Il-8 receptor anatagonists

A compound of the formula:

• 4
• wherein:
• R is selected from the group consisting of cyano, OR11, C(O)NR15R16, R18, C(O)OR11, C(O)R11, and S(O)2R17;
• R′R″ is independently selected from the group consisting of hydrogen, NR6R7, OH, ORa, C1-5alkyl, aryl, arylC1-4alkyl, aryl C2-4alkenyl;
• cycloalkyl, cycloalkyl C1-5 alkyl, heteroaryl, heteroarylC1-4alkyl, heteroarylC2-4 alkenyl, heterocyclic, heterocyclic C1-4alkyl, and a heterocyclic C2-4alkenyl moiety, all of which moieties may be optionally substituted one to three times independently by a substituent selected from the group consisting of halogen, nitro, halosubstituted C1-4 alkyl, C1-4alkyl, amino, mono or di-C1-4 alkyl substituted amine, ORa, C(O)Ra, NRaC(O)ORa, OC(O)NR6R7, hydroxy, NR9C(O)Ra, S(O)m′Ra, C(O)NR6R7, C(O)OH, C(O)ORa, S(O)tNR6R7, and NHS(O)tRa;
• or the two Rb substituents join to form a 3-10 membered ring, optionally substituted and containing, in addition to optionally substituted C1-4 alkyl, independently, 1 to 3 NRa, O, S, SO, or SO2 moieties, which moieties can be optionally unsaturated;
• R′″ is selected from the group consisting of Y hydrogen, halogen, nitro, cyano, halosubstituted C1-10 alkyl, C1-10 alkyl, C2-10 alkenyl, C1-10 alkoxy, halosubstituted C1-10 alkoxy, azide, (CR8R8)qS(O)tRa, (CR8R8)qORa, hydroxy, hydroxy substituted C1-4alkyl, aryl, aryl C1-4 alkyl, aryloxy, arylC-4alkyloxy, aryl C2-10 alkenyl, heteroaryl, heteroarylalkyl, heteroaryl C1-4 alkyloxy, heteroaryl C2-10 alkenyl, heterocyclic, heterocyclic C1-4alkyl, heterocyclicC2-10 alkenyl, (CR8R8)qNR4R5, C2-10 alkenyl C(O)NR14R15, (CR8R8)qC(O)NR4R5, (CR8R8)q C(O)NR4R10, S(O)3R8, (CR8R8)qC(O)R11, C2-10 alkenylC(O)R11, (CR8R8)qC(O)OR11, C2-10alkenylC(O)OR11, (CR8R8)qOC(O)R11, (CR8R8)qNR4C(O)R11, (CR8R8)q NHS(O)tR13, (CR8R8)q S(O)tNR4R5, (CR8R8)qC(NR4)NR4R5, and (CR8R8)q NR4C(NR5)R11;
• or two Y moieties together form O—(CH2)s—O or a 5 to 6 membered saturated or unsaturated ring, such that the alkyl, aryl, arylalkyl, heteroaryl, heteroaryl alkyl, heterocyclic, and heterocyclicalkyl groups may be optionally substituted;
• R1 is independently selected from the group consisting of hydrogen, halogen, nitro, cyano, C1-10 alkyl, halosubstituted C1-10 alkyl, C2-10 alkenyl, C1-10 alkoxy, halosubstituted C1-10alkoxy, azide, S(O)tR4, (CR8R8)q S(O)tR4, hydroxy, hydroxy substituted C1-4alkyl, aryl, aryl C1-4 alkyl, aryl C2-10 alkenyl, aryloxy, aryl C1-4 alkyloxy, heteroaryl, heteroarylalkyl, heteroaryl C2-10 alkenyl, heteroaryl C1-4 alkyloxy, heterocyclic, heterocyclic C1-4alkyl, heterocyclicC1-4alkyloxy, heterocyclicC2-10 alkenyl, (CR8R8)q NR4R5, (CR8R8)qC(O)NR4R5, C2-10-alkenyl C(O)NR4R5, (CR8R8)q C(O)NR4R10, S(O)3R8, (CR8R8)q C(O)R11, C2-10alkenyl C(O)R11, C2-10 alkenyl C(O)OR11, (CR8R8)q C(O)OR11, (CR8R8)q OC(O)R11, (CR8R8)qNR4C(O)R11, (CR8R8)q C(NR4)NR4R5, (CR8R8)q NR4C(NR5)R11, (CR8R8)q NHS(O)tR13, and (CR8R8)q S(O)tNR4R5;
• or two R1 moieties together form O—(CH2)sO or a 5 to 6 membered saturated or unsaturated ring, wherein the alkyl, aryl, arylalkyl, heteroaryl, and heterocyclic moieties may be optionally substituted.