2,4-diaminopyrimidine compounds useful as immunosuppressantsThe patent relates to novel compounds according to formula (I) and pharmaceutically acceptable salts, solvates, or hydrates thereof; wherein each occurrence of A is independently selected from CH or N; X is selected from the group consisting of -CH2-, -O-, -NH-, (C1-C6)alkylamino-, (C1-C6)alkylaminocarbonylamino-, (C1-C6)alkylcarbonylamino-, (C1-C6)alkylsulfonylamino-, phenylsulfonylamino-, carbonyl, -NH-C(O)-, -N(C1-C6)alkyl-C(O)-, -S(O)y- where y is 0, 1 or 2, and n in-(CH2)n- is 1, 2 or 3; and R, R, and R are as described herein; pharmaceutical compositions that include these compounds, and methods for the treatment of autoimmune disease, inflammation, allergy, transplant rejection, and other circumstances where administration of an immunosuppressive agent is of therapeutic benefit.Formula (i) compound or its pharmacy acceptable salt, solvate or hydrate: wherein: each a is independently selected from ch or n:x is selected from following group group :-ch 2-,-o-,-nh-, (c 1-c 6) alkylamino-, (c 1-c 6) alkyl amino-carbonyl amino-, (c 1-c 6) alkyl-carbonyl-amino-, (c 1-c 6) alkyl sulfonyl-amino-, phenyl sulfonyl amino-, carbonyl ,-nh-c (o)-,-n (c 1-c 6) alkyl-c (o)-,-s (o) y-, wherein y is 0,1 or 2, and (ch 2) nin n be 1,2 or 3; r ' is selected from the group of following group: (c6-c 10) aryl-, (c1-c 9) heteroaryl-, (c6-c 10) aryl (c6- c 10) aryl-, (c6-c 10) aryl (c1-c 9) heteroaryl-, (c1-c 9) heteroaryl (c1-c 9) heteroaryl-, (c1-c 9) heteroaryl (c6-c 10) aryl, (c6-c 10) aryl sulfonyl kia-, (c6-c 10) aryl (c6-c 10) aryl sulfonyl kia-, (c1-c 9) heteroaryl (c6-c 10) aryl sulfonyl kia-, (c6-c 10) aryl sulfonyl-, (c6-c 10) aryl (c6-c 10) aryl sulfonyl-, (c1-c 9) heteroaryl (c6-c 10) aryl sulfonyl-, (c1-c 9) the heteroaryl sulfinyl-, (c1-c 9) heteroaryl (c1-c 9) the heteroaryl sulfinyl-, (c6-c 10) aryl (c1-c 9) the heteroaryl sulfinyl-, (c1-c 9) the heteroaryl sulfonyl-, (c1-c 9) heteroaryl (c1-c 9) the heteroaryl sulfonyl-, (c6-c 10) aryl (c1-c 9) the heteroaryl sulfonyl-, (r4) sulfinyl-, (r4) sulfonyl-, (c6-c 10) aryl (r4) sulfinyl-, (c6-c 10) aryl (c6-c 10) aryl (r4) sulfinyl-, (c1-c 9) heteroaryl (c6-c 10) aryl (r4) sulfinyl-, (c6-c 10) aryl (r4) sulfonyl-, (c6-c 10) aryl (c6-c 10) aryl (r4) sulfonyl-, (c1- c 9) heteroaryl (c6-c 10) aryl (r4) sulfonyl-, (c1-c 9) heteroaryl (r4) sulfinyl-, (c6-c 10) aryl (c1-c 9) heteroaryl (r4) sulfinyl-, (c1-c 9) heteroaryl (c1-c 9) heteroaryl (r4) sulfinyl-, (c1- c 9) heteroaryl (r4) sulfonyl-, (c6-c 10) aryl (c1-c 9) heteroaryl (r4) sulfonyl-, (c1-c 9) heteroaryl (c1-c 9) heteroaryl (r4) sulfonyl-, (c6-c 10) aromatic yl aminocarbonyl-, (c6-c 10) aryl (c6-c 10) aromatic yl aminocarbonyl-(c1-c 9) heteroaryl (c6-c 10) aromatic yl aminocarbonyl-, (c1-c 9) the heteroaryl amino carbonyl-, (c6- c 10) aryl (c1-c 9) the heteroaryl amino carbonyl-, (c1-c 9) heteroaryl (c1-c 9) the heteroaryl amino carbonyl-, (c6- c 10) aryl carbonyl-, (c6-c 10) aryl (c6-c 10) aryl carbonyl-, (c1-c 9) heteroaryl (c6-c 10) aryl carbonyl-, (c1-c 9) the heteroaryl carbonyl-, (c6-c 10) aryl (c1-c 9) the heteroaryl carbonyl-, (c1-c 9) heteroaryl (c1- c 9) the heteroaryl carbonyl-, (c6-c 10) aryl carbonyl oxygen-, (c6-c 10) aryl (c6-c 10) aryl carbonyl oxygen-, (c1- c 9) heteroaryl (c6-c 10) aryl carbonyl oxygen-, (c1-c 9) assorted aryloxycarbonyl-, (c6-c 10) aryl (c1-c 9) assorted aryloxycarbonyl-, (c1-c 9) heteroaryl (c1-c 9) assorted aryloxycarbonyl-, (r4) carbonyl-, (r4) the oxygen carbonyl-, (r4) amino carbonyl-, (c6-c 10) aryl (r4) carbonyl-, (c6-c 10) aryl (r4) the oxygen carbonyl-, (c6-c 10) aryl (r4) amino carbonyl-, (c1-c 9) heteroaryl (r4) carbonyl-, (c1-c 9) heteroaryl (r4) the oxygen carbonyl-, and (c1-c 9) heteroaryl (r4) amino