Dihydro-pyrrolopyridinone bromodomain inhibitorsThe present invention provides for compounds of formula (I) wherein R1, R2, R3, R4, and R5 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).Formula (i) compound or pharmaceutically acceptable salt thereof,whereinr 1h, c 1-c 3alkyl or c 1-c 3haloalkyl; r 2h, c 1-c 3alkyl or c 1-c 3haloalkyl; r 3h, c 1-c 6alkyl, c 2-c 6thiazolinyl, c 2-c 6alkynyl, halogen ,-or 3a,-nr 3br 3c,-n (r 3b) c (o) r 3d,-n (r 3b) c (o) nr 3br 3c,-n (r 3b) s (o) 2nr 3br 3c,-c (o) r 3a,-c (o) or 3a,-c (o) nr 3br 3c,-s (o) r 3d,-s (o) 2r 3a,-s (o) 2nr 3br 3cor g 1; wherein said c 1-c 6alkyl, c 2-c 6thiazolinyl and c 2-c 6alkynyl is not substituted independently of one another or is independently selected from following substituting group by 1 or 2 and replaces: halogen, g 1,-or 3awith-nr 3br 3c; r 3a, r 3band r 3c, when occurring at every turn, be h, c independently of one another 1-c 6alkyl, c 1-c 6haloalkyl, g 1,-(c 1-c 6alkylidene group)-g 1,-(c 1-c 6alkylidene group)-cn ,-(c 1-c 6alkylidene group)-or z1or-(c 1-c 6alkylidene group)-nr z3r z4; r 3d, when occurring at every turn, be c independently 1-c 6alkyl, c 1-c 6haloalkyl, g 1or-(c 1-c 6alkylidene group)-g 1; g 1, when occurring at every turn, be aryl, heteroaryl, heterocycle, cycloalkyl or cycloalkenyl group independently, and each g 1optionally by 1,2,3,4 or 5 r 1ggroup replaces; r 4h, c 1-c 6alkyl, halogen or c 1-c 6haloalkyl; r 5the monocycle or the dicyclo that are selected from aryl and heteroaryl; it is independently selected from following substituting group by 1,2 or 3 separately and replaces: c 1-c 6alkyl, c 2-c 6thiazolinyl, c 2-c 6alkynyl, halogen, c 1-c 6haloalkyl ,-cn, no 2, g 2,-or a,-oc (o) r b,-oc (o) nr cr d,-sr a,-s (o) 2r a,-s (o) 2nr cr d,-c (o) r a,-c (o) or a,-c (o) nr cr d,-nr cr d,-n (r e) c (o) r b,-n (r e) s (o) 2r b,-n (r e) c (o) o (r b) ,-n (r e) c (o) nr cr d,-n (r e) s (o) 2nr cr d,-(c 1-c 6alkylidene group)-g 2,-(c 1-c 6alkylidene group)-or a,-(c 1-c 6alkylidene group)-oc (o) r b,-(c 1-c 6alkylidene