Aromatic 2-nitrosulfonyl fluoride antibiotics and methods of use thereof
AssigneeThe Regents of the University of California
InventorsNiren Murthy, Corinne Sadlowski, Bora Park
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Abstract
Aspects of the present disclosure include antibacterial aromatic sulfonyl fluoride agents. The subject aromatic sulfonyl fluoride agents have a pharmacophore that can provide for potent antibacterial activity. The subject agents are compounds including an aromatic group substituted with a sulfonyl fluoride warhead group and an electron withdrawing group. The subject agents find use in a variety of antibiotic applications. In some cases, the subject agents find use in methods of treating bacterial infections in a subject. Also provided are pharmaceutical compositions and kits that find use in practicing the subject methods.
Claims16
A method of treating a bacterial infection, the method comprising administering to a subject in need thereof a therapeutically effective amount of an antibacterial aromatic sulfonyl fluoride agent, wherein the aromatic sulfonyl fluoride agent is a compound of formula (II):
- wherein
- Z1 is O or S;
- Z2 and Z3 are independently CR6 or N;
- and
- R3, R4, R5 and R6 are independently selected from H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cyano, nitro, hydroxy, carboxy, carboxyamide, sulfonamide and sulfonate;
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition for treating a bacterial infection in a subject, comprising:
- a therapeutically effective amount of an antibacterial aromatic sulfonyl fluoride active agent;
- and a pharmaceutically acceptable excipient, wherein the antibacterial aromatic sulfonyl fluoride active agent is a compound of formula (III):
- wherein
- Z is O or S;
- and
- R1 and R2 are independently selected from H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cyano, nitro, hydroxy, carboxy, carboxyamide, sulfonamide and sulfonate;
- or a pharmaceutically acceptable salt thereof.
A kit for treating a bacterial infection in a subject, comprising:
- a therapeutically effective amount of an antibacterial aromatic sulfonyl fluoride active agent;
- and one or more additional agents selected from the group consisting of isoniazid, rifampin, pyrazinamide and ethambutol, rifabutin, rifapentine, amikacin, capremycin, cycloserine, ethionamide, levofloxacin, moxifloxacin, para-aminosalicylic, nitazoxanide, gleevec, CPZEN-45 and streptomycin, wherein the antibacterial aromatic sulfonyl fluoride active agent is a compound of formula (III):
- wherein
- Z is O or S;
- and
- R1 and R2 are independently selected from H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cyano, nitro, hydroxy, carboxy, carboxyamide, sulfonamide and sulfonate;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.