DIMETHOXYPHENYL SUBSTITUTED INDOLE COMPOUNDS AS TLR7, TLR8 OR TLR9 INHIBITORSDisclosed are compounds of Formula (I) or a salt thereof, wherein R1, R3, R4, R5, m, and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.A kind of compound of formula (i)or its salt, in which:r1it is h, cl ,-cn, c1-4alkyl, c1-3fluoroalkyl, c1-3hydroxyl-fluoroalkyl ,-crz=ch2、c3-6naphthenic base ,-ch2(c3-6 naphthenic base) ,-c (o) o (c1-3alkyl) or thp trtrahydropyranyl；r3it is:(a)-l1-a；or(b)h、c1-6alkyl, c1-3fluoroalkyl, c1-3cyanoalkyl, c1-6hydroxy alkyl, c1-3hydroxyl-fluoroalkyl ,-crxrxcrx (oh)crx=crxrx、-(crxrx)1-4o(c1-3alkyl) ,-(crxrx)1-4o(crxrx)1-3o(c1-3alkyl) ,-ch2ch(oh)ch2o (c1-3alkyl) ,-(crxrx)1-3s(c1-3alkyl) ,-(ch2)1-3c(o)oc(ch3)3、-(crxrx)0-3nrxry、-(crxrx)0-3nrx (c1-4hydroxy alkyl) ,-ch2ch(oh)ch2nrxry、-(crxrx)1-2nhc(o)(crxrx)1-4c≡ch、-c(o)h、-c(o)(c1-6 alkyl) ,-c (o) (c1-3hydroxy alkyl) ,-c (o) (c1-3fluoroalkyl) ,-c (o) (c1-3chlorine alkyl) ,-c (o) (c1-3cyano alkane base) ,-(crxrx)0-3c(o)oh、-c(o)(ch2)0-2o(c1-4alkyl) ,-c (o) (crxrx)0-2o(crxrx)1-2o(c1-3alkane base) ,-c (o) crxrxs(o)2(c1-3alkyl) ,-c (o) crxrxnrxs(o)2(c1-3alkyl) ,-c (o) crxrxoc(o)(c1-3alkane base) ,-c (o) (crxrx)0-3nryry、-c(o)(crxrx)0-1nrx(c1-3cyanoalkyl) ,-c (o) (crxrx)0-2nry(c1-6hydroxyl alkyl) ,-c (o) (crxrx)0-1nrx(c1-3fluoroalkyl) ,-c (o) (crxrx)0-1nrx(c1-5hydroxyl-fluoroalkyl) ,-c (o) (crxrx)0-1nrx(ch2)1-2o(c1-3hydroxy alkyl) ,-c (o) (crxrx)0-1nrx(ch2)1-2nrxc(o)(c1-2alkyl) ,-c (o) (crxrx)0-1nrx((crxrx)1-2o(c1-2alkyl)) ,-c (o) crx(nh2)(crxrx)1-4nrxrx、-c(o)crx(nh2) (crxrx)1-4nrxc(o)nrxrx、-c(o)(crxrx)0-3nrx(ch2)0-1c(o)(c1-3alkyl) ,-c (o) (crxrx)0-1nrx (ch2)0-1c(o)(c1-3cyanoalkyl) ,-c (o) (crxrx)0-1nrx(ch2)1-2c(o)nryry、-c(o)(crxrx)1-3c(o) nryry、-c(o)(crxrx)0-1nrx(chry(ch2oh))、-(crxrx)1-2c(o)nryry、-(crxrx)1-2c(o)nry(c1-3fluothane base) ,-(crxrx)1-2c(o)nry(c1-4hydroxy alkyl) ,-(crxrx)1-2c(o)nry(c1-3cyanoalkyl) ,-(crxrx)1-2c(o) nrx(ch2)1-2o(c1-3alkyl) ,-(crxrx)1-2c(o)nrxch(c1-4alkyl) (c1-3hydroxy