Granted Patent B2

US 12,577,208 · App. 18/336,562 · Granted Mar 17, 2026

Inventor: Alfredo C. Castro (Somerville, MA)

Assignee: EHE Foundation

C07D233/58A61P35/00C07C317/14C07D231/12C07D249/08C07D257/04C07D271/10C07D401/04C07D401/12C07D403/12C07D405/12C07D417/12C07F5/025

Abstract

Claims (57)

1 . A method for treating cancer in a patient, or inhibiting the progress of cancer in a patient, comprising administering to the patient a compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

L 1 is —NH—CH 2 — or —NH—C(O)—;

Ring A is phenyl, optionally substituted 1-2 times by halogen, —CN, —NO 2 , or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 ;

R 2 is an optionally substituted 5-membered heteroaryl ring having 2 nitrogen atoms;

R 3 is —H;

R 4 is halogen, —S(O) 2 N(R) 2 , —S(O)N(R) 2 , or —C(O)N(R) 2 ;

R 6 is —H or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 ; and

each R is independently —H or optionally substituted —C 1-6 aliphatic;

wherein the cancer is selected from the group consisting of lung cancer, breast cancer, basal cell carcinoma, squamous cell carcinoma, cancer of head or neck, melanoma, vascular cancer, prostate cancer, pancreatic cancer, meningioma, renal cell carcinoma, colorectal cancer, schwannoma, cholangiocarcinoma, glioma, liver cancer, and gastric cancer.

2 . The method of claim 1 , wherein L 1 is —NH—CH 2 —.

3 . The method of claim 1 , wherein Ring A is phenyl, optionally substituted 1-2 times by —C 1-6 aliphatic substituted 0-6 times by halogen.

4 . The method of claim 1 , wherein R 2 is

and R is unsubstituted —C 1-6 aliphatic.

5 . The method of claim 1 , wherein R 4 is —S(O) 2 NHR.

6 . The method of claim 1 , wherein R 6 is —H.

7 . The method of claim 1 , wherein the compound is of Formulae (IXa-1), (IXa-2), (Xa-1), or (Xa-2):

or a pharmaceutically acceptable salt thereof, wherein L 1 is —NH—CH 2 —, and each R is independently —H or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 .

8 . The method of claim 1 , wherein the compound is of Formulae (XIa-1) or (XIa-2):

or a pharmaceutically acceptable salt thereof, wherein L 1 is —NH—CH 2 —, and each R is independently —H or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 .

9 . The method of claim 1 , wherein the compound is of Formulae (XIIa-1) or (XIIa-2):

or a pharmaceutically acceptable salt thereof, wherein L 1 is —NH—CH 2 —, and R is —C 1-3 aliphatic substituted 1, 2, 3, 4, 5, or 6 times by —F.

10 . The method of claim 1 , wherein the compound is of Formulae (XIIIa-1) or (XIIIa-2):

or a pharmaceutically acceptable salt thereof, wherein L 1 is —NH—CH 2 —, and R is optionally substituted —C 1-6 aliphatic.

11 . The method of claim 1 , wherein the compound is of Formulae (XIVa-1) or (XIVa-2):

or a pharmaceutically acceptable salt thereof, wherein L 1 is —NH—CH 2 —.

12 . The method of claim 1 , wherein the compound is of Formulae (XVa-1), or (XVa-2):

or a pharmaceutically acceptable salt thereof.

13 . The method of claim 1 , wherein the compound is of Formulae (XVIa-1), or (XVIa-2):

or a pharmaceutically acceptable salt thereof.

14 . The method of claim 1 , wherein the compound is of Formula (II):

or a pharmaceutically acceptable salt thereof, wherein L 1 is —NH—CH 2 —, R 1 is —H, -halogen, —CN, —NO 2 , or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 , and R 7 is —H, -halogen, —CN, —NO 2 , or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 .

15 . The method of claim 1 , wherein R 2 is

16 . The method of claim 1 , wherein R 4 is —S(O) 2 NH—CH 3 .

17 . The method of claim 1 , wherein the compound is selected from:

or a pharmaceutically acceptable salt thereof.

18 . The method of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

19 . A method for treating a patient having a disease or disorder associated with increased TEAD expression or increased TEAD activity, comprising administering to the patient a compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

L 1 is —NH—CH 2 — or —NH—C(O)—;

Ring A is phenyl, optionally substituted 1-2 times by halogen, —CN, —NO 2 , or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 ;

R 2 is an optionally substituted 5-membered heteroaryl ring having 2 nitrogen atoms;

R 3 is —H;

R 4 is halogen, —S(O) 2 N(R) 2 , —S(O)N(R) 2 , or —C(O)N(R) 2 ;

R 6 is —H or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 ; and

each R is independently-H or optionally substituted-C 1-6 aliphatic.

20 . The method of claim 19 , wherein the disease or disorder is selected from the group consisting of lung cancer, breast cancer, basal cell carcinoma, squamous cell carcinoma, cancer of head or neck, melanoma, vascular cancer, prostate cancer, pancreatic cancer, meningioma, renal cell carcinoma, colorectal cancer, schwannoma, cholangiocarcinoma, glioma, liver cancer, and gastric cancer.

21 . A method for inhibiting TEAD activity or Hippo pathway in a patient in need thereof, comprising administering to the patient a compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

L 1 is —NH—CH 2 — or —NH—C(O)—;

Ring A is phenyl, optionally substituted 1-2 times by halogen, —CN, —NO 2 , or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 ;

R 2 is an optionally substituted 5-membered heteroaryl ring having 2 nitrogen atoms;

R 3 is —H;

R 4 is halogen, —S(O) 2 N(R) 2 , —S(O)N(R) 2 , or —C(O)N(R) 2 ;

R 6 is —H or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 ; and

each R is independently —H or optionally substituted-C 1-6 aliphatic.

Assignments (3)

Continuity (7)

References Cited (273)