| 摘要 |
A compound of the Formula (I) for treating chemokine mediated diseases, wherein the chemokine binds to an IL-8 a or b receptor. The chemokine mediated disease is selected from psoriasis, atopic dermatitis, asthma, chronic obstructive pulmonary disease, adult respiratory distress syndrome, arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, septic shock, endotoxic shock, gram negative sepsis, toxic shock syndrome, stroke, cardiac and renal reperfusion injury, glomerulonephritis, thrombosis, Alzheimer's disease, graft vs. host reaction, or allograft rejections. Wherein; R is -NH-C(X2)-NH-(CR13R14)v-Z, wherein Z is W, HET, Formula (II), an optionally substituted C1-10alkyl, C2-10alkenyl or C2-10alkynyl; X2 is =O, or =S; X is C(X1)2, C(O), C(S), S(O)2, PO(OR4), or C=N-R19, wherein X1 is hydrogen, halogen, C1- 10alkyl, NR4R5, C1-10alkyl-NR4R5, C(O)NR4R5, optionally substituted C1-10alkyl, C1-10alkoxy, halosubstituted C1-10alkoxy, hydroxy, aryl, aryl C1-4alkyl, aryloxy, aryl C1-4alkyloxy, heteroaryl, heteroarylalkyl, heterocyclic, heterocyclic C1-4alkyl, or heteroaryl C1-4alkyloxy; R1 is selected from hydrogen; halogen; nitro; cyano; halosubstituted C1-10alkyl; C1-10alkyl; C2-10alkenyl; C1-10alkoxy; halosubstituted C1-10alkoxy; azide; (CR8R8)q S(O)tR4, hydroxy; hydroxy C1-4alkyl; aryl; aryl C1-4alkyl; aryloxy; aryl C1-4alkyloxy; heteroaryl; heteroarylalkyl; heterocyclic; heterocyclic C1-4alkyl, heteroaryl C1-4alkyloxy; aryl C2-10alkenyl; heteroaryl C2-10alkenyl; heterocyclic C2-10alkenyl; (CR8R8)qNR4R5; C2-10alkenylC(O)NR4R5; (CR8R8)qC(O)NR4R5; (CR8R8)qC(O)NR4R10; S(O)3R8; (CR8R8)qC(O)R11; C2-10alkenylC(O)R11; C2-10alkenylC(O)OR11; C(O)R11; (CR8R8)qC(O)OR12; (CR8R8)qOC(O)R11; (CR8R8)qC(NR4)NR4R5; (CR8R8)qNR4C(NR5)R11; (CR8R8)qNR4C(O)R11; (CR8R8)qNHS(O) 2R17; (CR8R8)qS(O)2NR4R5; or two R1 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; n is an integer having a value of 1 to 3; m 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; p is an integer having a value of 1 to 3; HET is an optionally substituted heteroaryl; R4 and R5 are independently hydrogen, optionally substituted C1-4alkyl, optionally substituted aryl, optionally substituted aryl C1-4alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl C1-4alkyl, heterocyclic, or heterocyclic C1-4alkyl, 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; R18 is hydrogen, optionally substituted C1-10alkyl, C1-10alkoxy, halosubstituted C1-10alkoxy, hydroxy, arylC1-4alkyl, arylC2-4alkenyl, heteroaryl, heteroaryl C1-4alkyl, heteroarylC2-4alkenyl, heterocyclic, or heterocyclicC1-4alkyl, wherein all the aryl, heteroaryl and heterocyclic containing moieties may all be optionally substituted.
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