SUBSTITUTED INDOLE ETHER COMPOUNDSDisclosed are compounds of Formula (I) (I) N-oxides, or salts thereof, wherein R1, G, A, 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(n) 10-membered heterocyclic ring selected from A is L-Re;L is a bond, --(CRXRX)I-2-, -(CR.xRx)i-2CRx(OH)-, -(CRxRx)i-20-, -CRxRxC(Q)-, -CRXRXC(0)NRX(CRXRX)O-4 -, -CRXRXNRXC(0)(CRXRX)O-4-, or-CRXRXNRXC(0)(CRXRX)O-4-;Ri is H, Cl, -CN, Ci— 4 alkyl, C1-3 fluoroalkyl, C1-3 hydroxyalkyl, C1-3 hydroxy- fluoroalkyl, C!C P 1 ·, C3--6 cycloalkyl, P ! :((' : cycloalkyl), -C(0)0(Ci-3 alkyl), or tetrahydropyranyl;each R2 is independently halo, -CN, -OH, -NO2, C1-4 alkyl, C1--2 fluoroalkyl, C1-2cyanoa!ky!, C1-3 hydroxyalkyl, C1-3 aminoalkyl, -0(CH2)i-20H, -(CH2)o--40(Ci--4 alkyl), C1 --3 fluoroalkoxy, -(CH2)I-40(C I-3 alkyl), -0(CH2)i-20C(0)(Ci-3 alkyl), -0(CH2)I-2NRXRX, -C(())0(Ci-3 alkyl), -(CH2)o-2C(())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)(thiazolyi);R2.a is Ci— 6 alkyl, C1-3 fluoroalkyl, C1-0 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 R?b is independently H, halo, -CN, -NRxRx, Cr-e alkyl, CH fluoroalkyl, C1- 3hydroxyalkyl, C1-3 fluoroalkoxy, -(CH2)o-20(Cl-3 alkyl), (CI 1 · )·; (0)NR R — (CH2.) 1—3 (C 3-6 cycloalkyl), -C(0)0(Ci-3 alkyl), -C(0)NRx(Ci-3 alkyl),-CRx=CRxRx, or -CRx=CH(C3-6 cycloalkyl);R2C is R?.a or R2b;Rid is R?.a or Rib; provided that one of Ric and Rid is R?.a, and the other of Ric and Rid is Rib;each Rs is independently F, Cl, -CN, C1-3 alkyl, C1-2 fluoroalkyl, or -OCH3;Re is:(i) -NRxRx, -CRXRXC(0)NR (CR R )I-3OH, -CRXRXC(())NRX(CRXRX)I-INRXRX, or ---C:RXRXC(0)NR (CR R )I--ICHFCR R ()H, or(ii) azabicyclo[3 2.1]octanyl, azaspiro[5.5]undecanyl, azetidinyl, C3-6 cycloalkyl, diazabicyclo[2.2. l]heptanyl, diazaspiro[3.5]nonanyl, imidazolyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, octahydrocyclopenta[c]pyrrolyl, phenyl, piperazinyl, piperidinyl, pyrrolidinyl, pyridinyl, or quinuclidinyl, each substituted with zero to 3 Rea;each Rea is independently F, Cl, -OH, -CN, Ci-e alkyl, Ci-4 fluoroalkyl, Ci-ehydroxy alkyl, (C l 1 )i iO(C = ; alkyl), -NRxRx, -(CHi)i--2NRxRx,(CRxRx) 1— 2 S(0)2(C 1—3 al kyl), -iCRxRx)i-2C(0)ORy, -(CRxRx)i-iC(Q)NRxRx, C(O)(CRxRx)i iNRxRx, -(CRxRx)l-2(phenyl), oxetanyl, morpholinyl,tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, isopropylpiperidinyl, isobutylpiperidinyl, piperazinyl, or -O(piperidinyl);Rv is H, C1-2 alkyl, or C 1-2 fluoroalkyl;each Rx is independently H or -CFb;each Ry is independently H or Ci-6 alkyl;n is zero, 1, or 2; andp is zero, 1 , 2, 3, or 4.2 The compound according to claim 1, N-oxide, or a salt thereof, wherein:L is a bond, -CH2NRXC(0)CH2~;RI is H, Cl, -CN, Ci-4 alkyl, C1-2 fluoroalkyl, C1-2 hydroxyalkyl, or -C(0)0(Ci-2 alkyl); each R2 is independently F, Cl, -CN, -OH, Ci-4 alkyl, C1-2 