Phenyl Linked Quinolinyl Modulators Of Ror-Gamma-TThe present invention comprises compounds of Formula I. Formula I wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating ROR[gamma]t activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.The compound of formulas i and pharmaceutically acceptable salt thereof:wherein:r1for azete piperidinyl, pyrrole radicals, pyrazolyl, imidazole radicals, triazolyl, thiazolyl, pyridine radicals, n-pyridine oxide base, pyrazine base, pyrimidine radicals, pyridazinyl, piperidyl, thp trtrahydropyranyl, phenyl, oxazolyl, isoxazolyl, thienyl, benzoxazolyl group or quinoline quinoline base；wherein said piperidyl, pyridine radicals, n-pyridine oxide base, imidazole radicals, phenyl, thienyl, benzoxazolyl group and pyrazolyl optionally by so2ch3、c(o)ch3、c(o)nh2、ch3、ch2ch3、cf3、cl、f、-cn、och3、n(ch3)2、-(ch2)3och3、 sch3、oh、co2h、co2c(ch3)3or och2och3replace；and optionally added independently selected from following by most two substituent group replaces: cl, och3and ch3；and wherein said triazolyl, oxazolyl, isoxazolyl and thiazolyl are optionally by one or two ch3group replaces；and wherein said azete piperidinyl is optionally by co2c(ch3)3、c(o)nh2、ch3、so2ch3or c (o)ch3replace；r2for 1-methyl isophthalic acid, 2,3-triazolyl, pyridine radicals, n-pyridine oxide base, 1-methyl-pyrazol-4-yl, pyrimidine-5-base, pyridazine base, pyrazine-2-base, oxazolyl, isoxazolyl, n-acetyl group-azetidine-3-base, n-methyl sulphonyl-azetidine-3-base, n- boc-azetidine-3-base, n-methyl-azetidine-3-base, n-acetamido-azetidine-3-base, n-acetylpiperidinyl, 1-h- piperidyl, n-boc-piperidyl, n-c(1-2)alkyl-piperidinyl, thiazole-5-base, 1-methylimidazole .-2-base, 1-(3-methoxy propyl base)-imidazoles-5-base or 1-c(1-2)alkyl imidazole-5-base；wherein said 1-c(1-2)alkyl imidazole-5-base is optionally by most two additional ch3group, or one selected from sch3replace with the substituent group of cl；and described pyridine radicals and n-pyridine oxide base are appointed selection of land is replaced independently selected from following substituent group by most two: c (o) nh2、-cn、och3、cf3, cl and ch3；and it is described thiazole-5-base, oxazolyl