Tricyclic dihydropyridazinones and pharmaceutical compositions contaning them

Claim 2

A compound selected from the group consisting of : 4,4a-dihydro-5H-indeno/ 1 ,2-c / pyridazin-3-one-7-ami no; 4,4a-dihydro-5H-indeno/1,2-c/pyridazin-3-one-7-forma mide; 4,4a-dihydro-5H-indeno/1,2-c/pyridazin-3-one-7-aceta mide; 4,4a-dihydro-5H-indeno/1,2-c/pyridazin-3-one-7-benza mide; 4,4a-dihydro-5H-indeno/1,2-c/pyridazin-3-one-7-(3', 4',5'-trimethoxy)-benzamide; 4,4a-dihydro-5H-indeno/1,2-c/pyridazin-3-one-7-nicotinyl-amide; 4,4a,5,6-tetrahydro-2H-benzo(h)cinnolin-3-one-8-ami no; 4,4a,5,6-tetrahydro-2H-benzo(h)cinnolin-3-one-8-ace tamide; 4,4a,5,6-tetrahydro-2H-benzo(h)-cinnolin-3-one-8-2'-chloroacetamide; 2-n-butyl-4,4a,5,6-tetrahydro-2H-benzo(h)cinnolin-3- one-8-amino; 2-n-butyl-2,4,4a,5,6,7-hexahydro-3H-/ 6 ,7 / -cyclohepten- /l,2-c/-pyridazin-3-one-8-amino; 2-n-butyl-2,4,4a,5,6,7-hexahydro-3H-/6,7/-cyclohepten- /1,2-c/-pyridazin-3-one-8-benzamide; 2,4,4a,5,6,7-hexahydro-3H-benzo-[6,7]-cyclohepten[1,2- c/-pyridazin-3-one-8-amino; 2,4,4a,5,6,7-hexahydro-3H-benzo-[6,7]-cyclohepten[1,2- c/-pyridazin-3-one-8-acetamide; 2,4,4a,5,6,7-hexahydro-3H-benzo-/ 6 ,7 / -cyclohepten/ 1 ,2- c / -pyridazin-3-one-8-benzamide; and their non toxic salts.

Claim 3

A pharmaceutical or veterinary composition, suitable for use as hypotensive agent, said composition comprising a therapeutically effective amount of a compound as claimed in any of the claims 1, 2 and a pharmaceutically and/or veterinary acceptable car rier and/or diluent.

Claim 4

A pharmaceutical or veterinary composition, according to claim 3, suitable for use as a vasodilatory agent.

Claim 5

A pharmaceutical or veterinary composition, according to claim 3, suitable for use as an antiaggregating agent.

Claim 6

A pharmaceutical or veterinary composition, according to claim 3, suitable for use as an antithrombo tic agent.

Claim 7

A pharmaceutical or veterinary composition accor ding to claim 3, suitable for use as a cytoprotective agent on the mucus membranes of the gastrointestinal tract.

Claim 8

Process for the preparation of compounds of formula I characterized in that a compound of formula II wherein n, R 1 and R 2 have the above defined meanings and R d is hydrogen or a lower C 1 -C 6 alkyl is reacted with an hydrazino compound of formula III wherein R' has the above defined meanings and that the compounds so obtained are optionally alkylated, acylated and subjected to optical resolution.

Claim 9

CLAIMS for AT 1. Process for the preparation of compounds of formula I wherein: n is zero and an integer of 1 to 2 R is hydrogen, C 1 -C 6 lower alkyl, -CH 2 -CH=CH 2 , -CH-C≡CH and (CH 2 ) m -C 6 H 5 where m is zero or an integer of 1 to 3 R 1 and R 2 are independently selected from the group consisting of hydrogen, C 1 -C 6 lower alkyl, (CH 2 )m-C 6 H 5 , (CH 2 )m C 6 H 11 , (CH 2 )m-C 5 H 9 where m is zero or an integer of 1 to 3, -CH 2 -CH=CH 2 , -CH 2 -C≡CH, R 3 -CO -, wherein R 3 is selected from the group consisting of C 1 -C 16 branched and unbranched alkyl- chain containing hydroxy, amino, halogen, thiol groups or a free or esterified carboxy group, an heterocyclic ring, a substituted or unsubstituted aromatic ring, a cycloaliphatic ring, a cycloaliphatic alkyl, an aralkyl and heteroalkyl, a lower C 1 -C 6 alkoxy, benzyloxy or NHR 6 where R 6 is hydrogen, C 1 -C 6 lower alkyl or CH 2 -C 6 H 5 ' R 4 SO 2 wherein R 4 is selected in the group of CH 3 , C 2 H 5 , phenyl, p-methylphenyl as racemic or optically active enantiomers, and salts thereof, characterized in that a compound of formula II wherein n, R 1 and R 2 have the above defined meanings and R d is hydrogen or a lower C 1 -C 6 alkyl is reacted with an hydrazino compound of formula III H 2 N-NH-R' (III) wherein R' has the above defined meanings.

Claim 10

Process according to claim 1, characterized in that the reaction of the compound of formula II with an hydrazino compound of formula III is carried out in a solvent selected in the group consisting of and acetic acid.

Claim 11

Process according to claims 1-2, wherein in the starting compound of formula II either R 1 or R 2 is hydrogen, characterized in that the obtained compounds of formula I are optionally reacted with a convenient activated form of a carboxylic acid of formula R 3 COOH or of a sulphonic acid of formula R 4 S0 3 H, wherein R 3 and R 4 have the above defined mea nings.

Claim 12

Process according to claims 1-2, wherein in the starting compound of formula II both R 1 and R 2 are hydrogen, characterized in that the obtained compounds of formula I are optionally alkylated so as to obtain a compound of formula I wherein R l or R 2 has the above defined meanings other than hydrogen, then optionally reacted with a convenient activated form of a carboxylic acid of formula R 3 COOH or of a sulphonic acid of formula R 4 S0 3 H, wherein R 3 and R 4 have the above defined meanings.

Claim 13

Process according to claims 1-4 wherein in the starting compound of formula II R' is hydrogen, cha racterized in that the obtained compounds of formula I are optionally reacted with a halo compound of formula R'X, wherein R' has the above defined meanings other than hydrogen and X is Cl, Br or I.

Claim 14

Process according to claims 1-4, wherein the starting compounds of formula II are racemic compounds, characterized in that the obtained compounds of formula I are optionally submitted to optical resolution.