ARYL AND HETEROARYL SUBSTITUTED INDOLE COMPOUNDSDisclosed are compounds of Formula (I) or salts thereof, wherein A, G, R1, R5, 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 compound of Formula (I)N-oxide, or a salt thereof, wherein:G is:(iv) a 9-membered heterocyclic ring selected from:(v) lO-membered heterocyclic ring selected from:A is an aromatic group selected from [l,2,4]triazolo[l,5-a]pyridinyl,imidazo[l,2-a]pyridinyl, imidazolyl, indazolyl, isoquinolinyl, oxadiazolyl, oxazolyl, phenyl, pyrazinyl, pyrazolo[3,4-b]pyridinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinonyl, quinolinyl, quinoxalinyl, tetrahydro- [l,2,4]triazolo[l,5-a]pyrazinyl, tetrahydroimidazo[l,2-a]pyrazinyl,tetrahydroisoquinolinyl, tetrahydrothiazolo[5,4-c]pyridinyl,tetrahydrothieno[2,3-c]pyridinyl, thiadiazolyl, thiazolyl, thiooxadiazolyl, and triazolyl, each substituted with zero to 2 R a and zero to 3 Ri4t>;Ri is H, Cl, -CN, Ci— 4 alkyl, C1-3 fluoroalkyl, C1-3 hydroxyalkyl, C1-3 hydroxy- fluoroalkyl, -CRV=CH2, C3-6 cycloalkyl, -CH2(C3-6 cycloalkyl), -C(0)0(Ci-3 alkyl), or tetrahydropyranyl;each R2 is independently halo, -CN, -OH, -NO2, C1-4 alkyl, C1-2 fluoroalkyl, C1-2cyanoalkyl, C1-3 hydroxyalkyl, C1-3 aminoalkyl, -0(CH2)I-20H, -(CH2)O-40(CI-4 alkyl), C1-3 fluoroalkoxy, -(CH2)I-40(CI-3 alkyl), -0(CH2)i-20C(0)(Ci-3 alkyl), -0(CH2)I-2NRXRx, -C(0)0(CI-3 alkyl), -(CH2)o-2C(0)NRyRy, -C(0)NRx(Ci-5 hydroxyalkyl), -C(0)NRx(C2-6 alkoxyalkyl), -C(0)NRx(C3-6 cycloalkyl), -NRyRy, -NRy(Ci-3 fluoroalkyl), -NRy(Ci-4 hydroxyalkyl), -NRxCH2(phenyl),-NRXS(0)2(C3-6 cycloalkyl), -NRxC(0)(Ci-3 alkyl), -NRxCH2(C3-6 cycloalkyl), -(CH2)O-2S(0)2(CI-3 alkyl), -(CH2)o-2(C3-6 cycloalkyl), -(CH2)o-2(phenyl), morpholinyl, dioxothiomorpholinyl, dimethyl pyrazolyl, methylpiperidinyl, methylpiperazinyl, amino-oxadiazolyl, imidazolyl, triazolyl, or -C(0)(thiazolyl);R2a is Ci— 6 alkyl, C1-3 fluoroalkyl, C1-6 hydroxyalkyl, C1-3 aminoalkyl, -(CH2)O-40(CI-3 alkyl), C3-6 cycloalkyl, -(CH2)i-3C(0)NRxRx, -CH2(C3-6 cycloalkyl), -CH2(phenyl), tetrahydrofuranyl, tetrahydropyranyl, or phenyl;each R2b is independently