3-Amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine derivatives

Claim 2

A compound of the formula ##STR62## wherein R 1 and R 2 are independently hydrogen, halogen, trifluoromethyl, C 1-4 alkyl or C 1-4 alkoxy, or both jointly form tri- or tetramethylene, R 3 is hydrogen; optionally carboxy, C 1-4 alkoxycarbonyl, phenoxycarbonyl or phenyl-C 1-4 alkoxycarbonyl substituted C 1-6 alkyl; or optionally halogen, C 1-4 alkyl, C 1-4 alkoxy, methylenedioxy, amino, nitro or hydroxy substituted phenyl-C 1-4 alkyl, R 4 is C 1-16 alkyl substituted by oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiadinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydroxazepinyl, perhydrothiazepinyl, perhydroxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydro-diazocinyl, dithiocanyl, dioxocanyl, chromanyl, isochromanyl, 3,4-dihydro-2H-1-thianaphthyl, 3,4-dihydro-1H-2-thianaphthyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 2,3-dihydrobenzofuryl, 1,3-dihydroisobenzofuryl, 2,3-dihydro-benzo[b]thienyl, 1,3-dihydrobenzo[c]thienyl, indolinyl, isoindolinyl, 2,3,4,5-tetrahydro-1(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-3(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-2(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, 2,3-dihydro-1,4-benzodioxinyl, 2,3-dihydro-1,4-dithianaphthyl, 1,2,3,4-tetrahydroquinoxalinyl, 3,4-dihydro-2H-1,4-benzoxadinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzodioxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 3,4-dihydro-2H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydro-isoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl, each of said groups being unsubstituted or substituted by C 1-4 alkyl, phenyl, naphthyl, phenyl-C 1-4 alkyl, oxo, C 1-5 alkanoyl, benzoyl, phenyl-C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl, Y is carboxyl, C 1-4 alkoxycarbonyl, phenyl-C 1-4 alkoxycarbonyl or carboxyl amidated by an α-amino acid whose carboxyl group may be substituted by C 1-4 alkyl or phenyl-C 1-4 alkyl, the α-amino acid being glycine, valine, leucine, isoleucine, threonine, N.sup.α -lysine, methionine, phenylalanine or tryptophan, and the group C m H 2m represents methylene, ethylene or ethylidene, or a pharmaceutically acceptable salt thereof.

Claim 3

A compound according to claim 1, wherein R 4 is C 2-9 alkyl substituted by oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiadinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydroxazepinyl, perhydrothiazepinyl, perhydroxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydro-diazocinyl, dithiocanyl, dioxocanyl, chromanyl, isochromanyl, 3,4-dihydro-2H-1-thianaphthyl, 3,4-dihydro-1H-2-thianaphthyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 2,3-dihydrobenzofuryl, 1,3-dihydroisobenzofuryl, 2,3-dihydro-benzo[b]thienyl, 1,3-dihydrobenzo[c]thienyl, indolinyl, isoindolinyl, 2,3,4,5-tetrahydro-1(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-3(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-2(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, 2,3-dihydro-1,4-benzodioxinyl, 2,3-dihydro-1,4-dithianaphthyl, 1,2,3,4-tetrahydroquinoxalinyl, 3,4-dihydro-2H-1,4-benzoxadinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzodioxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 3,4-dihydro-2 H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydro-isoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl, each of said groups being substituted or substituted by C 1-4 alkyl, phenyl, naphthyl, phenyl-C 1-4 alkyl, oxo, C 1-5 alkanoyl, benzoyl, phenyl-C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl.

Claim 4

A compound according to claim 1, wherein R 4 is C 2-6 alkyl substituted by oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiadinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydroxazepinyl, perhydrothiazepinyl, perhydroxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydro-diazocinyl, dithiocanyl, dioxocanyl, chromanyl, isochromanyl, 3,4-dihydro-2H-1-thianaphthyl, 3,4-dihydro-1H-2-thianaphthyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 2,3-dihydrobenzofuryl, 1,3-dihydroisobenzofuryl, 2,3-dihydro-benzo[b]thienyl, 1,3-dihydrobenzo[c]thienyl, indolinyl, isoindolinyl, 2,3,4,5-tetrahydro-1(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-3(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-2-(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, 2,3,-dihydro-1,4-benzodioxinyl, 2,3-dihydro-1,4-dithianaphthyl, 1,2,3,4-tetrahydroquinoxalinyl, 3,4-dihydro-2H-1,4-benzoxadinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzodioxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 3,4-dihydro-2H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydro-isoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl, each of said groups being unsubstituted or substituted by C 1-4 alkyl, phenyl, naphthyl, phenyl-C 1-4 alkyl, oxo, C 1-5 alkanoyl, benzoyl, phenyl-C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl.

