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

• US 20150238492A1
• Filed: 05/13/2015
• Published: 08/27/2015
• Est. Priority Date: 12/13/2005
• Status: Abandoned Application

• Current Assignee: Incyte Corporation, Incyte Holdings Corporation (Incyte Corporation)
• Original Assignee: Incyte Corporation
• Inventors: Rodgers, James D., Shepard, Stacey, Fridman, Jordan S., Vaddi, Krishna
• Application Number:
  US14/711,576
• Publication Number:
  US 20150238492A1
• 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 skin disorder in a patient, comprising administering to the skin of said 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;

wherein said administering is topical administration.

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 said topical administration is transdermal administration.

92. The method of claim 90, wherein said topical administration is transdermal administration epidermal administration.

93. The method of claim 90, wherein said compound or salt is administered in the form of a pharmaceutical composition comprising said compound or salt and a pharmaceutically acceptable carrier.

94. The method of claim 93, wherein said pharmaceutical composition is a cream.

95. The method of claim 93, wherein said pharmaceutical composition is an ointment.

96. The method of claim 93, wherein said pharmaceutical composition is a lotion.

97. The method of claim 93, wherein said pharmaceutical composition is a gel.

98. The method of claim 90, wherein a therapeutically effective amount of said compound or salt is administered to the skin of said patient.

99. The method of claim 98, wherein the skin disorder is psoriasis.

100. The method of claim 98, wherein the skin disorder is psoriasis vulgaris.

101. The method of claim 98, wherein skin disorder is atopic dermatitis, skin rash, skin irritation, or skin sensitization.

102. The method of claim 90, wherein the individual is need of inhibition of JAK1 and/or JAK2.

103. A pharmaceutical composition, comprising a compound, which 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, and a pharmaceutically acceptable carrier, wherein said pharmaceutical composition is suitable for topical administration.

104. The pharmaceutical composition of claim 103, wherein the compound is a pharmaceutical salt of (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile.

105. The pharmaceutical composition of claim 103, wherein said composition is a cream.

106. The pharmaceutical composition of claim 103, wherein said composition is an ointment.

107. The pharmaceutical composition of claim 103, wherein said composition is a lotion.

108. The pharmaceutical composition of claim 103, wherein said composition is a gel.

109. The pharmaceutical composition of claim 103, wherein said composition is suitable for epidermal administration.

110. A method of treating a JAK-associated disease in a patient, comprising administering to the skin of said 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;

wherein said administering is topical administration.

111. The method of claim 110, 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.

112. The method of claim 111, wherein said topical administration is transdermal.

113. The method of claim 111, wherein said topical administration is epidermal.

114. The method of claim 111, wherein said compound or salt is administered in the form of pharmaceutical composition comprising said compound or salt and a pharmaceutically acceptable carrier.

115. The method of claim 114, wherein said pharmaceutical composition is a cream.

116. The method of claim 114, wherein said pharmaceutical composition is an ointment.

117. The method of claim 114, wherein said pharmaceutical composition is a lotion.

118. The method of claim 114, wherein said pharmaceutical composition is a gel.

119. The method of claim 111, wherein the JAK-associated skin disease in a patient is associated with inhibiting JAK1 and/or JAK2 in a patient in need thereof.

120. A method of inhibiting JAK1 and/or JAK2 associated with a skin disease in a patient in need thereof, comprising administering to the skin of said patient a compound, which 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;

wherein said administering is topical administration.