group)-oc (o) nr cr d,-(c 1-c 6alkylidene group)-s (o) 2r a,-(c 1-c 6alkylidene group)-s (o) 2nr cr d,-(c 1-c 6alkylidene group)-c (o) r a,-(c 1-c 6alkylidene group)-c (o) or a,-(c 1-c 6alkylidene group)-c (o) nr cr d,-(c 1-c 6alkylidene group)-nr cr d,-(c 1-c 6alkylidene group)-n (r e) c (o) r b,-(c 1-c 6alkylidene group)-n (r e) s (o) 2r b,-(c 1-c 6alkylidene group)-n (r e) c (o) o (r b) ,-(c 1-c 6alkylidene group)-n (r e) c (o) nr cr d,-(c 1-c 6alkylidene group)-n (r e) s (o) 2nr cr dwith-(c 1-c 6alkylidene group)-cn; r a, r c, r dand r e, when occurring at every turn, be h, c independently of one another 2-c 6thiazolinyl, c 2-c 6alkynyl, c 1-c 6haloalkyl, g 2or c 1-c 6alkyl, wherein said c 1-c 6alkyl is optionally selected from following substituting group by one and replaces :-or y1,-nr y3r y4,-c (o) or y1,-c (o) nr y3r y4,-s (o) 2r y1,-s (o) 2nr y3r y4and g 2; r b, when occurring at every turn, be c independently 2-c 6thiazolinyl, c 2-c 6alkynyl, c 1-c 6haloalkyl, g 2or c 1-c 6alkyl, wherein said c 1-c 6alkyl is optionally selected from following substituting group by one and replaces :-or y1,-nr y3r y4,-c (o) or y1,-c (o) nr y3r y4,-s (o) 2r y1,-s (o) 2nr y3r y4and g 2; g 2, when occurring at every turn, be aryl, heteroaryl, heterocycle, cycloalkyl or cycloalkenyl group independently of one another; and each g 2group is optionally by 1,2,3,4 or 5 r 2ggroup replaces; r 1g, when occurring at every turn, be c independently 1-c 6alkyl, c 2-c 6thiazolinyl, c 2-c 6alkynyl, halogen, c 1-c 6haloalkyl ,-cn, no 2,-or z1,-oc (o) r z2,-oc (o) nr z3r z4,-sr z1,-s (o) 2r z1,-s (o) 2nr z3r z4,-c (o) r z1,-c (o) (c 3-c 6cycloalkyl) ,-c (o) or z1,-c (o) nr z3r z4,-nr z3r z4,-n (r z3) c (o) r z2,-n (r z3) s (o) 2r z2,-n (r z3) c (o) o (r z2) ,-n (r z3) c (o) nr z3r z4,-n (r z3) s (o) 2nr z3r z4,-(c 1-c 6alkylidene group)-or z1,-(c 1-c 6alkylidene group)-oc (o) r z2,-(c 1-c 6alkylidene group)-oc (o) nr z3r z4,-(c 1-c 6alkylidene group)-s (o) 2r z1,-(c 1-c 6alkylidene group)-s (o) 2nr z3r z4,-(c 1-c 6alkylidene group)-c (o) r z1,-(c 