lower)alkyl in which acylamino represents lower alkanoylamino, lower alkoxycarbonylamino, phenyl(lower)alkoxycarbonylamino or benzoylamino; R 2 and R 5 are hydrogen or lower alkyl; R 3 and R 4 are hydrogen, lower alkoxy, lower alkyl, halogen or trifluoromethyl; or R 3 and R 4 taken together represent alkylenedioxy; X represents oxo, one hydroxy or lower alkanoyloxy and one hydrogen, or 2 hydrogens; R 6 and R 7 independently represent hydroxy, amino, lower alkoxy, phenyl(lower)alkoxy, lower alkoxycarbonyl(lower)alkoxy; or a pharmaceutically acceptable salt thereof; or any said compound wherein the carbocyclic ring is hexahydro.

Claim 7

A compound as claimed in claim 2 wherein R 1 is aryl(lower)alkoxycarbonylamino-(lower)alkyl wherein aryl represents phenyl unsubstituted or mono-substituted by lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, halogen or trifluoromethyl; R 2 and R 5 are hydrogen or lower alkyl; R 3 and R 4 are hydrogen, lower alkoxy, lower alkyl, halogen, or trifluoromethyl; or R 3 and R 4 taken together represent lower alkylenedioxy; X represents oxo, one hydroxy or lower alkanoyloxy and one hydrogen, or 2 hydrogens; R 6 and R 7 independently represent hydroxy, amino, lower alkoxy, phenyl(lower)alkoxy or lower alkoxycarbonyl(lower)alkoxy; or a pharmaceutically acceptable salt thereof.

Claim 8

A compound of claim 1 and formula IA wherein R 1 is ω-arylmethoxycarbonylamino-(lower) alkyl where aryl represents phenyl unsubstituted or mono-substituted by lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, halogen or trifluoromethyl; R 2 and R 5 are hydrogen or lower alkyl; R 3 is hydrogen; R 4 is hydrogen, lower alkoxy, lower alkyl, halogen, or trifluoromethyl; 7 X represents oxo, one hydroxy or lower alkanoyloxy and one hydrogen, or 2 hydrogens; R 6 and R 7 independently represent hydroxy, amino, lower alkoxy, phenyl(lower)alkoxy, lower alkoxycarbonyl(lower)alkoxy; or a pharmaceutically acceptable salt thereof; or any said compound wherein the carbocyclic ring is hexahydro.

Claim 9

A compound having the formula ##STR27## wherein the carboxylic ring may also be hexahydro; n represents an integer from 1 to 4; R 8 is amino, benzyloxycarbonylamino; R 6 and R 7 independently represent hydroxy, lower alkoxy of up to 4 carbon atoms, benzyloxy, amino; or a pharmaceutically acceptable salt thereof.

Claim 10

A compound having the formula ##STR27## wherein the carboxylic ring may also be hexahydro; n represents an integer from 1 to 4; R 8 is amino, benzyloxycarbonylamino; R 6 and R 7 independently represent hydroxy, lower alkoxy of up to 4 carbon atoms, benzyloxy, amino; or a pharmaceutically acceptable salt thereof.

Claim 11

A compound as claimed in claim 7 wherein C n H 2n represents n-propylene or n-butylene; R 8 represents amino or benzyloxycarbonylamino; R 6 and R 7 independently represent hydroxy or lower alkoxy with up to 4 carbon atoms; or a pharmaceutically acceptable salt thereof; or any said compound wherein the carboxyclic ring is hexahydro.

Claim 12

A compound of claim 7 being 3-[(5-benzyloxycarbonylamino-1-carboxy)pentylamino]-1-carboxymethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, a stereoisomer or a pharmaceutically acceptable salt thereof.

Claim 13

A compound of claim 1 being 5-acetoxy-1-carboxymethyl-3-(1-ethoxycarbonyl-3-phenylpropylamino)-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, a stereoisomer or a pharmaceutically acceptable salt thereof.

Claim 14

A pharmaceutical composition suitable for oral or parenteral administration to mammals for the treatment or prevention of diseases responsive to inhibition of angiotensin-converting enzyme comprising an effective amount of a compound of claim 2 in combination with one or more pharmaceutically acceptable carriers.

Claim 15

A method of treating hypertensive or cardiac conditions in mammals which comprises administering to a mammal in need thereof an effective amount of a composition of claim 11.

Claim 16

A method of inhibiting angiotensin-converting enzyme which comprises administering to a mammal in need thereof an effective amount of a composition of claim 11.

Claim 17

A compound according to claim 7 being 3-(5-amino-1-carboxypentylamino)-1-carboxymethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, a stereoisomer or a pharmaceutically acceptable salt thereof.

Claim 18

A pharmaceutical composition suitable for oral or parenteral administration to mammals for the treatment or prevention of diseases responsive to inhibition of angiotensin-converting enzyme comprising an effective amount of a compound of claim 1 in combination with one or more pharmaceutically acceptable carriers.

Claim 19

A method of treating hypertensive or cardiac conditions in mammals which comprises administering to a mammal in need thereof an effective amount of a composition of claim 15.

Claim 20

A method of inhibiting angiotensin-converting enzyme which comprises administering to a mammal in need thereof an effective amount of a composition of claim 15.

Claim 21

A pharmaceutical composition suitable for oral or parenteral administration to mammals for the treatment or prevention of diseases responsive to inhibition of angiotensin-converting enzyme comprising an effective amount of a compound of claim 7 in combination with one or more pharmaceutically acceptable carriers.

Claim 22

A method of treating hypertensive or cardiac conditions in mammals which comprises administering to a mammal in need thereof an effective amount of a composition of claim 18.

Claim 23

A method of inhibiting angiotensin-converting enzyme which comprises administering to a mammal in need thereof an effective amount of a composition of claim 18.

Claim 24

A compound according to claim 7 having the formula ##STR28## wherein S represents the chirality, n represents an integer from 1 to 4; R 8 is amino or benzyloxycarbonylamino; R 6 and R 7 independently represent hydroxy, lower alkoxy of up to 4 carbon atoms, benzyloxy or amino; or a pharmaceutically acceptable salt thereof.

Claim 25

A compound according to claim 21 being the S,S-stereoisomer of 3-(5-amino-1-carboxypentylamino)-1-carboxymethyl-2,3,4,5-tetrahydro-1H-[1]-benzazepin-2-one or a pharmaceutically acceptable salt thereof.