Heteroaryl Substituted Pyrrolo[2,3-B] Pyridines And Pyrrolo[2,3-B] Pyrimidines As Janus Kinase Inhibitors

• US 20160346286A1
• Filed: 08/10/2016
• Published: 12/01/2016
• Est. Priority Date: 12/13/2005
• Status: Active Grant

• Current Assignee: Incyte Corporation, Incyte Holdings Corporation (Incyte Corporation)
• Original Assignee: Incyte Corporation, Incyte Holdings Corporation (Incyte Corporation)
• Inventors: Rodgers, James D., Shepard, Stacey
• Granted Patent: US 9,814,722 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 59/002 Heterocyclic compounds
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The present invention provides heteroaryl substituted pyrrolo[2,3-b]pyridines and heteroaryl substituted pyrrolo[2,3-b]pyrimidines that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.

Claims

1-88. -88. (canceled)

89. A method of treating a disease selected from allograft rejection and graft versus host disease in a patient in need thereof, comprising administering to the patient a compound, which is 3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof.

90. The method of claim 89, wherein the compound is (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof.

91. The method of claim 90, wherein the disease is graft versus host disease.

92. The method of claim 91, wherein about 5 to about 1000 mg of the compound, or pharmaceutically acceptable salt thereof, is administered to the patient.

93. The method of claim 91, further comprising administering to the patient at least one additional therapeutic agent.

94. The method of claim 93, wherein the therapeutic agent is administered to a patient simultaneously or sequentially.

95. The method of claim 93, wherein said therapeutic agent is an immunosuppressant.

96. The method of claim 93, wherein said therapeutic agent is a steroid.

97. The method of claim 93, wherein said therapeutic agent is a corticosteroid.

98. The method of claim 97, wherein said corticosteroid is dexamethasone or prednisone.

99. The method of claim 97, wherein said corticosteroid is dexamethasone.

100. The method of claim 97, wherein said corticosteroid is prednisone.

101. The method of claim 90, wherein the disease is allograft rejection.

102. The method of claim 101, wherein about 5 to about 1000 mg of the compound, or pharmaceutically acceptable salt thereof, is administered to the patient.

103. The method of claim 101, further comprising administering to the patient at least one additional therapeutic agent.

104. The method of claim 103, wherein the therapeutic agent is administered to a patient simultaneously or sequentially.

105. The method of claim 103, wherein said therapeutic agent is an immunosuppressant.

106. The method of claim 103, wherein said therapeutic agent is a steroid.

107. The method of claim 103, wherein said therapeutic agent is a corticosteroid.

108. The method of claim 107, wherein said corticosteroid is dexamethasone or prednisone.

109. The method of claim 107, wherein said corticosteroid is dexamethasone.

110. The method of claim 107, wherein said corticosteroid is prednisone.

111. A method of treating a disease selected from allograft rejection and graft versus host disease in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of a compound, which is 3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof.

112. The method of claim 111, wherein the compound is (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof.

113. The method of claim 112, wherein the pharmaceutical composition is suitable for oral administration.

114. The method of claim 113, wherein the pharmaceutical composition is in tablet form.

115. The method of claim 114, wherein the disease is graft versus host disease.

116. The method of claim 114, wherein the disease is allograft rejection.

117. The method of claim 112, wherein the disease is graft versus host disease.

118. The method of claim 112, wherein the disease is allograft rejection.