| 摘要 |
Compounds of Formula I and Formula IA are inhibitors of dihydrofolate reductase and are suitable for use in compositions and methods for dihydrofolate reductase inhibition or, more specifically, treatment of a fungal infection, a bacterial infection or a protozoal infection, and, in specific embodiments, treatment of a fungal infection caused by C. albicans or C. glabrata:;;wherein R, R1, R2, R3, R4, A, B, E, V, W, X, Y and Z are as defined herein. |
| 主权项 |
1. A compound of Formula I: wherein R is selected from the group consisting of H, C1-5alkyl, C1-3alkoxy, and hydroxy; wherein R1, R2, R3, and R4 are each independently selected from the group consisting of hydrogen, and C1-5alkyl, cycloalkyl, alkoxyalkyl, alkoxyalkoxyalkyl, arylalkyl, alkylcarbonyl, cycloalkylcarbonyl, alkoxycarbonyl, alkoxyalkylcarbonyl, alkoxyalkoxyalkylcarbonyl, arylcarbonyl, pyridinylcarbonyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, and cyanoalkylcarbonyl; wherein A and B are each independently selected from the group consisting of hydrogen, C1-5alkyl, halogen, hydroxy, lower haloalkyl, lower alkoxy, lower haloalkoxy, lower alkoxyalkyl, carboxy, lower alkoxycarbonyl, cyano, nitro, aminocarbonyl, lower alkylsulfinyl, lower alkylcarbonylamino, lower alkylsulfonylamino, lower alkylthio, lower alkylsulfonyl, formyl, lower alkoxycarbonyl, dialkylsilyloxy, phenyl, phenoxy, arylalkoxy, and aryloxyalkoxy, wherein the phenyl, phenoxy, arylalkoxy, and aryloxyalkoxy substituents may themselves be optionally substituted with halogen, lower haloalkyl, lower alkyl, lower alkoxy, or lower alkylsulfonyl; wherein at least one of V, W, X, Y, and Z is an alkoxy group; wherein at least one of V, W, X, Y, and Z is a phenyl group having at least one substituent selected from the group consisting of hydroxyl, cyano, carbamate (—OC(O)NH2), N-lower alkyl carbamate, N,N-di-lower alkyl carbamate, alkoxycarbonyl, lower alkyl amine and di-lower alkyl amine; and wherein the remainder of V, W, X, Y, and Z are each independently selected from the group consisting of hydrogen, C1-5alkyl, halogen, hydroxy, lower haloalkyl, lower alkoxy, lower haloalkoxy, lower alkoxyalkyl, carboxy, lower alkoxycarbonyl, cyano, nitro, aminocarbonyl, lower alkylsulfinyl, lower alkylcarbonylamino, lower alkylsulfonylamino, lower alkylthio, lower alkylsulfonyl, formyl, lower alkoxycarbonyl, dialkylsilyloxy, phenyl, phenoxy, arylalkoxy, and aryloxyalkoxy, wherein the phenyl, phenoxy, arylalkoxy, and aryloxyalkoxy substituents may themselves be optionally independently substituted one or more times with halogen, lower haloalkyl, lower alkyl, lower alkoxy, or lower alkylsulfonyl; wherein each “lower” used in conjunction with any of the above groups is individually C1 to C6, or a pharmaceutically acceptable salt thereof. |
