Peptide derivatives as kininogenase inhibitors

A compound of the formula

• A.sup.1 --A.sup.2 --NH--(CH.sub.2).sub.n --B--D Formula V
• or a stereoisomer thereof or a physiologically acceptable salt thereof wherein:
• A.sup.1 represents a structural fragment of Formula IIa, IIb, IIc, IId or IIe;
• ##STR35## wherein:
• k is an integer 0, 1, 2, 3 or 4;
• m is an integer 1, 2, 3 or 4;
• q is an integer 0, 1, 2 or 3;
• R.sup.1 represents R.sup.11 OOC-alkyl-, wherein the alkyl group has 1 to 4 carbon atoms and is optionally substituted in the position which is alpha to the carbonyl group, and the alpha substituent is a group R.sup.17 --(CH.sub.2).sub.p --, wherein p is 0, 1 or 2 and R.sup.17 is COOR.sup.12 or CONHR.sup.12, wherein R.sup.12 is H, an alkyl group having 1 to 4 carbon atoms or a benzyl group, and R.sup.11 is H or an alkyl group having 1 to 6 carbon atoms or a benzyl group;
• or
• R.sup.1 represents Ph(4-COOR.sup.12)--CH.sub.2 --, wherein R.sup.12 is as defined above;
• or
• R.sup.1 represents R.sup.13 --NH--CO--alkyl-, wherein the alkyl group has 1 to 4 carbon atoms and is optionally substituted alpha to the carbonyl with an alkyl group having 1 to 4 carbon atoms and wherein R.sup.13 is H or an alkyl group having 1 to 4 carbon atoms or --CH.sub.2 COOR.sup.12, wherein R.sup.12 is as defined above;
• or
• R.sup.1 represents R.sup.12 OOC--CH.sub.2 --OOC-alkyl-, wherein the alkyl group has 1 to 4 carbon atoms and is optionally substituted alpha to the carbonyl with an alkyl group having 1 to 4 carbon atoms and wherein R.sup.12 is as defined above;
• or
• R.sup.1 represents R.sup.14 SO.sub.2 --, Ph(4-COOR.sup.12)--SO.sub.2 --, Ph(3-COOR.sup.12)--SO.sub.2 -- or Ph(2-COOR.sup.12)SO.sub.2 -- wherein R.sup.12 is as defined above and R.sup.14 is an alkyl group having 1-4 carbon atoms;
• or
• R.sup.1 represents --CO--R.sup.15, wherein R.sup.15 is an alkyl group having 1-4 carbon atoms;
• or
• R.sup.1 represents --CO--OR.sup.15, wherein R.sup.15 is as defined above;
• or
• R.sup.1 represents --CO--(CH.sub.2).sub.p -COOR.sup.12, wherein R.sup.12 is as defined above and p is an integer 0, 1 or 2;
• R.sup.2 represents H or an alkyl group having 1 to 4 carbon atoms or R.sup.21 OOC-alkyl-, wherein the alkyl group has 1 to 4 carbon atoms and wherein R.sup.21 is H or an alkyl group having 1 to 4 carbon atoms or a benzyl group;
• R.sup.3 represents an alkyl group having 1-4 carbon atoms, and the alkyl group may optionally carry one or more fluorine atoms;
• or
• R.sup.3 represents a cyclopentyl, cyclohexyl or a phenyl group which may optionally be substituted with an alkyl group having 1 to 4 carbon atoms;
• or
• R.sup.3 represents a phenyl group substituted with a OR.sup.31 group, wherein R.sup.31 is H or an alkyl group having 1 to 4 carbon atoms and k is 0 or 1;
• or
• R.sup.3 represents a 1-naphthyl or 2-naphthyl group and k is 0 or 1;
• or
• R.sup.3 represents a cis- or trans-decalin group and k is 0 or 1;
• or
• R.sup.3 represents 4-pyridyl, 3-pyrrolidyl or 3-indolyl which may optionally be substituted with a OR.sup.31 group, wherein R.sup.31 is as defined above and k is 0 or 1;
• or
• R.sup.3 represents Si(Me).sub.3 or CH(R.sup.32).sub.2, wherein R.sup.32 is a cyclohexyl or a phenyl group;
• R.sup.4 represents H, an alkyl group having 1 to 4 carbon atoms, a cyclohexyl or a phenyl group;
• A.sup.2 represents a structural fragment of Formula IIIb ##STR36## p is an integer 0, 1 or 2;
• R.sup.3 is as defined above;
• n is an integer 0, 1, 2, 3 or 4;
• B represents a structural fragment of Formula IVa, IVb, IVc or IVd ##STR37## wherein:
• r is an integer 0 or 1;
• X.sup.1 represents CH.sub.2 or NH or is absent;
• X.sup.2 represents CH.sub.2, NH or C.dbd.NH;
• X.sup.3 represents NH, C.dbd.NH, N--C(NH)--NH.sub.2, CH--C(NH)--NH.sub.2, CH--NH--C(NH)--NH.sub.2 or CH--CH.sub.2 --C(NH)--NH.sub.2 ;
• X.sup.4 represents CH.sub.2 or NH;
• X.sup.5 represents C(NH)--NH.sub.2 or NH--C(NH)--NH.sub.2 ;
• X.sup.6 represents CH or N;
• R.sup.6 is H or an alkyl group having 1-4 carbon atoms;
• D is Z or (Z).sub.2 ;
• and
• Z is a benzyloxy carbonyl group.

A compound selected from

• H--(R)Pro-Phe-Pab
• HOOC--CH.sub.2 --(R)Pro-Phe-Pab
• H--(R)Phe-Phe-Pab
• HOOC--CH.sub.2 --(R)Phe-Phe-Pab
• HOOC--CO--(R)Phe-Phe-Pab
• or a stereoisomer thereof or a physiologically acceptable salt thereof.

A compound selected from

• Boc-(R)Pro-Phe-Pab(Z)
• BnOOC--CH.sub.2 --(R)Pro-Phe-Pab(Z)
• Boc-(R)Phe-Phe-Pab(Z)
• MeOOC--CO--(R)Phe-Phe-Pab(Z)
• BnOOC--CH.sub.2 --(R)Phe-Phe-Pab(Z)
• or a stereoisomer thereof or a physiologically acceptable salt thereof.