IP Library Granted Patent US 10,399,963
Granted Patent B2
US 10,399,963 · App. 15/831,111 · Granted Sep 3, 2019

Substituted benzofuranyl and benzoxazolyl compounds and uses thereof

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Quick Facts
Patent No.
US 10,399,963
App. No.
15/831,111
Granted
Sep 3, 2019
Kind
B2
Abstract

The invention generally relates to substituted benzofuranyl and substituted benzoxazolyl compounds, and more particularly to a compound represented by Structural Formula A: or a pharmaceutically acceptable salt thereof, wherein the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of Structural Formula A, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment of cancer (e.g., mantle cell lymphoma), and other diseases and disorders.

Claims (28)

1. A compound represented by Structural Formula VII or VIII:

wherein

R 1a is selected from hydrogen, halogen, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl, —O—(C 1 -C 4 )alkyl, (C 3 -C 12 )carbocyclyl and (C 3 -C 7 )heterocyclyl, wherein each alkyl, carbocyclyl and heterocyclyl is optionally and independently substituted;

R 9a is optionally substituted aryl or optionally substituted heteroaryl;

m′ is 1 or 2;

or a pharmaceutically acceptable salt thereof.

2. A compound represented by

or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising:

(a) a compound of claim 1 , or a pharmaceutically acceptable salt thereof; and

(b) a pharmaceutically acceptable carrier.

4. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

5. The method of claim 4 , wherein the cancer is lymphoma.

6. The method of claim 4 , wherein the cancer is cervical cancer.

7. The method of claim 4 , wherein the cancer is mantle cell lymphoma.

8. The method of claim 4 , wherein the cancer is selected from non-Hodgkin lymphoma, acute myeloid leukemia, acute lymphoblastic leukemia, erythroleukemia, multiple myeloma, cervical cancer, ovarian cancer, osteosarcoma, prostate cancer, breast cancer, colorectal cancer, hepatocellular carcinoma, lung cancer, glioblastoma, glioma, liver cancer, bile duct cancer, pancreatic cancer, hepatoma, neuroblastoma, testicular cancer, mesothelioma, and fibrosarcoma.

9. The method of claim 8 , wherein the non-Hodgkin lymphoma is selected from histiocytic lymphoma, mantle cell lymphoma, Burkett lymphoma, and diffuse large B-cell lymphoma.

10. The method of claim 4 , wherein the cancer is selected from chronic lymphocytic leukemia, T-cell leukemia, and B-cell leukemia.

11. The compound of claim 1 , wherein R 1a is optionally substituted phenyl.

12. The compound of claim 11 , wherein one or more optional substituents on phenyl are selected from halogen, alkyl, haloalkyl, CN, and —OH.

13. The compound of claim 12 , wherein R 1a is substituted with halogen.

14. The compound of claim 1 , wherein R 9a is substituted with —C(O)(C 0 -C 1 alkylene)NR 11 R 12 ,

wherein R 11 and R 12 are taken together with the nitrogen atom to which they are commonly attached to form an optionally substituted (C 3 -C 7 )heterocyclyl; and is further optionally substituted with 1 or 2 substituents independently selected from halogen, (C 1 -C 4 )alkyl and (C 1 -C 4 )haloalkyl.

15. The compound of claim 14 , wherein R 9a is phenyl or a 6-membered heteroaryl having 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and sulfur;

substituted at the meta or para position relative to its attachment point with —C(O)(C 0 -C 1 alkylene)NR 11 R 12 , wherein R 11 and R 12 are taken together with the nitrogen atom to which they are commonly attached to form an optionally substituted (C 3 -C 7 )heterocyclyl; and further optionally substituted with 1 or 2 substituents independently selected from halogen, (C 1 -C 4 )alkyl and (C 1 -C 4 )haloalkyl.

16. The compound of claim 1 , wherein R 9a is selected from 4-(morpholine-4-carbonyl) phenyl, 4-(3,3-difluoroazetidine-1-carbonyl)phenyl), 4-(4-trifluoromethyl)phenyl, 4-methylsulfonylphenyl, 4-ethylsulfonylphenyl, 4-fluorophenoxy, 4,4-difluorocyclohexyloxy, and 4-fluoropyridyloxy.

17. A pharmaceutical composition comprising a compound represented by the following structural formula:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignments (7)
RELEASE OF SECURITY INTEREST IN PATENTS AT REEL/FRAME NO. 67396/0532 Recorded Oct 14, 2025
From: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS AGENT
To: KARYOPHARM THERAPEUTICS INC.
Reel/Frame 073111/0142 →
PATENT SECURITY AGREEMENT Recorded Oct 10, 2025
From: KARYOPHARM THERAPEUTICS INC.
To: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS COLLATERAL TRUSTEE
Reel/Frame 073058/0504 →
SECOND LIEN PATENT SECURITY AGREEMENT Recorded May 13, 2024
From: KARYOPHARM THERAPEUTICS INC.
To: WILMINGTON SAVINGS FUND SOCIETY, FSB
Reel/Frame 067396/0532 →
SECURITY INTEREST Recorded May 8, 2024
From: KARYOPHARM THERAPEUTICS INC.
To: WILMINGTON SAVINGS FUND SOCIETY, FSB
Reel/Frame 067345/0255 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 18, 2020
From: BALOGLU, ERAKAN; SHACHAM, SHARON; SENAPEDIS, WILLIAM; MCCAULEY, DILARA; LANDESMAN, YOSEF; GOLAN, GALI; KALID, ORI; SHECHTER, SHARON
To: KARYOPHARM THERAPEUTICS INC.
Reel/Frame 053523/0748 →
NOTICE OF SECURITY INTEREST IN PATENTS Recorded Sep 27, 2019
From: KARYOPHARM THERAPEUTICS INC.
To: HCR COLLATERAL MANAGEMENT, LLC
Reel/Frame 050575/0574 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 27, 2018
From: BALOGLU, ERKAN; SHACHAM, SHARON; SENAPEDIS, WILLIAM; MCCAULEY, DILARA; LANDESMAN, YOSEF; GOLAN, GALI; KALID, ORI; SHECHTER, SHARON
To: KARYOPHARM THERAPEUTICS INC.
Reel/Frame 047271/0195 →