Diazepine containing dual action inhibitors

A pharmaceutical composition useful in the treatment of cardiovascular diseases comprising a pharmaceutically acceptable carrier and at least one compound of the formula ##STR57## and pharmaceutically acceptable salts thereof wherein:

• ##STR58## R.sup.1 and R.sup.12 are each independently selected from hydrogen, alkyl, alkenyl, cycloalkyl, substituted alkyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, cycloalkyl-alkylene-, aryl-alkylene-, substituted aryl-alkylene- and heteroaryl-alkylene-, or R.sup.1 and R.sup.12 taken together with the carbon atom to which they are attached complete a cycloalkyl ring or a benzofused cycloalkyl ring;
• R.sup.2 is hydrogen, ##STR59## or R.sup.11 --S--;
• R.sup.3, R.sup.5 and R.sup.7 are each independently selected from hydrogen, alkyl, substituted alkyl, aryl-(CH.sub.2).sub.p --, substituted aryl-(CH.sub.2).sub.p --, heteroaryl-(CH.sub.2).sub.p --, ##STR60## R.sup.4 is alkyl, cycloalkyl-(CH.sub.2).sub.p --, substituted alkyl, aryl-(CH.sub.2).sub.p --, substituted aryl-(CH.sub.2).sub.p -- or heteroaryl-(CH.sub.2).sub.p --;
• R.sup.6 is alkyl, substituted alkyl, cycloalkyl-(CH.sub.2).sub.p --, aryl-(CH.sub.2).sub.p --, substituted aryl-(CH.sub.2).sub.p -- or heteroaryl-(CH.sub.2).sub.p --;
• R.sup.8 is hydrogen, lower alkyl, cycloalkyl or phenyl;
• R.sup.9 is hydrogen, lower alkyl, lower alkoxy or phenyl;
• R.sup.10 is lower alkyl or aryl-(CH.sub.2).sub.p --;
• R.sup.11 is hydrogen, alkyl, substituted alkyl, cycloalkyl-(CH.sub.2).sub.p --, aryl-(CH.sub.2).sub.p --, substituted aryl-(CH.sub.2).sub.p -- or heteroaryl-(CH.sub.2).sub.p --, or --S--R.sup.11 completes a symmetrical disulfide wherein R.sup.11 is ##STR61## R.sup.13 is alkyl, aryl, or aryl-alkylene-;
• R.sup.14 is hydrogen, alkyl, aryl or aryl-alkylene, or R.sup.13 and R.sup.14 taken together are --(CH.sub.2).sub.3 -- or --(CH.sub.2).sub.4 -- thus completing a five- or six-membered ring;
• R.sup.15 and R.sup.16 are each independently selected from hydrogen, alkyl, substituted alkyl, aryl and aryl-alkylene;
• n is zero or one;
• p is zero or an integer from 1 to 6;
• q is zero or an integer from 1 to 3;
• r is zero or one;
• the term "alkyl" refers to straight or branched chain radicals of one to seven carbon atoms;
• the term "lower alkyl" refers to straight or branched chain radicals of one to four carbon atoms;
• the term "substituted alkyl" refers to such straight or branched chain radicals of one to seven carbons wherein one or more hydrogens have been replaced by a hydroxy, amino, cyano, halo, trifluoromethyl, --NH(lower alkyl), --N(lower alkyl).sub.2, lower alkoxy, lower alkylthio, or carboxy;
• the terms "lower alkoxy" and "lower alkylthio" refer to such lower alkyl groups as defined above attached to oxygen or sulfur atom, respectively;
• the term "cycloalkyl" refers to saturated rings of 3 to 7 carbon atoms;
• the term "alkenyl" refers to straight or branched chain radicals of 3 to 7 carbon atoms having one or two double bonds;
• the term "substituted alkenyl" refers to such straight or branched chain radicals of 3 to 7 carbon atoms having one or two double bonds wherein a hydrogen has been replaced by hydroxy, amino, halo, trifluoromethyl, cyano, --NH(lower alkyl), --N(lower alkyl).sub.2, lower alkoxy, lower alkylthio, or carboxy;
• the term "alkylene" refers to straight or branched chain radicals having one to seven carbon atoms;
• the term "aryl" refers to phenyl, 1-naphthyl, and 2-naphthyl;
• the term "substituted aryl" refers to phenyl, 1-naphthyl, and 2-naphthyl having a substituent selected from lower alkyl, lower alkoxy, lower alkylthio, halo, hydroxy, trifluoromethyl, amino, --NH(lower alkyl), --N(lower alkyl).sub.2, and di and tri-substituted phenyl, 1-naphthyl, and 2-naphthyl wherein said substituents are selected from methyl, methoxy, methylthio, halo, hydroxy, and amino;
• the term "heteroaryl" refers to 2-pyridyl, 3-pyridyl, 4-pyridyl, 4-imidazolyl, 4-thiazolyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-indolyl, 3-indolyl, 4-quinolinyl, and 5-quinolinyl;
• and
• the term "halo" refers to chloro, bromo, fluoro and iodo.

A compound of the formula ##STR62## wherein:

• R.sup.13 is alkyl, aryl, or aryl-alkylene-;
• R.sup.14 is hydrogen, alkyl, aryl or aryl-alkylene- or R.sup.13 and R.sup.14 taken together are --(CH.sub.2).sub.3 -- or --(CH.sub.2).sub.4 -- thus completing a five- or six-membered ring;
• R.sup.15 and R.sup.16 are each independently selected from hydrogen, alkyl, substituted alkyl, aryl and aryl-alkylene-;
• R.sup.3 is hydrogen, alkyl, substituted alkyl, aryl-(CH.sub.2).sub.p --, or substituted aryl-(CH.sub.2).sub.p --;
• n is zero or one;
• p is zero or an integer from 1 to 6;
• the term "alkyl" refers to straight or branched chain radicals of one to seven carbon atoms;
• the term "lower alkyl" refers to straight or branched chain radicals of one to four carbon atoms;
• the term "substituted alkyl" refers to such straight or branched chain radicals of one to seven carbons wherein one or more hydrogens have been replaced by a hydroxy, amino, cyano, halo, trifluoromethyl, --NH(lower alkyl), --N(lower alkyl).sub.2, lower alkoxy, lower alkylthio, or carboxy;
• the terms "lower alkoxy" and "lower alkylthio" refer to such lower alkyl groups as defined above attached to oxygen or sulfur atom, respectively;
• the term "alkylene" refers to straight or branched chain radicals having one to seven carbon atoms;
• the term "aryl" refers to phenyl, 1-naphthyl, and 2-naphthyl;
• the term "substituted aryl" refers to phenyl, 1-naphthyl, and 2-naphthyl having a substituent selected from lower alkyl, lower alkoxy, lower alkylthio, halo, hydroxy, trifluoromethyl, amino, --NH(lower alkyl), --N(lower alkyl).sub.2, and di and tri-substituted phenyl, 1-naphthyl, and 2-naphthyl wherein said substituents are selected from methyl, methoxy, methylthio, halo hydroxy, and amino;
• and
• the term "halo" refers to chloro, bromo, fluoro and iodo.