PYRIDAZINE DERIVATIVES AS RORC MODULATORSCompounds of formula (I): (I) or pharmaceutical salts thereof, wherein m, n,, p, q A, B, Ri, R2, R3, R4, R5, R6and R7are as defined herein. Also disclosed are methods of making the compounds and using the compounds as RORs modulators for treatment of inflammatory diseases such as arthritis.A compound of formula Ior a pharmaceutical salt thereof, wherein: A is hetereoaryl selected from: pyridinyl; pyrimidinyl; pyridazinyl; and pyrazinyl; B is heteroaryl selected from: oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrrolyl; imidazolyl; pyridazolyl;triazolyl;oxadiazolyl;thiadiazolyl;pyridinyl;pyrimidinyl;pyrazinyl;pyridazinyl; or2,3-dihydro-1H-imidazo[4,5-b]pyridinyl; or B is piperidinyl;m is: 0; 1; or 2;n is: 0; or 1;p is: 0; or 1;q is: 0; or 1;R1 is:halo;R2 is:hydrogen;halo; ormethoxy;R3 is:hydrogen; cyano; C1-6alkyl; or halo;R4 is: C1-6alkyl which may be unsubstituted or substituted one or more times with halo; C2-6alkenyl; cyano; hydroxyl-C1-6alkyl wherein the C1-6alkyl moiety may be unsubstituted or substituted one or more times with halo; C1-6alkoxyC1-6alkyl wherein the C1-6alkyl moieties may be unsubstituted or substituted one or more times with halo; oxo; hydroxy; C1-6alkylsulfinyl; halo; R5 is: -(CRa1Ra2)p-NRbRc; -(CRa1Ra2)p-SO2-Rd; -(CRa1Ra2)p-C(O)-Re; -(CRa1Ra2)p-NRb-SO2-Rd; -(CRa1Ra2)p-NRb-C(O)-Re; -(CRa1Ra2)p-NRb-(CHRc)q-SO2-Rd; -(CRa1Ra2)p-NRb-(CHRc)q-C(O)-Re; -(CRa1Ra2)p-CN; -C2-6alkenyl-CN; -(CRa1Ra2)p-Z; -(CRa1Ra2)p-SO2-Z; C1-6alkylsulfonimidamido; or C1-6alkylsulfonimidoylC1-6alkyl; R6 is: C1-6alkyl; halo; or hydroxyl; R7 is: C1-6alkyl; C1-6alkoxy; halo; or hydroxyl; Z is: C3-6cycloalkyl which may be unsubstituted or substituted once or twice with with Rf; a four or five membered heterocyclyl selected from azetidinyl, oxetanyl, thietanyl or tetrahydrothiophenyl, each of which may be unsubstituted or substituted once or twice with with Rf; C1-6alkyl-heterocyclyl wherein the heterocyclyl is a four or five membered heterocyclyl selected from azetidinyl, oxetanyl, thietanyl or tetrahydrothiophenyl, each of which may be unsubstituted or substituted once or twice with with Rf; or C1-6alkylcarbonylaminoC1-6alkyl; p is: 0; 1; 2; or 3 q is: 1; or 2; Ra1 is: hydrogen ; C1-6alkyl which may be unsubstituted or substituted one or more times with halo; Ra2 is: hydrogen ; C1-6alkyl which may be unsubstituted or substituted one or more times with halo; or hydroxyl; or Ra1 and Ra2 may together form a =CH2 group; Rb is: hydrogen ; C1-6alkyl which may be unsubstituted or substituted one or more times with halo; or hydroxyl-C1-6alkyl wherein the C1-6alkyl moiety may be unsubstituted or substituted one or more times with halo; Rc is: hydrogen ; or C1-6alkyl which may be unsubstituted or substituted one or more times with halo; Rd is: C1-6alky which may be unsubstituted or substituted one or more times with halo; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; hydroxyC1-6alkyl; or NRbRc; Re is: C1-6alkyl which may be unsubstituted or substituted one or more times with halo; C1-6alkoxy; hydroxyl-C1-6alkyl or ; hydroxyl; or NRbRc; and Rf is: C1-6alkyl which may be unsubstituted or substituted one or more times with