SUBSTITUTED INDOLE COMPOUNDSDisclosed are compounds of Formula (I) or salts thereof, wherein Ring Het, R1, R2, R3, R4, R5, m, n, and p 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 compound of formula (i)or a salt thereof, wherein:ring het is:(i) a 9-membered heterocycle selected from:or(ii) a 10-membered heterocycle selected from:r1is h, cl, -cn, c1-4alkyl radical, c1-3fluoroalkyl radical, c1-3hydroxyalkyl radical, c1-3hydroxy-fluoroalkyl, -crz＝ch2、c3-6cycloalkyl, -ch2(c3-6cycloalkyl), -c (o) o (c)1-3alkyl) or tetrahydropyranyl;r2each independently is halogen, -cn, -oh, -no2、c1-4alkyl radical, c1-2fluoroalkyl radical, c1-2cyanoalkyl, c1-3hydroxyalkyl radical, c1-3aminoalkyl, -o (ch)2)1-2oh、-(ch2)0-4o(c1-4alkyl group), c1-3fluoroalkoxy, - (ch)2)1-4o(c1-3alkyl), -o (ch)2)1-2oc(o)(c1-3alkyl), -o (ch)2)1-2nrxrx、-c(o)o(c1-3alkyl), -c (o) nryry、-c(o)nrx(c1-5hydroxyalkyl), -c (o) nrx(c2-6alkoxyalkyl), -c (o) nrx(c3-6cycloalkyl), -nr-yry、-nry(c1-3fluoroalkyl group), -nry(c1-4hydroxyalkyl), -nrxch2(phenyl), -nrxs(o)2(c3-6cycloalkyl), -nr-xc(o)(c1-3alkyl), -nr-x(ch2-cyclopropyl), -s (o)2(c1-3alkyl group), c3-6cycloalkyl, phenyl, morpholinyl, dioxothiomorpholinyl, dimethylpyrazolyl, methylpiperidinyl, methylpiperazinyl, amino-oxadiazolyl, imidazolyl, triazolyl or-c (o) (thiazolyl);r3comprises the following steps:(a)-l1-a; or(b)h、c1-6alkyl radical, c1-3fluoroalkyl radical, c1-3cyanoalkyl, c1-6hydroxyalkyl radical, c1-3hydroxy-fluoroalkyl, -crxrxcrx(oh)crx＝crxrx、-c＝n(nrxrx)、-(crxrx)1-4o(c1-3alkyl), - (cr)xrx)1-4o(crxrx)1-3o(c1-3alkyl), -ch2ch(oh)ch2o(c1-3alkyl), - (cr)xrx)1-3s(c1-3alkyl), - (ch)2)1-3c(o)oc(ch3)3、-(crxrx)0-3nrxry、-(crxrx)0-3nrx(c1-4hydroxyalkyl), -ch2ch(oh)ch2nrxry、-c(o)h、-c(o)(c1-6alkyl), -c (o) (c)1-4hydroxyalkyl), -c (o) (c)1-3fluoroalkyl), -c (o) (c)1-3chloroalkyl), -c (o) (c)1-3cyanoalkyl), - (cr)xrx)0-3c(o)oh、-c(o)(ch2)0-2o(c1-4alkyl), -c (o) (cr)xrx)0-2o(crxrx)1-2o(c1-3alkyl), -c (o) (cr)xrx)0-2o(crxrx)1-2nryry、-c(o)crxrxs(o)2(c1-3alkyl), -c (o) crxrxnrxs(o)2(c1-3alkyl), -c (o) crxrxoc(o)(c1-3alkyl), -c (o) (cr)xrx)0-3nryry、-c(o)(crxrx)0-1nrx(c1-3cyanoalkyl), -c (o) (cr)xrx)0-2nry(c1-6hydroxyalkyl), -c (o) (cr)xrx)0-2nrx(c1-3fluoroalkyl), -c (o) (cr)xrx)0-1nrx(c1-5hydroxy-fluoroalkyl), -c (o) (cr)xrx)0-1nrx(ch2)1-2o(c1-3hydroxyalkyl), -c (o) (cr)xrx)0-2nrx(ch2)1-2nrxc(o)(c1-2alkyl), -c (o) (cr)xrx)0-2nrx((crxrx)1-2o(c1-2alkyl)), -c (o) (crxrx)0-2n((crxrx)1-2o(c1-2alkyl))2、-c(o)(crxrx)0-2nrx(crxrx)1-3nrxrx、-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) (cr)xrx)0-3n((ch2)0-1c(o)(c1-3alkyl))2、-c(o)(crxrx)0-1nrx(ch2)0-1c(o)(c1-3cyanoalkyl), -c (o) (cr)xrx)0-2nrx(ch2)1-2c(o)nryry、-c(o)(crxrx)1-3c(o)nryry、-c(o)(crxrx)1-3s(o)2nryry、-c(o)(crxrx)0-2nrx(chry(ch2oh))、-(crxrx)1-2c(o)nryry、-ch(cn)c(o)nryry、-(crxrx)1-2c(o)nry(c1-3fluoroalkyl group), - (cr)xrx)1-2c(o)nry(c1-4hydroxyalkyl), - (cr)xrx)1-2c(o)nry(c1-3cyanoalkyl), - (cr)xrx)1-2c(o)nrx(ch2)1-2o(c1-3alkyl), - (cr)xrx)1-2c(o)nrxch(c1-4alkyl) (c1-3hydroxyalkyl), - (cr)xrx)1-2c(o)nrxch(c1-3hydroxyalkyl) (c3-6cycloalkyl), - (ch)2)1-2c(o)nrx(ch2)1-2c(o)nrxrx、-(ch2)1-2c(o)nrx(ch2)1-2s(c1-3alkyl), - (ch)2)1-2c(o)nrx(ch2)1-2s(o)2oh、-(ch2)1-2c(o)nrx(ch2)1-2nrxc(o)(c1-3alkyl), - (ch)2)1-2c(o)nrx(ch2)1-3nrxrx、-(ch2)1-2c(o)n(ch2ch3)(ch2)1-3nrxrx、-(crxrx)0-3s(o)2(c1-4alkyl), - (ch)2)0-2s(o)2(c1-3fluoroalkyl group), - (cr)xrx)0-2s(o)2nryry、-(crxrx)0-2nrxs(o)2(c1-3alkyl, -c (o) oh, -c (o) nryryor-c (o) nry(crxrx)1-2nryry；l1is a bond, - (cr)xrx)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(c1-2hydroxyalkyl) (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(c1-2hydroxyalkyl) (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-or-s (o)2-；a is 3-oxa-8-azabicyclo [3.2.1]octyl, 8-oxa-3-azabicyclo [3.2.1]octyl, 1-thiomorpholinyl, 1, 2-dioxotetrahydro-2h-thiopyranyl, 1, 4-diazepanyl, 2-azabicyclo [3.1.0 ]]hexyl, azabicyclo [3.2.1]octyl, 2-oxa-6-azaspiro [3.3]heptyl, azepinyl, c3-7cycloalkyl, imidazo[1,2-a]pyridyl, imidazo [1,5-a ]]pyridyl, imidazolyl, isoxazolyl, morpholinyl, oxadiazolyl, oxazolyl, oxetanyl, phenyl, piperazinonyl, piperazinyl, piperidinonyl, piperidinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolidinonyl, pyrrolidinyl, pyrrolyl, quinolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrazolyl, thiadiazolyl, thiazolyl, or triazolyl, each of which is substituted with 0 to 4 substituents independently selected from f, cl, -oh, -cn, c1-6alkyl radical, c1-3fluoroalkyl radical, c1-5hydroxyalkyl, -ch2nrxrx、c1-3alkoxy, -o (ch)2)1-3nrxrx、-o(ch2)1-3nrx(pyridyl), -c (o) (c)1-3alkyl), -c (o) o (c)1-3alkyl), -c (o) nryry、-nrxrx、-nrxc(o)(c1-3alkyl), -o (pyrimidinyl), c3-6cycloalkyl, morpholinyl, phenyl, methylpiperazinyl, pyridyl and pyrrolidinyl;rxeach independently is h or-ch3；ryeach independently is h or c1-6an alkyl group;r4each independently of the other is f, -oh, c1-2alkyl or-o...
치환된 인돌 화합물하기 화학식 I의 화합물 또는 그의 염이 개시된다:[이미지] 상기 식에서, 고리 Het, R1, R2, R3, R4, R5, m, n, 및 p는 본원에 정의된다. 또한 톨-유사 수용체 7, 또는 8, 또는 9를 통한 신호전달의 억제제로서 이러한 화합물을 사용하는 방법 및 이러한 화합물을 포함하는 제약 조성물이 개시된다. 이들 화합물은 염증성 및 자가면역 질환을 치료하는데 유용하다.