5-PYRIDIN-3-YL-1,3-DIHYDRO-INDOL-2-ON DERIVATIVES AND THEIR USE AS MODULATORS OF ALDOSTERONE SYNTHASE AND/OR CYP11B1The present invention provides a compound a formula (I); or a pharmaceutically acceptable salt thereof, wherein: X is CH2, O, S or-NR1; each R1 are independently C1-7alkyl or C3-8cycloalkyl; each of R2 and R6 are independently hydrogen, halogen, cyano, C1-7alkyl, hydroxy-C1-7alkyl, -OR7, C3-8cycloalkyl, halo-C1-7alkyl or -CH2-NR8-SO2-R10; R3 and R4 are independently hydrogen, halogen or cyano; R5 is hydrogen, C1-2alkyl, halogen, cyano, hydroxy, hydroxy-C1-7alkyl, hydroxy-C3-8 cycloalkylalkyl, C1-7alkoxy-C3-3alkyl, -OR7, C6-10aryl, heteroaryl, heterocyclyl, C3-8 cycloalkyl, halo- C1-7alkyl, -NR8R9, -CH2NR8-C(O)NR8R9, -CH2-NR6-SO2-R10, -C(O)- R10, -SO2R10, -C(O)-NR5R9 -SO2-NR8R9, -NR3C(O)-R10 -CH2CN, or -NR8-SO2-R10. Compounds of the invention may be useful in the treatment of a disorder or disease mediated by aldosterone synthase and/or 11-beta hydroxylase (CYP1 181).A compound of Formula I a pharmaceutically acceptable salt thereof, whereinX is CH2 O, S or -NR1, each R1 are independently Ct.7alkyl or C3^cycloalkyl, each of R2 and R6 are independently hydrogen, halogen, cyano, C1-7alkyl, hydroxy-C1-7alkyl, -OR7, C3-8cycloalkyl ha!o-Cv?alkyl or -CH2-NR9-SO2-R'°,RJ and R4 are independently hydrogen halogen or cyano,R5 is hydrogen, C1-7alkyl, halogen, cyano, hydroxy, hydroxy-d.-alkyl, hydroxy-C3- βcycloalkylalkyl, C1-7aIkOXy-C3-8alkyl, -OR7, C6-10aryl, heteroaryl, heterocyclyl, C3- βcycloalkyl, halo- C1-7alkyl, -NR8R9, -CH2-NR6-C(O)NR3R9, -CH2-NR9-SO2-R10, -C(O)- R10, -SO2R10. -C(O)-NR8R9, -SO2-NR8R9, -NR9C(O)-R10 -CH2CN or -NR*-SO2-R10,R7 rs Ci-7alkyl, Ca-ecydoalkyl-C1-7alkyl, heterocyclyl-d >alkyl, Ce.^aryl-C1-7alkyl, heteroaryl-Ci -alkyl or -C(O)-R10 in which C6 10aryl, heteroaryl, Cf.7alkyl, heterocyclyl and C3 βcycloalkyl are optionally susbtituted with C1-TaIkOXy, halo, halo-C3 9alkoxy C1-7alkyl OH or halo-C1-7alkyl, each of R9, Rδ are independently hydrogen, C1-7alkyl, halo-C1-7alkyl, C6 ^aryl-d. ^alkyl or heterocyclyl or R6 and R9 can form together with the nitrogen atom to which they are attached a 5- or 6-membered ring heterocyclyl, wherein said heterocyclyl optionally contain an additional heteroatom selected from N. O or S and is optionally substituted with C1-7alkyl andR10 is hydrogen, d. -alkyl, halo-C1-7alkyl, C6 1caryl-C1-7a!kyf, -NRSRS, or heterocyclyl, wherein each heteroaryl is a mono- or bicyclic aromatic moiety comprising 5-10 ring atoms selected from