1-c 6alkylidene group)-c (o) or z1,-(c 1-c 6alkylidene group)-c (o) nr z3r z4,-(c 1-c 6alkylidene group)-nr z3r z4,-(c 1-c 6alkylidene group)-n (r z3) c (o) r z2,-(c 1-c 6alkylidene group)-n (r z3) s (o) 2r z2,-(c 1-c 6alkylidene group)-n (r z3) c (o) o (r z2) ,-(c 1-c 6alkylidene group)-n (r z3) c (o) nr z3r z4,-(c 1-c 6alkylidene group)-n (r z3) s (o) 2nr z3r z4,-(c 1-c 6alkylidene group)-cn or-o (phenyl); wherein said phenyl moiety and described c 3-c 6cycloalkyl moiety is optionally replaced independently selected from following substituting group by 1,2,3 or 4 separately: c 1-c 6alkyl, halogen, c 1-c 6haloalkyl ,-oh ,-o (alkyl) ,-o (haloalkyl), cn and no 2; r 2g, when occurring at every turn, be c independently 1-c 6alkyl, c 2-c 6thiazolinyl, c 2-c 6alkynyl, halogen, c 1-c 6haloalkyl, oxo ,-cn, no 2,-or y1,-oc (o) r y2,-oc (o) nr y3r y4,-sr y1,-s (o) 2r y1,-s (o) 2nr y3r y4,-c (o) r y1,-c (o) or y1,-c (o) nr y3r y4,-nr y3r y4,-n (r y3) c (o) r y2,-n (r y3) s (o) 2r y2,-n (r y3) c (o) o (r y2) ,-n (r y3) c (o) nr y3r y4,-n (r y3) s (o) 2nr y3r y4, g 2b,-(c 1-c 6alkylid...
디하이드로-피롤로피리디논 브로모도메인 억제제본 발명은, 염증성 질환, 암, 및 AIDS를 포함하는 질환 및 병태의 치료시 약제로서 유용한 화학식 I의 화합물 및 이의 약제학적으로 허용되는 염을 제공한다. 화학식 I 상기 화학식 I에서, R1, R2, R3, R4, 및 R5는 명세서에 정의된 모든 값을 갖는다. 또한, 하나 이상의 화학식 I의 화합물을 포함하는 조성물이 제공된다.화학식 I의 화합물 또는 이의 약제학적으로 허용되는 염.화학식 I[이미지]상기 화학식 I에서,R1은 H, C1-C3 알킬, 또는 C1-C3 할로알킬이고; R2는 H, C1-C3 알킬, 또는 C1-C3 할로알킬이고; R3은 H, C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, 할로겐, -OR3a, -NR3bR3c, -N(R3b)C(0)R3d, -N(R3b)C(0)NR3bR3c, -N(R3b)S(0)2NR3bR3c, -C(0)R3a, -C(0)OR3a, -C(0)NR3bR3c, -S(0)R3d, -S(0)2R3a, -S(0)2NR3bR3c, 또는 G1이고; 여기서, 상기 C1-C6 알킬, C2-C6 알케닐, 및 C2-C6 알키닐은 각각 독립적으로, 치환되지 않거나, 할로겐, G1, -OR3a, 및 -NR3bR3c로 이루어진 그룹으로부터 독립적으로 선택된 1개 또는 2개의 치환체로 치환되며; R3a, R3b, 및 R3c는, 각각의 경우, 각각 독립적으로 H, C1-C6 알킬, C1-C6 할로알킬, G1, -(C1-C6 알킬레닐)-G1, -(C1-C6 알킬레닐)-CN, -(C1-C6 알킬레닐)-ORzl, 또는 -(C1-C6 알킬레닐)-NRz3Rz4이고; R3d는, 각각의 경우, 독립적으로 C1-C6 알킬, C1-C6 할로알킬, G1, 또는 -(C1-C6 알킬레닐)-G1이고; G1은, 각각의 경우, 독립적으로 아릴, 헤테로아릴, 헤테로사이클, 사이클로알킬, 또는 