Protein-protein interaction antagonist screening libraries based upon 1,4-disubstituted naphthalenes and related scaffolds
View Patent ↗The present invention relates to 1,4-disubstituted naphthalene scaffold compounds and other closely related scaffold compounds. The present invention also relates to combinatorial libraries of such compounds. In addition, the present invention relates to a method of identifying a protein-protein interaction antagonist. The method first involves providing a compound as described herein. Next, the compound is contacted with interacting proteins of a protein-protein interaction target complex, whereby the compound is allowed to compete with the interacting proteins. Then, the activity of the compound for inhibiting formation of the protein-protein interaction target complex is measured. Finally, the compound that inhibits formation of the protein-protein interaction target complex is identified as a protein-protein interaction antagonist. Also disclosed is a method for modulating a protein-protein interaction. The method involves contacting interacting proteins of a protein-protein interaction target with a compound as described herein, whereby the protein-protein interaction between the interacting proteins is modulated.
1. A compound having the following formula:
wherein:
R 1 -R 2 are individually selected from the group consisting of: H, C 1 -C 12 alkyl, heteroatom and multiple heteroatom substituted C 1 -C 12 alkyl, C 1 -C 12 branched or cyclic alkyl, aryl and substituted aryl, heteroaryl and substituted heteroaryl, substituted alkylaryl, amines, CH 2 COOCH 2 CH 3 , CH 2 COOH, and CH 2 C≡C, wherein the substitution in any of the substituted groups comprises substituents selected from the group consisting of hydrogen, halogen, oxygen, OH, OCH 3 , and methyl;
R 3 is H; and
R 4 is 3-fluorophenyl.
2. The compound according to claim 1 , wherein the compound has the following structure:
3. The compound according to claim 1 , wherein the compound has the following structure:
4. The compound according to claim 1 , wherein the compound has the following structure:
5. The compound according to claim 1 , wherein the compound has the following structure:
6. The compound according to claim 1 , wherein the compound has the following structure:
7. The compound according to claim 1 , wherein the compound has the following structure:
8. The compound according to claim 1 , wherein the compound has the following structure:
9. The compound according to claim 1 , wherein the compound has the following structure:
10. The compound according to claim 1 , wherein the compound has the following structure:
11. The compound according to claim 1 , wherein the compound has the following structure:
12. The compound according to claim 1 , wherein the compound has the following structure:
13. The compound according to claim 1 , wherein the compound has the following structure:
14. The compound according to claim 1 , wherein the compound has the following structure:
15. The compound according to claim 1 , wherein the compound has the following structure:
16. The compound according to claim 1 , wherein the compound has the following structure:
17. The compound according to claim 1 , wherein the compound has the following structure:
18. The compound according to claim 1 , wherein the compound has the following structure:
19. The compound according to claim 1 , wherein the compound has the following structure:
20. The compound according to claim 1 , wherein the compound has the following structure:
21. The compound according to claim 1 , wherein the compound has the following structure:
22. The compound according to claim 1 , wherein the compound has the following structure:
23. The compound according to claim 1 , wherein the compound has the following structure:
24. The compound according to claim 1 , wherein the compound has the following structure:
25. The compound according to claim 1 , wherein the compound has the following structure:
26. The compound according to claim 1 , wherein the compound has the following structure:
27. The compound according to claim 1 , wherein the compound has the following structure:
28. The compound according to claim 1 , wherein the compound has the following structure:
29. The compound according to claim 1 , wherein the compound has the following structure:
30. The compound according to claim 1 , wherein the compound has the following structure:
31. The compound according to claim 1 , wherein the compound has the following structure:
32. The compound according to claim 1 , wherein the compound has the following structure:
33. The compound according to claim 1 , wherein the compound has the following structure:
34. The compound according to claim 1 , wherein the compound has the following structure:
35. The compound according to claim 1 , wherein the compound has the following structure:
36. The compound according to claim 1 , wherein the compound has the following structure:
37. The compound according to claim 1 , wherein the compound has the following structure:
38. The compound according to claim 1 , wherein the compound has the following structure:
39. A compound having the following formula:
wherein:
R 1 is selected from the group consisting of H, C 1 -C 12 alkyl, substituted C 1 -C 12 alkyl, C 3 -C 12 branched or cyclic alkyl, aryl and substituted aryl, heteroaryl and substituted heteroaryl, substituted alkylaryl, amines, CH 2 COOCH 2 CH 3 , CH 2 COOH, and CH 2 C≡C, wherein the substitution in any of the substituted groups comprises substituents selected from the group consisting of hydrogen, halogen, oxygen, OH, OCH 3 , and methyl;
R 2 is H or methyl;
R 3 is H; and
R 4 is 3-fluorophenyl.
40. The compound according to claim 39 , wherein R 2 is H.
41. The compound according to claim 39 , wherein R 1 is selected from the group consisting of H, C 1 -C 4 alkyl, substituted C 1 -C 4 alkyl, C 3 -C 4 branched or cyclic alkyl, aryl and substituted aryl, heteroaryl and substituted heteroaryl, and CH 2 C≡C, wherein the substitution in any of the substituted groups comprises substituents selected from the group consisting of hydrogen, halogen, OH, and OCH 3 .
42. The compound according to claim 39 , wherein R 1 is selected from the group consisting of H, C 1 -C 4 alkyl, C 3 -C 4 branched or cyclic alkyl, phenyl, benzyl, thiazole, thiadiazole, triazole, isoxazole, amines, CH 2 COOCH 2 CH 3 , CH 2 COOH, and CH 2 C≡C, wherein C 1 -C 4 alkyl, phenyl, benzyl, thiazole, thiadiazole, triazole, and isoxazole are optionally substituted with substituents selected from the group consisting of hydrogen, halogen, methyl, OH, and OCH 3 .
43. The compound according to claim 42 , wherein R 1 is selected from the group consisting of H, C 1 -C 4 alkyl, C 3 -C 4 branched or cyclic alkyl, phenyl, benzyl, thiazole, thiadiazole, triazole, isoxazole, and CH 2 C≡C, wherein C 1 -C 4 alkyl, phenyl, benzyl, thiazole, thiadiazole, triazole, and isoxazole are optionally substituted with substituents selected from the group consisting of hydrogen, halogen, methyl, OH, and OCH 3 .