Triazolopyridazine derivatives

Claim 2

A triazolopyridazine derivative of the formula: ##STR12## wherein A is methylene, ethylene or propylene which may be substituted by lower alkyl; R 1 is halogen, carboxyl, lower alkoxycarbonyl, aminocarbonyl, hydroxyaminocarbonyl, hydrazinocarbonyl, mercapto, lower alkanoylthio or aryl-lower alkylthio; R 2 is hydroxy, lower alkoxy or amino; R 3 and R 4 each is hydrogen or halogen or R 3 is hydrogen and R 4 is hydroxy; and R 5 is hydrogen, lower alkyl, aryl, carboxy, lower alkoxycarbonyl or aminocarbonyl; and the broken line denotes an optional carbon-carbon bond which can be present only when R 3 and R 4 each is hydrogen, or a salt of an acid of formula I with a pharmaceutically acceptable base.

Claim 3

The compound of claim 1 which is 5-carboxy-2,3,5,6,7,8-hexahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-2-acetic acid.

Claim 4

The compound of claim 1 which is methyl 2,3,5,6,7,8-hexahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-2-propionate.

Claim 5

The compound of claim 1 which is 2-(2-chloroethyl)-2,3,5,6,7,8-hexahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylic acid.

Claim 6

The compound of claim 1 which is methyl 2-(2-chloroethyl)-2,3,5,6,7,8-hexahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylate.

Claim 7

The compound of claim 1 which is 2,3,5,6,7,8-hexahydro-2-(2-mercaptoethyl)-1,3-dioxo-8-phenyl-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylic acid.

Claim 8

Triazolopyridazine derivatives of claim 1 wherein a double bond is present in the 6,7-position.

Claim 9

The compound of claim 7 which is methyl 2,3,5,8-tetrahydro-2-(3-acetylthiopropyl)-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylate.

Claim 10

The compound of claim 7 which is methyl 5-carboxy-2,3,5,8-tetrahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-2-propionate.

Claim 11

The compound of claim 7 which is 2-(2-benzylthioethyl)-2,3,5,8-tetrahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylic acid.

Claim 12

The compound of claim 7 which is methyl 2-acetylthiomethyl-2,3,5,8-tetrahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylate.

Claim 13

The compound of claim 7 which is 2-(3-chloropropyl)-2,3,5,8-tetrahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylic acid.

Claim 14

Triazolopyridazine derivatives of claim 7 wherein R 2 is hydroxy.

Claim 15

Triazolopyridazine derivatives of claim 13 wherein R 1 is carboxyl, hydroxyaminocarbonyl or mercapto.

Claim 16

The compound of claim 14 which is 5-carboxy-2,3,5,8-tetrahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-2-butyric acid.

Claim 17

The compound of claim 14 which is 5-carboxy-2,3,5,8-tetrahydro-8-methyl-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-2-propionic acid.

Claim 18

The compound of claim 14 which is 2,3,5,8-tetrahydro-2-mercaptomethyl-1,3-dioxo-1H-1,2,4,-triazolo[1,2-a]pyridazine-5-carboxylic acid.

Claim 19

The compound of claim 14 which is 5-carboxy-2,3,5,8-tetrahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-2-propionic acid.

Claim 20

The compound of claim 14 which is 5-carboxy-2,3,5,8-tetrahydro-8-phenyl-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-2-propionic acid.

Claim 21

Triazolopyridazine derivatives of claim 14 wherein A is ethylene.

Claim 22

A compound of the formula ##STR13## wherein R 2 is hydroxy, lower alkoxy or amino; R 3 and R 4 each is hydrogen or halogen, or R 3 is hydrogen and R 4 is hydroxy; and R 5 is hydrogen or lower alkyl, aryl, carboxy, lower alkoxycarbonyl or aminocarbonyl; and the broken line denotes an optional carbon-carbon bond which can be present only when R 3 and R 4 each is hydrogen, with the proviso that when a double bond is present in the 6,7-position and R 2 is hydroxy, or when R 3 and R 4 each is hydrogen and R 2 is hydroxy, R 5 is other than hydrogen.

Claim 23

A compound of the formula ##STR13## wherein R 2 is hydroxy, lower alkoxy or amino; R 3 and R 4 each is hydrogen or halogen, or R 3 is hydrogen and R 4 is hydroxy; and R 5 is hydrogen or lower alkyl, aryl, carboxy, lower alkoxycarbonyl or aminocarbonyl; and the broken line denotes an optional carbon-carbon bond which can be present only when R 3 and R 4 each is hydrogen, with the proviso that when a double bond is present in the 6,7-position and R 2 is hydroxy, or when R 3 and R 4 each is hydrogen and R 2 is hydroxy, R 5 is other than hydrogen.

Claim 24

The compound of claim 20 which is trans-2,3,5,8-tetrahydro-2-(2-mercaptoethyl)-1,3-dioxo-8-phenyl-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylic acid.

Claim 25

The compound of claim 20 which is cis 2-(2-chloroethyl)-2,3,5,8-tetrahydro-8-(4-methoxyphenyl)-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylic acid.

Claim 26

The compound of claim 20 which is cis-2-(2-chloroethyl)-2,3,5,8-tetrahydro-8-(4-nitrophenyl)-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylic acid.

Claim 27

The compound of claim 20 which is 2,3,5,8-tetrahydro-2-(2-mercaptoethyl)-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylic acid.

