HETEROARYL SUBSTITUTED PYRROLO[2,3-b]PYRIDINES AND PYRROLO[2,3-b]PYRIMIDINES AS JANUS KINASE INHIBITORS

• US 20110223210A1
• Filed: 03/30/2011
• Published: 09/15/2011
• Est. Priority Date: 12/13/2005
• Status: Active Grant

• Current Assignee: Incyte Holdings Corporation And Incyte Corporation
• Original Assignee: Incyte Corporation
• Inventors: Jalluri, Ravikumar, Vaddi, Krishna, Wang, Haisheng, Shepard, Stacey, Rodgers, James D., Falahatpisheh, Nikoo, Maduskuie, Thomas P. JR., Fridman, Jordan S., Storace, Louis, Rafalski, Maria, Arvanitis, Argyrios G.
• Granted Patent: US 8,530,485 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• 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 pharmaceutical composition comprising 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;

and a pharmaceutically acceptable carrier;

wherein said composition is suitable for oral administration and for providing sustained release of said compound or said salt.

90. A pharmaceutical composition 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 pharmaceutical composition of claim 90, wherein said composition is a unit dosage form.

92. The pharmaceutical composition of claim 91, wherein said unit dosage form is a tablet.

93. The pharmaceutical composition of claim 91, wherein said unit dosage form is a capsule.

94. The pharmaceutical composition of claim 91, wherein said unit dosage form further comprises an enteric coating.

95. The pharmaceutical composition according to claim 91, wherein the unit dosage form comprises from about 5 to about 1000 mg of said compound or said salt.

96. The pharmaceutical composition according to claim 90, further comprising one or more excipients selected from lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, and methyl cellulose.

97. The pharmaceutical composition according to claim 90, further comprising microcrystalline cellulose.

98. The pharmaceutical composition according to claim 90, further comprising lactose.

99. A method of treating a disease selected from a myeloproliferative disorder and cancer in a patient, comprising administering to said patient the pharmaceutical composition according to claim 89.

100. A method of treating a disease selected from cachexia, a myeloproliferative disorder and cancer in a patient, comprising administering to said patient the pharmaceutical composition according to claim 90.

101. The method according to claim 100, wherein the disease is a myeloproliferative disorder.

102. The method according to claim 101, wherein the myeloproliferative disorder is polycythemia vera (PV), essential thrombocythemia (ET), myeloid metaplasia with myelofibrosis (MMM), chronic myelogenous leukemia (CML), chronic myelomonocytic leukemia (CMML), hypereosinophilic syndrome (HES), or systemic mast cell disease (SMCD).

103. The method according to claim 101, wherein the myeloproliferative disorder is polycythemia vera (PV).

104. The method according to claim 101, wherein the myeloproliferative disorder is essential thrombocythemia (ET).

105. The method according to claim 101, wherein the myeloproliferative disorder is myeloid metaplasia with myelofibrosis (MMM).

106. The method according to claim 101, wherein the myeloproliferative disorder is chronic myelogenous leukemia (CML).

107. The method according to claim 101, wherein the myeloproliferative disorder is chronic myelomonocytic leukemia (CMML).

108. The method according to claim 100, wherein said disease is cancer.

109. The method according to claim 108, wherein said cancer is multiple myeloma.

110. The method according to claim 108, wherein said cancer is pancreatic cancer.

111. The method according to claim 108, wherein said cancer is leukemia.

112. The method according to claim 108, wherein said cancer is lymphoma.

113. The method according to claim 108, wherein said cancer is acute myelogenous leukemia.

114. The method according to claim 108, wherein said disease is breast cancer.

115. The method according to claim 108, wherein said cancer is lung cancer.

116. The method according to claim 108, wherein said cancer is cancer of the head and neck.

117. The method according to claim 100, wherein said disease is cachexia.

118. The method according to claim 117, wherein said cachexia results from or is associated with cancer.