[1,2,4]TRIAZOLO[4,3-a]PYRIDINYL SUBSTITUTED INDOLE COMPOUNDSDisclosed are compounds of Formula (I) or a salt thereof, wherein R1, R2, R3, R4a, R4b, R4c, R4d, R5, 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 Foor a salt thereof, wherein:Ri is H, CI, -CN, CM alkyl, C1-3 fluoroalkyl, C1-3 hydroxy-fluoroalkyl, -CRZ=CH2, C3-6 cycloalkyl, -CH2(C3-6 cycloalkyl), -C(0)0(Ci-3 alkyl), or tetrahydropyranyl;each R2 is independently halo, -CN, -OH, -N02+, Ci-3 alkyl, C1-2 fluoroalkyl, C1-3hydroxyalkyl, C1-3 aminoalkyl, -(CH2)o-40(Ci-3 alkyl), C1-3 fluoroalkoxy, C2-4 alkoxyalkoxy, -0(CH2)i-2NRxRx, -C(0)0(Ci-3 alkyl), -C(0)NRyRy, -NRyRy, -NRxC(0)(Ci-3 alkyl), -NRx(CH2-cyclopropyl), C3-6 cycloalkyl, methylpiperidinyl, methylpiperazinyl, amino-oxadiazolyl, imidazolyl, triazolyl, or -C(0)(thiazolyl);R3 is:(a) -Li-A; or(b) H, Ci-6 alkyl, C1-3 fluoroalkyl, C1-3 cyanoalkyl, Ci-6 hydroxyalkyl, C1-3 hydroxy- fluoroalkyl, -CRxRxCRx(OH)CRx=CRxRx, -(CRxRx)i-40(Ci-3 alkyl),-(CRxRx)i-40(CRxRx)i-30(Ci-3 alkyl), -CH2CH(OH)CH20(Ci-3 alkyl),-(CRxRx)i-3S(Ci-3 alkyl), -(CH2)i-3C(0)OC(CH3)3, -(CRxRx)o-3NRxRy,-(CRxRx)o-3NRx(Ci-4 hydroxyalkyl), -CH2CH(OH)CH2NRxRy, -C(0)H, -C(0)(Ci-e alkyl), -C(0)(Ci-3 hydroxyalkyl), -C(0)(Ci-3 fluoroalkyl), -C(0)(Ci-3 chloroalkyl), -C(0)(Ci-3 cyanoalkyl), -(CRxRx)o-3C(0)OH, -C(0)(CH2)o-20(Ci-4 alkyl),-C(0)(CRxRx)o-20(CRxRx)i-20(Ci-3 alkyl), -C(0)CRxRxS(0)2(Ci-3 alkyl),-C(0)CRxRxNRxS(0)2(Ci-3 alkyl), -C(0)CRxRxOC(0)(Ci-3 alkyl),-C(0)(CRxRx)o-3NRyRy, -C(0)(CRxRx)o-iNRx(Ci-3 cyanoalkyl),-C(0)(CRxRx)o-2NRy(Ci-6 hydroxyalkyl), -C(0)(CRxRx)o-iNRx(Ci-3 fluoroalkyl), -C(0)(CRxRx)o-iNRx(C 1-5 hydroxy-fluoroalkyl), -C(0)(CRxRx)o-iNRx(CH2)i-20(Ci-3 hydroxyalkyl), -C(0)(CRxRx)o-iNRx(CH2)i-2NRxC(0)(Ci-2 alkyl), -C(0)(CRxRx)o-iNRx((CRxRx)i-20(Ci-2 alkyl)), -C(0)CRx(NH2)(CRxRx)i-4NRxRx, -C(0)CRx(NH2)(CRxRx)i-4NRxC(0)NRxRx, -C(0)(CRxRx)o-3NRx(CH2)o-iC(0)(Ci-3 alkyl), -C(0)(CRxRx)o-iNRx(CH2)o-iC(0)(Ci-3 cyanoalkyl),-C(0)(CRxRx)o-iNRx(CH2)i-2C(0)NRyRy, -C(0)(CRxRx)i-3C(0)NRyRy,-C(0)(CRxRx)o-iNRx(CHRy(CH2OH)), -(CRxRx)i-2C(0)NRyRy,-(CRxRx)i-2C(0)NRy(Ci-3 fluoroalkyl), -(CRxRx)i-2C(0)NRy(Ci-4 hydroxyalkyl), -(CRxRx)i-2C(0)NRy(Ci-3 cyanoalkyl), -(CRxRx)i-2C(0)NRx(CH2)i-20(Ci-3 alkyl), -(CRxRx)i-2C(0)NRxCH(Ci-4 alkyl)(Ci-3 hydroxyalkyl), -(CH2)i- 2C(0)NRx(CH2)i_2C(0)NRxRx, -(CH2)i-2C(0)NRx(CH2)i-2S(0)2OH,-(CH2)i_2C(0)NRx(CH2)i-2NRxC(0)(Ci-3 alkyl), -(CH2)i-2C(0)NRx(CH2)i-3NRxRx, -(CH2)i-2C(0)N(CH2CH3)(CH2)i-3NRxRx, -(CH2)o-2S(0)2(Ci-4 alkyl),-(CH2)o-2S(0)2(Ci-3 fluoroalkyl), -(CH2)o-2S(0)2NRxRx, -C(0)C(0)OH,-C(0)C(0)NRyRy, or -C(0)C(0)NRy(CRxRx)i-2NRyRy;Li is a bond, -(CRxRx)i-2- -(CRxRx)i-2CRx(OH)-, -(CRxRx)i-20-, -CRxRxC(0)-, -(CRxRx)2NRx(CRxRx)o-i-, -CRxRxC(0)NRx(CRxRx)o-4-, -C(0)(CRxRx)o-3-, -C(0)(CRxRx)o-2NRx(CRxRx)o-2-, -C(0)(CRxRx)o-2N(C i-2hydroxyalkyl)(CRxRx)o-2-, -C(0)(CRxRx)o-2NRx(CRxRx)i-2CRx(OH)-,-C(0)(CRxRx)i-2C(0)NRx-, -(CRxRx)o-2C(0)NRx(CRxRx)i-2CRx(OH)-,-(CRxRx)o-2C(0)N(Ci-2 -C(0)(CRxRx)o-iO- -C(0)(CRxRx)i-2NHS(0)2-, -C(0)CRx(NH2)CRxRx-, -C(0)C(0)(CRxRx)o-2- -C(0)NRx(CRxRx)i-2- or -S(0)2-;A is 2-oxa-6-azaspiro[3,3]heptanyl, 