Aryl and heteroaryl fused lactams

• US 9,040,515 B2
• Filed: 12/18/2013
• Issued: 05/26/2015
• Est. Priority Date: 12/21/2012
• Status: Active Grant

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Edwards, Martin Paul, Kumpf, Robert Arnold, Kung, Pei-Pei, McAlpine, Indrawan James, Ninkovic, Sacha, Rui, Eugene Yuanjin, Sutton, Scott Channing, Tatlock, John Howard, Zehnder, Luke Raymond, Wythes, Martin James
• Primary Examiner(s): Pagonakis, Anna
• Application Number:
  US14/132,567
• Publication Number:
  US 20140179667A1
• Time in Patent Office: 524 Days
• US Class Current: 514/210.18
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 407/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

This invention relates to compounds of general formula (I)

in which R¹, R², U, V, L, M, R⁵, m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.

Claims

1. A compound of formula (II):

2. The compound or salt of claim 1, wherein U is CR³ and V is CR⁴.

3. The compound or salt of claim 2, wherein R³ is H and R⁴ is H or halo.

4. The compound or salt of claim 1, wherein R¹ is C₁-C₈ alkyl or halo.

5. The compound or salt of claim 1, wherein R² is 5-12 membered heteroaryl, where said 5-12 membered heteroaryl is optionally substituted by 1 to 3 R³².

6. The compound or salt of claim 1, wherein R² is OR⁶, where n is 0 or 1, and R¹³ is 3-12 membered heterocyclyl or 5-12 membered heteroaryl, where each said 3-12 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted by 1 to 3 R³².

7. The compound or salt of claim 1, wherein X and Z are independently selected from the group consisting of H, C₁-C₈ alkyl and C₃-C₈ cycloalkyl, and Y is H.

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

8. A compound of formula (II-A):

9. The compound or salt of claim 8, wherein R¹ is C₁-C₈ alkyl or halo.

10. The compound or salt of claim 8, wherein R² is 5-12 membered heteroaryl, where said 5-12 membered heteroaryl is optionally substituted by 1 to 3 R³².

11. The compound or salt of claim 10, wherein each R³² is independently selected from the group consisting of halo, C₁-C₈ alkyl, —

OR^c, —

SR^c, —

SO₂R^c and —

NR^cR^d, and each R^c and R^d is independently H or C₁-C₈ alkyl.

12. The compound or salt of claim 8, wherein R² is OR⁶, n is 0 or 1, and R¹³ is 3-12 membered heterocyclyl or 5-12 membered heteroaryl, where each said 3-12 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted by 1 to 3 R³².

13. The compound or salt of claim 12, wherein each R³² is independently selected from the group consisting of halo and C₁-C₈ alkyl, where each said C₁-C₈ alkyl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, —

OH, ═

O, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₆ haloalkyl, C₁-C₆ hydroxyalkyl, C₁-C₄ alkoxy-C₁-C₆ alkyl, —

CN, —

NH₂, —

NH(C₁-C₄ alkyl) and —

N(C₁-C₄ alkyl)₂.

14. The compound or salt of claim 8, wherein R³ is H and R⁴ is selected from the group consisting of H, halo, —

CN and C₁-C₈ alkyl, where said C₁-C₈ alkyl is optionally substituted by 1 to 3 R²⁴.

15. The compound or salt of claim 8, wherein X and Z are independently selected from the group consisting of H, C₁-C₈ alkyl and C₃-C₈ cycloalkyl, and Y is H.

16. The compound or salt of claim 8, wherein m is 0.