Substituted quinazolines as kinase inhibitors

• US 9,359,349 B2
• Filed: 09/19/2014
• Issued: 06/07/2016
• Est. Priority Date: 10/04/2007
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Intellikine LLC (Takeda Pharmaceutical Company Limited)
• Inventors: Ren, Pingda, Liu, Yi, Wilson, Troy Edward
• Primary Examiner(s): Willis, Douglas M
• Application Number:
  US14/491,929
• Publication Number:
  US 20150141442A1
• Time in Patent Office: 627 Days
• Field of Search: 514/266.4, 544/292, 546/113, 546/304
• US Class Current: 1/1
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 239/42 One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 239/84 Nitrogen atoms
• CPC Class Codes: C07D 239/94 Nitrogen atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides compounds of Formula I

that modulate PI3 kinase activity and methods of treatment of diseases and conditions associated with PI3 kinase activity.

Claims

1. A compound of Formula II:

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R¹ is unsubstituted methyl.

3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R¹ is methyl substituted with one or more fluoro.

4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R² is aryl, substituted at one or both meta positions.

5. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R² is a bicyclic aryl or bicyclic heteroaryl.

6. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R⁵ is alkyl, aryl, or heteroaryl, each of which is optionally substituted.

7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1, or a pharmaceutically acceptable salt thereof.

8. The pharmaceutical composition of claim 7 wherein the composition is formulated as a solid, semi-solid, liquid, or aerosol dosage form.

9. A compound selected from the group consisting of: