Tricyclic lactams active as antihypertensive agents

Claim 2

A tricyclic lactam having the formula: ##STR9## wherein R and R 1 are each hydrogen, methyl or ethyl; X is S or CH 2 ; R 2 is phenethyl; R 3 and R 4 are each H, C 1 -C 12 alkyl, phenyl, or benzyl; R 5 and R 6 are hydrogen; and the non-toxic physiologically acceptable esters and salts thereof.

Claim 3

A compound of claim 1 wherein X is S.

Claim 4

A compound of claim 1 wherein X is CH 2 .

Claim 5

A compound of claim 1 wherein R is H, R 1 is ethyl, X is CH 2 , R 2 is phenethyl, R 5 and R 6 are H.

Claim 6

A compound of claim 1 wherein R is H, R 1 is ethyl, X is S, R 2 is phenethyl, and R 5 and R 6 are H.

Claim 7

A compound of claim 1 wherein R and R 1 are H, X is CH 2 , R 5 and R 6 are H and R 2 is phenethyl.

Claim 8

A compound of claim 1 wherein R and R 1 are ethyl, X is CH 2 , R 5 and R 6 are H and R 2 is phenethyl.

Claim 9

A compound of claim 1 wherein R and R 1 are H, X is S, R 5 and R 6 are H and R 2 is phenethyl.

Claim 10

A compound of claim 1 wherein R and R 1 are ethyl, X is S, R 5 and R 6 are H and R 2 is phenethyl.

Claim 11

A process for the preparation of the compounds of claim which comprises: (a) coupling a fused lactam having the formula: ##STR10## wherein the symbols R, R 3 , R 4 , R 5 and R 6 are as previously described, coupling said lactam with a compound A, B or C having the formula: ##STR11## wherein R' 1 is methyl or ethyl and R 2 is as previously described; (b) said coupling with a compound of the type formula A being effected by contacting the reactants together in the presence of a base; (c) said coupling with a compound of the type formula B being effected by contracting the reactants together in the presence of a molecular sieve to form a Schiff's base and reducing said Schiff's base; (d) said coupling with a compound of the type formula C being effected in accordance with a 1,4-Michael addition reaction followed by a catalytic reduction of the ketone oxygen that is formed; and (e) optionally removing one or both of the R and R' 1 ester groups.

Claim 12

A process according to claim 10 wherein the coupling is effected with a formula A type compound in the presence of a base, such as 1,8-bis-(dimethylamine)-naphthalene.

Claim 13

A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutical carrier.

Claim 14

A pharmaceutical composition comprising a compound of claim 3 and a pharmaceutical carrier.

Claim 15

A pharmaceutical composition comprising the compound of claim 4 and a pharmaceutical carrier.

Claim 16

The composition of claim 12 in dosage unit form.

Claim 17

The composition of claim 13 in dosage unit form.

Claim 18

A method of treating hypertension which comprises administering to a mammal in need thereof an antihypertensive effective amount of a compound of claim 2.

Claim 19

A method of treating hypertension which comprises administering to a mammal in need thereof an antihypertensive effective amount of a compound of claim 3.

Claim 20

A method of treating hypertension which comprises administering to a mammal in need thereof an antihypertensive effective amount of a compound of claim 5.

Claim 21

A method of inhibiting angiotensin converting enzyme (ACE) in a patient in need thereof, which comprises administering to said patient an ACE inhibiting amount of a compound of claim 2.

Claim 22

A method of inhibiting angiotension converting enzyme (ACE) in a patient in need thereof, which comprises administering to said patient an ACE inhibiting amount of a compound of claim 3.