IL-8 receptor antagonistsThis invention relates to the novel use of dianilino squarates in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).Following formula: compound: wherein: r 1be selected from the c of hydrogen, halogen, nitro, cyano group, halogen replacement alone 1-10alkyl, c 1-10alkyl, c 2-10alkenyl, c 1-10the c that alkoxyl group, halogen replace 1-10alkoxyl group, azido-, (cr 8r 8) qs (o) tr 4, hydroxyl, hydroxyl c 1-4alkyl, aryl, aryl c 1-4alkyl, aryloxy, aryl c 1-4alkoxyl group, heteroaryl, heteroarylalkyl, heterocycle, heterocycle c 1-4alkyl, heteroaryl c 1-4alkoxyl group, aryl c 2-10alkenyl, heteroaryl c 2-10alkenyl, heterocycle 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) 3h, 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 12, (cr 8r 8) qoc (o) r 11, (cr 8r 8) qnr 4c (o) r 11, (cr 8r 8) qnhs (o) 2r 17, (cr 8r 8) qs (o) 2nr 4r 5perhaps two r 1part forms o-(ch together 2) so-or unsubstituted 5-6 unit ring; q is 0, or the integer of 1-10;t is 0, or the integer of 1-2;s is the integer of 1-3;r 4and r 5be selected from hydrogen separately, can be substituted or not substituted c 1-4alkyl, can be substituted or not substituted aryl, can be substituted or not substituted aryl c 1-4alkyl, can be substituted or not substituted heteroaryl, can be substituted or not substituted heteroaryl c 1-4alkyl, heterocycle and heterocycle c 1-4alkyl, or r 4and r 5the nitrogen that links to each other with them forms 5-7 unit ring, and described ring can comprise or not comprise the other heteroatoms that is selected from oxygen, nitrogen or sulphur; y is selected from the c of hydrogen, halogen, nitro, cyano group, halogen replacement alone 1-10alkyl, c 1-10alkyl, c 2-10alkenyl, c 1-10the c that alkoxyl group, halogen replace 1-10alkoxyl group, azido-, (cr 8r 8) qs (o) tr 4, hydroxyl, hydroxyl c 1-4alkyl, aryl, aryl c 1-4alkyl, aryloxy, aryl c 1-4alkoxyl group, heteroaryl, heteroarylalkyl, heteroaryl c 1-4alkoxyl group, heterocycle, heterocycle c 1-4alkyl, aryl c 2-10alkenyl, heteroaryl c 2-10alkenyl, heterocycle 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) 3h, 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, c (o) r 11, (cr 8r 8) qc (o) or 12, (cr 8r 8) qoc (o) r 11, (cr 8r 8) qnr 4c (o) r 11, (cr 8r 8) qnhs (o) 2r d, and (cr 8r 8) qs (o) 2nr 4r 5perhaps two y form o-(ch together 2) so-or unsaturated 5-6 unit ring; n is the integer of 1-5;m is the integer of 1-4;r 8be hydrogen or c 1-4alkyl; r 10be c 1-10alkyl c (o) 2r 8r 11be selected from hydrogen, c 1-4alkyl, can be substituted or not substituted aryl, can be substituted or not substituted aryl c 1-4alkyl, can be substituted or not substituted heteroaryl, can be substituted or not substituted heteroaryl c 1-4alkyl, can be substituted or not substituted heterocyclic radical and can being substituted or not substituted heterocycle c 1-4alkyl; r 12be selected from hydrogen, c 1-10alkyl, can be substituted or not substituted aryl, can be substituted or not substituted arylalkyl; r 17be selected from c 1-4alkyl, aryl, arylalkyl, heteroaryl, heteroaryl c 1-4alkyl, heterocycle and heterocycle c 1-4alkyl, wherein aryl, heteroaryl and heterocycle all can be substituted or not be substituted.
