Water-Soluble Prodrugs of Florfenicol and its Analogs

A compound having the Formula (I)

• in which:
• R is selected from the group consisting of
• A is oxygen and a is zero or 1;
• L is (a) CH2 and l is an integer from 1 to 6;
• (b) CHR1 where R1 is an amino acid side chain and l is 1;
• or (c) CHR1NHC(O)C(NH2)R2 where R1 and R2 are amino acid side chains and l is 1;
• M is (a) oxygen or sulfur and m is zero or one;
• (b) CH2 and m is zero or an integer from 1 to 4;
• or (e) NH and m is 1;
• X is (a) CH1 and x is zero or an integer from 1 to 4;
• or (b) C(O) and x is 1;
• and Y is (a) NH2;
• (b) NHRx where Rx is methyl, ethyl, n-propyl or isopropyl;
• (c) NRyRz where Ry and Rz are independently hydrogen, methyl, ethyl, n-propyl or isopropyl, or Ry and Rz taken together form a C2-C5 alkylene chain or a C2-C4 alkylene chain further including a nitrogen or oxygen heteroatom in said chain;
• (d) C(═NH)NH2;
• (e) N+R4R5R6 where R4, R5 and R6 are independently hydrogen, methyl or ethyl, or R4 and R5 taken together form a C2-C5 alkylene chain, or a C2-C4 alkylene chain further including a nitrogen or oxygen heteroatom in said chain;
• (f) pyridinium;
• (g) N-methyl or N-ethyl pyridinium;
• (h) N′-3-methyl-N-1-imidazolium;
• (i) a phenyl group substituted by a group having the formula NR4R5 or N+R4R5R6 where R4, R5 and R6 are as defined above;
• or (j) NH—CR3(═NH) where R3 is hydrogen, methyl or amino;
• and R7 is selected from the group consisting of dichloromethyl, difluoromethyl, trifluoromethyl, cyanomethyl, azidomethyl, and aminomethyl;
• provided that the group AaL1MmXxY is other than an alpha-N-unfunctionalized glycine, ornithine or lysine residue;
• and pharmaceutically acceptable salts thereof.