하기 화학식 I의 화합물 또는 그의 염:[이미지]상기 식에서,고리 Het는:(i) 하기로부터 선택된 9-원 헤테로시클릭 고리:[이미지][이미지][이미지];또는(ii) 하기로부터 선택된 10-원 헤테로시클릭 고리:[이미지]이고;R1은 H, Cl, -CN, C1-4 알킬, C1-3 플루오로알킬, C1-3 히드록시알킬, C1-3 히드록시-플루오로알킬, -CRz=CH2, C3-6 시클로알킬, -CH2(C3-6 시클로알킬), -C(O)O(C1-3 알킬), 또는 테트라히드로피라닐이고;각각의 R2는 독립적으로 할로, -CN, -OH, -NO2, C1-4 알킬, C1-2 플루오로알킬, C1-2 시아노알킬, C1-3 히드록시알킬, C1-3 아미노알킬, -O(CH2)1-2OH, -(CH2)0-4O(C1-4 알킬), C1-3 플루오로알콕시, -(CH2)1-4O(C1-3 알킬), -O(CH2)1-2OC(O)(C1-3 알킬), -O(CH2)1-2NRxRx, -C(O)O(C1-3 알킬), -C(O)NRyRy, -C(O)NRx(C1-5 히드록시알킬), -C(O)NRx(C2-6 알콕시알킬), -C(O)NRx(C3-6 시클로알킬), -NRyRy, -NRy(C1-3 플루오로알킬), -NRy(C1-4 히드록시알킬), -NRxCH2(페닐), -NRxS(O)2(C3-6 시클로알킬), -NRxC(O)(C1-3 알킬), -NRx(CH2-시클로프로필), -S(O)2(C1-3 알킬), C3-6 시클로알킬, 페닐, 모르폴리닐, 디옥소티오모르폴리닐, 디메틸 피라졸릴, 메틸피페리디닐, 메틸피페라지닐, 아미노-옥사디아졸릴, 이미다졸릴, 트리아졸릴, 또는 -C(O)(티아졸릴)이고;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, -C=N(NRxRx), -(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, -C(O)H, -C(O)(C1-6 알킬), -C(O)(C1-4 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)(CRxRx)0-2O(CRxRx)1-2NRyRy, -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)0-2NRx(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)0-2NRx(CH2)1-2NRxC(O)(C1-2 알킬), -C(O)(CRxRx)0-2NRx((CRxRx)1-2O(C1-2 알킬)), -C(O)(CRxRx)0-2N((CRxRx)1-2O(C1-2 알킬))2, -C(O)(CRxRx)0-2NRx(CRxRx)1-3NRxRx, -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)0-3N((CH2)0-1C(O)(C1-3 알킬))2, -C(O)(CRxRx)0-1NRx(CH2)0-1C(O)(C1-3 시아노알킬), -C(O)(CRxRx)0-2NRx(CH2)1-2C(O)NRyRy, -C(O)(CRxRx)1-3C(O)NRyRy, -C(O)(CRxRx)1-3S(O)2NRyRy, -C(O)(CRxRx)0-2NRx(CHRy(CH2OH)), -(CRxRx)1-2C(O)NRyRy, -CH(CN)C(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), -(CRxRx)1-2C(O)NRxCH(C1-3 히드록시알킬)(C3-6 시클로알킬), -(CH2)1-2C(O)NRx(CH2)1-2C(O)NRxRx, -(CH2)1-2C(O)NRx(CH2)1-2S(C1-3 알킬), -(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, -(CRxRx)0-3S(O)2(C1-4 알킬), -(CH2)0-2S(O)2(C1-3 플루오로알킬), -(CRxRx)0-2S(O)2NRyRy, -(CRxRx)0-2NRxS(O)2(C1-3 알킬), -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 3-옥사-8-아자비시클로[3.2.1]옥타닐, 8-옥사-3-아자비시클로[3.2.1]옥타닐, 1,1-디옥시도티오모르폴리닐, 1,2-디옥소테트라히드로-2H-티오피라닐, 1,4-디아제파닐, 2-아자비시클로[3.1.0]헥사닐, 아자비시클로[3.2.1]옥타닐,2-옥사-6-아자스피로[3.3]헵타닐, 아제파닐, C3-7 시클로알킬, 이미다조[1,2-a]피리디닐, 이미다조[1,5-a]피리디닐, 이미다졸릴, 이속사졸릴, 모르폴리닐, 옥사디아졸릴, 옥사졸릴, 옥세타닐, 페닐, 피페라지노닐, 피페라지닐, 피페리디노닐, 피페리디닐, 피라지닐, 피라졸릴, 피리다지닐, 피리디닐, 피리미디닐, 피롤리디노닐, 피롤리디닐, 피롤릴, 퀴놀리닐, 테트라히드로푸라닐, 테트라히드로피라닐, 테트라히드로티오피라닐, 테트라졸릴, 티아디아졸릴, 티아졸릴, 또는 트리아졸릴이고, 각각은 F, Cl, -OH, -CN, C1-6 알킬, C1-3 플루오로알킬, C1-5 히드록시알킬, -CH2NRxRx, C1-3 알콕시, -O(CH2)1-3NRxRx, -O(CH2)1-3NRx(피리디닐), -C(O)(C1-3 알킬), -C(O)O(C1-3 알킬), -C(O)NRyRy, -NRxRx, -NRxC(O)(C1-3 알킬), -O(피리미디닐), C3-6 시클로알킬, 모르폴리닐, 페닐, 메틸 피페라지닐, 피리디닐, 및 피롤리디닐로부터 독립적으로 선택된 0 내지 4개의 치환기로 치환되고;각각의 Rx는 독립적으로 H 또는 -CH3이고;각각의 Ry는 독립적으로 H 또는 C1-6 알킬이고;각각의 R4는 독립적으로 F, -OH, C1-2 알킬, 또는 -OCH3이거나; 또는 동일한 탄소 원자에 부착된 2개의 R4는 =O를 형성하거나; 또는 m이 적어도 2인 경우 피페리디닐 고리 내의 질소 원자에 인접한 상이한 탄소 원자에 각각 부착된 2개의 R4는 -CH2CH2- 가교를 형성할 수 있고;각각의 R5는 독립적으로 F, Cl, -CN, C1-2 알킬, C1-2 플루오로알킬, 또는 -OCH3이고;m은 0, 1, 2, 3, 또는 4이고;n은 0, 1, 또는 2이고;p는 0, 1, 2, 3, 또는 4이다.