TRIAZOLOPYRIDINE JAK INHIBITOR COMPOUNDS AND METHODSA compound of Formula I, enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4 and R5 are defined herein, are useful as JAK kinase inhibitors. A pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of JAK kinase activity in a patient are disclosed.A compound of Formula II enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein:R1 is H, C(O)ORa, phenyl or C1-C9 heteroaryl, wherein said phenyl and heteroaryl are optionally substituted by 1 to 6 R6;R2 is phenyl, C1-C9 heteroaryl or C1-C9 heterocyclyl, wherein the phenyl, heteroaryl and heterocyclyl are optionally substituted by 1 to 5 R7;R3, R4 and R5 are independently H, CH3, CH2CH3, CF3, F or Cl, with the proviso that when R1 is H, then R4 is H, CH3, CH2CH3, F or Cl;R6 is independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, (C0- C6 alkyl)ORa, (C0-C6 alkyl)NRaRb, halo, CN, S(O)1 -2R3, S(O)i-2NRaRb, NR3S(O) i-2Rb, NRaC(O)Rb, NRaC(0)0Rb, OC(O)NRaRb, CF3 (C0-C5 alkyl)C,- C5 heteroaryl, (C0-C5 alkyl)d-C5 heterocyclyl, (C0-C5 alkyl)C3-C6 cycloalkyl, (C0-C5 alkyl)C6-C9 aryl, C(O)OR3, C(O)(C0-C5 alkyl)NR3Rb, C(O)(C0-C5 alkyl)(Ci-C5 heterocyclyl), C(O)NRa(C0-C5 alkyl)(C,-C5 heterocyclyl), C(O)NR3(C0-C5 alkyl)(C3-C6 cycloalkyl), C(O)NRa(C0-C5 alkyl)(C,-C5 heteroaryl), C(O)NR3(Ci-C5 alkyl)NRaRb, C(O)NRa(C,-C5 alkyl)(C6 aryl), wherein said alkyl, alkenyl and alkynyl are optionally substituted by 1 to 5 substituents independently selected from ORa, NRcRd, oxo, S(O)i-2Ra, S(O)i. 2NRaRb, and halo, and said aryl, heterocyclyl, heteroaryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from (C0- C5 alkyl)0R3, oxo, halo, CF3, (C0-C5 alkyl)NRcRd, Ci-C4 alkyl and C(O)RC; R7 is independently H, Ci-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, (C0- C6 alkyl)ORa, (C0-C6 alkyl)NRaRb, (C0-C6 alkyl)C,-C5 heterocyclyl, C(O)(C0- C6 alkyl)Ci-C5 heterocyclyl, (C0-C6 alkyl)(C6-C9 aryl), halo, CF3, OCF3, C(O)NRa(C0-C6 alkyl)Ci-C5 heterocyclyl,C(O)NRaRb, NRaC(0)Rb, SO2(Ci-C6 alkyl), SO2NRaRb, S(O)]-2Ra, S(O)NRaRb, NRaS(0)1-2Rb, CN, nitro, wherein said alkyl, alkenyl and alkynyl are optionally substituted by 1 to 5 substituents independently selected from oxo and halo, and said aryl and heterocyclyl are optionally substituted by 1 to 5 substituents independently selected from 0Ra, halo, CF3, NRcRd, oxo and Ci-C4 alkyl; Ra and Rb are independently H, ORC, C(O)O(C1-C6 alkyl), CrC6 