alkyl) ,-(ch2)1-2c(o)nrx (ch2)1-2c(o)nrxrx、-(ch2)1-2c(o)nrx(ch2)1-2s(o)2oh、-(ch2)1-2c(o)nrx(ch2)1-2nrxc(o)(c1-3 alkyl) ,-(ch2)1-2c(o)nrx(ch2)1-3nrxrx、-(ch2)1-2c(o)n(ch2ch3)(ch2)1-3nrxrx、-(ch2)0-2s(o)2 (c1-4alkyl) ,-(ch2)0-2s(o)2(c1-3fluoroalkyl) ,-(ch2)0-2s(o)2nrxrx、-c(o)c(o)oh、-c(o)c(o) nryryor-c (o) c (o) nry(crxrx)1-2nryry；l1it is key ,-(crxrx)1-2-、-(crxrx)1-2crx(oh)-、- (crxrx)1-2o-、-crxrxc(o)-、-(crxrx)2nrx(crxrx)0-1-、-crxrxc(o)nrx(crxrx)0-4-、-c(o) (crxrx)0-3-、-c(o)(crxrx)0-2nrx(crxrx)0-2-、-c(o)(crxrx)0-2n(c1-2hydroxy alkyl) (crxrx)0-2-、-c (o)(crxrx)0-2nrx(crxrx)1-2crx(oh)-、-c(o)(crxrx)1-2c(o)nrx-、-(crxrx)0-2c(o)nrx(crxrx)1-2crx(oh)-、-(crxrx)0-2c(o)n(c1-2hydroxy alkyl) (crxrx)1-2-、-c(o)(crxrx)0-1o-、-c(o)(crxrx)1-2nhs(o)2-、-c(o)crx(nh2)crxrx-、-c(o)c(o)(crxrx)0-2-、-c(o)nrx(crxrx)1-2or-s (o)2-；a is 2- oxa- -6- azaspiro [3,3] heptyl, 4- oxaspiro [2.5] octyl, 7- azaspiro [3.5] nonyl, 8- azepine pair ring [3.2.1] octyl, 8- oxa- -3- azabicyclo [3.2.1] octyl, 9- azabicyclo [3.3.1] nonyl, adamantyl, nitrogen trioxepane base, azetidinyl, c3-6naphthenic base, diazesuberane base, dihydro isononyl, dihydro-pyrimidin ketone group, dioxy change isothiazole alkyl, titanium dioxide thia piperidine base, dioxotetrahydro thienyl, dioxotetrahydro thiapyran base, dioxo thio-morpholinyl, furyl, imidazole radicals, imidazolidinonyl, indyl, isoquinolyl, isoxazolyl, morpholinyl, morpholine ketone group, naphthalene, octahydro ring penta [b] pyranose, oxazolidine ketone group, oxadiazoles base, oxetanyl, oxazolyl, phenyl, piperidyl, piperazine pyridine ketone group, piperazinyl, piperazine ketone group, pyrazinyl, pyrazolyl, pyridazine ketone group, pyriconyl, pyridyl group, pyrimidine radicals, pyrrolidones base, pyrrolidinyl, pyrrole radicals, quinolyl, quinolizine ketone group, tetrahydrofuran base, thp trtrahydropyranyl, tetrazole radical, thiadiazolyl group, thiazole base or triazolyl, each quilt-l2-rawith 0 to 4 rbreplace；l2it is key or-crxrx-；rait is:(a)h、f、cl、–cn、-oh、c1-6alkyl, c1-3fluoroalkyl, c1-5hydroxy alkyl ,-(ch2)0-4o(c1-3alkyl) ,- (crxrx)1-3s(c1-3alkyl) ,-(crxrx)1-3nhc(o)o(c1-4alkyl) ,-(crxrx)1-3nryry、-(crxrx)1-3c(o) nryry、-o(c1-3fluoroalkyl) ,-s (o)2nrxrx、-o(crxrx)1-3nrxrx、-nhs(o)2(c1-3alkyl) ,-nrxrx、-nrx (c1-4alkyl) ,-nrxc(o)(c1-4alkyl) ,-(crxrx)0-3c(o)oh、-c(o)(c1-5alkyl) ,-c (o) (c1-3fluoroalkyl) ,- c(o)ch2n(c1-3alkyl)2、-c(o)o(c1-4alkyl) ,-c (o) nh (c1-3cyanoalkyl) ,-c (o) nryry、-c(o)nrxch2c (o)nrxrxor-c (o) nrxch2ch2nhc(o)(c1-3alkyl)；(b)c3-6naphthenic base or-c (o) nh (c3-6naphthenic base), wherein each naphthenic base is by 0 to 2 independently selected from-oh, c1-3 alkyl, c1-3hydroxy alkyl, c1-3fluoroalkyl and-c (o) o (c1-3alkyl) substituent group replace；or(c)a1、-ch2a1、–c(o)a1、-nrxa1or-c (o) nrxa1, wherein a1it is furyl, imidazole radicals, indyl, isoxazole base, morpholinyl, octahydro pyrrolo- [3,4-c] pyrrole radicals, oxazolyl, oxetanyl, phenyl, piperazinyl, piperidyl, pyrazoles base, pyridyl group, pyrimidine radicals, pyrrolidinyl, pyrrole radicals, tetrahydrofuran base, thp trtrahydropyranyl, thiadiazolyl group, thiazolyl, thiophene base or triazolyl, it is each by 0 to 3 independently selected from-oh, c1-3alkyl, c1-3hydroxy alkyl ,-c (o) (c1-2alkyl) ,-c (o)o(c1-3alkyl) ,-nrxrx...
TLR7, TLR8 또는 TLR9 억제제로서의 디메톡시페닐 치환된 인돌 화합물화학식 (I)의 화합물 또는 그의 염이 개시된다:[이미지] 여기서 R1, R3, R4, R5, m, 및 n은 본원에 정의된다. 톨-유사 수용체 7, 또는 8, 또는 9을 통한 신호전달의 억제제로서의 이러한 화합물을 사용하는 방법 및 이러한 화합물을 포함하는 제약 조성물이 또한 기재된다. 이들 화합물은 염증성 및 자가면역 질환을 치료하는데 유용하다.화학식 (I)의 화합물 또는 그의 염:[이미지]여기서R1은 H, Cl, -CN, C1-4 알킬, C1-3 플루오로알킬, C1-3 히드록시-플루오로알킬, -CRz=CH2, C3-6 시클로알킬, -CH2(C3-6 시클로알킬), -C(O)O(C1-3 알킬), 또는 테트라히드로피라닐이고;R3은(a) -L1-A; 또는(b) H, C1-6 알킬, C1-3 플루오로알킬, C1-3 시아노알킬, C1-6 히드록시알킬, C1-3 히드록시-플루오로알킬, -CRxRxCRx(OH)CRx=CRxRx, -(CRxRx)1-4O(C1-3 알킬), -(CRxRx)1-4O(CRxRx)1-3O(C1-3 