Anti-
A series of celecoxib derivatives defined by Formula I: were prepared and evaluated for their ability to inhibit the gram-negative bacteria Francisella tularensis . Pharmaceutical compositions including celecoxib derivatives and their use in methods for treating or preventing infection by Francisella tularensis in a subject are described.
1. A method of treating infection by Francisella tularensis in a subject in need thereof by administering a therapeutically effective amount of a composition consisting of a compound selected from the group consisting of:
4-(5-biphenyl-4-yl-3-trifluoromethyl-pyrazol-1-yl)-phenylamine;
4-(5-naphthalen-1-yl-3-trifluoromethyl-pyrazol-1-yl)-phenylamine;
4-[5-(6-methoxy-naphthalen-2-yl)-3-trifluormethyl-pyrazol-1-yl]-phenylamine; and
4-[5-(4′-bromo-biphenyl-4-yl)-3-trifluoromethyl-pyrazolyl]-phenylamine;
or a pharmaceutically acceptable salt thereof and optionally a pharmaceutically acceptable carrier.
2. The method of claim 1 , wherein the compound is selected from the group consisting of:
4-(5-biphenyl-4-yl-3-trifluoromethyl-pyrazol-1-yl)-phenylamine; and
4-[5-(4′-bromo-biphenyl-4-yl)-3-trifluoromethyl-pyrazolyl]-phenylamine;
and their pharmaceutically acceptable salts.
3. The method of claim 1 , wherein the compound is 4-[5-(4′-bromo-biphenyl-4-yl)-3-trifluoromethyl-pyrazolyl]-phenylamine or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the Francisella tularensis infection is inhibited in macrophage cells without significant toxicity to the macrophage cells.
5. The method of claim 1 , wherein the Francisella tularensis is antibiotic resistant.
6. The method of claim 1 , wherein the subject is a human.