alkyl,C6 aryl or C3-C6 cycloalkyl, wherein said alkyl, aryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from CpC4 alkyl, (C0-C3 alkyl)ORc, oxo, halo, NRcRd and C4-C5 heterocyclyl; orRa and Rb together with the atom to which they are attached form a Cp C5 heterocyclyl, optionally substituted by oxo, halo or Cj-C3 alkyl; andRc and Rd are independently H, Ci-C3 alkyl, C3-C6 cycloalkyl or phenyl, wherein said alkyl, cycloalkyl and phenyl are optionally substituted by 1 to 5 substituents independently selected from halo, CH3 OH or NH2, C(O)O(C1-C6 alkyl) and C(O)NH(C-C6 alkyl). 2. The compound of claim 1, selected from Formula I:enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein: R1 is H, C(O)ORa, phenyl or CpC9 heteroaryl, wherein said phenyl and heteroaryl are optionally substituted by 1 to 6 R6;R2 is phenyl, Ci-C9 heteroaryl or Ci-C9 heterocyclyl, wherein the phenyl, heteroaryl and heterocyclyl are optionally substituted by 1 to 5 R7; R3, R4 and R5 are independently H, CH3, CH2CH3, CF3, F or Cl, with the proviso that when R1 is H, then R4 is H, CH3, CH2CH3, F or Cl;R6 is independently H, Ci-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, (C0- C6 alkyl)ORa, (C0-C6 alkyl)NRaRb, halo, CN, Ci -C5 heteroaryl, Ci-C5 heterocyclyl, C3-C6 cycloalkyl, C6-C9 aryl, C(O)OR3, C(O)(C0-C5 alkyl)NRaRb, C(O)(C0-C5 alkyl)(Ci-C5 heterocyclyl), C(O)NRa(C0-C5 alkyl)(Ci-C5 heterocyclyl), C(O)NRa(C0-C5 alkyl)(C3-C6 cycloalkyl), C(O)NRa(C0-C5 alkyl)(C,-C5 heteroaryl), C(0)NRa(CrC5 alkyl)NRaRb, C(0)NRa(Ci-C5 alkyl)(C6 aryl), wherein said alkyl, alkenyl and alkynyl are optionally substituted by 1 to 5 substituents independently selected from 0Ra, NRcRd, oxo and halo, and said aryl, heterocyclyl, heteroaryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from 0Ra, oxo, halo, CF3, NRcRd, CrC4 alkyl and C(O)(C1-C4 alkyl);R7 is independently H, Ci-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, (C0- C6 alkyl)ORa, (C0-C6 alkyl)NRaRb, (C0-C6 alkyl)(C6-C9 aryl), halo, C(0)NRaRb, NRaC(0)Rb, SO2(C1-C6 alkyl), S02NRaRb, CN, nitro, wherein said alkyl, alkenyl and alkynyl are optionally substituted by 1 to 5 substituents independently selected from oxo and halo, and said aryl is optionally substituted by 1 to 5 substituents independently selected from 0Ra, halo, CF3, NRcRd and CrC4 alkyl; Ra and Rb are independently H, ORC, C(O)O(C-C6 alkyl), C-C6 alkyl,C6 aryl or C3-C6 cycloalkyl, wherein said alkyl, aryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from Ci-C4 alkyl, (C0-C3 alkyl)ORc, oxo, halo, NRcRd and C4-C5 heterocyclyl; orRa and Rb together with the atom to which they are attached form a C- C5 heterocyclyl; and R° and Rd are independently H, C1-C3 alkyl, C3-C6 cycloa...