알킬), -CH2CH(OH)CH2O(C1-3 알킬), -(CRxRx)1-3S(C1-3 알킬), -(CH2)1-3C(O)OC(CH3)3, -(CRxRx)0-3NRxRy, -(CRxRx)0-3NRx(C1-4 히드록시알킬), -CH2CH(OH)CH2NRxRy, -(CRxRx)1-2NHC(O)(CRxRx)1-4C≡CH, -C(O)H, -C(O)(C1-6 알킬), -C(O)(C1-3 히드록시알킬), -C(O)(C1-3 플루오로알킬), -C(O)(C1-3 클로로알킬), -C(O)(C1-3 시아노알킬), -(CRxRx)0-3C(O)OH, -C(O)(CH2)0-2O(C1-4 알킬), -C(O)(CRxRx)0-2O(CRxRx)1-2O(C1-3 알킬), -C(O)CRxRxS(O)2(C1-3 알킬), -C(O)CRxRxNRxS(O)2(C1-3 알킬), -C(O)CRxRxOC(O)(C1-3 알킬), -C(O)(CRxRx)0-3NRyRy, -C(O)(CRxRx)0-1NRx(C1-3 시아노알킬), -C(O)(CRxRx)0-2NRy(C1-6 히드록시알킬), -C(O)(CRxRx)0-1NRx(C1-3 플루오로알킬), -C(O)(CRxRx)0-1NRx(C1-5 히드록시-플루오로알킬), -C(O)(CRxRx)0-1NRx(CH2)1-2O(C1-3 히드록시알킬), -C(O)(CRxRx)0-1NRx(CH2)1-2NRxC(O)(C1-2 알킬), -C(O)(CRxRx)0-1NRx((CRxRx)1-2O(C1-2 알킬)), -C(O)CRx(NH2)(CRxRx)1-4NRxRx, -C(O)CRx(NH2)(CRxRx)1-4NRxC(O)NRxRx, -C(O)(CRxRx)0-3NRx(CH2)0-1C(O)(C1-3 알킬), -C(O)(CRxRx)0-1NRx(CH2)0-1C(O)(C1-3 시아노알킬), -C(O)(CRxRx)0-1NRx(CH2)1-2C(O)NRyRy, -C(O)(CRxRx)1-3C(O)NRyRy, -C(O)(CRxRx)0-1NRx(CHRy(CH2OH)), -(CRxRx)1-2C(O)NRyRy, -(CRxRx)1-2C(O)NRy(C1-3 플루오로알킬), -(CRxRx)1-2C(O)NRy(C1-4 히드록시알킬), -(CRxRx)1-2C(O)NRy(C1-3 시아노알킬), -(CRxRx)1-2C(O)NRx(CH2)1-2O(C1-3 알킬), -(CRxRx)1-2C(O)NRxCH(C1-4 알킬)(C1-3 히드록시알킬), -(CH2)1-2C(O)NRx(CH2)1-2C(O)NRxRx, -(CH2)1-2C(O)NRx(CH2)1-2S(O)2OH, -(CH2)1-2C(O)NRx(CH2)1-2NRxC(O)(C1-3 알킬), -(CH2)1-2C(O)NRx(CH2)1-3NRxRx, -(CH2)1-2C(O)N(CH2CH3)(CH2)1-3NRxRx, -(CH2)0-2S(O)2(C1-4 알킬), -(CH2)0-2S(O)2(C1-3 플루오로알킬), -(CH2)0-2S(O)2NRxRx, -C(O)C(O)OH, -C(O)C(O)NRyRy, 또는 -C(O)C(O)NRy(CRxRx)1-2NRyRy이고;L1은 결합, -(CRxRx)1-2-, -(CRxRx)1-2CRx(OH)-, -(CRxRx)1-2O-, -CRxRxC(O)-, -(CRxRx)2NRx(CRxRx)0-1-, -CRxRxC(O)NRx(CRxRx)0-4-, -C(O)(CRxRx)0-3-, -C(O)(CRxRx)0-2NRx(CRxRx)0-2-, -C(O)(CRxRx)0-2N(C1-2 히드록시알킬)(CRxRx)0-2-, -C(O)(CRxRx)0-2NRx(CRxRx)1-2CRx(OH)-, -C(O)(CRxRx)1-2C(O)NRx-, -(CRxRx)0-2C(O)NRx(CRxRx)1-2CRx(OH)-, -(CRxRx)0-2C(O)N(C1-2 히드록시알킬)(CRxRx)1-2-, -C(O)(CRxRx)0-1O-, -C(O)(CRxRx)1-2NHS(O)2-, -C(O)CRx(NH2)CRxRx-, -C(O)C(O)(CRxRx)0-2-, -C(O)NRx(CRxRx)1-2-, 