Claim 28

The compound of claim 20 which is 2-[2-(N-hydroxycarbamoyl)ethyl]-2,3,5,8-tetrahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylic acid.

Claim 29

The compound of claim 20 which is 2-(2-carbamoylethyl)-2,3,5,8-tetrahydro-1,3-dioxo-1H-1,2,4-triazolo[1,2-a]pyridazine-5-carboxylic acid.

Claim 30

An antihypertensive composition which comprises effective amounts of a triazolopyridazine derivative of the formula ##STR14## wherein A is methylene, ethylene or propylene which may be substituted by lower alkyl; R 1 is halogen, carboxyl, lower alkoxycarbonyl, aminocarbonyl, hydroxyaminocarbonyl, hydrazinocarbonyl, mercapto, lower alkanoylthio or aryl-lower alkylthio; R 2 is hydroxy, lower alkoxy or amino; R 3 and R 4 each is hydrogen or halogen or R 3 is hydrogen and R 4 is hydroxy; and R 5 is hydrogen, lower alkyl, aryl, carboxy, lower alkoxycarbonyl or aminocarbonyl; and the broken line denotes an optional carbon-carbon bond which can be present only when R 3 and R 4 each is hydrogen, or a pharmaceutically-acceptable salt of an acid thereof and a pharmaceutically-acceptable carrier.

Claim 31

An antihypertensive composition which comprises effective amounts of a triazolopyridazine derivative of the formula ##STR14## wherein A is methylene, ethylene or propylene which may be substituted by lower alkyl; R 1 is halogen, carboxyl, lower alkoxycarbonyl, aminocarbonyl, hydroxyaminocarbonyl, hydrazinocarbonyl, mercapto, lower alkanoylthio or aryl-lower alkylthio; R 2 is hydroxy, lower alkoxy or amino; R 3 and R 4 each is hydrogen or halogen or R 3 is hydrogen and R 4 is hydroxy; and R 5 is hydrogen, lower alkyl, aryl, carboxy, lower alkoxycarbonyl or aminocarbonyl; and the broken line denotes an optional carbon-carbon bond which can be present only when R 3 and R 4 each is hydrogen, or a pharmaceutically-acceptable salt of an acid thereof and a pharmaceutically-acceptable carrier.

Claim 32

An antihypertensive composition according to claim 21 wherein A is ethylene; R 1 is carboxy, hydroxyaminocarbonyl or mercapto; R 2 is hydroxy; R 3 and R 4 each is hydrogen; R 5 is lower alkyl, aryl, carboxy, lower alkoxycarbonyl or aminocarbonyl and a double bond is present in the 6,7-position, or a pharmaceutically-acceptable salt of an acid thereof and a pharmaceutically-acceptable carrier.

Claim 33

Compounds of the general formula ##STR15## wherein A is methylene, ethylene or propylene which may be substituted by lower alkyl; and R 10 is halogen, carboxyl or lower alkoxycarbonyl.

Claim 34

Compounds of the general formula ##STR15## wherein A is methylene, ethylene or propylene which may be substituted by lower alkyl; and R 10 is halogen, carboxyl or lower alkoxycarbonyl.

Claim 35

Compounds of the general formula ##STR16## wherein A is methylene, ethylene or propylene which may be substituted by lower alkyl; R 1 is halogen, carboxyl, lower alkoxycarbonyl, aminocarbonyl, hydroxyaminocarbonyl, hydrazinocarbonyl, mercapto, lower alkanoylthio or aryl-lower alkylthio; R 2 is hydroxy, lower alkoxy or amino; R 3 and R 4 each is hydrogen or halogen or R 3 is hydrogen and R 4 is hydroxy; R 5 is hydrogen, lower alkyl, aryl, carboxy, lower alkoxycarbonyl or aminocarbonyl; and the broken line denotes an optional carbon-carbon bond which can be present only when R 3 and R 4 each is hydrogen.

Claim 36

Compounds of the general formula ##STR16## wherein A is methylene, ethylene or propylene which may be substituted by lower alkyl; R 1 is halogen, carboxyl, lower alkoxycarbonyl, aminocarbonyl, hydroxyaminocarbonyl, hydrazinocarbonyl, mercapto, lower alkanoylthio or aryl-lower alkylthio; R 2 is hydroxy, lower alkoxy or amino; R 3 and R 4 each is hydrogen or halogen or R 3 is hydrogen and R 4 is hydroxy; R 5 is hydrogen, lower alkyl, aryl, carboxy, lower alkoxycarbonyl or aminocarbonyl; and the broken line denotes an optional carbon-carbon bond which can be present only when R 3 and R 4 each is hydrogen.

Claim 37

Compounds of the general formula ##STR17## wherein R 2 is hydroxy, lower alkoxy or amino; R 3 and R 4 each is hydrogen or halogen or R 3 is hydrogen and R 4 is hydroxy; and R 5 is hydrogen, lower alkyl, aryl, carboxy, lower alkoxycarbonyl or aminocarbonyl; and the broken line denotes an optional carbon-carbon bond which can be present only when R 3 and R 4 each is hydrogen.

Claim 38

Compounds of the general formula ##STR17## wherein R 2 is hydroxy, lower alkoxy or amino; R 3 and R 4 each is hydrogen or halogen or R 3 is hydrogen and R 4 is hydroxy; and R 5 is hydrogen, lower alkyl, aryl, carboxy, lower alkoxycarbonyl or aminocarbonyl; and the broken line denotes an optional carbon-carbon bond which can be present only when R 3 and R 4 each is hydrogen.