IP Library › Granted Patent US 12667568

Granted Patent B2

US 12667568 · App. 18/040,940 · Granted Jun 30, 2026

Compositions and methods for the treatment and diagnosis of cancer

Inventors: Hong-yu Li (Little Rock, AR); Wei Yan (Little Rock, AR); Li Lan (Boston, MA)

Assignees: The General Hospital Corporation; Bio Ventures, LLC

A61K31/517 A61K31/502 A61K33/243 A61P35/00

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Quick Facts

Patent No.: US 12667568
App. No.: 18/040,940
Granted: Jun 30, 2026
Kind: B2

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Abstract

Disclosed herein are RNA methyltransferase inhibitors and methods of using the same. The inhibitors may be used in a method for the treatment of a subject in need of a treatment for a cancer by administering an effective amount of an RNA methyltransferase inhibitor to the subject.

Claims (76)

1 . A method for treatment of a subject in need of a treatment for a cancer, the method comprising administering an effective amount of an RNA methyltransferase inhibitor to the subject, wherein the cancer has upregulated SYCP2 expression or upregulated SYCP2 activity.

2 . A method for treatment of a subject in need of a treatment for a cancer, the method comprising administering an effective amount of an RNA methyltransferase inhibitor to the subject, wherein the cancer is a homologous recombination (HR) deficient cancer.

3 . A method for treatment of a subject in need of a treatment for a breast cancer, the method comprising administering an effective amount of an RNA methyltransferase inhibitor to the subject, wherein the breast cancer is a BRCA proficient breast cancer.

4 . The method of claim 1 , wherein the cancer is a homologous recombination (HR) deficient cancer, the cancer is a cancer resistant to therapy with a DNA damaging agent, or a combination thereof.

5 . The method of claim 1 , wherein the cancer is a breast cancer, ovarian cancer, esophageal cancer, stomach cancer, colon cancer, lung cancer, skin cancer, prostate cancer, head and neck cancer, bone cancer, kidney cancer, urinary tract cancer, bladder cancer, pancreatic cancer, pediatric cancer, or blood cancer.

6 . The method of claim 1 , wherein the cancer is a breast cancer.

7 . The method of claim 1 , wherein the RNA methyltransferase inhibitor is a compound of formula

or a pharmaceutically acceptable salt thereof,

wherein R 1 and R 2 are independently selected from hydrogen; an unsubstituted or substituted, unbranched or branched, saturated or unsaturated, acyclic or cyclic C 1 -C 6 alkyl; hydroxide; an unsubstituted or substituted, unbranched or branched, saturated or unsaturated, acyclic or cyclic C 1 -C 6 alkoxy; an unsubstituted or substituted, unbranched or branched, saturated or unsaturated, acyclic or cyclic C 1 -C 6 amino; an unsubstituted or substituted aryl; or an unsubstituted or substituted heteroaryl; and

wherein Ar 1 and Ar 2 are independently selected from an unsubstituted or substituted aryl or an unsubstituted or substituted heteroaryl.

8 . The method of claim 7 , wherein

R 1 and R 2 are independently the unsubstituted or substituted, unbranched or branched, saturated or unsaturated, acyclic or cyclic C 1 -C 6 alkoxy;

Ar 1 is the unsubstituted heteroaryl; and/or

Ar 2 is the substituted aryl.

9 . The method of claim 7 , wherein

R 1 and R 2 are methoxy;

Ar 1 is an unsubstituted thiophene; and/or

Ar 2 is a sulfonyl substituted phenyl.

