Unsaturated hydroxyalkylquinoline acids as leukotriene antagonists

A pharmaceutical composition comprising an effective amount of a H.sub.1 -receptor antagonist and an effective amount of a second compound of the formula:

• ##STR11## wherein:
• R.sup.1 is H, halogen, --CF.sub.3, --CN, --NO.sub.2, or N.sub.3 ;
• R.sup.2 is lower alkyl, lower alkenyl, lower alkynyl, --CF.sub.3, --CH.sub.2 F, --CHF.sub.2, CH.sub.2 CF.sub.3, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, substituted or unsubstituted 2-phenethyl, or two R.sup.2 groups joined to the same carbon may form a ring of up to 8 members containing 0-2 heteroatoms chosen from O, S, and N;
• R.sup.3 is H or R.sup.2 ;
• R.sup.4 is halogen, --NO.sub.2, --CN, --OR.sup.3, --SR.sup.3, NR.sup.3 R.sup.3, NR.sup.3 C(O)R.sup.7 or R.sup.3 ;
• R.sup.5 is H, halogen, --NO.sub.2, --N.sub.3, --CN, --SR.sup.2, --NR.sup.3 R.sup.3, --OR.sup.3, lower alkyl, or --C(O)R.sup.3 ;
• R.sup.6 is --(CH.sub.2).sub.s --C(R.sup.7 R.sup.7)--(CH.sub.2).sub.s --R.sup.8 or --CH.sub.2 C(O)NR.sup.12 R.sup.12 ;
• R.sup.7 is H or C.sub.1 -C.sub.4 alkyl;
• R.sup.8 is A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms selected from N, S or O and with each ring in the heterocyclic radical being formed of 5 or 6 atoms, or B) the radical W--R.sup.9 ;
• R.sup.9 contains up to 20 carbon atoms and is (1) an alkyl group or (2) an alkylcarbonyl group of an organic acyclic or monocyclic carboxylic acid containing not more than 1 heteroatom in the ring;
• R.sup.10 is --SR.sup.11, OR.sup.12, or --NR.sup.12 R.sup.12 ;
• R.sup.11 is lower alkyl, --C(O)R.sup.14, unsubstituted phenyl, or unsubstituted benzyl;
• R.sup.12 is H.sub.1 R.sup.11, or two R.sup.12 groups joined to the same N may form a ring of 5 or 6 members containing 1-2 heteroatoms chosen from O, S, and N;
• R.sup.13 is lower alkyl, lower alkenyl, lower alkynyl, --CF.sub.3 or substituted or unsubstituted phenyl, benzyl, or 2-phenethyl;
• R.sup.14 is H or R.sup.13 ;
• R.sup.16 is H, C.sub.1 -C.sub.4 alkyl, or OH;
• R.sup.17 is lower alkyl, lower alkenyl, lower alkynyl, or substituted or unsubstituted phenyl, benzyl, or 2-phenethyl;
• R.sup.18 is lower alkyl, lower alkenyl, lower alkynyl, --CF.sub.3 or substituted or unsubstituted phenyl, benzyl, or 2-phenethyl;
• R.sup.19 is lower alkyl, lower alkenyl, lower alkynyl, --CF.sub.3 or substituted or unsubstituted phenyl, benzyl, or 2-phenethyl;
• R.sup.20 is H, C.sub.1 -C.sub.4 alkyl, substituted or unsubstituted phenyl, benzyl, phenethyl, or pyridinyl or two R.sup.20 groups joined to the same N may form a saturated ring of 5 or 6 members containing 1-2 heteroatoms chosen from O, S, and N;
• R.sup.21 is H or R.sup.17 ;
• R.sup.22 is R.sup.4, CHR.sup.7 OR.sup.3, or CHR.sup.7 SR.sup.2 ;
• m and m' are independently 0-8;
• n and n' are independently 0 or 1,
• p and p' are independently 0-8;
• m+n+p is 1-10 when r is 1 and X.sup.2 is O, S, S(O), or S(O).sub.2 ;
• m+n+p is 0-10 when r is 1 and X.sup.2 is CR.sup.3 R.sup.16 ;
• m+n+p is 0-10 when r is 0;
• m'+n'+p' is 0-10;
• r and r' are independently 0 or 1;
• s is 0-3;
• Q.sup.1 is --C(O)OR.sup.3, 1H (or 2H)-tetrazol-5-yl, --C(O)OR.sup.6, --C(O)NHS(O).sub.2 R.sup.13, --CN, --C(O)NR.sup.12 R.sup.12, --NR.sup.21 S(O).sub.2 R.sup.13, --NR.sup.12 C(O)NR.sup.12 R.sup.12, --NR.sup.21 C(O)R.sup.18, --OC(O)NR.sup.12 R.sup.12, --C(O)R.sup.19, --S(O)R.sup.18, --S(O).sub.2 R.sup.18, --S(O).sub.2 NR.sup.12 R.sup.12, --NO.sub.2, --NR.sup.21 C(O)OR.sup.17, --C(NR.sup.12 R.sup.12).dbd.NR.sup.12, --C(R.sup.13).dbd.NOH;
• or if Q.sup.1 is --C(O)OH and R.sup.22 is --OH, --SH, --CHR.sup.7 OH or --NHR.sup.3, then Q.sup.1 and R.sup.22 and the carbons through which they are attached may form a heterocyclic ring by loss of water;
• Q.sup.2 is OH or NR.sup.2 OR.sup.20 ;
• W is O, S, or NR.sup.3 ;
• X.sup.2 and X.sup.3 are independently O, S, S(O), S(O).sub.2, or CR.sup.3 R.sup.16 ;
• Y is --CR.sup.3 .dbd.CR.sup.3 -- or --C.tbd.C;
• Z.sup.1 and Z.sup.2 are independently --HET(--R.sup.3 --R.sup.5)--;
• HET is the diradical of a benzene, a pyridine, a furan, or a thiophene;
• or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.