IL-8 receptor antagonists

A compound of the formula:

• wherein
• R is —NH—C(X)—NH—(CR13R14)v—Z;
• X is oxygen or sulfur;
• Z is W, HET,
• an optionally substituted C1-10 alkyl, an optionally substituted C2-10 alkenyl, or an optionally substituted C2-10 alkynyl;
• R1 is independently selected from hydrogen, halogen, nitro, cyano, halosubstituted C1-10 alkyl, C1-10 alkyl, C2-10 alkenyl, C1-10 alkoxy, halosubstituted C1-10 alkoxy, (CR8R8)qS(O)tR4, hydroxy, hydroxy C1-4alkyl, aryl, aryl C1-4 alkyl, aryloxy, aryl C1-4 alkyloxy, heteroaryl, heteroarylalkyl, heterocyclic, heterocyclic C1-4alkyl, heteroaryl C1-4 alkyloxy, aryl C2-10 alkenyl, heteroaryl C2-10 alkenyl, heterocyclic C2-10 alkenyl, (CR8R8)qNR4R5, C2-10 alkenyl C(O)NR4R5, (CR8R8)qC(O)NR4R5, (CR8R8)qC(O)NR4R10, S(O)3R8, (CR8R8)qC(O)R11, C2-10 alkenyl C(O)R11, C2-10 alkenyl C(O)OR11, C(O)R11, (CR8R8)qC(O)OR12, (CR8R8)qOC(O)R11, (CR8R8)qNR4C(O)R11, (CR8R8)qC(NR4)NR4R5, (CR8R8)qNR4C(NR5)R11, (CR8R8)qNHS(O)2R17, or (CR8R8)qS(O)2NR4R5;
• and wherein the aryl, heteroaryl, and heterocyclic containing moieties may all be optionally substituted;
• m is an integer having a value of 1 to 3;
• n is an integer having a value of 1 to 3;
• p is an integer having a value of 1 to 3;
• q is 0, or an integer having a value of 1 to 10;
• s is an integer having a value of 1 to 3;
• t is 0, or an integer having a value of 1 or 2;
• v is 0, or an integer having a value of 1 to 4;
• HET is an optionally substituted heteroaryl;
• R4 and R5 are independently hydrogen, optionally substituted C1-4 alkyl, optionally substituted aryl, optionally substituted aryl C1-4alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl C1-4alkyl, heterocyclic, heterocyclic C1-4 alkyl, or R4 and R5 together with the nitrogen to which they are attached form a 5 to 7 member ring which may optionally comprise an additional heteroatom selected from O/N/S;
• Y is independently selected from hydrogen, halogen, nitro, cyano, halosubstituted C1-10 alkyl, C1-10 alkyl, C2-10 alkenyl, C1-10 alkoxy, halosubstituted C1-10 alkoxy, (CR8R8)qS(O)tR4, hydroxy, hydroxyC1-4alkyl, aryl, aryl C1-4 alkyl, aryloxy, arylC1-4 alkyloxy, heteroaryl, heteroarylalkyl, heteroaryl C1-4 alkyloxy, heterocyclic, heterocyclic C1-4alkyl, aryl C2-10 alkenyl, heteroaryl C2-10 alkenyl, heterocyclic C2-10 alkenyl, (CR8R8)qNR4R5, C2-10 alkenyl C(O)NR4R5, (CR8R8)qC(O)NR4R5, (CR8R8)qC(O)NR4R10, S(O)3R8;
• (CR8R8)qC(O)R11, C2-10 alkenyl C(O)R11, C2-10 alkenyl C(O)OR11, (CR8R8)qC(O)OR12, (CR8R8)qOC(O) R11, (CR8R8)qNR4C(O)R11, (CR8R8)qC(NR4)NR4R5, (CR8R8)qNR4C(NR5)R11, (CR8R8)qNHS(O)2Ra, or (CR8R8)qS(O)2NR4R5;
• or two Y moieties together may form O—(CH2)sO or a 5 to 6 membered saturated or unsaturated ring;
• and wherein the aryl, heteroaryl, and heterocyclic containing moieties may all be optionally substituted;
• R8 is hydrogen or C1-4 alkyl;
• R10is C1-10 alkyl C(O)2R8;
• R11 is hydrogen, C1-4 alkyl, optionally substituted aryl, optionally substituted aryl C1-4alkyl, optionally substituted heteroaryl, optionally substituted heteroarylC1-4alkyl, optionally substituted heterocyclic, or optionally substituted heterocyclicC1-4alkyl;
• R12 is hydrogen, C1-10 alkyl, optionally substituted aryl or optionally substituted arylalkyl;
• R13 and R14 are independently hydrogen, optionally substituted C1-4 alkyl, or one of R13 and R14 may be optionally substituted aryl;
• R17 is C1-4 alkyl, optionally substituted aryl, optionally substituted aryl C1-4alkyl, optionally substituted heteroaryl, optionally substituted heteroarylC 1-4alkyl, optionally substituted heterocyclic, or optionally substituted heterocyclicC1-4alkyl;
• R18 is hydrogen, optionally substituted C1-10 alkyl, C1-10 alkoxy, halosubstituted C1-10 alkoxy, hydroxy, arylC1-4 alkyl, arylC2-4 alkenyl, heteroaryl, heteroaryl-C1-4alkyl, heteroarylC2-4 alkenyl, heterocyclic, or heterocyclicC1-4 alkyl, wherein the aryl, heteroaryl and heterocyclic containing moieties may all be optionally substituted;
• Ra is NR4R5, alkyl, arylC1-4 alkyl, arylC2-4 alkenyl, heteroaryl, heteroaryl-C1-4alkyl, heteroarylC2-4 alkenyl, heterocyclic, or heterocyclicC1-4 alkyl;
• and wherein the aryl, heteroaryl and heterocyclic containing moieties may all be optionally substituted;
• W is
• the E containing ring is optionally selected from
• the asterix * denoting point of attachment of the ring;
• or a pharmaceutically acceptable salt thereof.