Antifungal agents with enhanced activity in acidic ph

A method of treating a fungal infection in a subject in need thereof, the method comprising administering to the subject a compound of Formula (II):

• which is (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[2-amino-2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-pyridinyl)-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid,
• or a pharmaceutically acceptable salt or hydrate thereof,
• wherein the fungal infection is a yeast or mold infection occurring in a condition or an anatomic area in which the pH is lower than about 7.

A method of preventing a fungal infection in a subject, the method comprising administering to the subject a compound of Formula (II):

• which is (1S,4aR,6aS,7R, 8R,10aR,10bR,12aR,14R,15R)-15-[[2-amino-2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-pyridinyl)-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid,
• or a pharmaceutically acceptable salt or hydrate thereof,
• wherein the fungal infection is a yeast or mold infection occurring in a condition or an anatomic area in which the pH is lower than about 7.

A method of treating vulvovaginal candidiasis (VVC) infection in a subject in need thereof, the method comprising administering to the subject a compound of Formula (II):

• which is (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[2-amino-2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-pyridinyl)-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid,
• wherein the VVC infection occurs in a condition or an anatomic area in which the pH is lower than about 5.

A method of treating vulvovaginal candidiasis (VVC) infection in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of a compound of Formula (II):

• the compound being (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[2-amino-2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-pyridinyl)-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid,
• wherein the VVC infection occurs in a condition or an anatomic area in which the pH is lower than about 5.

A method of treating a fungal infection in a subject in need thereof, the method comprising administering to the subject a compound of Formula (IIa):

• which is (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-pyridinyl)-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid,
• or a pharmaceutically acceptable salt or hydrate thereof,
• wherein the fungal infection is a yeast or mold infection occurring in a condition or an anatomic area in which the pH is lower than about 7.

A method of preventing a fungal infection in a subject, the method comprising administering to the subject a compound of Formula (IIa):

• which is (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-pyridinyl)-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid,
• or a pharmaceutically acceptable salt or hydrate thereof,
• wherein the fungal infection is a yeast or mold infection occurring in a condition or an anatomic area in which the pH is lower than about 7.

A method of treating vulvovaginal candidiasis (VVC) infection in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of a compound of Formula (IIa):

• the compound being (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-pyridinyl)-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10, 10a, 10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid,
• wherein the VVC infection occurs in a condition or an anatomic area in which the pH is lower than about 5.