IL-8 receptor antagonistsThis invention relates to novel compounds of Formula (I), and compositions thereof, useful in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).Formula (i) chemical compound: wherein r is selected from cyano group, or 11, c (o) nr 15r 16, r 18, c (o) or 11, c (o) r 11and s (o) 2r 17r ' r ' is independently selected from hydrogen, nr 6r 7, oh, ora, c 1-5alkyl, aryl, aryl c 1-4alkyl, aryl c 2-4alkenyl, cycloalkyl, cycloalkyl c 1-5alkyl, heteroaryl, heteroaryl c 1-4alkyl, heteroaryl c 2-4alkenyl, heterocyclic radical, heterocyclic radical c 1-4alkyl and heterocyclic radical c 2-4kiki alkenyl group, all these groups all are unsubstituted or are replaced 1-3 time by substituent group independently that described substituent group is selected from halogen, nitro, the c that halogen replaces 1-4alkyl, c 1-4alkyl, amino, one and two-c 1-4the amine that alkyl replaces, or a, c (o) r a, nr ac (o) or a, oc (o) nr 6r 7, hydroxyl, nr 9c (o) r a, s (o) m 'r a, c (o) nr 6r 7, c (o) oh, c (o) or a, s (o) tnr 6r 7and nhs (o) tr aperhaps two r bsubstituent group couple together form 3-10 unit unsubstituted or replace and except comprising c unsubstituted or that replace 1-4outside the alkyl, comprise 1-3 nra, o, s, so and so independently 2unsaturated or the saturated rings of group. r is y, is selected from hydrogen, halogen, nitro, cyano group, the c that halogen replaces 1-10alkyl, c 1-10alkyl, c 2-10alkenyl, c 1-10alkoxyl, the c that halogen replaces 1-10alkoxyl, azide, (cr 8r 8) qs (o) tr a, (cr 8r 8) qor a, hydroxyl, the c that hydroxyl replaces 1-4alkyl, aryl, aryl c 1-4alkyl, aryloxy group, aryl c 1-4alkoxyl, aryl c 2-10alkenyl, heteroaryl, heteroaryl alkyl, heteroaryl c 1-4alkoxyl, heteroaryl c 2-10alkenyl, heterocyclic radical, heterocyclic radical c 1-4alkyl, heterocyclic radical c 2-10alkenyl, (cr 8r 8) qnr 4r 5, c 2-10alkenyl c (o) nr 4r 5, (cr 8r 8) qc (o) nr 4r 5, (cr 8r 8) qc (o) nr 4r 10, s (o) 3r 8, (cr 8r 8) qc (o) r 11, c 2-10alkenyl c (o) r 11, (cr 8r 8) qc (o) or 11, c 2-10alkenyl c (o) or 11, (cr 8r 8) qoc (o) r 11, (cr 8r 8) qnr 4c (o) r 11, (cr 8r 8) qnhs (o) tr 13, (cr 8r 8) qs (o) tnr 4r 5, (cr 8r 8) qc (nr 4) nr 4r 5(cr 8r 8) qnr 4c (nr 5) r 11perhaps two y groups form o-(ch together 2) sthe saturated or unsaturated ring of-o or 5-6 unit, wherein alkyl, aryl, aralkyl, heteroaryl, heteroaryl alkyl, heterocyclic radical and heterocyclic radical alkyl can be unsubstituted or replace; r 1be independently selected from hydrogen, halogen, nitro, cyano group, c 1-10alkyl, the c that halogen replaces 1-10alkyl, c 2-10alkenyl, c 1-10alkoxyl, the c that halogen replaces 1-10alkoxyl, azide, s (o) tr 4, (cr 8r 8) qs (o) tr 4, hydroxyl, the c that hydroxyl replaces 1-4alkyl, aryl, aryl c 1-4alkyl, aryl c 2-10alkenyl, aryloxy group, aryl c 1-4alkoxyl, heteroaryl, heteroaryl alkyl, heteroaryl c 2-10alkenyl, heteroaryl c 1-4alkoxyl, heterocyclic radical, heterocyclic radical c 1-4alkyl, heterocyclic radical c 1-4alkoxyl, heterocyclic radical c 2-10alkenyl, (cr 8r 8) qnr 4r 5, (cr 8r 8) qc (o) nr 4r 5, c 2-10alkenyl c (o) nr 4r 5, (cr 8r 8) qc (o) nr 4r 10, s (o) 3r 8, (cr 8r 8) qc (o) r 11, c 2-10alkenyl c (o) r 11, c 2-10alkenyl c (o) or 11, (cr 8r 8) qc (o) or 11, (cr 8r 8) qoc (o) r 11, (cr 8r 8) qnr 4c (o) r 11, (cr 8r 8) qc (nr 4) nr 4r 5, (cr 8r 8) qnr 4c (nr 5) r 11, (cr 8r 8) qnhs (o) tr 13(cr 8r 8) qs (o) tnr 4r 5, perhaps two r 1part forms o-(ch together 2) sthe saturated or unsaturated ring of-o or 5-6 unit, wherein alkyl, aryl, aralkyl, heteroaryl or heterocyclic radical part can be unsubstituted or replace.