Claim 5

A compound according to claim 1, wherein R 4 is C 2-9 alkyl substituted by oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiadinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydroxazepinyl, perhydrothiazepinyl, perhydroxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydro-diazocinyl, dithiocanyl, dioxocanyl, chromanyl, isochromanyl, 3,4-dihydro-2H-1-thianaphthyl, 3,4-dihydro-1H-2-thianaphthyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 2,3-dihydrobenzofuryl, 1,3-dihydroisobenzofuryl, 2,3-dihydro-benzo[b]thienyl, 1,3-dihydrobenzo[c]thienyl, indolinyl, isoindolinyl, 2,3,4,5-tetrahydro-1(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-3(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-2(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, 2,3-dihydro-1,4-benzodioxinyl, 2,3-dihydro-1,4-dithianaphthyl, 1,2,3,4-tetrahydroquinoxalinyl, 3,4-dihydro-2H-1,4-benzoxadinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzodioxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 3,4-dihydro-2H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydro-isoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl.

Claim 6

A compound according to claim 1, wherein R 4 is C 2-6 alkyl substituted by oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiadinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydroxazepinyl, perhydrothiazepinyl, perhydroxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydro-diazocinyl, dithiocanyl, dixocanyl, chromanyl, isochromanyl, 3,4-dihydro-2H-1-thianaphthyl, 3,4-dihydro-1H-2-thianaphthyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 2,3-dihydrobenzofuryl, 1,3-dihydroisobenzofuryl, 2,3-dihydro-benzo[b]thienyl, 1,3-dihydro-benzo[c]thienyl, indolinyl, isoindolinyl, 2,3,4,5-tetrahydro-1(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-3(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-2(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, 2,3-dihydro-1,4-benzodioxinyl, 2,3-dihydro-1,4-dithianaphthyl, 1,2,3,4-tetrahydroquinoxalinyl, 3,4-dihydro-2H-1,4-benzoxadinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzodioxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 3,4-dihydro-2H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydro-isoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl.

Claim 7

A compound according to claim 1, wherein R 4 is C 1-16 alkyl substituted by oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl or perhydroazocinyl, each of said groups being unsubstituted or substituted by C 1-4 alkyl, phenyl, naphthyl, phenyl-C 1-4 alkyl, oxo, C 1-5 alkanoyl, benzoyl, phenyl-C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl.

Claim 8

A compound according to claim 1, wherein R 1 and R 2 are hydrogen.

Claim 9

A compound according to claim 1, wherein R 3 is hydrogen, C 1-6 alkyl or phenyl-C 1-4 alkyl.

Claim 10

A compound according to claim 1, wherein R 4 is C 2-9 alkyl substituted by piperidyl, oxanyl or thianyl.

Claim 11

A compound according to claim 1, wherein R 4 is C 2-9 alkyl substituted by piperidyl.

Claim 12

A compound according to claim 1, wherein R 4 is C 2-9 alkyl substituted by 4-piperidyl.

Claim 13

A compound according to claim 1, wherein R 4 is (4-piperidyl)butyl.

Claim 14

A compound according to claim 1, wherein Y is carboxyl.

Claim 15

A compound according to claim 1, wherein the group C m H 2m is methylene.

Claim 16

The compound according to claim 1, which is 3(S)-[1(S)-carboxy-6-(4-piperidyl)hexyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetic acid.

Claim 17

The compound according to claim 1, which is 3(S)-[1(S)-ethoxycarbonyl-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetic acid.

Claim 18

The compound according to claim 1, which is 3(S)-[1(S)-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetic acid.