10 . The method of claim 7 , wherein the compound, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of

6,7-dimethoxy-4-phenyl-2-(4-(pyridin-3-yl)-1H-pyrazol-1-yl)quinazoline,

6,7-dimethoxy-2-(4-(pyridin-3-yl)-1H-pyrazol-1-yl)-4-(quinolin-8-yl)quinazoline,

5-(6,7-dimethoxy-2-(4-(pyridin-3-yl)-1H-pyrazol-1-yl)quinazolin-4-yl)-N,N-dimethylpyridin-2-amine,

6,7-dimethoxy-4-(pyridin-3-yl)-2-(4-(pyridin-3-yl)-1H-pyrazol-1-yl)quinazoline,

1-(4-(6,7-dimethoxy-2-(4-(pyridin-3-yl)-1H-pyrazol-1-yl)quinazolin-4-yl)phenyl)ethanone,

6,7-dimethoxy-2-(4-(4-(methylsulfonyl)phenyl)-1H-pyrazol-1-yl)-4-(quinolin-8-yl)quinazoline,

6,7-dimethoxy-2-(4-(4-(methylsulfonyl)phenyl)-1H-pyrazol-1-yl)-4-(pyridin-3-yl)quinazoline,

4-(furan-3-yl)-6, 7-dimethoxy-2-(4-(4-(methylsulfonyl)phenyl)-1H-pyrazol-1-yl)quinazoline,

6,7-dimethoxy-2-(4-(4-(methylsulfonyl)phenyl)-1H-pyrazol-1-yl)-4-(thiophen-3-yl)quinazoline,

6,7-dimethoxy-2-(4-(4-(methylsulfonyl)phenyl)-1H-pyrazol-1-yl)-4-(p-tolyl)quinazoline,

2-(4-(4-(methylsulfonyl)phenyl)-1H-pyrazol-1-yl)-4-(thiophen-3-yl)quinazoline,

7-(4-ethylpiperazin-1-yl)-2-(4-(4-(methylsulfonyl)phenyl)-1H-pyrazol-1-yl)-4-(thiophen-3-yl)quinazoline,

4-(1-(6,7-dimethoxy-4-(thiophen-3-yl)quinazolin-2-yl)-1H-pyrazol-4-yl)-N-(2-(dimethylamino)ethyl)benzenesulfonamide,

6,7-dimethoxy-4-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-2-(4-(4-(methylsulfonyl)phenyl)-1H-pyrazol-1-yl)quinazoline, and

6,7-dimethoxy-4-(3-methoxyphenyl)-2-(4-(4-(methylsulfonyl)phenyl)-1H-pyrazol-1-yl)quinazoline.

11 . The method of claim 7 , wherein the RNA methyltransferase inhibitor is

or a pharmaceutically acceptable salt thereof.

12 . The method of claim 2 , wherein the cancer has upregulated SYCP2 expression or upregulated SYCP2 activity, the cancer is a cancer resistant to therapy with a DNA damaging agent, or a combination thereof.

13 . The method of claim 2 , wherein the cancer is a breast cancer, ovarian cancer, esophageal cancer, stomach cancer, colon cancer, lung cancer, skin cancer, prostate cancer, head and neck cancer, bone cancer, kidney cancer, urinary tract cancer, bladder cancer, pancreatic cancer, pediatric cancer, or blood cancer.

14 . The method of claim 2 , wherein the cancer is a breast cancer.

15 . The method of claim 2 , wherein the RNA methyltransferase inhibitor is a compound of formula

or a pharmaceutically acceptable salt thereof,

wherein Ar 1 and Ar 2 are independently selected from an unsubstituted or substituted aryl or an unsubstituted or substituted heteroaryl.

16 . The method of claim 15 , wherein

R 1 and R 2 are independently the unsubstituted or substituted, unbranched or branched,

saturated or unsaturated, acyclic or cyclic C 1 -C 6 alkoxy;

Ar 1 is the unsubstituted heteroaryl; and/or

Ar 2 is the substituted aryl.

17 . The method of claim 15 , wherein

R 1 and R 2 are methoxy;

Ar 1 is an unsubstituted thiophene; and/or

Ar 2 is a sulfonyl substituted phenyl.

18 . The method of claim 15 , wherein the compound, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of