Valiolamine derivatives as glucosidase inhibitors
This disclosure is directed to N-substituted valiolamine compounds, their use as glycosidase inhibitors, and in methods of treating diseases or conditions in which glycosidase inhibition provides benefit.
1 . A compound according to Formula (I):
or a pharmaceutically acceptable salt thereof,
wherein
W 1 -W 5 are each independently selected from the group consisting of —H, benzyl, —C(═O)—C 1 -C 9 alkyl, and —C(═O)O—C 1 -C 9 alkyl;
R 1 is optionally substituted C 1 -C 9 alkylene;
R 2 is absent or selected from the group consisting of —NH—, —O—, —C(═O)—, and —NH—C(═O)O—;
R 3 is absent or selected from the group consisting of —O—, —C(═O)—, —C(═O)O, and optionally substituted C 1 -C 6 alkylene;
R 4 is —NH—;
R 5 is
wherein
X 1 , X 2 , X 3 , X 4 , and X 5 are each independently selected from the group consisting of —H, —NO 2 , —N 3 , optionally substituted C 2 -C 12 heterocycle, and optionally substituted C 1 -C 12 heteroaryl.
2 . The compound of claim 1 , wherein W 1 -W 5 are each independently —H.
3 . The compound of claim 2 , wherein R 1 is a C 1 -C 9 alkylene.
4 . The compound of claim 1 , wherein R 3 is a C 1 -C 6 alkylene or —C(═O)O—.
5 . The compound of claim 1 , wherein R 5 is
and wherein X 1 , X 2 , X 3 , X 4 , and X 5 are each independently selected from the group consisting of —H, —NO 2 , —N 3 , a C 2 -C 12 heterocycle, and a C 1 -C 12 heteroaryl.
6 . The compound of claim 5 , wherein X 3 is —N 3 or a C 1 -C 12 heteroaryl.
7 . The compound of claim 5 , wherein X 3 is —N 3 .
8 . The compound of claim 5 , wherein X 3 is a C 1 -C 12 heteroaryl, and wherein the C 1 -C 12 heteroaryl is selected from the group consisting of
9 . The compound of claim 5 , wherein X 1 is —NO 2 .
10 . The compound of claim 5 , wherein X 2 , X 4 , and X 5 are each —H.
11 . The compound of claim 1 , wherein the compound is selected from the group consisting of:
12 . A pharmaceutical composition comprising the compound of claim 1 and at least one pharmaceutically acceptable excipient.
13 . A method of treating diabetes, the method comprising administering to a subject in need thereof, a therapeutically effective amount of the compound of claim 1 .
14 . The method of claim 13 , wherein the diabetes is Type I diabetes or Type II diabetes.
15 . A method for inhibiting glycosidase function, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1 .
16 . A method for treating or preventing a viral infection, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1 .
17 . The method of claim 16 , wherein the viral infection is selected from the group consisting of hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, dengue virus (DENV) infection, Marburg virus (MARV) infection, Ebola virus (EBOV) infection, BVHV, human immunodeficiency virus (HIV) infection, influenza A infection, influenza B infection, encephalitis virus infection, Zika virus infection, and yellow fever virus (YFV) infection.
18 . The method of claim 17 , wherein the encephalitis virus infection is eastern equine encephalitis virus infection, western equine encephalitis virus infection, and Japanese encephalitis virus (JEV) infection.
19 . The compound of claim 1 , wherein R 2 is —O— or —NH—C(═O)O—.