ＩＬ-８ 수용체 길항제본 발명은 케모킨, 인터루킨-8(IL-8)에 의해 매개되는 질환 상태를 치료하는데 있어서 디아닐리노 스쿠아레이트의 신규 용도에 관한 것이다.하기 화학식 I의 화합물. <화학식 I> [이미지] 식 중, R1은 수소, 할로겐, 니트로, 시아노, 할로치환된 C1-10알킬, C1-10알킬, C2-10알케닐, C1-10알콕시, 할로치환된 C1-10알콕시, 아지드, (CR8R8) qS(O)tR4, 히드록시, 히드록시C1-4알킬, 아릴, 아릴C1-4알킬, 아릴옥시, 아릴C1-4알킬옥시, 헤테로아릴, 헤테로아릴알킬, 헤테로시클릭, 헤테로시클릭C1-4알킬, 헤테로아릴C1-4알킬옥시, 아릴C2-10 알케닐, 헤테로아릴C2-10알케닐, 헤테로시클릭C2-10알케닐, (CR8R8) qNR4R5, C2-10알케닐C(O)NR4R5, (CR8R8)qC(O)NR 4R5, (CR8R8)qC(O)NR4R10, S(0)3H, S(O)3R8, (CR8R8)qC(O)R11, C2-10알케닐C(O)R11, C2-10알케닐C(O)OR11(CR8R8)qC(O)OR12, (CR8R8)qOC(O)R11, (CR8R8)qNR 4C(O)R11, (CR8R8)qNHS(O)2R17 , (CR8R8)qS(O)2NR4R5로 이루어진 군으로부터 독립적으로 선택되거나; 2개의 R1 잔기가 함께 O-(CH2)sO- 또는 5원 내지 6원 불포화 고리를 형성하고; q는 0, 또는 1 내지 10의 정수이고; t는 0, 또는 1 또는 2의 정수이고; s는 1 내지 3의 정수이고; R4 및 R5는 수소, 임의 치환된 C1-4알킬, 임의 치환된 아릴, 임의 치환된 아릴C1-4알킬, 임의 치환된 헤테로아릴, 임의 치환된 헤테로아릴C1-4알킬, 헤테로시클릭, 및 헤테로시클릭C1-4알킬로 이루어진 군으로부터 독립적으로 선택되거나, R4 및 R5는 이들이 결합되어 있는 질소와 함께 산소, 질소 또는 황으로부터 선택되는 추가의 헤테로원자를 임의로 포함하는 5원 내지 7원 고리를 형성하고; Y는 수소, 할로겐, 니트로, 시아노, 할로치환된 C1-10알킬, C1-10알킬, C2-10 알케닐, C1-10알콕시, 할로치환된 C1-10알콕시, 아지드, (CR8R8) qS(O)tR4, 히드록시, 히드록시C1-4알킬, 아릴, 아릴C1-4알킬, 아릴옥시, 아릴C1-4알킬옥시, 헤테로아릴, 헤테로아릴알킬, 헤테로아릴C1-4알킬옥시, 헤테로시클릭, 헤테로시클릭C1-4알킬, 아릴C2-10 알케닐, 헤테로아릴C2-10알케닐, 헤테로시클릭C2-10알케닐, (CR8R8) qNR4R5, C2-10알케닐C(O)NR4R5, (CR8R8)qC(O)NR 4R5, (CR8R8)qC(O)NR4R10, S(0)3H, S(0)3R8, (CR8R8)qC(O)R11, C2-10알케닐C(O)R11, C2-10알케닐C(O)OR11, C(O)R11, (CR8R8)qC(O)OR 12, (CR8R8)qOC(O)R11, (CR8R8)qNR 4C(O)R11, (CR8R8)qNHS(O)2Rd 및 (CR8R8)qS(O)2NR4R5로 이루어진 군으로부터 독립적으로 선택되거나; 2개의 Y 잔기가 함께 0-(CH2)sO- 또는 5원 내지 6원 불포화 고리를 형성하고; n은 1 내지 5의 정수이고; m은 1 내지 4의 정수이고; R8은 수소 또는 C1-4알킬이고; R10은 C1-10알킬C(O)2R8이고; R11은 수소, C1-4알킬, 임의 치환된 아릴, 임의 치환된 아릴C1-4알킬, 임의 치환된 헤테로아릴, 임의 치환된 헤테로아릴C1-4알킬, 임의 치환된 헤테로시클릭 및 임의 치환된 헤테로시클릭C1-4알킬로 이루어진 군으로부터 선택되고; R12는 수소, C1-10알킬, 임의 치환된 아릴 및 임의 치환된 아릴알킬로부터 선택되고; R17은 C1-4알킬, 아릴, 아릴알킬, 헤테로아릴, 헤테로아릴C1-4알킬, 헤테로시클릭 및 헤테로시클릭C1-4알킬로 이루어진 군으로부터 선택되고, 여기서, 아릴, 헤테로아릴 및 헤테로시클릭 고리는 모두 임의 치환된다.