H, halo, -CN, -NRXRX, C1-6 alkyl, C1-3 fluoroalkyl, C1-3hydroxyalkyl, C1-3 fluoroalkoxy, -(CH2)O-20(CI-3 alkyl), -(CH2)o-3C(0)NRxRx, -(CH2)i-3(C3-6 cycloalkyl), -C(0)0(Ci-3 alkyl), -C(0)NRx(Ci-3 alkyl),-CRJ^CRJCRJC, or -CRx=CH(C3-6 cycloalkyl);R2C is R2a or R2b;R2d is R2a or R2b; provided that one of R2c and R2d is R2a, and the other of R2c and R2 is R2b;each R5 is independently F, Cl, -CN, C1-3 alkyl, C1-2 fluoroalkyl, or -OCH3;each Ri4a is independently selected from:(i) H, halo, -OH, C1-6 alkyl, C1-3 fluoroalkyl, C1-4 hydroxyalkyl, -(CH2)O-20(CI-3 alkyl), -CRxRxNRyRy, -CRXRXNRX(CI-3 cyanoalkyl), -CRXRXNRX((CH2)I-20(CI-2 alkyl)), -CRXRXN((CH2)I-20CH3)2, -CRXRXNRX(CH2CºCRX), -CRXRXNRX(CH2)I-3NRXRx, -(CRXRX)I-3CRXRXNRXRx, -CRX(NH2)(CH2)I-4NRXRx, -CRXRXNRX(CH2) I-20(C i-3 alkyl), -CRxRxNRx(CH2)i-20(CH2)i-20H,-CRXRXNRX(CH2)I-3S(0)20H, -CRXRXC(0)NRXRx, -NRxRy, -NRX(CH2)I-3NRXRx, -NRXC(0)(CI-3 alkyl), -NRxC(0)(Ci-3 fluoroalkyl), -NRxC(0)0(Ci-3 alkyl), -NRXC(0)(CH2)I-3NRXRx, -NRXCH2C(0)CH2NRXRx, -C(0)(CI-3 alkyl),-C(0)(CRXRX)I-30H, -C(0)CRXRXNRXRx, -C(0)NRXRx, -C(0)NRX(CI-2 cyanoalkyl), -C(0)NRx(CRxRx)i-3NRxRx, -C(0)N(CH2CH3)(CRxRx)i-3NRxRx, -C(0)NRX(CRXRX)I-2C(0)NRXRx, -C(0)NRX(CRXRX)I-3NRXC(0)(CI-2 alkyl), -0(CRXRX)I-3NRXRx, -S(0)2NRXRx, and -C(0)(CRxRx)i-2S(0)2(Ci-2 alkyl);(ii) 8-azabicyclo[3.2. l]octanyl, azaspiro[3.5]nonanyl, azetidinyl,benzo[c][l,2,5]oxadiazolyl, cyclopentyl, cyclohexyl, diazepanyl, morpholinyl, phenyl, piperazinyl, piperidinyl, pyrazolyl, pyridinyl, pyrrolidinonyl, quinolinyl, quinuclidinyl, tetrahydroisoquinolinyl, tetrahydropyridinyl, or thiazolidinyl, each substituted with zero to 2 substituents independently selected from Ci-4 alkyl, Ci-2 fluoroalkyl, Ci-4 hydroxyalkyl, -NRXRX, -(CH2) I-2NRXRx, -C(0)(Ci-2 alkyl), -C(0)CH2NRXRX, -C(0)0(CI-3 alkyl), -CH2C(0)NRxRx, Cw, cycloalkyl,-CH2(phenyl), -CH2(pyrrolyl), -CH2(morpholinyl), -CH2(methylpiperazinyl), -CH2(thiophenyl), methylpiperidinyl, isobutylpiperidinyl, and pyridinyl; or(iii) -L3-Ri4C;each Ri4b is F, Cl, -OH, -CH3, or -OCH3;L3 is -(CRXRX)I-3-, -CH(NH2)-, -CRXRXNH-, -Geo)-, -C(0)NRX(CH2)O-4-, -NRx-, -NRxC(0)-, -NRXCH2-, -NRXCH2C(0)-, or -0(CH2)o-2-;Ri4c is adamantanyl, azepanyl, azetidinyl, C3-7 cycloalkyl, diazepanyl, imidazolyl,indolyl, morpholinyl, octahydropyrrolo[3,4-c]pyrrolyl, phenyl, piperazinonyl, piperazinyl, piperidinyl, pyridinyl, pyrrolidinonyl, pyrrolidinyl, pyrrolyl, triazolyl, or tetrazolyl, each substituted with zero to 1 substituent selected from F, -OH, Ci-4 alkyl, Ci-3 hydroxyalkyl, -NRxRy, -NRxC(0)CH3, -C(0)(Ci-2 alkyl), -C(0)NRxRx, -C(0)N(CH2CH3)2, -C(0)(tetrahydrofuranyl), -C(0)0(Ci-2 alkyl),-CH2C(0)NRxRy, morpholinyl, methylpiperidinyl, pyrazinyl, pyridinyl, and pyrrolidinyl; Rv is H, Ci— 2 alkyl, or Ci-2 fluoroalkyl;each Rx is independently H or -CH3;each Ry is independently H or Ci-6 alkyl;n is zero, 1, or 2; andp is zero, 1, 2, 3, or 4.
아릴 및 헤테로아릴 치환된 인돌 화합물하기 화학식 I의 화합물 또는 그의 염이 개시된다: 상기 식에서, A, G, R1, R5, 및 n은 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, 그의 N-옥시드, 또는 염:상기 식에서,G는:(i) (ii) (iii) (iv) 하기로부터 선택된 9-원 헤테로시클릭 고리:;또는(v) 하기로부터 선택된 10-원 헤테로시클릭 고리:이고;A는 [1,2,4]트리아졸로[1,5-a]피리디닐, 이미다조[1,2-a]피리디닐, 이미다졸릴, 인다졸릴, 이소퀴놀리닐, 옥사디아졸릴, 옥사졸릴, 페닐, 피라지닐, 피라졸로[3,4-b]피리디닐, 피라졸릴, 피리다지닐, 피리디닐, 피리미디닐, 피롤릴, 퀴놀리노닐, 퀴놀리닐, 퀴녹살리닐, 테트라히드로- [1,2,4]트리아졸로[1,5-a]피라지닐, 테트라히드로이미다조[1,2-a]피라지닐, 테트라히드로이소퀴놀리닐, 테트라히드로티아졸로[5,4-c]피리디닐, 테트라히드로티에노[2,3-c]피리디닐, 티아디아졸릴, 티아졸릴, 티오옥사디아졸릴, 및 트리아졸릴로부터 선택된 방향족 기이고, 각각은 0 내지 2개의 R14a 및 0 내지 3개의 R14b로 치환되고;R1은 H, Cl, -CN, C1-4 알킬, C1-3 플루오로알킬, C1-3 히드록시알킬, C1-3 히드록시-플루오로알킬, -CRv=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), -(CH2)0-2C(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), -NRxCH2(C3-6 시클로알킬), -(CH2)0-2S(O)2(C1-3 알킬), -(CH2)0-2(C3-6 시클로알킬), -(CH2)0-2(페닐), 모르폴리닐, 디옥소티오모르폴리닐, 디메틸 피라졸릴, 메틸피페리디닐, 메틸피페라지닐, 아미노-옥사디아졸릴, 이미다졸릴, 트리아졸릴, 또는 -C(O)(티아졸릴)이고;R2a는 C1-6 알킬, C1-3 플루오로알킬, C1-6 히드록시알킬, C1-3 아미노알킬, -(CH2)0-4O(C1-3 알킬), C3-6 시클로알킬, -(CH2)1-3C(O)NRxRx, -CH2(C3-6 시클로알킬), -CH2(페닐), 테트라히드로푸라닐, 테트라히드로피라닐, 또는 페닐이고;각각의 R2b는 독립적으로 H, 할로, -CN, -NRxRx, C1-6 알킬, C1-3 플루오로알킬, C1-3 히드록시알킬, C1-3 플루오로알콕시, -(CH2)0-2O(C1-3 알킬), -(CH2)0-3C(O)NRxRx, -(CH2)1-3(C3-6 시클로알킬), -C(O)O(C1-3 알킬), -C(O)NRx(C1-3 