Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors

摘要

The disclosure relates to a family of compounds as shown in Formula I, wherein A, L, W, X, Y, Z, R1, R2, R3 and R5 are as disclosed in the specification. These cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives are useful as Janus kinase (JAK) inhibitors. The disclosure also relates to a method of treating an autoimmune disease, a cancer, a myeloproliferative disorder, an inflammatory disease, a bone resorption disease, or organ transplant rejection in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of these compounds. Examples of these compounds include: 4-{ cis-3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutyl} -N-[(1R)-1-methylpropyl]piperazine-1-carboxamide; { cis-3-(4-{ [6-(azetidin-1-ylmethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy} piperidin-1-yl)-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutyl} acetonitrile; { trans-3-(4-{ [4-(1-hydroxy-1-methylethyl)-6-(trifluoromethyl)pyridin-2-yl]carbonyl} piperazin-1-yl)-1-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]cyclobutyl} acetonitrile; { trans-3-(4-{ [6-(1-hydroxy-1-methylethyl)-2-(trifluoromethyl)pyrimidin-4-yl]carbonyl} piperazin-1-yl)-1-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]cyclobutyl} acetonitrile.