사이클로알케닐이고; G1은 각각 1, 2, 3, 4, 또는 5개의 R1g 그룹으로 임의로 치환되며; R4는 H, C1-C6 알킬, 할로겐, 또는 C1-C6 할로알킬이고; R5는 아릴 및 헤테로아릴로 이루어진 그룹으로부터 선택된 모노사이클릭 또는 바이사이클릭 환이며; 각각은 C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, 할로겐, C1-C6 할로알킬, -CN, N02, G2, -ORa, -OC(0)Rb, -OC(0)NRcRd, -SRa, -S(0)2Ra, -S(0)2NRcRd, -C(0)Ra, -C(0)ORa, -C(0)NRcRd, -NRcRd, -N(Re)C(0)Rb, -N(Re)S(0)2Rb, -N(Re)C(0)0(Rb), -N(Re)C(0)NRcRd, -N(Re)S(0)2NRcRd, -(C1-C6 알킬레닐)-G2, -(C1-C6 알킬레닐)-ORa, -(C1-C6 알킬레닐)-OC(0)Rb, -(C1-C6 알킬레닐)-OC(0)NRcRd, -(C1-C6 알킬레닐)-S(0)2Ra, -(C1-C6 알킬레닐)-S(0)2NRcRd, -(C1-C6 알킬레닐)-C(0)Ra, -(C1-C6 알킬레닐)-C(0)ORa, -(C1-C6 알킬레닐)-C(0)NRcRd, -(C1-C6 알킬레닐)-NRcRd, -(C1-C6 알킬레닐)-N(Re)C(0)Rb, -(C1-C6 알킬레닐)-N(Re)S(0)2Rb, -(C1-C6 알킬레닐)-N(Re)C(0)0(Rb), -(C1-C6 알킬레닐)-N(Re)C(0)NRcRd, -(C1-C6 알킬레닐)-N(Re)S(0)2NRcRd, 및 -(C1-C6 알킬레닐)-CN으로 이루어진 그룹으로부터 독립적으로 선택된 1, 2, 또는 3개의 치환체로 치환되며;Ra, Rc, Rd, 및 Re는, 각각의 경우, 각각 독립적으로 H, C2-C6 알케닐, C2-C6 알키닐, C1-C6 할로알킬, G2, 또는 C1-C6 알킬이고, 여기서, 상기 C1-C6 알킬은 -ORy1, -NRy3Ry4, -C(0)ORy1, -C(0)NRy3Ry4, -S(0)2Ry1, -S(0)2NRy3Ry4, 및 G2로 이루어진 그룹으로부터 선택된 1개의 치환체로 임의로 치환되며; Rb는, 각각의 경우, 독립적으로 C2-C6 알케닐, C2-C6 알키닐, C1-C6 할로알킬, G2, 또는 C1-C6 알킬이고, 여기서, 상기 C1-C6 알킬은 -ORy1, -NRy3Ry4, -C(0)ORy1, -C(0)NRy3Ry4, -S(0)2Ry1, -S(0)2NRy3Ry4, 및 G2로 이루어진 그룹으로부터 선택된 1개의 치환체로 임의로 치환되며; G2는, 각각의 경우, 각각 독립적으로 아릴, 헤테로아릴, 헤테로사이클, 사이클로알킬, 또는 사이클로알케닐이고; G2 그룹은 각각 1, 2, 3, 4, 또는 5개의 R2g 그룹으로 임의로 치환되며; R1g는, 각각의 경우, 독립적으로 C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, 할로겐, C1-C6 할로알킬, -CN, N02, -ORzl, -OC(0)Rz2, -OC(0)NRz3Rz4, -SRzl, -S(0)2Rzl, -S(0)2NRz3Rz4, -C(0)Rzl, -C(0)(C3-C6 사이클로알킬), -C(0)ORzl, -C(0)NRz3Rz4, -NRz3Rz4, -N(Rz3)C(0)Rz2, -N(Rz3)S(0)2Rz2, -N(Rz3)C(0)0(Rz2), -N(Rz3)C(0)NRz3Rz4, -N(Rz3)S(0)2NRz3Rz4, -(C1-C6 알킬레닐)-ORzl, -(C1-C6 알킬레닐)-OC(0)Rz2, -(C1-C6 알킬레닐)-OC(0)NRz3Rz4, -(C1-C6 알킬레닐)-S(0)2Rzl, -(C1-C6 알킬레닐)-S(0)2NRz3Rz4, -(C1-C6 알킬레닐)-C(0)Rzl, -(C1-C6 알킬레닐)-C(0)ORzl, -(C1-C6 알킬레닐)-C(0)NRz3Rz4, -(C1-C6 알킬레닐)-NRz3Rz4, -(C1-C6 알킬레닐)-N(Rz3)C(0)Rz2, -(C1-C6 알킬레닐)-N(Rz3)S(0)2Rz2, -(C1-C6 알킬레닐)-N(Rz3)C(0)0(Rz2), -(C1-C6 알킬레닐)-N(Rz3)C(0)NRz3Rz4, -(C1-C6 