IP Library › Granted Patent US 12,187,720
Granted Patent B2
US 12,187,720 · App. 17/370,201 · Granted Jan 7, 2025

Compounds for treatment of cancer

Inventors: Wei Li (Germantown, TN); Duane D Miller (Collierville, TN); Kinsie E. Arnst (Gulf Breeze, FL); Dong-Jin Hwang (Arlington, TN)
Assignee: UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION
C07D417/14A61P35/00C07C49/786C07D211/14C07D213/76C07D217/04C07D233/64C07D277/24C07D405/06C07D417/04C07D417/12
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Quick Facts
Patent No.
US 12,187,720
App. No.
17/370,201
Granted
Jan 7, 2025
Kind
B2
Abstract

The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.

Claims (22)

1. A compound of Formula IX having the structure

wherein R 4 and R 5 are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CN, —CH 2 CN, NH 2 , hydroxyl, —(CH 2 ) i NHCH 3 , —(CH 2 ) i NH 2 , —(CH 2 ) i N(CH 3 ) 2 , —OC(O)CF 3 , C 1 -C 5 linear or branched alkyl, alkylamino, aminoalkyl, —OCH 2 Ph, —NHCO-alkyl, COOH, —C(O)Ph, C(O)O-alkyl, C(O)H, —C(O)NH 2 or NO 2 ;

A′ is halogen; substituted or unsubstituted single-, fused- or multiple-ring, aryl or (hetero)cyclic ring systems; substituted or unsubstituted, saturated or unsaturated N-heterocycles; substituted or unsubstituted, saturated or unsaturated S-heterocycles; substituted or unsubstituted, saturated or unsaturated O-heterocycles; substituted or unsubstituted, saturated or unsaturated cyclic hydrocarbons; or substituted or unsubstituted, saturated or unsaturated mixed heterocycles;

wherein said A′ ring is optionally substituted by 1-5 substituents which are independently O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CN, —CH 2 CN, NH 2 , hydroxyl, —(CH 2 ) i NHCH 3 , —(CH 2 ) i NH 2 , —(CH 2 ) i N(CH 3 ) 2 , —OC(O)CF 3 , C 1 -C 5 linear or branched alkyl, alkylamino, aminoalkyl, —OCH 2 Ph, —NHCO-alkyl, COOH, —C(O)Ph, C(O)O-alkyl, C(O)H, —C(O)NH 2 or NO 2 ;

i is an integer between 1-5; and

n is an integer between 1-3;

or its pharmaceutically acceptable salt, hydrate, polymorph, or isomer.

2. The compound according to claim 1 , wherein the compound is at least one of 7-(3,4,5-trimethoxyphenyl)-1-(1H-indol-5-yl)isoquinoline (6a), 1,7-bis-(1H-indol-5-yl)isoquinoline (6b), 1-(4-fluorophenyl)-7-(1H-indol-5-yl)isoquinoline (6c), or 1-chloro-7-(1H-indol-5-yl)isoquinoline (6d).

3. The compound according to claim 1 , wherein A′ is 3,4,5-trimethoxyphenyl.

4. The compound according to claim 1 , wherein A′ is indolyl.

5. The compound according to claim 4 , wherein A′ is 2-indolyl.

6. The compound according to claim 4 , wherein A′ is a substituted or unsubstituted 3-indolyl.

7. The compound according to claim 4 , wherein A′ is 5-indolyl.

8. The compound according to claim 1 , wherein A′ is 4-fluorophenyl.

9. The compound according to claim 1 , wherein A′ is 3,4,5-trimethoxyphenyl and R 4 and R 5 are hydrogen.

10. The compound according to claim 1 , wherein A′ is indolyl and R 4 and R 5 are hydrogen.

11. The compound according to claim 1 , wherein A′ is 5-indolyl and R 4 and R 5 are hydrogen.

12. The compound according to claim 1 , wherein A′ is 4-fluorophenyl and and R 4 and R 5 are hydrogen.

13. The compound according to claim 1 , wherein A′ is a halogen.

14. The compound according to claim 1 , wherein A′ is phenyl.

15. The compound according to claim 1 , wherein A′ is a substituted phenyl.

16. A compound, wherein the compound is at least one of 1-chloro-7-(4-fluorophenyl)isoquinoline, 7-(4-fluorophenyl)-1-(1H-indol-5-yl)isoquinoline, 7-(4-fluorophenyl)-1-(3,4,5-trimethoxyphenyl)isoquinoline, 1,7-bis(4-fluorophenyl)isoquinoline, 1,7-bis(3,4,5-trimethoxyphenyl)isoquinoline, 1-(4-fluorophenyl)-7-(3,4,5-trimethoxyphenyl)isoquinoline, 1-(1H-indol-5-yl)-7-(3,4,5-trimethoxyphenyl)isoquinoline, or 1-chloro-7-(3,4,5-trimethoxyphenyl)isoquinoline.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 10, 2024
From: HWANG, DONG-JIN; ARNST, KINSIE E.
To: UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION
Reel/Frame 068547/0217 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2022
From: DALTON, JAMES T.; AHN, SUNJOO
To: GTX, INC.
Reel/Frame 060007/0584 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2022
From: LI, WEI; XIAO, MIN; MILLER, DUANE D.; WANG, JIN
To: UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION
Reel/Frame 060007/0597 →
CHANGE OF NAME Recorded May 24, 2022
From: GTX, INC.
To: ONCTERNAL THERAPEUTICS, INC.
Reel/Frame 060175/0728 →
Continuity (9)
Continuation 16281291 · Feb 21, 2019
Continuation In Part 15270359 · Sep 20, 2016
Continuation 13676650 · Nov 14, 2012
Continuation In Part 13216927 · Aug 24, 2011
Continuation In Part 12981233 · Dec 29, 2010
Provisional Application 61376675 · Aug 24, 2010
Provisional Application 61315790 · Mar 19, 2010
Provisional Application 61309360 · Mar 1, 2010
Related Publication 20220024912A1 · Jan 27, 2022
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