and isoxazolyl are optionally by most two ch3group replaces；and described 1-methyl-pyrazol-4-yl optionally by most two additional ch3group replaces；r3for h, oh, och3、nhch3、n(ch3)2or nh2；r4for h or f；r5for h, cl ,-cn, cf3、sch3、oc(1-3)alkyl, oh, c(1-4)alkyl, n (ch3)och3、nh(c(1-2)alkyl), n (c(1-2) alkyl)2, nh-cyclopropyl, ochf2, 4-hydroxy-piperdine base, azetidine-1-base or furan-2-base；r6for 2-chloro-thiophene-5-base, 1-methyl pyrazole-4-base, phenyl, pyrimidine radicals or pyridine radicals, wherein said phenyl, pyrimidine base and pyridine radicals are optionally by so2ch3、nhso2ch3、cf3、f、cl、-cn、och3or ocf3replace；r7for h, cl ,-cn, c(1-4)alkyl, och2cf3、och2ch2och3、cf3、sch3、so2ch3、ochf2、na1a2、c(o) nhch3、n(ch3)ch2ch2na1a2、och2ch2na1a2、och2ch2nh2、oc(1-3)alkyl, och2-(1-methyl)-imidazoles-2- base, imidazoles-2-base, furan-2-base, pyrazoles-4-base, pyridin-3-yl or pyrimidine-5-base；thiene-3-yl, 1-methyl-indazol- 5-base, 1-methyl-indazol-6-base, phenyl or, wherein said imidazole radicals or pyrazolyl can be optionally by ch3 group replaces；a1for h or c(1-4)alkyl；a2for c(1-4)alkyl, cyclopropyl, c(1-4)alkyl oc(1-4)alkyl, c(1-4)alkyl oh, c (o) c(1-2)alkyl or och3；or a1and a2nitrogen that can be in connection is formed selected from following ring together:rafor h, f, och3or oh；rbfor ch3or phenyl；r8for h, ch3、och3or f；r9for h or f；precondition is, present claims does not includes (4-chloro-3-phenylchinoline-6-base) (1-methyl isophthalic acid h-imidazoles-5-base) (pyrrole pyridine-3-base) methylamine, (4-chlorphenyl) (the chloro-3-of 2,4-bis-(2-chlorphenyl) quinoline-6-base) (1-methyl isophthalic acid h-imidazoles-2-base) methanol, (4-chloro-3-phenylchinoline-6-base) (1-methyl isophthalic acid h-imidazoles-5-base) (pyridin-4-yl) methylamine, (4-chlorphenyl) (3- (2,6-dichlorobenzene base) quinoline-6-base) (1-methyl isophthalic acid h-imidazoles-5-base) methanol, (4-chloro-3-phenylchinoline-6-base) (2- (dimethylamino) pyridin-4-yl) (1-methyl isophthalic acid h-imidazoles-2-base) methanol, 4-(2-((the chloro-6-of 4-((4-chlorphenyl) (hydroxyl base) (1-methyl isophthalic acid h-imidazoles-5-base) methyl)-3-phenylchinoline-2-base) epoxide) ethyl) thiomorpholine 