또는 -S(O)2-이고;A는 2-옥사-6-아자스피로[3,3]헵타닐, 4-옥사스피로[2.5]옥타닐, 7-아자스피로[3.5]노나닐, 8-아자비시클로[3.2.1]옥타닐, 8-옥사-3-아자비시클로[3.2.1]옥타닐, 9-아자비시클로[3.3.1]노나닐, 아다만타닐, 아제파닐, 아제티디닐, C3-6 시클로알킬, 디아제파닐, 디히드로이노닐, 디히드로피리미디노닐, 디옥시도이소티아졸리디닐, 디옥시도티아지나닐, 디옥소테트라히드로티오페닐, 디옥소테트라히드로티오피라닐, 디옥소티오모르폴리닐, 푸라닐, 이미다졸릴, 이미다졸리디노닐, 인돌릴, 이소퀴놀리닐, 이속사졸릴, 모르폴리닐, 모르폴리노닐, 나프탈레닐, 옥타히드로시클로펜타[b]피라닐, 옥사졸리디노닐, 옥사디아졸릴, 옥세타닐, 옥사졸릴, 페닐, 피페리디닐, 피페리디노닐, 피페라지닐, 피페라지노닐, 피라지닐, 피라졸릴, 피리다지노닐, 피리디노닐, 피리디닐, 피리미디닐, 피롤리디노닐, 피롤리디닐, 피롤릴, 퀴놀리닐, 퀴놀리지노닐, 테트라히드로푸라닐, 테트라히드로피라닐, 테트라졸릴, 티아디아졸릴, 티아졸릴, 또는 트리아졸릴이고, 각각은 -L2-Ra 및 0 내지 4개의 Rb로 치환되고;L2은 결합 또는 -CRxRx-이고;Ra는(a) H, F, Cl, -CN, -OH, C1-6 알킬, C1-3 플루오로알킬, C1-5 히드록시알킬, -(CH2)0-4O(C1-3 알킬), -(CRxRx)1-3S(C1-3 알킬), -(CRxRx)1-3NHC(O)O(C1-4 알킬), -(CRxRx)1-3NRyRy, -(CRxRx)1-3C(O)NRyRy, -O(C1-3 플루오로알킬), -S(O)2NRxRx, -O(CRxRx)1-3NRxRx, -NHS(O)2(C1-3 알킬), -NRxRx, -NRx(C1-4 알킬), -NRxC(O)(C1-4 알킬), -(CRxRx)0-3C(O)OH, -C(O)(C1-5 알킬), -C(O)(C1-3 플루오로알킬), -C(O)CH2N(C1-3 알킬)2, -C(O)O(C1-4 알킬), -C(O)NH(C1-3 시아노알킬), -C(O)NRyRy, -C(O)NRxCH2C(O)NRxRx, 또는 -C(O)NRxCH2CH2NHC(O)(C1-3 알킬)이거나;(b) C3-6 시클로알킬 또는 -C(O)NH(C3-6 시클로알킬)이며, 여기서 각각의 시클로알킬은 -OH, C1-3 알킬, C1-3 히드록시알킬, C1-3 플루오로알킬, 및 -C(O)O(C1-3 알킬)로부터 독립적으로 선택된 0 내지 2개의 치환기로 치환되거나; 또는(c) A1, -CH2A1, -C(O)A1, -NRxA1, 또는 -C(O)NRxA1이며, 여기서 A1은 푸라닐, 이미다졸릴, 인돌릴, 이속사졸릴, 모르폴리닐, 옥타히드로피롤로[3,4-c]피롤릴, 옥사졸릴, 옥세타닐, 페닐, 피페라지닐, 피페리디닐, 피라졸릴, 피리디닐, 피리미디닐, 피롤리디닐, 피롤릴, 테트라히드로푸라닐, 테트라히드로피라닐, 티아디아졸릴, 티아졸릴, 티오페닐, 또는 트리아졸릴이고, 각각은 -OH, C1-3 알킬, C1-3 히드록시알킬, -C(O)(C1-2 알킬), -C(O)O(C1-3 알킬), -NRxRx, 페닐, 트리플루오로메틸-페닐, -CH2(브로모페닐), 및 -CH2CH2(피롤리디닐)로부터 독립적으로 선택된 0 내지 3개의 치환기로 치환되고;각각의 Rb는 독립적으로 F, -CH3, -CF3, 또는 -OCH3이고;각각의 Rx는 독립적으로 H 또는 -CH3이고;각각의 Ry는 독립적으로 H 또는 C1-6 알킬이고;Rz는 H, C1-2 알킬, 또는 C1-2 플루오로알킬이고;각각의 R4는 독립적으로 F 또는 -OH이거나; 또는 동일한 탄소 원자에 부착되어 있는 2개의 R4는 =O를 형성하고;R5는 F, Cl, -CN, C1-2 알킬, C1-2 플루오로알킬, 또는 -OCH3이고;m은 0, 1, 2, 3, 또는 4이고;n은 0, 1, 또는 2이고;단 R1이 -CH3인 경우에, R3은 -CH2CH2NH(CH3)이 아니다.