알킬레닐)-N(Rz3)S(0)2NRz3Rz4, -(C1-C6 알킬레닐)-CN, 또는 -0(페닐)이고; 여기서, 상기 페닐 모이어티 및 상기 C3-C6 사이클로알킬 모이어티는 각각 C1-C6 알킬, 할로겐, C1-C6 할로알킬, -OH, -O(알킬), -0(할로알킬), CN, 및 N02로 이루어진 그룹으로부터 독립적으로 선택된 1, 2, 3, 또는 4개의 치환체로 임의로 치환되며; R2g는, 각각의 경우, 독립적으로 C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, 할로겐, C1-C6 할로알킬, 옥소, -CN, N02, -ORy1, -OC(0)Ry2, -OC(0)NRy3Ry4, -SRy1, -S(0)2Ry1, -S(0)2NRy3Ry4, -C(0)Ry1, -C(0)ORy1, -C(0)NRy3Ry4, -NRy3Ry4, -N(Ry3)C(0)Ry2, -N(Ry3)S(0)2Ry2, -N(Ry3)C(0)0(Ry2), -N(Ry3)C(0)NRy3Ry4, -N(Ry3)S(0)2NRy3Ry4, G2b, -(C1-C6 알킬레닐)-ORy1, -(C1-C6 알킬레닐)-OC(0)Ry2, -(C1-C6 알킬레닐)-OC(0)NRy3Ry4, -(C1-C6 알킬레닐)-S(0)2Ry1, -(C1-C6 알킬레닐)-S(0)2NRy3Ry4, -(C1-C6 알킬레닐)-C(0)Ry1, -(C1-C6 알킬레닐)-C(0)ORy1, -(C1-C6 알킬레닐)-C(0)NRy3Ry4, -(C1-C6 알킬레닐)-NRy3Ry4, -(C1-C6 알킬레닐)-N(Ry3)C(0)Ry2, -(C1-C6 알킬레닐)-N(Ry3)S(0)2Ry2, -(C1-C6 알킬레닐)-N(Ry3)C(0)0(Ry2), -(C1-C6 알킬레닐)-N(Ry3)C(0)NRy3Ry4, -(C1-C6 알킬레닐)-N(Ry3)S(0)2NRy3Ry4, -(C1-C6 알킬레닐)-CN, 또는 -(C1-C6 알킬레닐)-G2b이고; Ry1, Ry3, 및 Ry4는, 각각의 경우, 각각 독립적으로 H, C1-C6 알킬, C1-C6 할로알킬, G2b, 또는 -(C1-C6 알킬레닐)-G2b이고; Ry2는, 각각의 경우, 독립적으로 C1-C6 알킬, C1-C6 할로알킬, G2b, 또는 -(C1-C6 알킬레닐)-G2b이고; G2b는, 각각의 경우, 독립적으로 아릴, 헤테로아릴, 사이클로알킬, 사이클로알케닐, 또는 헤테로사이클이고; G2b 그룹은 각각 C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐, 할로겐, C1-C6 할로알킬, -CN, N02, -ORzl, -OC(0)Rz2, -OC(0)NRz3Rz4, -SRzl, -S(0)2Rzl, -S(0)2NRz3Rz4, -C(0)Rzl, -C(0)ORzl, -C(0)NRz3Rz4, -NRz3Rz4, -N(Rz3)C(0)Rz2, -N(Rz3)S(0)2Rz2, -N(Rz3)C(0)0(Rz2), -N(Rz3)C(0)NRz3Rz4, -N(Rz3)S(0)2NRz3Rz4, -(C1-C6 알킬레닐)-ORzl, -(C1-C6 알킬레닐)-OC(0)Rz2, -(C1-C6 알킬레닐)-OC(0)NRz3Rz4, -(C1-C6 알킬레닐)-S(0)2Rzl, -(C1-C6 알킬레닐)-S(0)2NRz3Rz4, -(C1-C6 알킬레닐)-C(0)Rzl, -(C1-C6 알킬레닐)-C(0)ORzl, -(C1-C6 알킬레닐)-C(0)NRz3Rz4, -(C1-C6 알킬레닐)-NRz3Rz4, -(C1-C6 알킬레닐)-N(Rz3)C(0)Rz2, -(C1-C6 알킬레닐)-N(Rz3)S(0)2Rz2, -(C1-C6 알킬레닐)-N(Rz3)C(0)0(Rz2), -(C1-C6 알킬레닐)-N(Rz3)C(0)NRz3Rz4, -(C1-C6 알킬레닐)-N(Rz3)S(0)2NRz3Rz4, 및 -(C1-C6 알킬레닐)-CN으로 이루어진 그룹으로부터 독립적으로 선택된 1, 2, 3, 4, 또는 5개의 치환체로 임의로 치환되며; Rzl, Rz3, 및 Rz4는, 각각의 경우, 각각 독립적으로 H, C1-C6 알킬, 또는 C1-C6 할로알킬이고; Rz2는, 각각의 경우, 독립적으로 C1-C6 알킬 또는 C1-C6 할로알킬이다.