fluoroalkyl, C1-2 cyanoalkyl, C1-3 hydroxyalkyl, C1-3 aminoalkyl, (P f ' . '()((' i ί alkyl), -NRyRy,-(CH2)o-2C(0)NRyRy,— C (O)NRx(C 1-4 hydroxyalkyl), -C(0)NRx(C2-4 alkoxy alkyl), -C(0)NRX(C3~6 cycloalkyl), -(CH2)o-2S(0)2(Cl-3 alkyl), -(CH2)O-I(C3-6 eyeloalkyl), morpholinyl, (CH2)o i(pheny)), or dimethyl pyrazolyl;R2a is Ci— 4 alkyl, C1--2 fluoroalkyl, Ci-4 hydroxyalkyl, -(CH2)I-30CH3, C3-6 cycloalky), -CH2C(0)NRXRx, (Ί f ((' ; ·, cycloalkyl), -CH2(phenyl), tetrahydrofuranyl, or phenyl;each Rzb is independently H, F, Cl, -CN, -NRxRx, Ci-e alkyl, C1-2 fluoroalkyl, C1-3hydroxyalkyl, -(CH2)O-2G(CI-2 alkyl), -(CH2)O-2C(0)NRXRX,-<CH2) I (cy cl opropy 1), -C(0)0(Ci-2 alkyl), -C(0)NRX(CI-3 alkyl), CRx Ci h, or -CH=CH(C3-6 cycloalkyl);each Rs is independently F, Cl, -CN, Ci-2 alkyl, or -OCH3;Re is!(i ) -NRxRx, -CH2C(0)NHCH2CRxRx0H, (Ί 1 '(()}M K Ί I2P I’CR jCOi I,C! ! C(i))Xi KΊ l2Ci I’NRxRx, or ('! !2i'(0)M 1P FCi li C ICRxOI I. or(ii) azabicyclo[3.2.1]octanyl, azaspiro[5.5]undecanyl, azetidinyl, C3-6 eyeloalkyl, diazabicyclo[2.2. l]heptanyl, diazaspiro[3.5]nonanyl, imidazolyl, morpholinyl, tetrahydrofuranyl , tetrahydropyranyl, octahydrocyclopenta[c]pyrrolyl, phenyl, piperazinyl, piperidinyl, pyrrolidinyl, pyridinyl, or quinuclidinyl, each substituted with zero to 3 Rea,each Rea is independently F, -OH, Ci-4 alkyl, Ci 4 fluoroalkyl, Ci 4 hydroxyalkyl, -(CH2)i-2GCH3, -NRxRx, -(CH2)i-2NRxRx, { C 1 i y i 28(0)i(' ; ’ alkyl),(CRXRX)I-2C(0)ORX, -iCH2)i-2C(0)NRxRx, -C(0)CH2NRxRx, -CRxRx(phenyl), oxetanyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, isopropylpiperidinyl, isobutylpiperidinyl, piperazinyl, or -O(piperidinyl); and p is zero, 1, 2, or 3.3 The compound ...
치환된 인돌 에테르 화합물하기 화학식 I의 화합물, 그의 N-옥시드 또는 염이 개시된다: 상기 식에서, R1, G, A, 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 -L-R6이고;L은 결합, -(CRxRx)1-2-, -(CRxRx)1-2CRx(OH)-, -(CRxRx)1-2O-, -CRxRxC(O)-, -CRxRxC(O)NRx(CRxRx)0-4-, -CRxRxNRxC(O)(CRxRx)0-4-, 또는 -CRxRxNRxC(O)(CRxRx)0-4-이고;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 R2d 중 다른 하나는 R2b이고;각각의 R5는 독립적으로 F, Cl, -CN, C1-3 알킬, C1-2 플루오로알킬, 또는 -OCH3이고;R6은:(i) -NRxRx, -CRxRxC(O)NRx(CRxRx)1-3OH, -CRxRxC(O)NRx(CRxRx)1-2NRxRx, 또는 -CRxRxC(O)NRx(CRxRx)1-2CHFCRxRxOH; 또는(ii) 아자비시클로[3.2.1]옥타닐, 아자스피로[5.5]운데카닐, 아제티디닐, C3-6 시클로알킬, 디아자비시클로[2.2.1]헵타닐, 디아자스피로[3.5]노나닐, 이미다졸릴, 모르폴리닐, 테트라히드로푸라닐, 테트라히드로피라닐, 옥타히드로시클로펜타[c]피롤릴, 페닐, 피페라지닐, 피페리디닐, 피롤리디닐, 피리디닐, 또는 퀴누클리디닐 (각각은 0 내지 3개의 R6a로 치환됨)이고;각각의 R6a는 독립적으로 F, Cl, -OH, -CN, C1-6 알킬, C1-4 플루오로알킬, C1-6 히드록시알킬, -(CH2)1-2O(C1-3 알킬), -NRxRx, -(CH2)1-2NRxRx, -(CRxRx)1-2S(O)2(C1-3 알킬), -(CRxRx)1-2C(O)ORy, -(CRxRx)1-2C(O)NRxRx, -C(O)(CRxRx)1-2NRxRx, -(CRxRx)1-2(페닐), 옥세타닐, 모르폴리닐, 테트라히드로푸라닐, 테트라히드로피라닐, 아제티디닐, 피롤리디닐, 피페리디닐, 이소프로필피페리디닐, 이소부틸피페리디닐, 피페라지닐, 또는 -O(피페리디닐)이고;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.