carbonyl-;r wherein 4be to be selected from following group group: (a) (c 1-c 6) alkyl-, (c 2-c 6) alkenyl-, or (c 2-c 6) alkynyl-, alkyl wherein-, alkenyl-and alkynyl-randomly replaced by following group: hydroxyl, halogen, amino, trifluoromethyl, hydroxyl (c 2-c 6) alkyl-, (c 1-c 6) alkoxyl group-, (c 1-c 6) acyloxy-, (c 1-c 6) alkylamino-, ((c 1-c 6) alkyl) 2amino-, (c 1-c 6) acyl amino-, cyano group, nitro, (c 1-c 6) alkyl-, (c 2-c 6) alkenyl-, (c 2-c 6) alkynyl-, (c 1-c 6) acyl amino-, cyano group (c 1-c 6) alkyl-, trifluoromethyl (c 1-c 6) alkyl-, (c 1-c 3) alkyl (difluoro methylene) (c 1-c 3) alkyl-, or nitro (c 1-c 6) alkyl-; (b) (c 3-c 10) cycloalkyl-, cycloalkyl is wherein randomly replaced by following group: hydroxyl, halogen, amino, trifluoromethyl, hydroxyl (c 2-c 6) alkyl-, (c 1-c 6) alkoxyl group-, (c 1-c 6) acyloxy-, (c 1-c 6) alkylamino-, ((c 1-c 6) alkyl) 2amino-, (c 1-c 6) acyl amino-, cyano group, nitro, (c 1-c 6) alkyl-, (c 2-c 6) alkenyl-, (c 2-c 6) alkynyl-, (c 1-c 6) acyl amino-, cyano group (c 1-c 6) alkyl-, trifluoromethyl (c 1-c 6) alkyl-, (c 1-c 3) alkyl (difluoro methylene) (c 1-c 3) alkyl-, or nitro (c 1-c 6) alkyl-; or (c) (c 3-c 10) heterocyclylalkyl-, heterocyclylalkyl wherein-randomly replaced: hydroxyl, halogen, amino, trifluoromethyl, hydroxyl (c by following group 2-c 6) alkyl-, (c 1-c 6) alkoxyl group-, (c 1-c 6) acyloxy-, (c 1-c 6) alkylamino-, ((c 1-c 6) alkyl) 2amino-, (c 1-c 6) acyl amino-, cyano group, nitro, (c 1-c 6) alkyl-, (c 2-c 6) alkenyl-, (c 2-c 6) alkynyl-, (c 1-c 6) acyl amino-, cyano group (c 1-c 6) alkyl-, trifluoromethyl (c 1-c 6) alkyl-, (c 1-c 3) alkyl (difluoro methylene) (c 1-c 3) alkyl-, or nitro (c 1-c 6) alkyl-; and described any (the c among the r ' wherein 6-c 10) aryl-or (c 1-c 9) heteroaryl-can randomly be replaced by 1-5 following group: (a) deuterium, hydroxyl, halogen, amino, trifluoromethyl, carboxyl, (c1-c 6) alkoxyl-, (c1-c 6) acyloxy-, (c1-c 6) alkyl amino-, ((c1-c 6) alkyl)2amino-, (c1-c 6) acyl group amino-, cyano group, nitro, (c1-c 6) alkyl-, (c2-c 6) alkenyl-, (c2-c 6...
면역 억제제로 유용한 2,4-디아미노피리미딘 화합물 하기 화학식 I의 화합물, 또는 제약학적으로 허용 가능한 이들의 염, 용매화물 또는 수화물; 이러한 화합물을 포함하는 제약 조성물; 자가 면역 질병, 염증성 질병, 알레르기, 이식 거부, 및 면역 억제제의 투여가 치료적 유용성을 가져다 주는 또 다른 경우를 치료하기 위한 방법. [화학식 I]  (상기 식에서, 각각의 A는 CH 또는 N에서 독립적으로 선택되고, X는 -CH2-,-O-, -NH-, (C1-C6)알킬아미노-, (C1-C6)알킬아미노카르보닐아미노-, (C1-C6)알킬카르보닐아미노-, (C1-C6)알킬설포닐아미노-, 페닐설포닐아미노-, 카르보닐, -NH-C(O)-, -N(C1-C6)알킬-C(O)-, 및 -S(O)y-(여기서 y는 0, 1 또는 2임)로 구성되는 군에서 선택되고, (CH2)n의 n은 1, 2 또는 3이고, R1, R2, 및 R3은 명세서에 정의된 것과 같음)하기 화학식 I의 화합물, 또는 제약학적으로 허용 가능한 이들의 염, 용매화물 또는 수화물. [화학식 I] [이미지] 상기 식에서, 각각의 A는 CH 또는 N에서 독립적으로 선택되고, X는 -CH2-,-O-, -NH-, (C1-C6)알킬아미노-, (C1-C6)알킬아미노카르보닐아미노-, (C1-C6)알킬카르보닐아미노-, (C1-C6)알킬설포닐아미노-, 페닐설포닐아미노-, 카르보닐, -NH-C(O)-, -N(C1-C6)알킬-C(O)-, 및 -S(O)y-(여기서 y는 0, 1 또는 2임)로 구성되는 군에서 선택되고, (CH2)n의 n은 1, 2 또는 3이고, R1은 (C6-C10)아릴-, (C1-C9)헤테로아릴-, (C6-C10)아릴(C6-C10)아릴-, (C6-C10)아릴(C1-C9)헤테로아릴-, (C1-C9)헤테로아릴(C1-C9)헤테로아릴-, (C1-C9)헤테로아릴(C6-C10)아릴-, (C6-C10)아릴설피닐-, (C6-C10)아릴(C6-C10)아릴설피닐-, (C1-C9)헤테로아릴(C6-C10)아릴설피닐-, (C6-C10)아릴설포닐-, (C6-C10)아릴(C6-C10)아릴설포닐-, (C1-C9)헤테로아릴(C6-C10)아릴설포닐-, (C1-C9)헤테로아릴설피닐-, (C1-C9)헤테로아릴(C1-C9)헤테로아릴설피닐-, (C6-C10)아릴(C1-C9)헤테로아릴설피닐-, (C1-C9)헤테로아릴설포닐-, (C1-C9)헤테로아릴(C1-C9)헤테로아릴설포닐-, (C6-C10)아릴(C1-C9)헤테로아릴설포닐-, (R4)설피닐-, (R4)설포닐-, (C6-C10)아릴(R4)설피닐-, (C6-C10)아릴(C6-C10)아릴(R4)설피닐-, (C1-C9)헤테로아릴(C6-C10)아릴(R4)설피닐-, (C6-C10)아릴(R4)설포닐-, (C6-C10)아릴(C6-C10)아릴 (R4)설포닐-, (C1-C9)헤테로아릴(C6-C10)아릴(R4)설포닐-, (C1-C9)헤테로아릴(R4) 설피닐-, (C6-C10)아릴(C1-C9)헤테로아릴(R4)설피닐-, (C1-C9)헤테로아릴(C1-C9)헤테로아릴(R4)설피닐-, (C1-C9)헤테로아릴(R4)설포닐-, (C6-C10)아릴(C1-C9)헤테로아릴(R4)설포닐-, (C1-C9)헤테로아릴(C1-C9)헤테로아릴(R4)설포닐-, (C6-C10)아릴아미노카르보닐-, (C6-C10)아릴(C6-C10)아릴아미노카르보닐-, (C1-C9)헤테로아릴(C6-C10)아릴아미노카르보닐-, (C1-C9)헤테로아릴아미노카르보닐-, (C6-C10)아릴(C1-C9)헤테로아릴아