Antitumor arylnaphthalene ligand glycosides

Patent metadata

Field	Value
Publication number	US-10682367-B2
Application number	US-201716079754-A
Country	US
Kind code	B2
Filing date	Apr 26, 2017
Priority date	Feb 26, 2016
Publication date	Jun 16, 2020
Grant date	Jun 16, 2020

Abstract

Described are arylnaphthalene lactone derivatives. Also disclosed herein are methods of use of the arylnaphthalene lactone derivatives as anticancer agents.

First claim

What is claimed is:

1. A compound having a structure according to Formula I or a pharmaceutically acceptable salt or prodrug thereof:

wherein
R, R 1 , R 2 , R 6 , and R 7 are independently hydrogen, halogen, substituted or unsubstituted C 1 -C 4 alkyl, substituted or unsubstituted C 2 -C 4 alkenyl, substituted or unsubstituted C 2 -C 4 alkynyl, substituted or unsubstituted C 1 -C 4 alkoxy, substituted or unsubstituted C 1 -C 4 alkoxycarbonyl, hydroxycarbonyl, substituted or unsubstituted C 1 -C 4 acyl, substituted or unsubstituted amino, substituted or unsubstituted amido, substituted or unsubstituted C 1 -C 4 carbamoyl, substituted or unsubstituted phosphonyl, substituted or unsubstituted sulfinyl, substituted or unsubstituted sulfonyl, substituted or unsubstituted sulfonamide, or substituted or unsubstituted thio, R and R 1 taken together with the atoms to which they are attached form a substituted or unsubstituted 5 to 7 membered heterocyclic moiety, or R 6 and R 7 taken together with the atoms to which they are attached form a substituted or unsubstituted 5 to 7 membered heterocyclic moiety;
R 5 and R 8 are independently hydrogen, halogen, hydroxyl, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted C 1 -C 6 alkylhydroxyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 alkoxycarbonyl, hydroxycarbonyl, substituted or unsubstituted C 1 -C 6 acyl, substituted or unsubstituted C 1 -C 6 ether, substituted or unsubstituted amino, substituted or unsubstituted amido, substituted or unsubstituted C 1 -C 6 carbamoyl, substituted or unsubstituted phosphonyl, substituted or unsubstituted sulfinyl, substituted or unsubstituted sulfonyl, substituted or unsubstituted sulfonamide, or substituted or unsubstituted thio;
R 3 is hydrogen, halogen, substituted or unsubstituted C 1 -C 4 alkyl, substituted or unsubstituted C 1 -C 4 alkoxy, substituted or unsubstituted C 1 -C 4 alkoxycarbonyl, hydroxycarbonyl, substituted or unsubstituted C 1 -C 4 acyl, substituted or unsubstituted amino, substituted or unsubstituted amido, substituted or unsubstituted C 1 -C 4 carbamoyl, substituted or unsubstituted phosphonyl, substituted or unsubstituted sulfinyl, substituted or unsubstituted sulfonyl, substituted or unsubstituted sulfonamide, or substituted or unsubstituted thio; and
wherein R 3 and R 4 taken together with the atoms to which they are attached form a substituted or unsubstituted 5 to 7 membered heterocyclic moiety, or
R 4 and R 5 taken together with the atoms to which they are attached form a substituted or unsubstituted 5 to 7 membered heterocyclic moiety;
with the proviso that when R 4 and R 5 taken together with the atoms to which they are attached form a substituted or unsubstituted 5 to 7 membered heterocyclic moiety, R, R 1 , and R 2 are not all CH 3 .

2. The compound of claim 1 , wherein one or more of R, R 1 , R 2 , R 6 , and R 7 are substituted or unsubstituted phosphonyl, substituted or unsubstituted sulfinyl, substituted or unsubstituted sulfonyl, or substituted or unsubstituted sulfonamide.

3. The compound of claim 1 , wherein R 1 is a substituted or unsubstituted phosphonyl, substituted or unsubstituted sulfinyl, substituted or unsubstituted sulfonyl, or substituted or unsubstituted sulfonamide.