halo; halo; oxo; cyanoC1-6alkyl; hydroxy; -CH2COOH; hydroxyC1-6alkyl; or C1-6alkylsulfonylC1-6alkyl; and wherein the compound is selected from: 3-[2-[6-[(1S,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4-diazatricyclo[6.2.1.02,7]undeca- 2(7),3,5-trien-1-yl]pyrazin-2-yl]oxazol-4-yl]oxetan-3-ol; [2-[6-[(1S,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4-diazatricyclo[6.2.1.02,7]undeca- 2(7),3,5-trien-1-yl]pyrazin-2-yl]oxazol-4-yl]methanamine; N-[[2-[6-[(1S,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4-diazatricyclo[6.2.1.02,7]undeca- 2(7),3,5-trien-1-yl]pyrazin-2-yl]oxazol-4-yl]methyl]methanesulfonamide; 2,2,2-trifluoro-N-[[2-[6-[(1S,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4- diazatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-1-yl]pyrazin-2-yl]oxazol-4-yl]methyl]ethanamine; [2-[6-[(1S,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4-diazatricyclo[6.2.1.02,7]undeca- 2(7),3,5-trien-1-yl]pyrazin-2-yl]oxazol-4-yl]methylurea; (2S)-2-[2-[6-[(1S,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4- diazatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-1-yl]pyrazin-2-yl]oxazol-4-yl]propane-1,2-diol; (S)-cyclopropyl-[2-[6-[(1R,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4- diazatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-1-yl]pyrazin-2-yl]oxazol-4-yl]methanol; (R)-cyclopropyl-[2-[6-[(1R,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4- diazatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-1-yl]pyrazin-2-yl]oxazol-4-yl]methanol; (1R)-2,2-difluoro-1-[2-[6-[(1R,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4- diazatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-1-yl]pyrazin-2-yl]oxazol-4-yl]ethanol; (1S)-2,2-difluoro-1-[2-[6-[(1R,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4- diazatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-1-yl]pyrazin-2-yl]oxazol-4-yl]ethanol (1S)-2-methyl-1-[2-[6-[(1R,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4- diazatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-1-yl]pyrazin-2-yl]oxazol-4-yl]propan-1-ol; 2-[6-[(1S,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4-diazatricyclo[6.2.1.02,7]undeca- 2(7),3,5-trien-1-yl]pyrazin-2-yl]-4-[(1R)-1-methylsulfonylethyl]oxazole; 2-[6-[(1S,8R)-5-(2,6-difluorophenyl)-11,11-dimethyl-3,4-diazatricyc...
RORc 조절제로서의 피리다진 유도체하기 화학식 I의 화합물 또는 이의 약학적인 염이 개시된다: [화학식 I] 상기 식에서, m, n, p, q, A, B, R1, R2, R3, R4, R5, R6 및 R7은 본원에서 정의된 바와 같다. 또한, 상기 화합물의 제조 방법, 및 염증성 질환(예컨대, 관절염)의 치료를 위한 RORc 조절제로서 상기 화합물을 사용하는 방법이 개시된다.하기 화학식 I의 화합물 또는 이의 약학적으로 허용가능한 염:[화학식 I]상기 식에서,A는, 피리딘일, 피리미딘일, 피리다진일 및 피라진일로부터 선택되는 헤테로아릴이고; B는, 옥사졸릴, 이속사졸릴, 티아졸릴, 이소티아졸릴, 피롤릴, 이미다졸릴, 피리다졸릴, 트라이아졸릴, 옥사다이아졸릴, 티아다이아졸릴, 피리딘일, 피리미딘일, 피라진일, 피리다진일 및 2,3-다이하이드로-1H-이미다조[4,5-b]피리딘일로부터 선택되는 헤테로아릴이거나, B는 피페리딘일이고;m은 0, 1 또는 2이고;n은 0 또는 1이고;p는 0 또는 1이고;q는 0 또는 1이고;R1은 할로이고;R2는 수소, 할로 또는 메톡시이고;R3은 수소, 시아노, C1-6알킬, 또는 할로이고; R4는 C1-6알킬(이는 비치환되거나 할로로 1회 이상 치환될 수 있음), C2-6알켄일, 시아노, 하이드록실-C1-6알킬(이때, 상기 C1-6알킬 잔기는 비치환되거나 할로로 1회 이상 치환될 수 있음), C1-6알콕시C1-6알킬(이때, 상기 C1-6알킬 잔기는 비치환되거나 할로로 1회 이상 치환될 수 있음), 옥소, 하이드록시, C1-6알킬설핀일, 또는 할로이고;R5는-(CRa1Ra2)p-NRbRc,-(CRa1Ra2)p-SO2-Rd,-(CRa1Ra2)p-C(O)-Re, -(CRa1Ra2)p-NRb-SO2-Rd,-(CRa1Ra2)p-NRb-C(O)-Re,-(CRa1Ra2)p-NRb-(CHRc)q-SO2-Rd,-(CRa1Ra2)p-NRb-(CHRc)q-C(O)-Re,-(CRa1Ra2)p-CN,-C2-6알켄일-CN, -(CRa1Ra2)p-Z, -(CRa1Ra2)p-SO2-Z, C1-6알킬설폰이미드아마이도, 또는C1-6알킬설폰이미도일C1-6알킬이고;R6는 C1-6알킬, 할로 또는 하이드록실이고;R7은 C1-6알킬, C1-6알콕시, 할로 또는 하이드록실이고;Z는C3-6사이클로알킬(이는 비치환되거나 Rf로 1 또는 2회 치환될 수 있음),4원 또는 5원 헤테로사이클릴(이는, 각각 비치환되거나 Rf로 1회 또는 2회 치환될 수 있는, 아제티딘일, 옥세탄일, 티에탄일 및 테트라하이드로티오페닐로부터 선택됨),C1-6알킬-헤테로사이클릴(이때, 상기 헤테로사이클릴은, 각각 비치환되거나 Rf로 1회 또는 2회 치환될 수 있는, 아제티딘일, 옥세탄일, 티에탄일 및 테트라하이드로티오페닐로부터 선택되는 4원 또는 5원 헤테로사이클릴임), 또는C1-6알킬카보닐아미노C1-6알킬이고;p는 0, 1, 2 또는 3이고;q는 1 또는 2이고;Ra1은 수소 또는 C1-6알킬(이는 비치환되거나 할로로 1회 이상 치환될 수 있음)이고;Ra2는 수소, C1-6알킬(이는 비치환되거나 할로로 1회 이상 치환될 수 있음) 또는 하이드록실이거나;Ra1과 Ra2가 함께 =CH2 기를 형성할 수 있고;Rb는 수소, C1-6알킬(이는 비치환되거나 할로로 1회 이상 치환될 수 있음), 또는 하이드록실-C1-6알킬(이때, 상기 C1-6알킬 잔기는 비치환되거나 할로로 1회 이상 치환될 수 있음)이고;Rc는 수소 또는 C1-6알킬(이는 비치환되거나 할로로 1회 이상 치환될 수 있음)이고; Rd는 C1-6알킬(이는 비치환되거나 할로로 1회 이상 치환될 수 있음), C3-6사이클로알킬, C3-6사이클로알킬-C1-6알킬, 하이드록시C1-6알킬, 또는 NRbRc이고;Re는 C1-6알킬(이는 비치환되거나 할로로 1회 이상 치환될 수 있음), C1-6알콕시, 하이드록실-C1-6알킬, 하이드록실, 또는 NRbRc이고;Rf는 C1-6알킬(이는 비치환되거나 할로로 1회 이상 치환될 수 있음), 할로, 옥소, 시아노C1-6알킬, 하이드록시, -CH2COOH, 하이드록시C1-6알킬, 또는 C1-6알킬설폰일C1-6알킬이고;이때 상기 화합물은 하기로부터 선택된다:3-[2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]옥세탄-3-올;[2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]메탄아민;N-[[2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]메틸]메탄설폰아마이드;2,2,2-트라이플루오로-N-[[2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]메틸]에탄아민;[2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]메틸우레아;(2S)-2-[2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]프로판-1,2-다이올;(S)-사이클로프로필-[2-[6-[(1R,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]메탄올;(R)-사이클로프로필-[2-[6-[(1R,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]메탄올;(1R)-2,2-다이플루오로-1-[2-[6-[(1R,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]에탄올;(1S)-2,2-다이플루오로-1-[2-[6-[(1R,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]에탄올(1S)-2-메틸-1-[2-[6-[(1R,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]프로판-1-올;2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]-4-[(1R)-1-메틸설폰일에틸]옥사졸;2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]-4-[(1S)-1-메틸설폰일에틸]옥사졸;4-(이소프로필설폰일메틸)-2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸;(2S)-2-[2-[6-[(1R,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]프로판아마이드;(2R)-2-[2-[6-[(1R,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]프로판아마이드;N-(2-하이드록시에틸)-2-[2-[6-[(1R,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]아세트아마이드;3-[4-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]피라졸-1-일]프로판나이트릴;(2R)-1-[4-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]피라졸-1-일]프로판-2-올;(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-1-[6-[1-(2-메틸설폰일에틸)피라졸-4-일]피라진-2-일]-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔;(2S)-1-[4-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]피라졸-1-일]프로판-2-올;N-[(1R)-1-[2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]에틸]메탄설폰아마이드;[5-메틸-2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]메탄올;5-메틸-4-(메틸설폰일메틸)-2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸;에틸 N-[[2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔-1-일]피라진-2-일]옥사졸-4-일]메틸]카바메이트;[2-[6-[(1S,8R)-5-(2,6-다이플루오로페닐)-11,11-다이메틸-3,4-다이아자트라이사이클로[6.2.1.02,7]운데카-2(7),3,5-트라이엔...