Patent ID: 7045507

Claim:
A method for increasing the antifungal activity of an antifungal agent, comprising administering said antifungal agent in combination with an effective amount of a substituted tetracycline compound, such that the antifingal activity of said antifungal agent is increased, wherein said substituted tetracycline compound is of formula I: X is CHC(R 13 Y′Y), C═CR 13 Y, CR 6′ R 6 , S, NR 6 , or O; R 2 , R 2′ , R 4 , and R 4′ are each independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, aryl, heterocyclic, heteroaromatic or a prodrug moiety; R 3 , R 10 , R 11 and R 12 are each hydrogen or a pro-drug moiety; R 5 is hydroxyl, hydrogen, thiol, alkanoyl, aroyl, alkaroyl, aryl, heteroaromatic, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, alkyl carbonyloxy, or aryl carbonyloxy; R 6 and R 6′ are each independently hydrogen, methylene, absent, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl; R 7 is bromine, fluorine, iodine, nitro, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, arylalkyl, amino, arylalkenyl, arylalkynyl, or —(CH 2 ) 0-3 NR 7c C(═W′)WR 7a ; R 9 is hydrogen, halogen, nitro, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, arylalkyl, amino, arylalkenyl, arylalkynyl, thionitroso, or —(CH 2 ) 0-3 NR 9c C(═Z′)ZR 9a ; Z is CR 9d R 9e , S, NR 9b or O; Z′is O, S, or NR 9f ; W is CR 7d R 7e , S, NR 7b or O; W′is O, NR 7f S; R 7a , R 7b , R 7c , R 7d , R 7e , R 7f R 9a , R 9b , R 9c , R 9d , R 9e , and R 9f are each independently hydrogen, acyl, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, aryl, heterocyclic, heteroaromatic or a prodrug moiety; R 8 is hydrogen, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl; R 13 is hydrogen, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, aryl, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl; and Y′ and Y are each independently hydrogen, halogen, hydroxyl, cyano, sulfhydryl, amino, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl, and pharmaceutically acceptable salts and enantiomers thereof, wherein said tetracycline compound is not minocycline.