IL-8 receptor antagonists

A compound of the formula:

• ##STR15## wherein X is oxygen;
• X.sub.1 is oxygen;
• R.sub.1 is independently selected from hydrogen;
• halogen;
• cyano;
• halosubstituted C.sub.1-10 alkyl;
• C.sub.1-10 alkyl;
• C.sub.2-10 alkenyl;
• C.sub.1-10 alkoxy;
• halosubstituted C.sub.1-10 alkoxy;
• azide;
• S(O).sub.t R.sub.4 ;
• hydroxy;
• hydroxyC.sub.1-4 alkyl;
• aryl;
• aryl C.sub.1-4 alkyl;
• aryloxy;
• aryl C.sub.1-4 alkyloxy;
• heteroaryl;
• heteroarylalkyl;
• heterocyclic;
• heterocyclicC.sub.1-4 alkyl;
• heteroarylC.sub.1-4 alkyloxy;
• aryl C.sub.2-10 alkenyl;
• heteroaryl C.sub.2-10 alkenyl;
• heterocyclic C.sub.2-10 alkenyl;
• NR.sub.4 R.sub.5 ;
• C.sub.2-10 alkenyl C(O)NR.sub.4 R.sub.5 ;
• C(O)NR.sub.4 R.sub.5 ;
• C(O)NR.sub.4 R.sub.10 ;
• S(O).sub.3 H;
• S(O).sub.3 R.sub.8 ;
• C.sub.1-10 alkyl C(O)R.sub.11 ;
• C.sub.2-10 alkenyl C(O)R.sub.11 ;
• C.sub.2-10 alkenyl C(O)OR.sub.11 ;
• C(O)R.sub.11 ;
• C(O)OR.sub.12 ;
• OC(O)R.sub.11 ;
• NR.sub.4 C(O)R.sub.11 ;
• or two R.sub.1 moieties together may form O--(CH.sub.2).sub.S O-- or a 5 to 6 membered unsaturated ring;
• t is 0, or an integer having a value of 1 or 2;
• s is an integer having a value of 1 to 3;
• R.sub.4 and R.sub.5 are independently hydrogen, optionally substituted C.sub.1-4 alkyl, optionally substituted aryl, optionally substituted aryl C.sub.1-4 alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl C.sub.1-4 alkyl, heterocyclic, heterocyclic C.sub.1-4 alkyl, or R.sub.4 and R.sub.5 together with the nitrogen to which they are attached from a 5 to 7 member ring which may optionally comprise an additional heteroatom selected from O/N/S;
• Y is independently selected from halogen;
• nitro;
• cyano;
• halosubstituted C.sub.1-10 alkyl;
• C.sub.1-10 alkyl;
• C.sub.2-10 alkenyl;
• C.sub.1-10 alkoxy;
• halosubstituted C.sub.1-10 alkoxy;
• azide;
• S(O).sub.t R.sub.4 ;
• hydroxy;
• hydroxyC.sub.1-4 alkyl;
• aryl;
• aryl C.sub.1-4 alkyl;
• aryloxy;
• arylC.sub.1-4 alkyloxy;
• heteroaryl;
• heteroarylalkyl;
• heteroarylC.sub.1-4 alkyloxy;
• heterocyclic;
• heterocyclic C.sub.1-4 alkyl;
• aryl C.sub.2-10 alkenyl;
• heteroarylC.sub.2-10 alkenyl;
• heterocyclic C.sub.2-10 alkenyl;
• NR.sub.4 R.sub.5 ;
• C.sub.2-10 alkenyl C(O)NR.sub.4 R.sub.5 ;
• C(O)NR.sub.4 R.sub.5 ;
• C(O)NR.sub.4 R.sub.10 ;
• S(O).sub.3 H;
• S(O).sub.3 R.sub.8 ;
• C.sub.1-10 alkyl C(O)R.sub.11 ;
• C.sub.2-10 alkenyl C(O)R.sub.11 ;
• C.sub.2-10 alkenyl C(O)OR.sub.11 ;
• C(O)R.sub.11 ;
• C(O)OR.sub.12 ;
• OC(O)R.sub.11 ;
• NR.sub.4 C(O)R.sub.11 ;
• or two Y moieties together may form O--(CH.sub.2).sub.S O-- or a 5 to 6 membered unsaturated ring;
• n is an integer having a value of 1 to 2;
• m is an integer having a value of 1 to 3;
• R.sub.8 is hydrogen or C.sub.1-4 alkyl;
• R.sub.10 is C.sub.1-10 alkyl C(O).sub.2 R.sub.8 ;
• R.sub.11 is hydrogen, C.sub.1-4 alkyl, optionally substituted aryl, optionally substituted aryl C.sub.1-4 alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl C.sub.1-4 alkyl, optionally substituted heterocyclic, or optionally substituted heterocyclic C.sub.1-4 alkyl;
• R.sub.12 is hydrogen, C.sub.1-10 alkyl, optionally substituted aryl or optionally substituted arylalkyl;
• provided that:
• when n=1 then Y is substituted in the 2- or 3-position;
• when n=2 then Y is di-substituted in the 2'- or 3'-position, the 2'-5'-position, the 2'-6' position, the 3'-5' or the 3'-6' position;
• when n=3 then Y is trisubstituted in the 2'-3'-5' or the 2'-3'-6'-positions;
• further provided that
• when m=1, R.sub.1 is hydrogen, and n=1 than Y is not 2'--OH, 2'-nitro, 2'--Cl, or 2'--Br;
• when m=1, R.sub.1 is COOH, and n=2 than Y is not 2'--OH, 3'--COOH;
• when m=2, R.sub.1 is 2-t-butyl, 4-methyl, and n=3 than Y is not 2'--OH, 3'-t-butyl, 5'-methyl;
• when m=1, R.sub.1 is 4-methyl, and n=2 then Y is not 2'--OH, 5'-methyl;
• when m=1, R.sub.1 is hydrogen, and n=2 then Y is not 2'-6'-diethyl;
• when m=1, R.sub.1 is 6--OH, and n=2 then Y is not 2'-5'-methyl;
• when m=1, R.sub.1 is 5-nitro, and n=2 then Y is not 2-fluoro-5-nitro;
• or 2-methyl-5-nitro, or 2,3,-dichloro, or 2-methyl-6-chloro, or 2,5-dimethoxy, or 2-methyl-3-chloro;
• when m=1, R.sub.1 is 3-nitro, and n=1, then Y is not hydrogen;
• when m=1, R.sub.1 is 3-nitro, and n=2, then Y is not 2,5-dichloro;
• when m=1, R.sub.1 is hydrogen, and n=2, then Y is not 2-methyl-5-chloro;
• when m=1, R.sub.1 is 5-chloro, and n=1, then Y is not hydrogen;
• when m=1, R.sub.1 is 5-chloro, and n=2, then Y is not 2-fluoro-5-nitro, or 3,4,-dichloro, or 2-methyl-5-nitro;
• when m=1, R.sub.1 is 4-amino, and n=1, then Y is not hydrogen;
• or a pharmaceutically acceptable salt thereof.