Soft protease inhibitors and pro-soft forms thereof

A method of treating cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound represented by:

• or a pharmaceutical acceptable salt thereof;
• wherein, independently for each occurrence:
• R1 represents hydrogen, a C-terminally linked amino acid residue or amino acid analog, or a C-terminally linked peptide or peptide analog;
• R9a represents hydrogen or alkyl;
• R9b represents hydrogen or alkyl;
• R10 represents the side chain of a natural or non-natural amino acid;
• R11 represents hydrogen, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aralkyl, heteroaralkyl, aryl, heteroaryl, or the side chain of a natural or non-natural amino acid;
• and
• Y1 and Y2, independently, are OH, or a group capable of being hydrolyzed to a hydroxyl group, or Y1 and Y2 are connected via a ring having from 5 to 8 atoms in the ring structure which is capable of being hydrolyzed to two hydroxyl groups.

A method of treating cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound represented by:

• or a pharmaceutically acceptable salt thereof;
• wherein, independently for each occurrence:
• W represents —CN, —CH=NR5,
• R1 represents a C-terminally linked peptide or peptide analog which is a substrate for an activating enzyme;
• R3 represents a hydrogen or lower alkyl;
• R4 represents hydrogen, halogen, lower alkyl, lower alkenyl, or lower alkynyl;
• R5 represents independently for each occurrence H, alkyl, alkenyl, alkynyl, —C(X1)(X2)X3, —(CH2)m—R7, —(CH2)n—OH, —(CH2)n—O-alkyl, —(CH2)n—O-alkenyl, —(CH2)n—O-alkynyl, —(CH2)n—O—(CH2)m—R7, —(CH2)n—SH, —(CH2)n—S-alkyl, —(CH2)n—S-alkenyl, —(CH2)n—S-alkynyl, —(CH2)n—S—(CH2)m—R7, —C(O)C(O)NH2, or —C(O)C(O)OR′7;
• R6 represents independently for each occurrence a substituted or unsubstituted aryl, aralkyl, cycloalkyl, cycloalkenyl, or heterocycle;
• R7 represents independently for each occurrence hydrogen, or a substituted or unsubstituted alkyl, alkenyl, aryl, aralkyl, cycloalkyl, cycloalkenyl, or heterocycle;
• R8 represents hydrogen, —CH3, or —(CH2)n—CH3;
• Y1 and Y2 are independently OH, or a group capable of being hydrolyzed to a hydroxyl group, or Y1 and Y2 are connected via a ring having from 5 to 8 atoms in the ring structure which is capable of being hydrolyzed to two hydroxyl groups;
• R10 represents hydrogen, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aralkyl, heteroaralkyl, aryl, heteroaryl, or the side chain of a natural or non-natural amino acid;
• R50 represents O or S;
• R51 represents N3, SH, NH2, NO2 or —OR7;
• R52 represents hydrogen, a lower alkyl, an amine, —OR7, or a pharmaceutically acceptable salt, or R51 and R52 taken together with the phosphorous atom to which they are attached complete a heterocyclic ring having from 5 to 8 atoms in the ring structure;
• X1 represents a halogen;
• X2 and X3 each represent a hydrogen or a halogen;
• m is zero or an integer in the range of 1 to 8;
• and
• n is an integer in the range of 1 to 8.