Triazolopyridine JAK inhibitor compounds and methods

摘要

A 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.;

主权项

1. A compound of Formula Ienantiomers, diastereomers, tautomers or pharmaceutically acceptable salts thereof, wherein:
R1 is C(O)ORa, phenyl, C1-C9 heterocyclyl or C1-C9 heteroaryl, wherein said phenyl and heteroaryl are optionally substituted by 1 to 5 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, OCH3, CF3, 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, CF3, S(O)1-2NRaRb, C(O)Ra, NRaC(O)ORb, NRaS(O)1-2NRb, (C0-C6 alkyl)C1-C5 heteroaryl, (C0-C6 alkyl)C1-C5 heterocyclyl, (C0-C6 alkyl)C3-C6 cycloalkyl, (C0-C6 alkyl)C6-C9 aryl, (C0-C6 alkyl)C(O)ORa, C(O)(C0-C5 alkyl)NRaRb, C(O)(C0-C5 alkyl)(C1-C5 heterocyclyl), C(O)NRa(C0-C5 alkyl)(C1-C5 heterocyclyl), C(O)NRa(C0-C5 alkyl)(C3-C6 cycloalkyl), C(O)NRa(C0-C5 alkyl)(C1-C5 heteroaryl), C(O)NRa(C1-C5 alkyl)NRaRb or C(O)NRa(C1-C5 alkyl)(C6 aryl), wherein said alkyl, alkenyl and alkynyl are optionally substituted by 1 to 5 substituents independently selected from ORa, NRcRd, oxo and halo, and said aryl, heterocyclyl, heteroaryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from ORa, oxo, halo, CF3, NRcRd, C1-C4 alkyl, (C0-C6 alkyl)C1-C5 heterocyclyl and C(O)(C1-C4 alkyl); R7 is independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, (C0-C6 alkyl)ORa, (C0-C6 alkyl)NRaRb, (C0-C6 alkyl)(C6-C9 aryl), halo, C(O)NRaRb, NRaC(O)Rb, SO2(C1-C6 alkyl), SO2NRaRb, CN, CF3, CH2CF3, nitro, S(O)(C1-C6 alkyl), S(O)NRaRb, NRaS(O)1-2Rb, C(O)Ra, C(O)ORa, (C0-C6 alkyl)C1-C5 heteroaryl, (C0-C6 alkyl)C1-C5 heterocyclyl or (C0-C6 alkyl)C3-C6 cycloalkyl, wherein said alkyl, alkenyl and alkynyl are optionally substituted by 1 to 5 substituents independently selected from oxo, NRaRb, ORa, and halo, and said aryl, heteroaryl, heterocyclyl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from ORa, halo, CF3, NRcRd and C1-C4 alkyl; Ra and Rb are independently H, ORc, C(O)O(C1-C6 alkyl), C1-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 C1-C4 alkyl, (C0-C3 alkyl)ORc, oxo, halo, NRcRd and C4-C5 heterocyclyl; or Ra and Rb together with the atom to which they are attached form a C1-C5 heterocyclyl; and Rc and Rd are independently H, C1-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, CH3OH or NH2, C(O)O(C1-C6 alkyl) and C(O)NH(C1-C6 alkyl).