PCNA inhibitors

Patent metadata

Field	Value
Publication number	US-10913706-B2
Application number	US-201916714062-A
Country	US
Kind code	B2
Filing date	Dec 13, 2019
Priority date	Sep 17, 2015
Publication date	Feb 9, 2021
Grant date	Feb 9, 2021

Abstract

Described herein, inter alia, are compositions of PCNA modulators and methods for treating or preventing cancer.

First claim

What is claimed is:

1. A compound having the formula:

wherein
Ring A is phenyl or 5 to 6 membered heteroaryl;
Ring B is 1-naphthyl or isoquinolinyl;
R 1 is independently a halogen, —CX 1 3 , —CHX 1 2 , —CH 2 X, —CN, —SO n1 R 10 , —SO v1 NR 7 R 8 , —NHNH 2 , —ONR 7 R 8 , —NHC═(O)NHNH 2 , —NHC═(O)NR 7 R 8 , —N(O) m1 , —NR 7 R 8 , —C(O)R 9 , —C(O)—OR 9 , —C(O)NR 7 R 8 , —OR 10 , —NR 7 SO 2 R 10 , —NR 7 C═(O)R 9 , —NR 7 C(O)—OR 9 , —NR 7 OR 9 , —OCX 1 3 , —OCHX 1 2 , —OCH 2 X 1 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 2 is independently hydrogen, halogen, —CX 2 3 , —CHX 2 2 , —CH 2 X 2 , —CN, —COOH, —CONH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 3 is independently hydrogen, halogen, —CX 3 3 , —CHX 3 2 , —CH 2 X 3 , —CN, —COOH, —CONH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 4 is independently a halogen, —CX 4 3 , —CHX 4 2 , —CH 2 X 4 , —CN, —SO n4 R 14 , —SO v4 NR 11 R 12 , —NHNR 11 R 12 , —ONR 11 R 12 , —NHC═(O)NHNR 11 R 12 , —NHC═(O)NR 11 R 12 , —N(O) m4 , —NR 11 R 12 , —C(O)R 13 , —C(O)—OR 13 , —C(O)NR 11 R 12 , —OR 14 , —NR 11 SO 2 R 14 , —NR 11 C═(O)R 13 , —NR 11 C(O)—OR 13 , —NR 11 OR 13 , —OCX 4 3 , —OCHX 4 2 , —OCH 2 X 4 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or two adjacent R 4 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 5 is independently a halogen, —CX 5 3 , —CHX 5 2 , —CH 2 X 5 , —CN, —SO n5 R 18 , —SO v5 NR 15 R 16 , —NHNR 15 R 16 , —ONR 15 R 16 , —NHC═(O)NHNR 15 R 16 , —NHC═(O)NR 15 R 16 , —N(O) m5 , —NR 15 R 16 , —C(O)R 17 , —C(O)—OR 17 , —C(O)NR 15 R 16 , —OR 18 , —NR 15 SO 2 R 18 , —NR 15 C═(O)R 17 , —NR 15 C(O)—OR 17 , —NR 15 OR 17 , —OCX 5 3 , —OCHX 5 2 , —OCH 2 X 5 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or two adjacent R 5 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 7 , R 8 , R 9 , and R 10 are independently hydrogen, halogen, —CX A 3 , —CHX A 2 , —CH 2 X A , —CN, —COOH, —CONH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R 7 and R 8 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
R 11 , R 12 , R 13 ,and R 14 are independently hydrogen, halogen, —CX B 3 , —CHX B 2 , —CH 2 X, —CN, —COOH, —CONH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R 11 and R 12 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
R 15 , R 16 , R 17 , and R 18 are independently hydrogen, halogen, —CX C 3 , —CHX C 2 , —CH 2 X C , —CN, —COOH, —CONH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R 15 and R 16 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
z1 is independently an integer from 0 to 4;
z2 is independently an integer from 0 to 5;
z3 is independently an integer from 0 to 7;
m1, m4, m5, v1, v4, and v5 are independently 1 or 2;
n1, n4, and n5 are independently an integer from 0 to 4; and
X 1 , X 2 , X 3 , X 4 , X 5 , X A , X B , and X C are independently —Cl, —Br, —I, or —F.

2. The compound of claim 1 , wherein R 1 is independently halogen, —CF 3 , —OH, —NH 2 , —SH, substituted or unsubstituted C 1 -C 4 alkyl, substituted or unsubstituted 2 to 4 membered heteroalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted 5 to 6 membered heteroaryl.

3. The compound of claim 1 , wherein R 4 is independently halogen, —CF 3 , —OH, —NH 2 , —SH, substituted or unsubstituted C 1 -C 4 alkyl, substituted or unsubstituted 2 to 4 membered heteroalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted 5 to 6 membered heteroaryl.

4. The compound of claim 1 , wherein R 4 is independently —OR 14 , and R 14 is hydrogen or unsubstituted C 1 -C 5 alkyl.

5. The compound of claim 1 , wherein R 5 is independently halogen, —CF 3 , —OH, —NH 2 , —SH, substituted or unsubstituted C 1 -C 4 alkyl, substituted or unsubstituted 2 to 4 membered heteroalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted 5 to 6 membered heteroaryl.

6. The compound of claim 1 , wherein
R 2 is hydrogen, unsubstituted methyl, unsubstituted ethyl, or unsubstituted isopropyl; and
R 3 is hydrogen, unsubstituted methyl, unsubstituted ethyl, or unsubstituted isopropyl.

7. The compound of claim 1 , wherein Ring A is phenyl.

8. The compound of claim 1 , wherein Ring A is a 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl.

9. The compound of claim 1 , wherein Ring B is a 1-naphthyl.

10. The compound of claim 1 , wherein Ring B is a 1-isoquinolinyl, 3-isoquinolinyl, or 4-isoquinolinyl.

11. The compound of claim 1 , having the formula:

12. The compound of claim 1 , having th

Assignees

• Hope City

Inventors

• Malkas Linda H
• Horne David
• Hickey Robert J
• Gu Long

Classifications

• A61K31/4409

  only substituted in position 4, e.g. isoniazid, iproniazid · CPC title

• A61K33/243

  Platinum; Compounds thereof · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• C07D401/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D213/68

  attached in position 4 · CPC title