미노카르보닐-, (C1-C9)헤테로아릴(C1-C9)헤테로아릴아미노카르보닐-, (C6-C10)아릴카르보닐-, (C6-C10)아릴(C6-C10)아릴카르보닐-, (C1-C9)헤테로아릴(C6-C10)아릴카르보닐-, (C1-C9)헤테로아릴카르보닐-, (C6-C10)아릴(C1-C9)헤테로아릴카르보닐-, (C1-C9)헤테로아릴(C1-C9)헤테로아릴카르보닐-, (C6-C10)아릴옥시카르보닐-, (C6-C10)아릴(C6-C10)아릴옥시카르보닐-, (C1-C9)헤테로아릴(C6-C10)아릴옥시카르보닐-, (C1-C9)헤테로아릴옥시카르보닐-, (C6-C10)아릴(C1-C9)헤테로아릴옥시카르보닐-, (C1-C9)헤테로아릴(C1-C9)헤테로아릴옥시카르보닐-, (R4)카르보닐-, (R4)옥시카르보닐-, (R4)아미노카르보닐-, (C6-C10)아릴(R4)카르보닐-, (C6-C10)아릴(R4)옥시카르보닐-, (C6-C10)아릴(R4)아미노카르보닐-, (C1-C9)헤테로아릴(R4)카르보닐-, (C1-C9)헤테로아릴(R4)옥시카르보닐-, 및 (C1-C9)헤테로아릴(R4)아미노카르보닐- 로 구성되는 군에서 선택되고, 여기서, R4는 하기 (a) 내지 (c)로 구성되는 군에서 선택되고, (a) (C1-C6)알킬-, (C2-C6)알케닐-, 또는 (C2-C6)알키닐- (이때, 알킬-, 알케닐- 및 알키닐- 기는 하이드록시, 할로, 아미노, 트리플루오로메틸, 하이드록시(C2-C6)알킬-, (C1-C6)알콕시-, (C1-C6)아실옥시-, (C1-C6)알킬아미노-, ((C1-C6)알킬)2아미노-, (C1-C6)아실아미노-, 시아노, 니트로, (C1-C6)알킬-, (C2-C6)알케닐-, (C2-C6)알키닐-, (C1-C6)아실아미노-, 시아노(C1-C6)알킬-, 트리플루오로메틸(C1-C6)알킬-, (C1-C3)알킬(디플루오로메틸렌)(C1-C3)알킬-, 또는 니트로(C1-C6)알킬- 에 의해 임의적으로 치환됨), (b) (C3-C10)시클로알킬- (이때, 시클로알킬- 기는 하이드록시, 할로, 아미노, 트리플루오로메틸, 하이드록시(C2-C6)알킬-, (C1-C6)알콕시-, (C1-C6)아실옥시-, (C1-C6)알킬아미노-, ((C1-C6)알킬)2아미노-, (C1-C6)아실아미노-, 시아노, 니트로, (C1-C6)알킬-, (C2-C6)알케닐-, (C2-C6)알키닐-, (C1-C6)아실아미노-, 시아노(C1-C6)알킬-, 트리플루오로메틸(C1-C6)알킬-, (C1-C3)알킬(디플루오로메틸렌)(C1-C3)알킬-, 또는 니트로(C1-C6)알킬- 에 의해 임의적으로 치환됨), 및 (c) (C3-C10)헤테로시클로알킬- (이때, 헤테로시클로알킬- 기는 하이드록시, 할로, 아미노, 트리플루오로메틸, 하이드록시(C2-C6)알킬-, (C1-C6)알콕시-, (C1-C6)아실옥시-, (C1-C6)알킬아미노-, ((C1-C6)알킬)2아미노-, (C1-C6)아실아미노-, 시아노, 니트로, (C1-C6)알킬-, (C2-C6)알케닐-, (C2-C6)알키닐-, (C1-C6)아실아미노-, 시아노(C1-C6)알킬-, 트리플루오로메틸(C1-C6)알킬-, (C1-C3)알킬(디플루오로메틸렌)(C1-C3)알킬-, 또는 니트로(C1-C6)알킬- 에 의해 임의적으로 치환됨) 이때, R1기의 임의의 (C6-C10)아릴- 또는 (C1-C9)헤테로아릴- 기는 하기 (a) 내지 (c)에서 선택되는 1개 내지 5개의 기에 의해 임의적으로 치환될 수 있고, (a) 중수소, 하이드록시, 할로, 아미노, 트리플루오로메틸, 카르복시, (C1-C6)알콕시-, (C1-C6)아실옥시-, (C1-C6)알킬아미노-, ((C1-C6)알킬)2아미노-, (C1-C6)아실아미노-, 시아노, 니트로, (C1-C6)알킬-, (C2-C6)알케닐-, (C2-C6)알키닐-, (C1-C6)아실아미노-, 시아노(C1-C6)알킬-, 트리플루오로메틸(C1-C6)알킬-, 또는 니트로 (C1-C6)알킬-, (C1-C3)알킬(디플루오로메틸렌)(C1-C3)알킬-, (C1-C6)아실아미노(C1-C6)알킬-, (C1-C6)알콕시(C1-C6)아실아미노-, 아미노(C1-C6)아실-, 아미노(C1-C6)아실(C1-C6)알킬-, (C1-C6)알킬아미노(C1-C6)아실-, ((C1-C6)알킬)2아미노(C1-C6)아실-, (C3-C10)시클로알킬(C1-C6)알킬-, (C1-C6)아실옥시 (C1-C6)알킬-, (C2-C6)알콕시(C1-C6)알킬-, 피페라지닐(C1-C6)알킬-, (C1-C6)아실아미노(C1-C6)알킬-, (C6-C10)아릴(C1-C6)알콕시(C1-C6)알킬-, (C5-C9)헤테로아릴(C1-C6)알콕시(C1-C6)알킬-, (C1-C6)알킬티오(C1-C6)알킬-, (C6-C10)아릴티오(C1-C6)알킬-, (C1-C6)알킬설피닐(C1-C6)알킬-, (C6-C10)아릴설피닐(C1-C6)알킬-, (C1-C6)알킬설포닐(C1-C6)알킬-, (C6-C10)아릴설포닐(C1-C6)알킬-, 아미노(C1-C6)알킬-, (C1-C6)알킬아미노(C1-C6)알킬-, (C1-C6)알킬(디플루오로메틸렌)-, (C1-C3)알킬(디플루오로메틸렌)(C1-C3)알킬-, (C1-C6)알콕시(C1-C6)아실-, (C1-C6)알킬아미노(C1-C6)아실-, ((C1-C6)알킬)2아미노(C1-C6)아실-, (C6-C10)아릴-, (C1-C9)헤테로아릴-, (C6-C10)아릴(C1-C6)알킬-, (C1-C9)헤테로아릴(C1-C6)알킬-, (C6-C10)아릴(C6-C10)아릴-, (C6-C10)아릴(C6-C10)아릴(C1-C6)알킬-, (C3-C10)시클로알킬-, (C3-C6)시클로알킬(C1-C6)알킬-, (C3-C10)헤테로시클로알킬-, (C3-C10)헤테로시클로알킬(C1-C6)알킬-, 하이드록시(C2-C6)알킬-, (C1-C6)아실옥시(C2-C6)알킬-, (C1-C6)알콕시(C2-C6)알킬-, 피페라지닐(C1-C6)알킬-, (C1-C6)아실아미노(C1-C6)알킬-, (C6-C10)아릴(C1-C6)알콕시(C1-C6)알킬-, (C1-C9)헤테로아릴(C1-C6)알콕시(C1-C6)알킬-, (C1-C6)알킬티오(C1-C6)알킬-, (C6-C10)아릴티오(C1-C6)알킬-, (C1-C6)알킬설피닐(C1-C6)알킬-, (C6-C10)아릴설피닐(C1-C6)알킬-, (C1-C6)알킬설포닐(C1-C6)알킬-, (C6-C10)아릴설포닐(C1-C6)알킬-, 아미노(C1-C6)알킬-, (C1-C6)알킬아미노(C1-C6)알킬-, ((C1-C6)알킬)2아미노(C1-C6)알킬-, (b) R5OCO(C1-C6)알킬- (이때, R5는 수소, (C1-C6)알킬-, (C6-C10)아릴(C1-C6)알킬-, (C1-C9)헤테로아릴(C1-C6)알킬- 로 구성되는 군에서 선택됨), (c) R6(C0-C6)알킬- (이때, R6은 피페라지노, (C1-C6)아실피페라지노-, (C6-C10)아릴피페라지노, (C5-C9)헤테로아릴피페라지노, (C1-C6)알킬피페라지노-, (C6-C10)아릴(C1-C6)알킬피페라지노-, (C1-C9)헤테로아릴(C1-C6)알킬피페라지노-, 모르폴리노-, (C1-C6)아실모르폴리노-, (C6-C10)아릴모르폴리노-, (C1-C9)헤테로아릴모르폴리노-, (C1-C6)알킬모르폴리노-, (C6-C10)아릴(C1-C6)알킬모르폴리노-, (C1-C9)헤테로아릴(C1-C6)알킬모르폴리노-, 티오모르폴리노-, (C1-C6)아실티오모르폴리노-, (C6-C10)아릴티오모르폴리노-, (C1-C9)헤테로아릴티오모르폴리노-, (C1-C6)알킬티오모르폴리노-, (C6-C10)아릴(C1-C6)알킬티오모르폴리노-, (C1-C9)헤테로아릴(C1-C6)알킬티오모르폴리노-, 피페리디노-, (C1-C6)아실피페리디노-, (C6-C10)아릴피페리디노-, (C1-C9)헤테로아...