트리아졸로피리딘 ＪＡＫ 억제제 화합물 및 방법하기 화학식 I의 화합물, 그의 거울상이성질체, 부분입체이성질체, 호변이성질체 또는 제약상 허용가능한 염은 JAK 키나제 억제제로서 유용하다. 화학식 I의 화합물 및 제약상 허용가능한 담체, 보조제 또는 비히클을 포함하는 제약 조성물, 및 환자에서 JAK 키나제 활성의 억제에 반응성인 질환 또는 상태의 중증도를 치료하거나 감소시키는 방법이 개시된다. <화학식 I> (여기서, R1, R2, R3, R4 및 R5는 본원에서 정의됨)하기 화학식 I의 화합물, 그의 거울상이성질체, 부분입체이성질체, 호변이성질체 또는 제약상 허용가능한 염:<화학식 I>상기 식에서,R1은 H, C(O)ORa, 페닐 또는 C1-C9헤테로아릴이고, 여기서 상기 페닐 및 헤테로아릴은 1개 내지 6개의 R6으로 임의로 치환되고,R2는 페닐, C1-C9헤테로아릴 또는 C1-C9헤테로시클릴이고, 여기서 페닐, 헤테로아릴 및 헤테로시클릴은 1개 내지 5개의 R7로 임의로 치환되고,R3, R4 및 R5는 독립적으로 H, CH3, CH2CH3, CF3, F 또는 Cl이지만, 단, R1이 H인 경우에는 R4가 H, CH3, CH2CH3, F 또는 Cl이고,R6은 독립적으로 H, C1-C6알킬, C2-C6알케닐, C2-C6알키닐, (C0-C6알킬)ORa, (C0-C6알킬)NRaRb, 할로, CN, S(O)1-2Ra, S(O)1-2NRaRb, NRaS(O)1-2Rb, NRaC(O)Rb, NRaC(O)ORb, OC(O)NRaRb, CF3, (C0-C5알킬)C1-C5헤테로아릴, (C0-C5알킬)C1-C5헤테로시클릴, (C0-C5알킬)C3-C6시클로알킬, (C0-C5알킬)C6-C9아릴, C(O)ORa, C(O)(C0-C5알킬)NRaRb, C(O)(C0-C5알킬)(C1-C5헤테로시클릴), C(O)NRa(C0-C5알킬)(C1-C5헤테로시클릴), C(O)NRa(C0-C5알킬)(C3-C6시클로알킬), C(O)NRa(C0-C5알킬)(C1-C5헤테로아릴), C(O)NRa(C1-C5알킬)NRaRb 또는 C(O)NRa(C1-C5알킬)(C6아릴)이고, 여기서 상기 알킬, 알케닐 및 알키닐은 ORa, NRcRd, 옥소, S(O)1-2Ra, S(O)1-2NRaRb 및 할로로부터 독립적으로 선택된 1개 내지 5개의 치환기로 임의로 치환되고, 상기 아릴, 헤테로시클릴, 헤테로아릴 및 시클로알킬은 (C0-C5알킬)ORa, 옥소, 할로, CF3, (C0-C5알킬)NRcRd, C1-C4알킬 및 C(O)Rc로부터 독립적으로 선택된 1개 내지 5개의 치환기로 임의로 치환되고,R7은 독립적으로 H, C1-C6알킬, C2-C6알케닐, C2-C6알키닐, (C0-C6알킬)ORa, (C0-C6알킬)NRaRb, (C0-C6알킬)C1-C5헤테로시클릴, C(O)(C0-C6알킬)C1-C5헤테로시클릴, (C0-C6알킬)(C6-C9아릴), 할로, CF3, OCF3, C(O)NRa(C0-C6알킬)C1-C5헤테로시클릴, C(O)NRaRb, NRaC(O)Rb, SO2(C1-C6알킬), SO2NRaRb, S(O)1-2Ra, S(O)NRaRb, NRaS(O)1-2Rb, CN 또는 니트로이고, 여기서 상기 알킬, 알케닐 및 알키닐은 옥소 및 할로로부터 독립적으로 선택된 1개 내지 5개의 치환기로 임의로 치환되고, 상기 아릴 및 헤테로시클릴은 ORa, 할로, CF3, NRcRd, 옥소 및 C1-C4알킬로부터 독립적으로 선택된 1개 내지 5개의 치환기로 임의로 치환되고,Ra 및 Rb는 독립적으로 H, ORc, C(O)O(C1-C6알킬), C1-C6알킬, C6아릴 또는 C3-C6시클로알킬이고, 여기서 상기 알킬, 아릴 및 시클로알킬은 C1-C4알킬, (C0-C3알킬)ORc, 옥소, 할로, NRcRd 및 C4-C5헤테로시클릴로부터 독립적으로 선택된 1개 내지 5개의 치환기로 임의로 치환되거나, 또는Ra 및 Rb는 이들이 부착된 원자와 함께 옥소, 할로 또는 C1-C3알킬로 임의로 치환된 C1-C5헤테로시클릴을 형성하며, Rc 및 Rd는 독립적으로 H, C1-C3알킬, C3-C6시클로알킬 또는 페닐이고, 여기서 상기 알킬, 시클로알킬 및 페닐은 할로, CH3, OH 또는 NH2, C(O)O(C1-C6알킬) 및 C(O)NH(C1-C6알킬)로부터 독립적으로 선택된 1개 내지 5개의 치환기로 임의로 치환된다.