Granted Patent B2

US 12,195,419 · App. 16/754,053 · Granted Jan 14, 2025

Inventors: Barbara Slusher (Kingsville, MD); Rana Rais (Owings Mills, MD); Pavel Majer (Sykesville, MD); Lukas Tenora (Czechia, CZ); Katerina Novotna (Czechia, CZ); Jesse Alt (Nottingham, MD)

Assignees: The John Hopkins University; Ustav organické chemie a biochemie AV CR, v.v.i.

C07C271/22A61P35/00C07C245/18C07D209/20C07C2603/18

Abstract

Claims (27)

1. A compound having a structure of formula (Ih):

wherein:

R 6 is selected from the group consisting of H, —(CH 2 ) t —CH(NH—C(CH 3 )(═O))—(CH 2 ) t —R 9 , —C(═O)—X 2 —R 10 , and one or more substituted or unsubstituted amino acids, wherein the one or more substituted or unsubstituted amino acids is bound to the nitrogen atom adjacent to R 6 through a carboxyl moiety of the one or more substituted or unsubstituted amino acids, wherein X 2 is present or absent and, when present, is selected from the group consisting of —O—, —O—(CH 2 ) q —, —(CH 2 ) t —, and —(CH 2 ) v —CH═CH—(CH 2 ) v —, wherein q and t are each independently selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, and 8, each v is independently selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, and 8, and R 9 and R 10 are each independently selected from the group consisting of straight chain or branched alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

or an ester or pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R 6 is H.

3. The compound of claim 2 , wherein the compound is:

4. The compound of claim 1 , wherein R 6 is —(CH 2 ) t —CH(NH—C(CH 3 )(═O))—(CH 2 ) t —R 9 .

5. The compound of claim 4 , wherein each t is 1 and R 9 is aryl.

6. The compound of claim 5 , wherein the compound is:

7. The compound of claim 1 , wherein R 6 is —C(═O)—X 2 —R 10 .

8. The compound of claim 7 , wherein X 2 is present and is —O—.

9. The compound of claim 8 , wherein R 10 is selected from the group consisting of t-butyl and adamantanyl.

10. The compound of claim 9 , wherein the compound is:

11. The compound of claim 7 , wherein X 2 is present and is —O—(CH 2 ) q —.

12. The compound of claim 11 , wherein q is 1 and R 10 is selected from the group consisting of 9H-fluoren-9-yl and phenyl.

13. The compound of claim 12 , wherein the compound is:

14. The compound of claim 7 , wherein X 2 is absent and R 10 is selected from the group consisting of C 2 -C 20 alkyl, adamantanyl, 1,2,3,4-tetrahydroisoquinolinyl, pyridinyl, and substituted decahydrophenanthrenyl.

15. The compound of claim 14 , wherein the compound is:

16. The compound of claim 7 , wherein X 2 is —(CH 2 ) t — and R 10 is 1H-indol-3-yl.

17. The compound of claim 16 , wherein the compound is:

18. The compound of claim 7 , wherein X 2 is —(CH 2 ) v —CH═CH—(CH 2 ) v — and R 10 is aryl.

19. The compound of claim 18 , wherein the compound is:

20. The compound of claim 1 , wherein R 6 is one or more substituted or unsubstituted amino acids.

21. The compound of claim 20 , wherein the compound is:

22. The compound of claim 20 , wherein the one or more amino acids are valine-leucine.

23. A pharmaceutical composition comprising the compound of any one of claim 1 or 2-22 and a pharmaceutically acceptable carrier, diluent or excipient.

24. The pharmaceutical composition of claim 23 , further comprising at least one oncological, immunological, anti-infectious, or neurological agent.

Assignments (2)

Continuity (3)

References Cited (96)