Claim 19

An antihypertensive pharmaceutical composition containing an antihypertensive amount of a compound of the formula ##STR63## wherein R 1 and R 2 are independently hydrogen, halogen, trifluoromethyl, C 1-4 alkyl or C 1-4 alkoxy, or both jointly form tri- or tetramethylene, R 3 is hydrogen; optionally carboxy, C 1-4 alkoxycarbonyl, phenoxycarbonyl or phenyl-C 1-4 alkoxycarbonyl substituted C 1-6 alkyl; or optionally halogen, C 1-4 alkyl, C 1-4 alkoxy, methylenedioxy, amino, nitro or hydroxy substituted phenyl-C 1-4 alkyl, R 4 is C 1-16 alkyl substituted by oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiadinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydroxazepinyl, perhydrothiazepinyl, perhydroxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydro-diazocinyl, dithiocanyl, dioxocanyl, chromanyl, isochromanyl, 3,4-dihydro-2H-1-thianaphthyl, 3,4-dihydro-1H-2-thianaphthyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 2,3-dihydrobenzofuryl, 1,3-dihydroisobenzofuryl, 2,3-dihydro-benzo[b]thienyl, 1,3-dihydrobenzo[c]thienyl, indolinyl, isoindolinyl, 2,3,4,5-tetrahydro-1(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-3(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-2(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, 2,3,-dihydro-1,4-benzodioxinyl, 2,3-dihydro-1,4-dithianaphthyl, 1,2,3,4-tetrahydroquinoxalinyl, 3,4-dihydro-2H-1,4-benzoxadinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzodioxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 3,4-dihydro-2H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydro-isoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl, each of said groups being unsubstituted or substituted by C 1-4 alkyl, phenyl, naphthyl, phenyl-C 1-4 alkyl, oxo, C 1-5 alkanoyl, benzoyl, phenyl-C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl, Y is carboxyl, C 1-4 alkoxycarbonyl, phenyl-C 1-4 alkoxycarbonyl or carboxyl amidated by an α-amino acid whose carboxyl group may be substituted by C 1-4 alkyl or phenyl-C 1-4 alkyl, the α-amino acid being glycine, valine, leucine, isoleucine, threonine, N.sup.α -lysine, methionine, phenylalanine or tryptophan, and the group C m H 2m represents methylene, ethylene or ethylidene, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, excipient or diluent therefor.

Claim 20

An antihypertensive pharmaceutical composition containing an antihypertensive amount of a compound of the formula ##STR63## wherein R 1 and R 2 are independently hydrogen, halogen, trifluoromethyl, C 1-4 alkyl or C 1-4 alkoxy, or both jointly form tri- or tetramethylene, R 3 is hydrogen; optionally carboxy, C 1-4 alkoxycarbonyl, phenoxycarbonyl or phenyl-C 1-4 alkoxycarbonyl substituted C 1-6 alkyl; or optionally halogen, C 1-4 alkyl, C 1-4 alkoxy, methylenedioxy, amino, nitro or hydroxy substituted phenyl-C 1-4 alkyl, R 4 is C 1-16 alkyl substituted by oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiadinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydroxazepinyl, perhydrothiazepinyl, perhydroxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydro-diazocinyl, dithiocanyl, dioxocanyl, chromanyl, isochromanyl, 3,4-dihydro-2H-1-thianaphthyl, 3,4-dihydro-1H-2-thianaphthyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 2,3-dihydrobenzofuryl, 1,3-dihydroisobenzofuryl, 2,3-dihydro-benzo[b]thienyl, 1,3-dihydrobenzo[c]thienyl, indolinyl, isoindolinyl, 2,3,4,5-tetrahydro-1(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-3(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-2(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, 2,3,-dihydro-1,4-benzodioxinyl, 2,3-dihydro-1,4-dithianaphthyl, 1,2,3,4-tetrahydroquinoxalinyl, 3,4-dihydro-2H-1,4-benzoxadinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzodioxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 3,4-dihydro-2H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydro-isoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl, each of said groups being unsubstituted or substituted by C 1-4 alkyl, phenyl, naphthyl, phenyl-C 1-4 alkyl, oxo, C 1-5 alkanoyl, benzoyl, phenyl-C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl, Y is carboxyl, C 1-4 alkoxycarbonyl, phenyl-C 1-4 alkoxycarbonyl or carboxyl amidated by an α-amino acid whose carboxyl group may be substituted by C 1-4 alkyl or phenyl-C 1-4 alkyl, the α-amino acid being glycine, valine, leucine, isoleucine, threonine, N.sup.α -lysine, methionine, phenylalanine or tryptophan, and the group C m H 2m represents methylene, ethylene or ethylidene, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, excipient or diluent therefor.

Claim 21

Method for treatment of hypertension which comprises administration of an effective antihypertensive amount of a compound ##STR64## wherein R 1 and R 2 are independently hydrogen, halogen, trifluoromethyl, C 1-4 alkyl or C 1-4 alkoxy, or both jointly form tri- or tetramethylene, R 3 is hydrogen; optionally carboxy, C 1-4 alkoxycarbonyl, phenoxycarbonyl or phenyl-C 1-4 alkoxycarbonyl substituted C 1-6 alkyl; or optionally halogen, C 1-4 alkyl, C 1-4 alkoxy, methylenedioxy, amino, nitro or hydroxy substituted phenyl-C 1-4 alkyl, R 4 is C 1-16 alkyl substituted by oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiadinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydroxazepinyl, perhydrothiazepinyl, perhydroxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydro-diazocinyl, dithiocanyl, dioxocanyl, chromanyl, isochromanyl, 3,4-dihydro-2H-1-thianaphthyl, 3,4-dihydro-1H-2-thianaphthyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 2,3-dihydrobenzofuryl, 1,3-dihydroisobenzofuryl, 2,3-dihydro-benzo[b]thienyl, 1,3-dihydrobenzo[c]thienyl, indolinyl, isoindolinyl, 2,3,4,5-tetrahydro-1(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-3(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-2(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, 2,3-dihydro-1,4-benzodioxinyl, 2,3-dihydro-1,4-dithianaphthyl, 1,2,3,4-tetrahydroquinoxalinyl, 3,4-dihydro-2H-1,4-benzoxadinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzodioxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 3,4-dihydro-2H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydro-isoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl, each of said groups being unsubstituted or substituted by C 1-4 alkyl, phenyl, naphthyl, phenyl-C 1-4 alkyl, oxo, C 1-5 alkanoyl, benzoyl, phenyl-C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl, Y is carboxyl, C 1-4 alkoxycarbonyl, phenyl-C 1-4 alkoxycarbonyl or carboxyl amidated by an α-amino acid whose carboxyl group may be substituted by C 1-4 alkyl or phenyl-C 1-4 alkyl, the α-amino acid being glycine, valine, leucine, isoleucine, threonine, N.sup.α -lysine, methionine, phenylalanine or tryptophan, and the group C m H 2m represents methylene, ethylene or ethylidene, or a pharmaceutically acceptable salt thereof.

Claim 22

Method for treatment of hypertension which comprises administration of an effective antihypertensive amount of a compound ##STR64## wherein R 1 and R 2 are independently hydrogen, halogen, trifluoromethyl, C 1-4 alkyl or C 1-4 alkoxy, or both jointly form tri- or tetramethylene, R 3 is hydrogen; optionally carboxy, C 1-4 alkoxycarbonyl, phenoxycarbonyl or phenyl-C 1-4 alkoxycarbonyl substituted C 1-6 alkyl; or optionally halogen, C 1-4 alkyl, C 1-4 alkoxy, methylenedioxy, amino, nitro or hydroxy substituted phenyl-C 1-4 alkyl, R 4 is C 1-16 alkyl substituted by oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiadinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydroxazepinyl, perhydrothiazepinyl, perhydroxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydro-diazocinyl, dithiocanyl, dioxocanyl, chromanyl, isochromanyl, 3,4-dihydro-2H-1-thianaphthyl, 3,4-dihydro-1H-2-thianaphthyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 2,3-dihydrobenzofuryl, 1,3-dihydroisobenzofuryl, 2,3-dihydro-benzo[b]thienyl, 1,3-dihydrobenzo[c]thienyl, indolinyl, isoindolinyl, 2,3,4,5-tetrahydro-1(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-3(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-2(1H)-benzoazepinyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, 2,3-dihydro-1,4-benzodioxinyl, 2,3-dihydro-1,4-dithianaphthyl, 1,2,3,4-tetrahydroquinoxalinyl, 3,4-dihydro-2H-1,4-benzoxadinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzodioxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 3,4-dihydro-2H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydro-isoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl, each of said groups being unsubstituted or substituted by C 1-4 alkyl, phenyl, naphthyl, phenyl-C 1-4 alkyl, oxo, C 1-5 alkanoyl, benzoyl, phenyl-C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl, Y is carboxyl, C 1-4 alkoxycarbonyl, phenyl-C 1-4 alkoxycarbonyl or carboxyl amidated by an α-amino acid whose carboxyl group may be substituted by C 1-4 alkyl or phenyl-C 1-4 alkyl, the α-amino acid being glycine, valine, leucine, isoleucine, threonine, N.sup.α -lysine, methionine, phenylalanine or tryptophan, and the group C m H 2m represents methylene, ethylene or ethylidene, or a pharmaceutically acceptable salt thereof.