Heterocyclylamines as PI3K inhibitors

• US 10,646,492 B2
• Filed: 06/19/2019
• Issued: 05/12/2020
• Est. Priority Date: 09/02/2011
• Status: Active Grant

• Current Assignee: Incyte Corporation, Incyte Holdings Corporation (Incyte Corporation)
• Original Assignee: Incyte Corporation
• Inventors: Li, Yun-Long, Yao, Wenqing, Combs, Andrew P., Mei, Song, Glenn, Joseph, Maduskuie, Jr., Thomas P., Sparks, Richard B.
• Primary Examiner(s): Baek, Bong-Sook
• Application Number:
  US16/446,098
• Publication Number:
  US 20190298724A1
• Time in Patent Office: 328 Days
• Field of Search: None
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• 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: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The present invention provides heterocyclylamine derivatives of Formula I:

wherein the variables are defined herein, that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.

Claims

1. A compound of Formula VIIa:

2. The compound of claim 1, having Formula VIIb:

3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:

G is NH;

n is 0;

V is O;

R² is C_1-3 alkoxy;

R⁴ is halo, CN, or C_1-4 alkyl;

R⁵ is halo; and

R⁶ is H.

4. The compound of claim 1, selected from:

4[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-6-chloro-3-ethoxy-2-(2-oxo-1,3-oxazolidin-5-yl)benzonitrile;

5-{3-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}-1,3-oxazolidin-2-one;

5-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl}-1,3-oxazolidin-2-one,

or a pharmaceutically acceptable salt thereof of any of the aforementioned.

5. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.