Compounds for inhibition of memapsin 1
Various embodiments of the present invention relate to, among other things, compounds that are inhibitors of Memapsin 1 and, as a result, are effective in the treatment of Alzheimer's disease or diabetes (e.g., Type 2 diabetes).
1. A compound of the formula (IIa)-(IIc):
or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof,
wherein:
R 1 is hydrogen, alkyl or arylalkyl;
R 2 , R 4 , and R 6 are each, independently, hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted arylalkyl;
R 3 is hydrogen, substituted or unsubstituted alkyl or —NR 8 2 (wherein each R 8 is, independently, hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted arylalkyl or —SO 2 R 9 , wherein R 9 is hydrogen or substituted or unsubstituted alkyl);
R 5 and R 7 are each independently hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted arylalkyl;
Het represents a substituted or unsubstituted heterocycle; and
R 10 and R 11 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted arylalkyl.
2. The compound of claim 1 , wherein Het represents a substituted or unsubstituted 5-membered heterocycle.
3. The compound of claim 1 , wherein Het represents a substituted or unsubstituted thiazole.
4. The compound of claim 1 , wherein R 1 is hydrogen.
5. The compound of claim 1 , wherein R 2 is hydrogen or unsubstituted (C 1 -C 4 ) alkyl.
6. The compound of claim 1 , wherein R 3 is hydrogen or unsubstituted alkyl.
7. The compound of claim 1 , wherein at least one of R 4 and R 6 is hydrogen.
8. The compound of claim 1 , wherein R 5 is substituted or unsubstituted (C 6 -C 10 )-aryl-(C 1 -C 4 )-alkyl.
9. The compound of claim 1 , wherein R 7 is hydrogen or substituted or unsubstituted (C 1 -C 4 ) alkyl.
10. The compound of claim 9 , wherein R 7 is OH-substituted (C 1 -C 4 ) alkyl.
11. The compound of claim 9 , wherein R 7 is NHR 12 -substituted (C 1 -C 4 ) alkyl, wherein R 12 is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted arylalkyl.
12. The compound of claim 1 , wherein R 10 is hydrogen and R 11 is substituted or unsubstituted (C 1 -C 4 ) alkyl.
13. The compound of claim 1 selected from the group consisting of:
wherein R 12 is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted arylalkyl; and
pharmaceutically acceptable salts, polymorphs, prodrugs, solvates or clathrates thereof.
14. A pharmaceutical composition comprising one or more compounds of claim 1 and one or more pharmaceutically acceptable carriers, diluents, excipients or combinations thereof.