알킬), -CRx=CRxRx, 또는 -CRx=CH(C3-6 시클로알킬)이고;R2c는 R2a 또는 R2b이고;R2d는 R2a 또는 R2b이고; 단 R2c 및 R2d 중 하나는 R2a이고, R2c 및 R2 중 다른 하나는 R2b이고;각각의 R5는 독립적으로 F, Cl, -CN, C1-3 알킬, C1-2 플루오로알킬, 또는 -OCH3이고;각각의 R14a는 독립적으로 다음으로부터 선택되고:(i) H, 할로, -OH, C1-6 알킬, C1-3 플루오로알킬, C1-4 히드록시알킬, -(CH2)0-2O(C1-3 알킬), -CRxRxNRyRy, -CRxRxNRx(C1-3 시아노알킬), -CRxRxNRx((CH2)1-2O(C1-2 알킬)), -CRxRxN((CH2)1-2OCH3)2, -CRxRxNRx(CH2C≡CRx), -CRxRxNRx(CH2)1-3NRxRx, -(CRxRx)1-3CRxRxNRxRx, -CRx(NH2)(CH2)1-4NRxRx, -CRxRxNRx(CH2)1-2O(C1-3 알킬), -CRxRxNRx(CH2)1-2O(CH2)1-2OH, -CRxRxNRx(CH2)1-3S(O)2OH, -CRxRxC(O)NRxRx, -NRxRy, -NRx(CH2)1-3NRxRx, -NRxC(O)(C1-3 알킬), -NRxC(O)(C1-3 플루오로알킬), -NRxC(O)O(C1-3 알킬), -NRxC(O)(CH2)1-3NRxRx, -NRxCH2C(O)CH2NRxRx, -C(O)(C1-3 알킬), -C(O)(CRxRx)1-3OH, -C(O)CRxRxNRxRx, -C(O)NRxRx, -C(O)NRx(C1-2 시아노알킬), -C(O)NRx(CRxRx)1-3NRxRx, -C(O)N(CH2CH3)(CRxRx)1-3NRxRx, -C(O)NRx(CRxRx)1-2C(O)NRxRx, -C(O)NRx(CRxRx)1-3NRxC(O)(C1-2 알킬), -O(CRxRx)1-3NRxRx, -S(O)2NRxRx, 및 -C(O)(CRxRx)1-2S(O)2(C1-2 알킬);(ii) 8-아자비시클로[3.2.1]옥타닐, 아자스피로[3.5]노나닐, 아제티디닐, 벤조[c][1,2,5]옥사디아졸릴, 시클로펜틸, 시클로헥실, 디아제파닐, 모르폴리닐, 페닐, 피페라지닐, 피페리디닐, 피라졸릴, 피리디닐, 피롤리디노닐, 퀴놀리닐, 퀴누클리디닐, 테트라히드로이소퀴놀리닐, 테트라히드로피리디닐, 또는 티아졸리디닐 (각각은 C1-4 알킬, C1-2 플루오로알킬, C1-4 히드록시알킬, -NRxRx, -(CH2) 1-2NRxRx, -C(O)(C1-2 알킬), -C(O)CH2NRxRx, -C(O)O(C1-3 알킬), -CH2C(O)NRxRx, C3-6 시클로알킬, -CH2(페닐), -CH2(피롤릴), -CH2(모르폴리닐), -CH2(메틸피페라지닐), -CH2(티오페닐), 메틸피페리디닐, 이소부틸피페리디닐, 및 피리디닐로부터 독립적으로 선택된 0 내지 2개의 치환기로 치환됨); 또는(iii) -L3-R14c;각각의 R14b는 F, Cl, -OH, -CH3, 또는 -OCH3이고;L3은 -(CRxRx)1-3-, -CH(NH2)-, -CRxRxNH-, -C(O)-, -C(O)NRx(CH2)0-4-, -NRx-, -NRxC(O)-, -NRxCH2-, -NRxCH2C(O)-, 또는 -O(CH2)0-2-이고;R14c는 아다만타닐, 아제파닐, 아제티디닐, C3-7 시클로알킬, 디아제파닐, 이미다졸릴, 인돌릴, 모르폴리닐, 옥타히드로피롤로[3,4-c]피롤릴, 페닐, 피페라지노닐, 피페라지닐, 피페리디닐, 피리디닐, 피롤리디노닐, 피롤리디닐, 피롤릴, 트리아졸릴, 또는 테트라졸릴이고, 각각은 F, -OH, C1-4 알킬, C1-3 히드록시알킬, -NRxRy, -NRxC(O)CH3, -C(O)(C1-2 알킬), -C(O)NRxRx, -C(O)N(CH2CH3)2, -C(O)(테트라히드로푸라닐), -C(O)O(C1-2 알킬), -CH2C(O)NRxRy, 모르폴리닐, 메틸피페리디닐, 피라지닐, 피리디닐, 및 피롤리디닐로부터 선택된 0 내지 1개의 치환기로 치환되고;Rv는 H, C1-2 알킬, 또는 C1-2 플루오로알킬이고;각각의 Rx는 독립적으로 H 또는 -CH3이고;각각의 Ry는 독립적으로 H 또는 C1-6 알킬이고;n은 0, 1, 또는 2이고;p는 0, 1, 2, 3, 또는 4이다.