Substituted biphenyl derivatives

A method of treating asthma or allergic or inflammatory diseases in a mammal in need thereof, the method comprising administering to said mammal an effective amount of a compound having the formula:

• ##STR11## wherein R.sub.8 =H:
• R.sub.1 =alkyl, cycloalkyl, arylalkyl, aryl;
• R.sub.2 =cycloalkyl, aryl, C.sub.3 -C.sub.10 alkyl;
• X,Y=O, S(O).sub.n, NH;
• Z=CO.sub.2 R.sub.3, C(O)CO.sub.2 R.sub.3, CH(OH)CO.sub.2 R.sub.3, CHFCO.sub.2 R.sub.3, CF.sub.2 CO.sub.2 R.sub.3, CONH.sub.2, CONHOR.sub.4, CONHNR.sub.4 R.sub.5, 5(1H)-tetrazole,
• C(O)CONR.sub.3 R.sub.4, CH(OH)CONR.sub.3 R.sub.4, CF.sub.2 CONR.sub.3 R.sub.4 ;
• R.sub.3, R.sub.4, R.sub.5 =hydrogen, alkyl, aryl, aryalkyl, cycloalkyl, or fluoroalkyl;
• halo=Cl, Br, or I;
• fluoroalkyl=CF.sub.3, CHF.sub.2, CH.sub.2 F, CH.sub.2 CF.sub.3, C.sub.2 F.sub.5 ;
• cycloalkyl=C.sub.3 -C.sub.6 cycloalkyl;
• arylalkyl=C.sub.1 -C.sub.4 alkyl aryl;
• aryl=phenyl, furanyl, thienyl, or pyridyl;
• and
• n=0-2;
• or a pharmaceutically acceptable salt thereof.

A pharmaceutical composition for use in treating asthma and allergic and inflammatory diseases in a mammal in need thereof, the composition comprising an effective amount of a compound of the formula:

• ##STR12## wherein R.sub.8 =H:
• R.sub.1 =alkyl, cycloalkyl, arylalkyl, aryl;
• R.sub.2 =cycloalkyl, aryl, C.sub.3 -C.sub.10 alkyl;
• X,Y=O, S(O).sub.n, NH;
• Z=CO.sub.2 R.sub.3, C(O)CO.sub.2 R.sub.3, CH(OH)CO.sub.2 R.sub.3, CHFCO.sub.2 R.sub.3, CF.sub.2 CO.sub.2 R.sub.3, CONH.sub.2, CONHOR.sub.4, CONHNR.sub.4 R.sub.5, 5(1H)-tetrazole,
• C(O)CONR.sub.3 R.sub.4, CH(OH)CONR.sub.3 R.sub.4, CF.sub.2 CONR.sub.3 R.sub.4 ;
• R.sub.3, R.sub.4, R.sub.5 =hydrogen, alkyl, aryl, aryalkyl, cycloalkyl, or fluoroalkyl;
• halo=Cl, Br, or I;
• fluoroalkyl=CF.sub.3, CHF.sub.2, CH.sub.2 F, CH.sub.2 CF.sub.3, C.sub.2 F.sub.5 ;
• cycloalkyl=C.sub.3 -C.sub.6 cycloalkyl;
• arylalkyl=C.sub.1 -C.sub.4 alkyl aryl;
• aryl=phenyl, furanyl, thienyl, or pyridyl;
• and
• n=0-2;
• or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.