4-oxaspiro[2.5]octanyl, 7-azaspiro[3.5]nonanyl,8- azabicyclo[3.2.1]octanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl,9- azabicyclo[3.3.1]nonanyl, adamantanyl, azepanyl, azetidinyl, C3-6 cycloalkyl, diazepanyl, dihydroinonyl, dihydropyrimidinonyl, dioxidoisothiazolidinyl, dioxidothiazinanyl, dioxotetrahydrothiophenyl, dioxotetrahydrothiopyranyl, dioxothiomorpholinyl, furanyl, imidazolyl, imidazolidinonyl, indolyl, isoquinolinyl, isoxazolyl, morpholinyl, mo holinonyl, naphthalenyl,octahydrocyclopenta[b]pyranyl, oxazolidinonyl, oxadiazolyl, oxetanyl, oxazolyl, phenyl, piperidinyl, piperidinonyl, piperazinyl, piperazinonyl, pyrazinyl, pyrazolyl, pyridazinonyl, pyridinonyl, pyridinyl, pyrimidinyl, pyrrolidinonyl, pyrrolidinyl, pyrrolyl, quinolinyl, quinolizinonyl, tetrahydrofuranyl, tetrahydropyranyl, tetrazolyl, thiadiazolyl, thiazolyl, or triazolyl, each substituted with -L2-Ra and zero to 4 Rb;L2 is a bond or -CRXRX-;Ra is:(a) H, F, CI, -CN, -OH, Ci-e alkyl, C1-3 fluoroalkyl, C1-5 hydroxyalkyl, -(CH2)o-40(Ci-3 alkyl), -(CRxRx)i-3S(Ci-3 alkyl), -(CRxRx)i-3NHC(0)0(Ci-4 alkyl),-(CRxRx)i-3NRyRy, -(CRxRx)i-3C(0)NRyRy, -0(Ci-3 fluoroalkyl), -S(0)2NRxRx, -0(CRxRx)i-3NRxRx, -NHS(0)2(Ci-3 alkyl), -NRXRX, -NRx(Ci-4 alkyl),-NRxC(0)(Ci-4 alkyl), -(CRxRx)o-3C(0)OH, -C(0)(Ci-5 alkyl), -C(0)(Ci-3fluoroalkyl), -C(0)0(Ci-4 alkyl), -C(0)NH(Ci-3 cyanoalkyl), -C(0)NRyRy, -C(0)NRxCH2C(0)NRxRx, or -C(0)NRxCH2CH2NHC(0)(Ci-3 alkyl);(b) C3-6 cycloalkyl or -C(0)NH(C3-6 cycloalkyl), wherein each cycloalkyl is substituted with zero to 2 substituents independently selected from -OH, Ci-3 alkyl, Ci-3 hydroxyalkyl, Ci-3 fluoroalkyl, and -C(0)0(Ci-3 alkyl); or(c) Ai, -CH2Ai, -C(0)Ai, -NRxAi, or -C(0)NRxAi, wherein Ai is furanyl, imidazolyl, indolyl, isoxazolyl, mo holinyl, octahydropyrrolo[3,4-c]pyrrolyl, oxazolyl, oxetanyl, phenyl, piperazinyl, piperidinyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrrolidinyl, pyrrolyl, tetrahydrofuranyl, tetrahydropyranyl, thiadiazolyl, thiazolyl, thiophenyl, or triazolyl, each substituted with zero to three substituentsindependently selected from -OH, Ci-3 alkyl, Ci-3 hydroxyalkyl, -C(0)(Ci-...
[1,2,4]트리아졸로[4,3-a]피리디닐 치환된 인돌 화합물화학식 (I)의 화합물 또는 그의 염이 개시된다: 여기서 R1, R2, R3, R4a, R4b, R4c, R4d, R5, n, 및 p는 본원에 정의되어 있다. 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.화학식 (I)의 화합물 또는 그의 염.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;각각의 R2는 독립적으로 할로, -CN, -OH, -NO2+, C1-3 알킬, C1-2 플루오로알킬, C1-3 히드록시알킬, C1-3 아미노알킬, -(CH2)0-4O(C1-3 알킬), C1-3 플루오로알콕시, C2-4 알콕시알콕시, -O(CH2)1-2NRxRx, -C(O)O(C1-3 알킬), -C(O)NRyRy, -NRyRy, -NRxC(O)(C1-3 알킬), -NRx(CH2-시클로프로필), C3-6 시클로알킬, 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, -(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)(C1-3 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;L2는 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)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;R4a, R4b, R4c, 및 R4c는 독립적으로 H, F, -OH, C1-2 알킬, 또는 -OCH3이거나; 또는 R4a 및 R4c는 함께 -CH2CH2-를 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;p는 0, 1, 2, 3, 또는 4이다.