4. The compound of claim 1 , wherein R, R 1 , and R 2 are independently hydrogen, substituted or unsubstituted C 1 -C 4 alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted phosphonyl.

5. The compound of claim 4 , wherein R, R 1 , and R 2 are independently hydrogen, CH 3 , or PO 3 H 2 .

6. The compound of claim 1 , wherein R and R 1 are both CH 3 .

7. The compound of claim 1 , wherein R 2 is a substituted or unsubstituted phosphonyl, substituted or unsubstituted sulfinyl, substituted or unsubstituted sulfonyl, or substituted or unsubstituted sulfonamide.

8. The compound of claim 1 , wherein R 2 is H, CH 3 , or benzyl.

9. The compound of claim 1 , wherein R 3 and R 4 taken together with the atoms to which they are attached form a substituted or unsubstituted 5 membered heterocyclic moiety or a substituted or unsubstituted 6 membered heterocyclic moiety.

10. The compound of claim 9 , wherein the heterocyclic moiety formed by R 3 and R 4 is substituted with a C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 acyl, or phosphonyl.

11. The compound of claim 10 , wherein the heterocyclic moiety formed by R 3 and R 4 is substituted with CH 3 , OCH 3 , C(O)CH 3 , CO(O)CH 3 , or PO 3 H 2 .

12. The compound of claim 1 , wherein R 5 is hydrogen, hydroxyl, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 4 alkenyl, substituted or unsubstituted C 2 -C 4 alkynyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 alkylhydroxyl, or substituted or unsubstituted C 1 -C 6 ether.

13. The compound of claim 12 , wherein R 5 is hydrogen, hydroxyl, OCH 3 , CH 2 OCH 3 , CH 2 OH or OCCH.

14. The compound of claim 1 , wherein R 5 is a substituted or unsubstituted phosphonyl, substituted or unsubstituted sulfinyl, substituted or unsubstituted sulfonyl, or substituted or unsubstituted sulfonamide.

15. The compound of claim 1 , wherein R 6 and R 7 taken together with the atoms to which they are attached form a 5 membered heterocyclic moiety.

16. The compound of claim 1 , wherein R 8 is hydrogen, substituted or unsubstituted C 1 -C 4 alkyl, or substituted or unsubstituted phosphonyl.

17. The compound of claim 16 , wherein R 8 is hydrogen, CH 3 , or PO 3 H 2 .

18. The compound of claim 1 , wherein the compound is of Formula I-B, or a pharmaceutically acceptable salt or prodrug thereof:

wherein
R 9 and R 10 are independently hydrogen, halogen, hydroxyl, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 alkoxycarbonyl, hydroxycarbonyl, substituted or unsubstituted C 1 -C 6 alkylhydroxyl, substituted or unsubstituted C 1 -C 6 acyl, substituted or unsubstituted C 1 -C 6 ether, substituted or unsubstituted amino, substituted or unsubstituted amido, substituted or unsubstituted C 1 -C 6 carbamoyl, substituted or unsubstituted phosphonyl, substituted or unsubstituted sulfinyl, substituted or unsubstituted sulfonyl, substituted or unsubstituted sulfonamide, substituted or unsubstituted thio, or R 9 and R 10 taken together with the atoms to which they are attached form a substituted or unsubstituted 5 to 7 membered cyclic moiety.

19. The compound of claim 1 , wherein the compound is of Formula I-C, or a pharmaceutically acceptable salt or prodrug thereof:

wherein
R 9 and R 10 are independently hydrogen, halogen, hydroxyl, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 alkoxycarbonyl, hydroxycarbonyl, substituted or unsubstituted C 1 -C 6 alkylhydroxyl, substituted or unsubstituted C 1 -C 6 acyl, substituted or unsubstituted C 1 -C 6 ether, substituted or unsubstituted amino, substituted or

Assignees

• Ohio State Innovation Foundation

Inventors

• Fuchs James
• Kinghorn Alan Douglas
• Huntsman Andrew

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/7048 Primary

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• A61K31/365

  Lactones · CPC title

• C07H17/08

  Hetero rings containing eight or more ring members, e.g. erythromycins · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title