AZETIDINE AND CYCLOBUTANE DERIVATIVES AS JAK INHIBITORS

• US 20130225556A1
• Filed: 03/29/2013
• Published: 08/29/2013
• Est. Priority Date: 03/11/2008
• Status: Abandoned Application

• Current Assignee: Incyte Holdings Corporation And Incyte Corporation
• Original Assignee: Incyte Corporation
• Inventors: RODGERS, James D., SHEPARD, Stacey, LI, Yun-Long, ZHOU, Jiacheng, LIU, Pingli, MELONI, David, XIA, Michael
• Application Number:
  US13/853,475
• Publication Number:
  US 20130225556A1
• Time in Patent Office: Days
• US Class Current: 514/210.21
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: B60Q 3/76 : for spotlighting, e.g. reading lamps spotlighting on or for specific fittings B60Q3/20; spotlighting in mass transit vehicles B60Q3/44
• CPC Class Codes: B60Q 3/80 : Circuits; Control arrangements for dashboards B60Q3/16; for mass transit vehicles B60Q3/47
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: Y10S 362/80 : Light emitting diode
• CPC Class Codes: Y10S 362/802 : Position or condition responsive switch

Abstract

The present invention relates to azetidine and cyclobutane derivatives, as well as their compositions, methods of use, and processes for preparation, which are JAK inhibitors useful in the treatment of JAK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.

Claims

1-130. -130. (canceled)

131. {1-(cyclopropylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, or a pharmaceutically acceptable salt thereof.

136. A composition comprising a compound of claim 131, or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

137. A method of treating an autoimmune disease in a patient in need thereof, comprising administering to said patient an effective amount of a compound of claim 131, or pharmaceutically acceptable salt thereof.

138. A method of treating an inflammatory disease in a patient in need thereof, comprising administering to said patient an effective amount of a compound of claim 131, or pharmaceutically acceptable salt thereof.

132. {1-(propylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, or a pharmaceutically acceptable salt thereof.

139. A composition comprising a compound of claim 132, or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

140. A method of treating an autoimmune disease in a patient in need thereof, comprising administering to said patient an effective amount of a compound of claim 132, or pharmaceutically acceptable salt thereof.

141. A method of treating an inflammatory disease in a patient in need thereof, comprising administering to said patient an effective amount of a compound of claim 132, or pharmaceutically acceptable salt thereof.

133. {1-[(1-methyl-1H-pyrazol-3-yl)sulfonyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, or a pharmaceutically acceptable salt thereof.

142. A composition comprising a compound of claim 133, or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

143. A method of treating an autoimmune disease in a patient in need thereof, comprising administering to said patient an effective amount of a compound of claim 133, or pharmaceutically acceptable salt thereof.

144. A method of treating an inflammatory disease in a patient in need thereof, comprising administering to said patient an effective amount of a compound of claim 133, or pharmaceutically acceptable salt thereof.

134. 3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutanecarbonitrile, or a pharmaceutically acceptable salt thereof.

145. A composition comprising a compound of claim 134, or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

146. A method of treating an autoimmune disease in a patient in need thereof, comprising administering to said patient an effective amount of a compound of claim 134, or pharmaceutically acceptable salt thereof.

147. A method of treating an inflammatory disease in a patient in need thereof, comprising administering to said patient an effective amount of a compound of claim 134, or pharmaceutically acceptable salt thereof.

135. {1-(ethylsulfonyl)-3-[3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile, or a pharmaceutically acceptable salt thereof.

148. A composition comprising a compound of claim 135, or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

149. A method of treating an autoimmune disease in a patient in need thereof, comprising administering to said patient an effective amount of a compound of claim 135, or pharmaceutically acceptable salt thereof.

150. A method of treating an inflammatory disease in a patient in need thereof, comprising administering to said patient an effective amount of a compound of claim 135, or pharmaceutically acceptable salt thereof.