IL-8 receptor antagonists

A compound of the formula:

• wherein
• X is oxygen;
• X1 is oxygen or sulfur;
• R1 is independently selected from 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)q C(O)NR4R5;
• C2-10 alkenyl C(O)NR4R5;
• (CR8R8)q C(O)NR4R10;
• S(O)3R8;
• (CR8R8)q C(O)R11;
• C2-10 alkenyl 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)2R13;
• (CR8R8)q S(O)2NR4R5;
• or two R1 moieties together may form O—(CH2)sO— or a 5 to 6 membered unsaturated ring, and wherein the alkyl, aryl, arylalkyl, heteroaryl, and heterocyclic moieties are substituted;
• or unsubstituted
• t is 0, or an integer having a value of 1 or 2;
• s is an integer having a value of 1 to 3;
• R4 and R5 are independently hydrogen, substituted or unsubstituted C1-4 alkyl, substituted aryl, substituted aryl C1-4alkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroaryl C1-4 alkyl, 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 does or does not contain an additional heteroatom selected from O, N or S;
• Y is 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)tR4;
• (CR8R8)qOR4;
• hydroxy;
• hydroxy substituted C1-4alkyl;
• aryl, aryl C1-4 alkyl;
• aryloxy;
• arylC1-4 alkyloxy;
• 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)NR4R5;
• (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)2Rb;
• (CR8R8)q S(O)2NR4R5, (CR8R8)qC(NR4)NR4R5;
• (CR8R8)q NR4C(NR5)R11;
• or two Y moieties together may form O—(CH2)sO— or a 5 to 6 membered unsaturated ring;
• and wherein the alkyl, aryl, arylalkyl, heteroaryl, heteroaryl alkyl, heterocyclic, heterocyclicalkyl groups are substituted;
• or unsubstituted
• q is 0 or an integer having a value of 1 to 10;
• n is an integer having a value of 1 to 3;
• m is an integer having a value of 1 to 3;
• R6 and R7 are independently hydrogen or a C1-4 alkyl group, or R6 and R7 together with the nitrogen to which they are attached form a 5 to 7 member ring which ring does or does not contain an additional heteroatom which heteroatom is selected from oxygen, nitrogen or sulfur;
• R8 is hydrogen or C1-4 alkyl;
• R10 is C1-10 alkyl C(O)2R8;
• R11 is hydrogen, substituted or unsubstituted C1-4 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted aryl C1-4alkyl, substituted or substituted heteroaryl, substituted heteroaryl C1-4alkyl, substituted or substituted heterocyclic, or substituted or unsubstituted heterocyclicC1-4alkyl;
• R12 is hydrogen, C1-1alkyl, substituted or substituted aryl or substituted or substituted arylalkyl;
• R13 is C1-4 alkyl, aryl, aryl C1-4alkyl, heteroaryl, heteroarylC1-4alkyl, heterocyclic, or heterocyclicC1-4alkyl;
• Rb is NR6R7, alkyl, aryl, aryl C1-4 alkyl, aryl C2-4 alkenyl, heteroaryl, heteroaryl C1-4 alkyl, heteroarylC2-4 alkenyl, heterocyclic, heterocyclic C1-4 alkyl, heterocyclic C2-4 alkenyl, or camphor, all of which groups are optionally substituted;
• provided that
• when n=1 than Y is substituted in the 2- or 3-position;
• when n=2 than Y is di-substituted in the 2′-3′-position, the 2′-5′-position, the 2′-6′ position, the 3′-5′ or the 3′-6′ position;
• when n=3 than Y is trisubstituted in the 2′-3′-5′ or the 2′-3′-6′-positions;
• further provided that
• when X1 is O, m=2, R1 is 2-t-butyl, 4-methyl, and n=3 than Y is not 2′-OH, 3′-t-butyl, 5′-methyl;
• when X1 is O, m=1, R1 is 4-methyl, and n=2 than Y is not 2′-OH, 5′-methyl;
• when X1 is O, m=1, R1 is hydrogen, and n=2 than Y is not 2′-6′-diethyl;
• when X1 is O, m=1, R1 is 6—OH, and n=2 than Y is not 2′-5′-methyl;
• when X1 is S, m=1, R1 is 4-ethyl, and n=1 than Y is not 2-methoxy;
• when X1 is O, m=1, R1 is 5-nitro, and, n=2 than 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 X1 is O, m=1, R1 is 3-nitro, and n=1, than Y is not hydrogen;
• when X1 is O, m=1, R1 is 3-nitro, and n=2, than Y is not 2,5-dichloro;
• when X1 is O, m=1, R1 is hydrogen, and n=2, than Y is not 2-methyl-5-chloro;
• when X1 is O, m=1, R1 is 5-chloro, and n=1, than Y is not hydrogen;
• when X1 is O, m=1, R1 is 5-chloro, and n=2, than Y is not 2-fluoro-5-nitro, or 3,4,-dichloro, or 2-methyl-5-nitro;
• when X1 is O, m=1, R1 is 4-amino, and n=1, than Y is not hydrogen;
• or a pharmaceutically acceptable salt thereof.