Compositions and methods for treating cancer

• US 11,136,297 B2
• Filed: 12/15/2017
• Issued: 10/05/2021
• Est. Priority Date: 12/15/2016
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Shokat, Kevan M., Gentile, Daniel, Moss, Steven
• Primary Examiner(s): Kosack, Joseph R
• Application Number:
  US16/468,948
• Publication Number:
  US 20200131135A1
• Time in Patent Office: 1,390 Days
• Field of Search: None
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 231/14 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07K 14/82 Translation products from oncogenes
• CPC Class Codes: C12N 9/14 Hydrolases (3)
• CPC Class Codes: C12N 9/96 Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
• CPC Class Codes: C12Y 306/05002 Small monomeric GTPase (3.6.5.2)
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92

Abstract

Disclosed herein, inter alia, are compositions and methods for modulating Ras and treating cancer.

Claims

1. A compound having the formula:

2. The compound of claim 1 having the formula:

3. The compound of claim 1 having the formula:

4. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of any one of claims 1, 2, or 3.

5. The compound of claim 1, wherein R¹ is independently halogen, —

CX¹₃, —

CHX¹₂, —

CH₂X¹, —

OCX¹₃, —

OCH₂X¹, —

OCHX¹₂, —

CN, —

SO_n10R^1D, —

SO_v1NR^1AR^1B, —

NHC(O)NR^1AR^1B, —

N(O)_m1, —

NR^1AR^1B, —

C(O)R^1C, —

C(O)—

OR^1C, —

C(O)NR^1AR^1B, —

OR^1D, —

NR^1ASO₂R^1D, —

NR^1AC(O)R^1C, —

NR^1AC(O)OR^1C, —

NR^1AOR^1C, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl.

6. The compound of claim 1, wherein R¹ is independently —

OR^1D, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl.

7. The compound of claim 1, wherein R¹ is independently —

OR^1D, wherein R^1D is substituted or unsubstituted alkyl.

8. The compound of claim 1, wherein R¹ is independently —

OR^1D, wherein R^1D is substituted or unsubstituted C₁-C₆ alkyl.

9. The compound of claim 1, wherein R² is independently halogen, —

CX²₃, —

CHX²₂, —

CH₂X², —

OCX²₃, —

OCH₂X², —

OCHX²₂, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl.

10. The compound of claim 1, wherein R² is independently halogen, —

CX²₃, —

CHX²₂, or —

CH₂X².

11. The compound of claim 1, wherein R⁷ is independently halogen, —

CX⁷₃, —

CHX⁷₂, —

CH₂X⁷, —

OCX⁷₃, —

OCH₂X⁷, —

OCHX⁷₂, —

CN, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl.

12. The compound of claim 1, wherein R⁷ is independently halogen.

13. The compound of claim 1, wherein L³ is independently a bond, —

N(H)—

, —

C(O)N(H)—

, —

N(H)C(O)—

, —

N(H)C(O)NH—

, —

C(O)O—

, —

OC(O)—

, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

14. The compound of claim 1, wherein L³ is independently a —

N(H)—

, —

C(O)N(H)—

, or —

N(H)C(O)—

.

15. The compound of claim 1, wherein E is independently

16. The compound of claim 1, wherein R¹⁵ is independently hydrogen or substituted or unsubstituted alkyl, R¹⁶ independently hydrogen or substituted or unsubstituted alkyl, and R¹⁷ is independently hydrogen or substituted or unsubstituted alkyl.

17. The compound of claim 1, wherein R¹⁵ is independently hydrogen or unsubstituted C₁-C₄ alkyl, R¹⁶ independently hydrogen or unsubstituted C₁-C₄, and R¹⁷ is independently hydrogen or unsubstituted C₁-C₄ alkyl.

18. The compound of claim 1, wherein R¹⁵ is hydrogen;

R¹⁶ is hydrogen; and

R¹⁷ is hydrogen.

19. The compound of claim 2, wherein

L³ is —

NH—

;

R¹ is unsubstituted C₁-C₄ alkoxy;

R² is —

CX²₃; and

R⁸ is E.

20. The compound of claim 1 having the formula: