Condensed seven-membered ring compounds, their production and use

Claim 2

A compound of the formula: ##STR107## 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 and R 5 are independently hydrogen, C 1-4 alkyl or phenyl-C 1-4 alkyl, R 4 is hydrogen or C 1-4 alkyl, R 6 is oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazeipinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiazinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydrooxazepinyl, perhydrothiazepinyl, perhydrooxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydrodiazocinyl, 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-dihydrobenzothienyl, 1,3-dihydrobenzothienyl, 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-bemzoxepinyl, 2,3,4,5-tetrahydro-1-benzothiapinyl, 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-benzothiadinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzoxepanyl, 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, perhydroisoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl, each of said groups being unsubstituted or substituted by C 1-4 alkyl, oxo, C 1-5 alkanoyl, benzoyl, phenyl-C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl, A is C 1-16 alkylene and the group CnH 2 n represents methylene, ethylene or ethylidene, or a pharmaceutically acceptable salt thereof.

Claim 3

A compound according to claim 1, wherein R 6 is oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiazinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydrooxazepinyl, perhydrothiazepinyl, perhydrooxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydrodiazocinyl, 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-dihydrobenzothienyl, 1,3-dihydrobenzothienyl, 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-benzothiadinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzoxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-1H-1,4benzodiazepinyl, 3,4-dihydro-2H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydroisoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl, each of said groups being unsubstituted or substituted by one member selected from the group consisting of C 1-4 alkyl, oxo, C 1-5 alkanoyl, benzoyl, phenyl-C 1-4 alkoxycarbonyl and C 1-4 alkoxycarbonyl.

Claim 4

A compound according to claim 1, wherein R 6 is oxanyl, thianyl or piperidyl, each of said groups being unsubstituted or substituted by 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 6 is piperidyl being unsubstituted or substituted by C 1-4 alkyl, oxo, C 1-5 alkanoyl, benzoyl, phenyl-C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl.

Claim 6

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

Claim 7

A compound according to claim 1, wherein R 3 and R 5 are independently hydrogen or C 1-4 alkyl.

Claim 8

A compound according to claim 1, wherein R 3 and R 5 are hydrogen.

Claim 9

A compound according to claim 1, wherein R 4 is hydrogen.

Claim 10

A compound according to claim 4, wherein the piperidyl group is 4-piperidyl.

Claim 11

A compound according to claim 1, wherein R 6 is 4-piperidyl.

Claim 12

A compound according to claim 1, wherein the group CnH 2 n is methylene.

Claim 13

A compound according to claim 1, wherein A is C 2-9 alkylene.

Claim 14

A compound according to claim 1, wherein A is tetramethylene.

Claim 15

A compound according to claim 1, wherein R 6 is 1,3-dioxoisoindolinyl.

Claim 16

A compound of the formula ##STR108## wherein A is C 2-9 alkylene, or a pharmaceutically acceptable salt thereof.

Claim 17

A compound of the formula ##STR108## wherein A is C 2-9 alkylene, or a pharmaceutically acceptable salt thereof.

Claim 18

A compound according to claim 15, wherein A is C 2-6 alkylene.

Claim 19

A compound according to claim 15, wherein A is tetramethylene.

Claim 20

The compound according to claim 1, which is 3(R)-[1(S)-ethoxycarbonyl-7-phthalimidoheptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid.

Claim 21

The compound according to claim 1, which is 3(R)-[1(S)-ethoxycarbonyl-3-(3,4,5,6-tetrahydro-2H-pyran-4-yl)propyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine5-acetic acid.

Claim 22

The compound according to claim 1, which is 3(R)-[1(S)-ethoxycarbonyl-3-(thian-4-yl)propyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid.

Claim 23

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

Claim 24

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

Claim 25

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

Claim 26

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

Claim 27

The compound according to claim 1, which is 3(R)[1(S)-ethoxycarbonyl-4-(4-piperadyl)butyl]amino-4-oxo2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid.

Claim 28

A pharmaceutical composition suitable for prevention or treatment of hypertension which comprises, as an active ingredient, an effective antihypertensive amount of a compound of the formula: ##STR109## 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 and R 5 are independently hydrogen, C 1-4 alkyl or phenyl-C 1-4 alkyl, R 4 is hydrogen or C 1-4 alkyl, R 6 is oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiazinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydrooxazepinyl, perhydrothiazepinyl, perhydrooxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydrodiazocinyl, 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-dihydrobenzothienyl, 1,3-dihydrobenzothienyl, 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-benzothiadinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzoxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-lH-1,4-benzodiazepinyl, 3,4-dihydro-2H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydroisoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl, each of said groups being unsubstituted or substituted by C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl, A is C 1-16 alkylene and the group CnH 2 n represents methylene, ethylene or ethylidene, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient or diluent therefor.

Claim 29

A pharmaceutical composition suitable for prevention or treatment of hypertension which comprises, as an active ingredient, an effective antihypertensive amount of a compound of the formula: ##STR109## 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 and R 5 are independently hydrogen, C 1-4 alkyl or phenyl-C 1-4 alkyl, R 4 is hydrogen or C 1-4 alkyl, R 6 is oxetanyl, thietanyl, azetidinyl, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, oxanyl, thianyl, piperidyl, oxepanyl, thiepanyl, perhydroazepinyl, oxocanyl, thiocanyl, perhydroazocinyl, dioxanyl, dithianyl, piperazinyl, morpholinyl, perhydrothiazinyl, oxathianyl, perhydrodiazepinyl, oxathiepanyl, dioxepanyl, dithiepanyl, perhydrooxazepinyl, perhydrothiazepinyl, perhydrooxazocinyl, perhydrothiazocinyl, oxathiocanyl, perhydrodiazocinyl, 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-dihydrobenzothienyl, 1,3-dihydrobenzothienyl, 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-benzothiadinyl, 2,3-dihydro-1,4-benzoxathienyl, 3,4-dihydro-2H-1,5-benzoxepanyl, 2,3-dihydro-5H-1,4-benzodioxepinyl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 2,3,4,5-tetrahydro-lH-1,4-benzodiazepinyl, 3,4-dihydro-2H-1,5-benzodithiepinyl, 2,3-dihydro-5H-1,4-benzodithiepinyl, perhydroindolyl, perhydroisoindolyl, perhydroquinolyl, perhydroisoquinolyl, perhydro-1-thianaphthyl or perhydro-2-thianaphthyl, each of said groups being unsubstituted or substituted by C 1-4 alkoxycarbonyl or C 1-4 alkoxycarbonyl, A is C 1-16 alkylene and the group CnH 2 n represents methylene, ethylene or ethylidene, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient or diluent therefor.