Granted Patent
B2
US 12,448,398 · App. 17/613,640 · Granted Oct 21, 2025
Semi-synthetic analogues of epipolythiodioxopiperazine alkaloids
Inventors:
James Robert Fuchs (Columbus, OH); Andrew Huntsman (Fort Jennings, OH); Nicholas Hunter Oberlies (Greensboro, NC); Chiraz Soumia Amrine (Greensboro, NC); Huzefa Raja (Greensboro, NC); Joanna Burdette (Chicago, IL); Cedric Pearce (Chapel Hill, NC)
Assignees:
Ohio State Innovation Foundation; University of North Carolina at Greensboro; The Board of Trustees of the University of Illinois; Mycosynthetix, Inc.
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Abstract
Disclosed herein are compounds, compositions, and methods for inhibiting a histone methyltransferase. The compounds are verticillin derivatives that exhibit anti-proliferative activity against cancer cells. The compounds, compositions, and methods can be used to treat a subject with cancer.
Claims (45)
1. A compound having Formula I:
wherein
R 1 and R 10 are independently unsubstituted alkyl;
R 4 and R 7 are both halogen or hydrogen; R 4 is hydrogen and R 7 is halogen; or R 4 is halogen and R 7 is hydrogen;
R 2 , R 3 , R 5 , R 6 , R 8 , and R 9 are independently hydrogen; halogen; amino; hydroxy; thiol; ester; carbamate; carbonate; sulfonate; substituted or unsubstituted alkyl, alkenyl, alkynyl, or alkoxy; and
R 11 is a hydroxy, ester, carbamate, carbonate, or sulfonate;
wherein when R 11 is a hydroxy, then R 4 and R 7 are both halogen, R 4 is hydrogen and R 7 is halogen, or R 4 is halogen and R 7 is hydrogen;
wherein when R 1 and R 10 are methyl, R 2 , R 3 , R 5 , R 6 , R 8 , and R 9 are H, and R 11 is
then R 4 and R 7 are both halogen; R 4 is hydrogen and R 7 is halogen; or R 7 is halogen and R 4 is hydrogen;
or a pharmaceutically acceptable salt thereof.
2. A compound having Formula II:
wherein
R 1 and R 10 are independently substituted or unsubstituted alkyl;
R 12 and R 13 are both halogen; R 12 is hydrogen and R 13 is halogen; or R 12 is halogen and R 13 is hydrogen;
R 2 , R 3 , R 5 , R 6 , R 8 , and R 9 are independently hydrogen; halogen; amino; hydroxy; thiol; ester; carbamate; carbonate; sulfonate; substituted or unsubstituted alkyl, alkenyl, alkynyl, or alkoxy; and
R 11 is a hydroxy, ester, carbamate, carbonate, or sulfonate;
or a pharmaceutically acceptable salt thereof.
3. A compound having Formula III:
wherein
R 1 and R 10 are independently unsubstituted alkyl;
R 4 and R 7 are both halogen or hydrogen; R 4 is hydrogen and R 7 is halogen; or R 4 is halogen and R 7 is hydrogen;
R 2 , R 3 , R 5 , R 6 , R 8 , and R 9 are independently hydrogen; halogen; amino; hydroxy; thiol; ester; carbamate; carbonate; sulfonate; substituted or unsubstituted alkyl, alkenyl, alkynyl, or alkoxy; and
R 14 is an ester, carbamate, carbonate, or sulfonate;
wherein when R 1 and R 10 are methyl, R 2 , R 3 , R 5 , R 6 , R 8 , and R 9 are H, and R 14 is,
then R 4 and R 7 are both halogen; R 4 is hydrogen and R 7 is halogen; or R 7 is halogen and R 4 is hydrogen;
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein R 11 is a carbamate or an ester.
5. The compound of claim 3 , wherein R 14 is a carbamate or an ester.
6. The compound of claim 1 , wherein R 11 is selected from one of the following:
7. The compound of claim 3 , wherein R 14 is selected from one of the following:
8. The compound of claim 1 , wherein R 1 and R 10 are independently methyl, ethyl, or a combination thereof.
9. The compound of claim 1 , wherein R 4 and R 7 are halogen, hydrogen, or a combination thereof.
10. The compound of claim 1 , wherein R 2 , R 3 , R 5 , R 6 , R 8 , and R 9 are hydrogen.
11. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
14. The compound of claim 12 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
15. A pharmaceutical composition comprising a compound of claim 1 and one or more pharmaceutically acceptable carriers.
16. A method for treating cancer comprising administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 ;
wherein the cancer is breast cancer, ovarian cancer, melanoma, or any combination thereof.
17. The method of claim 16 , wherein the pharmaceutical composition is administered by one or more routes selected from the group consisting of buccal, sublingual, intravenous, subcutaneous, intradermal, transdermal, intraperitoneal, oral, eye drops, parenteral, and topical administration.
Assignments (6)
CONFIRMATORY LICENSE
Recorded Dec 13, 2023
From: OHIO STATE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065987/0908 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 17, 2022
From: FUCHS, JAMES ROBERT; HUNTSMAN, ANDREW
To: OHIO STATE INNOVATION FOUNDATION
Reel/Frame 060239/0670 →
CORRECTIVE ASSIGNMENT TO CORRECT THE THE POSTAL CODE OF THE ASSIGNEES ADDRESS PREVIOUSLY RECORDED AT REEL: 058288 FRAME: 0278. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT.
Recorded May 26, 2022
From: OBERLIES, NICHOLAS HUNTER; AMRINE, CHIRAZ SOUMIA; RAJA, HUZEFA
To: UNIVERSITY OF NORTH CAROLINA AT GREENSBORO
Reel/Frame 060199/0177 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 4, 2021
From: PEARCE, CEDRIC
To: MYCOSYNTHETIX, INC.
Reel/Frame 058288/0264 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 4, 2021
From: BURDETTE, JOANNA
To: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS
Reel/Frame 058288/0274 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 4, 2021
From: OBERLIES, NICHOLAS HUNTER; AMRINE, CHIRAZ SOUMIA; RAJA, HUZEFA
To: UNIVERSITY OF NORTH CAROLINA AT GREENSBORO
Reel/Frame 058288/0278 →
Continuity (2)
Provisional Application
62851939
· May 23, 2019
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