Inhibitors of glutathione s-transferases (GSTs) and NAD(P)H:quinone oxidoreductase 1 (NQO1), pharmaceutical compositions, and uses in managing cancer
This disclosure relates to compounds that inhibit glutathione S-transferases (GSTs) and/or NAD(P)H:quinone oxidore-ductase 1 (NQO1) for uses in treating cancer. In certain embodiments, this disclosure relates to compositions and uses of N-(thia-zol-2-yl)-carboxamide derivatives such as a N-(5-nitrothiazol-2-yl)-carboxamide derivatives for treating cancer such as glioblastoma. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a N-(thiazol-2-yl)-carboxamide derivative such as a N-(5-nitrothiazol-2-yl)-carboxamide derivative which is a compound of formula (I), or derivative, prodrug or salt thereof and a pharmaceutically acceptable excipient, wherein X, R 1 , R 2 , and R 3 substituents are reported herein.
1 . A pharmaceutical composition comprising a compound 5-methyl-N-(5-nitrothiazol-2-yl)-3-phenylisoxazole-4-carboxamide or salt thereof.
2 . The pharmaceutical composition of claim 1 in the form of a pill, capsule, or tablet.
3 . The pharmaceutical composition of claim 1 in the form of a saline aqueous buffer.
4 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is selected from a saccharide, disaccharide, or polysaccharide.
5 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is sucrose, lactose, glucose, mannitol, sorbitol, xylitol, or maltitol.
6 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is gelatin.
7 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is polyvinylpyrrolidone (PVP).
8 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is cellulose, microcrystalline cellulose, cellulose ether, hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), or crosslinked sodium carboxymethyl cellulose.
9 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is polyethylene glycol (PEG).
10 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is dibasic calcium phosphate, calcium carbonate, or magnesium carbonate.
11 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is stearic acid or magnesium stearate.
12 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is talc or silica.
13 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is vitamin A or vitamin E.
14 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is vitamin C.
15 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is retinyl palmitate.
16 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is selenium.
17 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is cysteine or methionine.
18 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is citric acid or sodium citrate.
19 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is methyl paraben or propyl paraben.