1,1-dioxide, 1-(2-((the chloro-6-of 4-((4-chlorphenyl) (hydroxyl) (1-methyl isophthalic acid h-imidazoles-5-base) methyl)-3-phenylchinoline-2-base) oxygen base) ethyl) pyrrolidin-2-one, (2-chloro-4-(dimethylamino)-3-phenylchinoline-6-base) (pyridine-2-base) (pyridine-4- base) methanol, (4-chloro-3-phenylchinoline-6-base) (2-fluorine pyridin-4-yl) (1-methyl isophthalic acid h-imidazoles-2-base) methanol, (4-is chloro- 2-(1-methyl isophthalic acid h-pyrazoles-4-base)-3-phenylchinoline-6-base) (4-chlorphenyl) (pyridin-3-yl) methanol, (2,4-bis-is chloro- 3-phenylchinoline-6-base) two (pyridine-2-base) methanol, 6-((3-chlorphenyl) (hydroxyl) (2-(trifluoromethyl) pyridin-4-yl) methyl)-3-phenylchinoline-2-formonitrile hcn, (2,4-bis-chloro-8-methyl-3-phenylchinoline-6-base) (1-methyl isophthalic acid h-imidazoles-4- base) (6-picoline-3-base) methanol, (4-chlorphenyl) (the chloro-3-...
ROR-GAMMA-T의 페닐 결합 퀴놀리닐 조절제본 발명은 화학식 I의 화합물을 포함한다.화학식 I 상기 식에서, R1, R2, R3, R4, R5, R6, R7, R8 및 R9은 본 명세서에 정의된다. 본 발명은 또한 류머티스성 관절염 또는 건선인 증후군, 장애 또는 질환을 치료하거나 개선시키는 방법을 포함한다. 본 발명은 또한 적어도 하나의 제1항의 화합물의 치료적 유효량을 투여함으로써 포유동물에서 RORγt 활성을 조절하는 방법을 포함한다.(4-클로로-3-페닐퀴놀린-6-일)(1-메틸-1H-이미다졸-5-일)(피리딘-3-일)메탄아민, (4-클로로페닐)(2,4-다이클로로-3-(2-클로로페닐)퀴놀린-6-일)(1-메틸-1H-이미다졸-2-일)메탄올, (4-클로로-3-페닐퀴놀린-6-일)(1-메틸-1H-이미다졸-5-일)(피리딘-4-일)메탄아민, (4-클로로페닐)(3-(2,6-다이클로로페닐)퀴놀린-6-일)(1-메틸-1H-이미다졸-5-일)메탄올, (4-클로로-3-페닐퀴놀린-6-일)(2-(다이메틸아미노)피리딘-4-일)(1-메틸-1H-이미다졸-2-일)메탄올, 4-(2-((4-클로로-6-((4-클로로페닐)(하이드록시)(1-메틸-1H-이미다졸-5-일)메틸)-3-페닐퀴놀린-2-일)옥시)에틸)티오모르폴린 1,1-다이옥사이드, 1-(2-((4-클로로-6-((4-클로로페닐)(하이드록시)(1-메틸-1H-이미다졸-5-일)메틸)-3-페닐퀴놀린-2-일)옥시)에틸)피롤리딘-2-온, (2-클로로-4-(다이메틸아미노)-3-페닐퀴놀린-6-일)(피리딘-2-일)(피리딘-4-일)메탄올, (4-클로로-3-페닐퀴놀린-6-일)(2-플루오로피리딘-4-일)(1-메틸-1H-이미다졸-2-일)메탄올, (4-클로로-2-(1-메틸-1H-피라졸-4-일)-3-페닐퀴놀린-6-일)(4-클로로페닐)(피리딘-3-일)메탄올, (2,4-다이클로로-3-페닐퀴놀린-6-일)다이(피리딘-2-일)메탄올, 6-((3-클로로페닐)(하이드록시)(2-(트라이플루오로메틸)피리딘-4-일)메틸)-3-페닐퀴놀린-2-카르보니트릴, (2,4-다이클로로-8-메틸-3-페닐퀴놀린-6-일)(1-메틸-1H-이미다졸-4-일)(6-메틸피리딘-3-일)메탄올, (4-클로로페닐)(2,4-다이클로로-3-(2-클로로페닐)퀴놀린-6-일)(1-메틸-1H-이미다졸-5-일)메탄올, (2,4-다이클로로-3-페닐퀴놀린-6-일)(페닐)(피리딘-2-일)메탄올, (2,4-다이클로로-3-페닐퀴놀린-6-일)(옥사졸-2-일)(페닐)메탄올, (4-메톡시-3-페닐-2-(트라이플루오로메틸)퀴놀린-6-일)(1-메틸-1H-이미다졸-5-일)(피리딘-2-일)메탄올의 두 번째로 용출되는 거울상 이성질체 및 (4-클로로-2-메톡시-3-페닐퀴놀린-6-일)(1-메틸-1H-이미다졸-5-일)피리미딘-2-일메탄올의 두 번째로 용출되는 거울상 이성질체(키랄셀(chiralcel) OD 컬럼상에서 정제한 경우)를 제외한 화학식 I의 화합물 및 이의 약제학적으로 허용가능한 염:[이미지] 화학식 I상기 식에서,R1은 아제티디닐, 피롤릴, 피라졸릴, 이미다졸릴, 트라이아졸릴, 티아졸릴, 피리딜, 피리딜 N-옥사이드, 피라지닐, 피리미디닐, 피리다질, 피페리디닐, 테트라하이드로피라닐, 페닐, 옥사졸릴, 아이속사졸릴, 티오페닐, 벤즈옥사졸릴 또는 퀴놀리닐이고; 여기서, 상기 피페리디닐, 피리딜, 피리딜 N-옥사이드, 이미다졸릴, 페닐, 티오페닐, 벤즈옥사졸릴 및 피라졸릴은 SO2CH3, C(O)CH3, C(O)NH2, CH3, CH2CH3, CF3, Cl, F, -CN, OCH3, N(CH3)2, -(CH2)3OCH3, SCH3, OH, CO2H, CO2C(CH3)3 또는 OCH2OCH3로 임의로 치환되며; Cl, OCH3 및 CH3로 이루어진 군으로부터 독립적으로 선택되는 2개 이하의 추가의 치환기로 임의로 치환되고; 상기 트라이아졸릴, 옥사졸릴, 아이속사졸릴 및 티아졸릴은 1개 또는 2개의 CH3 기로 임의로 치환되며; 상기 아제티디닐은 CO2C(CH3)3, C(O)NH2, CH3, SO2CH3 또는 C(O)CH3로 임의로 치환되고;R2는 1-메틸-1,2,3-트라이아졸릴, 피리딜, 피리딜-N-옥사이드, 1-메틸 피라졸-4-일, 피리미딘-5-일, 피리다질, 피라진-2-일, 옥사졸릴, 아이속사졸릴, N-아세틸-아제티딘-3-일, N-메틸설포닐-아제티딘-3-일, N-Boc-아제티딘-3-일, N-메틸-아제티딘-3-일, N-아세트아미딜-아제티딘-3-일, N-아세틸 피페리디닐, 1-H-피페리디닐, N-Boc-피페리디닐, N-C(1-2)알킬-피페리디닐, 티아졸-5-일, 1-메틸 이미다졸-2-일, 1-(3-메톡시프로필)-이미다졸-5-일 또는 1-C(1-2)알킬 이미다졸-5-일이고; 여기서, 상기 1-C(1-2)알킬 이미다졸-5-일은 2개 이하의 추가의 CH3 기, 또는 SCH3 및 Cl로 이루어진 군으로부터 선택되는 1개의 치환기로 임의로 치환되며; 상기 피리딜 및 피리딜-N-옥사이드는 C(O)NH2, -CN, OCH3, CF3, Cl 및 CH3로 이루어진 군으로부터 독립적으로 선택되는 2개 이하의 치환기로 임의로 치환되고; 상기 티아졸-5-일, 옥사졸릴 및 아이속사졸릴은 2개 이하의 CH3 기로 임의로 치환되며; 상기 1-메틸 피라졸-4-일은 2개 이하의 추가의 CH3 기로 임의로 치환되고;R3는 H, OH, OCH3, NHCH3, N(CH3)2 또는 NH2이며;R4는 H 또는 F이고;R5는 H, Cl, -CN, CF3, SCH3, OC(1-3)알킬, OH, C(1-4)알킬, N(CH3)OCH3, NH(C(1-2)알킬), N(C(1-2)알킬)2, NH-사이클로프로필, OCHF2, 4-하이드록시-피페리디닐, 아제티딘-1-일 또는 푸르-2-일이며;R6는 2-클로로-티오펜-5-일, 1-메틸-피라졸-4-일, 페닐, 피리미디닐 또는 피리딜이고, 여기서 상기 페닐, 피리미디닐 및 피리딜은 SO2CH3, NHSO2CH3, CF3, F, Cl, -CN, OCH3 또는 OCF3로 임의로 치환되며;R7은 H, Cl, -CN, C(1-4)알킬, OCH2CF3, OCH2CH2OCH3, CF3, SCH3, SO2CH3, OCHF2, NA1A2, C(O)NHCH3, N(CH3)CH2CH2NA1A2, OCH2CH2NA1A2, OCH2CH2NH2, OC(1-3)알킬, OCH2-(1-메틸)-이미다졸-2-일, 이미다졸-2-일, 푸르-2-일, 피라졸-4-일, 피리드-3-일, 또는 피리미딘-5-일; 티오펜-3-일, 1-메틸-인다졸-5-일, 1-메틸-인다졸-6-일, 페닐 또는 [이미지]이고, 여기서 상기 이미다졸릴 또는 피라졸릴은 CH3 기로 임의로 치환될 수 있으며;A1은 H 또는 C(1-4)알킬이고;A2는 C(1-4)알킬, 사이클로프로필, C(1-4)알킬OC(1-4)알킬, C(1-4)알킬OH, C(O)C(1-2)알킬 또는 OCH3이거나; A1 및 A2는 이들이 부착된 질소와 함께,[이미지]로 이루어진 군으로부터 선택되는 환을 형성할 수 있으며;Ra는 H, F, OCH3 또는 OH이고;Rb는 CH3 또는 페닐이며;R8은 H, CH3, OCH3 또는 F이고;R9는 H 또는 F이다.