Enzyme Inhibitors

A compound having the structure:

• and the tautomers, acceptable salts, and biohydrolyzable amides, ester, and imides thereof, wherein:
• (a) B1 is selected from the group consisting of a methylene group connected to B2 through a single bond such that B1 and B2 form a five-membered ring, and a methylene group connected to B2 through another methylene group such that B1 and B2 form a six membered ring;
• (b) B2 is selected from the group consisting of a methylene group connected to B1 through a single bond such that B1 and B2 form a five-membered ring, and a methylene group connected to B2 through another methylene group such that B1 and B2 form a six membered ring;
• (c) X is selected from the group consisting of nil, —CH2—, and —NH—;
• (d) Z is a heterocyclic ring;
• (e) L1, L2, and L3 are each, independently, selected from the group consisting of nil, —NH—, —O—, —S—, —C(O)—, —CF2—, alkylene, alkenylene, cycloalkylene, arylene, arylalkylene, arylalkenylene, —C(O)NH—, —NHSO2R1—, —C(O)R2—, —C(O)R3—O—, —C(O)R4—S—, —C(O)R5—NH—, —NH—R6—, —OR7—, —C(O)O—R8—, —C(O)NH—R9—, —NHC(O)—R10—, —OC(O)R11— and —C(O)—CH(R12)—N(R13)—Y—, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are, independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, alkylamino, protected alkylamino, arylamino protected arylamino, arylalkylamino, protected arylalkylamino, wherein R12 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, alkylamino, protected alkylamino, arylamino, protected arylamino, arylalkylamino, protected arylalkylamino, and —AA wherein —AA is an amino acid side chain, or R12 and R13 together form a monocyclic of polycyclic heterocyclic ring including the nitrogen to which R13 is bonded, and wherein Y is nil or —C(O)—CH(R14)—N(R15)— wherein R14 is selected from the group consisting of hydrogen alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, alkylamino, protected alkylamino, arylamino, protected arylamino, arylalkylamino, protected arylalkylamino, and —AA wherein —AA is an amino acid side chain, or R14 and R15 together form a second monocyclic or polycyclic heterocyclic ring including the nitrogen to which R15 is bonded;
• (f) L4 is nil or —C(O)—;
• (g) P is a poly(alkylene oxide) polymer selected from the group consisting of a linear poly(alkylene oxide), a branched chain poly(alkylene oxide), and a star poly(alkylene oxide);
• (h) n is an integer from 1 to about 100;
• (i) Q is nil or —O—;
• and
• (j) A is selected from the group consisting of alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, Z′, wherein Z′ is an aromatic, substituted or unsubstituted monocyclic or polycyclic, carbocyclic ring;
• —C(O)—Z′, and —C(O)—R15—CF3, wherein R15 is nil or alkyl, and
• wherein L1′, L2′, L3′, Z′, X′, B1′, and B2′ are defined as for, respectively L1, L2, L3, Z, X, B1, and B2.