ＩＬ-８ 수용체 길항제본 발명은 화학식 I의 신규 화합물, 및 케모킨, 인터루킨-8(IL-8)에 의해 매개되는 질환 상태를 치료하는데 유용한 그의 조성물에 관한 것이다.하기 화학식 I의 화합물. <화학식 I> [이미지] 식 중, R은 시아노, OR11, C(O)NR15R16, R18, C(O)OR11, C(O)R11 및 S(O)2R17로 이루어진 군으로부터 선택되고; R' 및 R"는 각각 수소, NR6R7, OH, ORa, C1-5알킬, 아릴, 아릴C1-4알킬, 아릴C2-4알케닐, 시클로알킬, 시클로알킬C1-5알킬, 헤테로아릴, 헤테로아릴C1-4알킬, 헤테로아릴C2-4알케닐, 헤테로시클릭, 헤테로시클릭C1-4알킬 및 헤테로시클릭C2-4알케닐 잔기로 이루어진 군으로부터 독립적으로 선택되고, 이들 모든 잔기들은 할로겐, 니트로, 할로 치환된 C1-4알킬, C1-4알킬, 아미노, 모노- 또는 디-C1-4알킬 치환된 아민, ORa, C(O)Ra, NRaC(O)ORa, OC(O)NR6R7, 히드록시, NR9C(O)Ra, S(O)m'Ra, C(O)NR6R7 , C(O)OH, C(O)ORa, S(O)tNR6R7 및 NHS(O)tRa 로 이루어진 군으로부터 선택된 치환기로 독립적으로 1 내지 3회 임의 치환될 수 있거나; 또는 R' 및 R"가 함께, 임의 치환된 C1-4알킬 잔기 이외에 1 내지 3개의 NRa, O, S, SO 또는 SO2 잔기를 독립적으로 포함하며, 임의로 치환되는 3원 내지 10원 고리를 형성하고; 이들 잔기들은 임의로 불포화될 수 있고; R"'는 n개의 Y로 구성되고, Y는 각각 수소, 할로겐, 니트로, 시아노, 할로 치환된 C1-10알킬, C1-10알킬, C2-10알케닐, C1-10알콕시, 할로 치환된 C1-10알콕시, 아지드, (CR8R8)qS(O)tRa, (CR8R8) qORa, 히드록시, 히드록시 치환된 C1-4알킬, 아릴, 아릴C1-4알킬, 아릴옥시, 아릴C1-4알킬옥시, 아릴C2-10알케닐, 헤테로아릴, 헤테로아릴알킬, 헤테로아릴C1-4알킬옥시, 헤테로아릴C2-10알케닐, 헤테로시클릭, 헤테로시클릭C1-4 알킬, 헤테로시클릭C2-10알케닐, (CR8R8)qNR4R5 , C2-10알케닐C(O)NR4R5, (CR8R8)qC(O)NR 4R5, (CR8R8)qC(O)NR4R10, S(O)3R8, (CR8R8)qC(O)R11, C2-10알케닐C(O)R11, (CR8R8)qC(O)OR11, C2-10알케닐C(O)OR11, (CR8R8)qOC(O)R11, (CR 8R8)qNR4C(O)R11, (CR8R8)qNHS(O) tR13, (CR8R8)qS(O)tNR4R5, (CR8R 8)qC(NR4)NR4R5 및 (CR8R8) qNR4C(NR5)R11로 이루어진 군으로부터 선택되거나; 또는 2개의 Y 잔기가 함께 O-(CH2)s-O 또는 5원 내지 6원 포화 또는 불포화 고리를 형성하고; 여기서 알킬, 아릴, 아릴알킬, 헤테로아릴, 헤테로아릴 알킬, 헤테로시클릭 및 헤테로시클릭알킬기는 임의로 치환될 수 있고; R1은 수소, 할로겐, 니트로, 시아노, C1-10알킬, 할로 치환된 C1-10알킬, C2-10알케닐, C1-10알콕시, 할로 치환된 C1-10알콕시, 아지드, S(O)tR4, (CR8R8)qS(O)tR4, 히드록시, 히드록시 치환된 C1-4알킬, 아릴, 아릴C1-4알킬, 아릴C2-10알케닐, 아릴옥시, 아릴C1-4알킬옥시, 헤테로아릴, 헤테로아릴알킬, 헤테로아릴C2-10알케닐, 헤테로아릴C 1-4알킬옥시, 헤테로시클릭, 헤테로시클릭C1-4알킬, 헤테로시클릭C1-4알킬옥시, 헤테로시클릭C2-10알케닐, (CR8R8)qNR4R5, (CR 8R8)qC(O)NR4R5, C2-10알케닐C(O)NR 4R5, (CR8R8)qC(O)NR4R10, S(O)3R8, (CR8R8)qC(O)R11, C2-10알케닐C(O)R11, C2-10알케닐C(O)OR11, (CR8R8)qC(O)OR11, (CR8R8)qOC(O)R 11, (CR8R8)qNR4C(O)R11, (CR8 R8)qC(NR4)NR4R5, (CR8R8)qNR4C(NR5)R11, (CR8R 8)qNHS(O)tR13 및 (CR8R8)qS(O) tNR4R5로 이루어진 군으로부터 독립적으로 선택되거나; 2개의 R1 잔기가 함께 O-(CH2)sO 또는 5원 내지 6원 포화 또는 불포화 고리를 형성하고, 여기서 알킬, 아릴, 아릴아킬, 헤테로아릴 및 헤테로시클릭 잔기는 임의로 치환될 수 있다.