carbon atoms and 1 to 5 heteroatoms, and each heterocyclyl is a mono- or bicyclic saturated or partially saturated but non- aromatic moiety comprising 4-10 ring ring atoms selected from carbon atoms and 1 to 5 heteroatoms, and each heteroatoms being O. N or S, and with the proviso that when R5 is halogen or hydrogen than at least one of R2 and R6 is other than H 2 The compound according to claim 1 , whereinX iS CH2. O, S or -NR1, each R' are independently C1-?alkyl or C^βcycloalkyl, each of R2 and R6 are independently hydrogen, halogen, cyano, C, 7alkyl, hydroxy-C1-7alkyl -OR7, C3 scycloalkyl, halo-C1-7alkyl or -CH2-NR9-SO2-R'0,R3 and R4 are independently hydrogen, halogen or cyano,R5 IS hydrogen, C1-7alkyl halogen, cyano, hydroxy, hydroxy-C1-7alkyl, hydroxy-C^ βcycloalkylalkyl, C1-7alkoxy-C3 9alkyl, -OR7 C6-10aryl, heteroaryl, heterocyclyl, C3 βcycloalkyl, halo- C1-7alkyl, -NR6R9, -CH2-NR8-C(O)NR6R9, -CH2-NR8-SO2-R10, -C(O)- R10, -SO5R10, -C(O)-NR8Rδ, -SO2-NR9R9, -NR8C(O)-R10 -CH2CN, or -NR8-SO2-R1c,R7 is C1-?alkyl, C3-8cycloalkyl-Ci /alkyl, heterocyclyl-C1-7alkyl, C6-10arykC1-7alkylt heteroaryl-C1-7alkyl Or -C(O)-R10, in which C6-10aryl, heteroaryl C1-7alkyl heterocyclyl and Cj.βcycloalkyl are optionally susbtituted with C1-7alkoxy, halo, halo-C3 βalkoxy, C1-7alkyl, OH or halo-C1-7alkyl, each of R8 R9 are independently hydrogen, C1-7a!kyl, halo-C1-7alkyl, Cδ 10aryl-Ci ?alkyl or heterocyclyl, or R8 and R9 can form together with the nitrogen atom to which they are attached a 5- or 6-membered ring heterocyclyl wherein said heterocyclyl optionally contain an additional heteroatom selected from N1 O or S and is optionally substituted with Cv7alkyl, andR'0 is hydrogen, C1-7alkyl, halo-C1-7alkyl, C6-10aryl-C1-7alkyl, -NR6R9, or heterocyciyl, wherein each heteroaryl is a mono- or btcyclic aromatic moiety comprising 5-10 ring atoms selected from carbon atoms and 1 to 5 heteroatoms, and each heterocyclyl is a mono- or txcyclic saturated or partially saturated but non- aromatic moiety comprismg 4-10 ring ring atoms selected from carbon atoms and 1 to 5 heteroatoms, and each heteroatoms being O1 N or S, and with the proviso that when R5 is halogen or hydrogen than R2 is other than H or a pharmaceutically acceptable salt thereof3 The compound according to claim 1 or 2, whereinR5 is C1-7alkyl, cyano. hydroxy, hydroxy-C1-7alkyl, hydroxy-C3-8cycloalkylalkyl, C1-7alkoxy- C3-8alkyl, -OR7, Cc.10aryl, heteroaryl, heterocyclyl, C3 9cycloalkyl, halo- C1-7alkyl -NR9R9, -CH2-NR8-C(O)NR8R9 -CH2-NR8-SO2-R10, -C(O)-R10 -SO2R10, -C(O)-NR8R9 -SO2- NR8R9 -NR8C(O)-R'0 -CH2CN1 or -NR8-SO2-R10, or pharmaceutically acceptable salt thereof4 The compound according to anyone of claim 1 or 2 wherein R' is methyl1 R2 is hydrogen, halogen, -OR7 or C1-7alkyl,R3 and R4 are hydrogen,R5 is hydrogen, C1-7alkyl, halogen, halo-C1-7alkyl, hydroxy, hydroxy-djalkyl, C1 ralkoxy, benzyloxy, Cβ.ioaryl, heteroaryl, C3-8cycloalkyl, -CH2NR8SO2R10, -SO2NR8R10 or -NR8R9-R6 Is hydrogen or C1-7alkyl;R'' is C1-7alkyl, or C6-10aryl-C1-ralkyl; and each of R8 R9 and R10 are independently Ci ,-alkyl or H, or a pharmaceutically acceptable salt thereof
5-피리딘-3-일-1,3-디히드로-인돌-2-온 유도체, 및 알도스테론 신타제 및/또는 ＣＹＰ11Ｂ1의 조절제로서의 그의 용도본 발명은 하기 화학식 I의 화합물 또는 그의 제약상 허용되는 염을 제공한다. 본 발명의 화합물은 알도스테론 신타제 및/또는 11-베타 히드록실라제 (CYP1 181)에 의해 매개되는 장애 또는 질환의 치료에 유용할 수 있다. <화학식 I> 상기 식에서, X는 CH2, O, S 또는 -NR1이고; 각각의 R1은 독립적으로 C1-7알킬 또는 C3-8시클로알킬이고; 각각의 R2 및 R6은 독립적으로 수소, 할로겐, 시아노, C1-7알킬, 히드록시-C1-7알킬, -OR7, C3-8시클로알킬, 할로-C1-7알킬 또는 -CH2-NR8-SO2-R10이고; R3 및 R4는 독립적으로 수소, 할로겐 또는 시아노이고; R5는 수소, C1-2알킬, 할로겐, 시아노, 히드록시, 히드록시-C1-7알킬, 히드록시-C3-8시클로알킬알킬, C1-7알콕시-C3-3알킬, -OR7, C6-10아릴, 헤테로아릴, 헤테로시클릴, C3-8시클로알킬, 할로-C1-7알킬, -NR8R9, -CH2-NR8-C(O)NR8R9, -CH2-NR6-SO2-R10, -C(O)-R10, -SO2R10, -C(O)-NR5R9, -SO2-NR8R9, -NR3C(O)-R10, -CH2CN 또는 -NR8-SO2-R10이다.하기 화학식 I의 화합물 또는 그의 제약상 허용되는 염.<화학식 I>상기 식에서,X는 CH2, O, S 또는 -NR1이고;각각의 R1은 독립적으로 C1-7알킬 또는 C3-8시클로알킬이고;각각의 R2 및 R6은 독립적으로 수소, 할로겐, 시아노, C1-7알킬, 히드록시-C1-7알킬, -OR7, C3-8시클로알킬, 할로-C1-7알킬 또는 -CH2-NR8-SO2-R10이고;R3 및 R4는 독립적으로 수소, 할로겐 또는 시아노이고;R5는 수소, C1-7알킬, 할로겐, 시아노, 히드록시, 히드록시-C1-7알킬, 히드록시-C3-8시클로알킬알킬, C1-7알콕시-C3-8알킬, -OR7, C6-10아릴, 헤테로아릴, 헤테로시클릴, C3-8시클로알킬, 할로-C1-7알킬, -NR8R9, -CH2-NR8-C(O)NR8R9, -CH2-NR8-SO2-R10, -C(O)-R10, -SO2R10, -C(O)-NR8R9, -SO2-NR8R9, -NR8C(O)-R10, -CH2CN 또는 -NR8-SO2-R10이고;R7은 C1-7알킬, C3-8시클로알킬-C1-7알킬, 헤테로시클릴-C1-7알킬, C6-10아릴-C1-7알킬, 헤테로아릴-C1-7알킬 또는 -C(O)-R10이고; 여기서, C6-10아릴, 헤테로아릴, C1-7알킬, 헤테로시클릴 및 C3-8시클로알킬은 C1-7알콕시, 할로, 할로-C3-8알콕시, C1-7알킬, OH 또는 할로-C1-7알킬로 임의로 치환되고;각각의 R8, R9는 독립적으로 수소, C1-7알킬, 할로-C1-7알킬, C6-10아릴-C1-7알킬 또는 헤테로시클릴이거나; 또는 R8 및 R9는 이들이 부착되어 있는 질소 원자와 함께 5- 또는 6-원 고리 헤테로시클릴을 형성할 수 있고, 여기서 상기 헤테로시클릴은 N, O 또는 S로부터 선택된 추가의 헤테로원자를 임의로 함유하고, C1-7알킬로 임의로 치환되고;R10은 수소, C1-7알킬, 할로-C1-7알킬, C6-10아릴-C1-7알킬, -NR8R9 또는 헤테로시클릴이고;여기서, 각각의 헤테로아릴은 탄소 원자 및 1 내지 5개의 헤테로원자로부터 선택된 5 내지 10개의 고리 원자를 포함하는 모노- 또는 비시클릭 방향족 잔기이고;각각의 헤테로시클릴은 탄소 원자 및 1 내지 5개의 헤테로원자로부터 선택된 4 내지 10개의 고리 원자를 포함하는 모노- 또는 비시클릭 포화 또는 부분 포화이지만 비-방향족인 잔기이고; 각각의 헤테로원자는 O, N 또는 S이고; 단, R5가 할로겐 또는 수소인 경우에, R2 및 R6 중 적어도 하나는 H 이외의 것이다.