The invention relates to a tizoxanide carbamate compound of Formula I and a pharmaceutically acceptable salt, a hydrate or a solvate thereof, and their pharmaceutical use. ##STR00001##

Prodrugs of tizoxanide, an analog or salt thereof are disclosed. The prodrugs have an ester moiety comprising an amino acid moiety, and increase the bioavailability of the tizoxanide, an analog or salt thereof. Compositions and methods of treating an intracellular protozoan infection, a viral infection or a cancer are also disclosed.

Prodrugs of tizoxanide, an analog or salt thereof are disclosed. The prodrugs have an ester moiety comprising an amino acid moiety, and increase the bioavailability of the tizoxanide, an analog or salt thereof. Compositions and methods of treating an intracellular protozoan infection, a viral infection or a cancer are also disclosed.

A compound represented by formula (I) is effective in inhibiting the growth of Clostridium difficile. Compared with nitazoxanide and other antibiotics, the compound also has significantly less influence on intestinal probiotics and lower toxic side effects while significantly inhibiting the activity of Clostridium difficile, and the disease is not easy to relapse after the drug is stopped.

A compound represented by formula (I) is effective in inhibiting the growth of Clostridium difficile. Compared with nitazoxanide and other antibiotics, the compound also has significantly less influence on intestinal probiotics and lower toxic side effects while significantly inhibiting the activity of Clostridium difficile, and the disease is not easy to relapse after the drug is stopped.

The present invention relates to the process for the preparation of Nitazoxanide and intermediates thereof. The invention explores readily available starting materials with reaction conditions that are suitable for industrial scale applications. The present invention discloses, a single vessel process to prepare 5-nitrothiazol-2-amine starting from a very basic starting material 1,1-dimethoxy-N, N-dimethylmethanamine. Overall intermediates throughout the process is free from column chromatography and the final product Nitazoxanide is purified by precipitation. All the synthesized compounds were confirmed by various spectroscopic techniques such as Fourier transform infrared spectroscopy, .sup.1H NMR, .sup.13C NMR, HRMS and elemental analysis.

##STR00001##

The present invention relates to the process for the preparation of Nitazoxanide and intermediates thereof. The invention explores readily available starting materials with reaction conditions that are suitable for industrial scale applications. The present invention discloses, a single vessel process to prepare 5-nitrothiazol-2-amine starting from a very basic starting material 1,1-dimethoxy-N, N-dimethylmethanamine. Overall intermediates throughout the process is free from column chromatography and the final product Nitazoxanide is purified by precipitation. All the synthesized compounds were confirmed by various spectroscopic techniques such as Fourier transform infrared spectroscopy, .sup.1H NMR, .sup.13C NMR, HRMS and elemental analysis.

##STR00001##

A pharmaceutical composition contains tizoxanide and choline hydroxide, a choline salt of tizoxanide and crystal form thereof. A mixture of tizoxanide and choline hydroxide, or a salt thereof and crystal form of the salt significantly improve the solubility and bioavailability of tizoxanide, and exhibits favorable effects in drugs for treating viruses, fibrosis, bacteria, tumors and intestinal parasites.

A pharmaceutical composition contains tizoxanide and choline hydroxide, a choline salt of tizoxanide and crystal form thereof. A mixture of tizoxanide and choline hydroxide, or a salt thereof and crystal form of the salt significantly improve the solubility and bioavailability of tizoxanide, and exhibits favorable effects in drugs for treating viruses, fibrosis, bacteria, tumors and intestinal parasites.

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.sup.1, R.sup.2, and R.sup.3 substituents are reported herein. ##STR00001##