Cysteinyl protease inhibitors

A cysteine protease inhibitor compound represented by FORMULA I or II:

• or a salt, isostere, or stereoisomer thereof, wherein:
• R1 is a W-substituted or unsubstituted lower alkenyl or a lower alkynyl, wherein said W-substituent is a halo, a hydroxy, an alkyl, an aryl, a heterocycle, a heteroaryl, an alkoxy, an aminosulfonyl, an alkylcarbonyl, an arylcarbonyl, a heteroarylcarbonyl, a heterocycle-carbonyl, a nitro, a haloalkyl, an amino or aminocarbonyl;
• X is —CH═CH—(CH═CH)k—(CH2)j or —CH2CH2—(CH2)b, wherein k is an integer selected from 0 to 9, j is an integer selected from 0 to 4, b is an integer selected from 3 to 6;
• Y is S, SO, SO2, NR20, —N(O)(R20), —PR20, —P(O)(R20)—, —P(O)O— or —P(O)(OR20)O, wherein R20 is a hydrogen atom, an alkyl, or an aryl;
• Z is —(CH2)i—A, wherein i is an integer selected from 0 to 4 and A is an L, substituted or unsubstituted heterocycle, a heteroaryl or an aryl, and further, wherein said L-substituent is a halogen, a lower alkyl, a lower alkenyl, a lower alkynyl, an alkoxy, an aryloxy, a hydroxy, a haloalkyl, a trifluoromethyl, a cyano, a nitro, a nitrile, an alkylthio, a phenyl, or an —NR30R31 group and wherein R30 and R31 each independently is H, alkyl, hydroxy or halo lower alkyl;
• R2, R3, R4, R5, R6, R7, R8, Q, and n are each selected according to a group selected from among groups (i), (ii), (iii), (iv), (v), (vi) and (vii) as follows:
• (i) R3 and R5 each independently is a side chain of a naturally occurring α-amino acid, a hydrogen atom, an alkyl, an alkenyl, an alkynyl, an aryl, an aralkyl, an aralkenyl, an aralkynyl, a heteroaryl, a heteroaralkyl, a heteroaralkenyl, a heteroaralkynyl, an L-substituted aryl, an L-substituted aralkyl, an L-substituted aralkenyl, an L-substituted aralkynyl, an M-substituted heteroaryl, an M-substituted heteroaralkyl, an M-substituted heteroaralkenyl or an M-substituted heteroaralkynyl, wherein M is a lower alkyl or a halo lower alkyl;
• R2, R4, R6, and R8 each independently is a hydrogen atom, a lower alkyl, a cycloalkyl or a cycloalkylalkyl;
• R7 is a C1-6 alkyl, an RARBCH, an aryl, an alkenyl, an alkynyl, a 9-fluorenyl, an aralkyl, an aralkenyl, an aralkynyl, a monocylic or a bicyclic heterocycle or a monocyclic or a bicyclic aryl, heteroaryl or aryl-heteroaryl, wherein said aryl, said heterocycle and said heteroaryl groups are optionally substituted with L;
• Q is —C(O)—, —O—C(O)—, —S(O)2— or —HN—C(O)—;
• n is zero or the integer 1;
• RA is —(T)m—(D)m—R3, wherein T is 0 or NH, D is C1-4 alkyl or C2-4 alkenyl, and m is zero or the integer 1, and
• RB is a substituent selected as set forth for R3 and R5;
• or alternatively,
• (ii) Q, R2, R5 and R8 each independently is as set forth in (i);
• R3 and R4 each independently is as recited in (i) or (iv);
• n is zero;
• and
• R6 and R7 together with the atoms to which each is attached form a 3-10 membered heterocyclic moiety containing& 1-5 heteroatoms, wherein said moiety is optionally substituted with L;
• or alternatively,
• (iii) R2, R3, R4, R5 and R8 each independently is as set forth in (i);
• Q is —C(O)—;
• n is 1;
• and
• R6 and R7 each independently is a substituted or unsubstituted carbonyl (—(C═O)—), phenylene, heteroatom, lower alkylene, or lower alkylene linked to a heteroatom, wherein said substituent is L and also wherein R6 and R7 together with the atoms to which they are attached form a cyclic or a bicyclic moiety, further wherein when R6 and R7 are both carbonyl at least one is substituted;
• or alternatively,
• (iv) R2, R5, R6, R7, R3 and Q each independently is as set forth in any of (i)-(iii) or (v-vii), and n is zero or 1;
• R3 and R4 each independently is a) a heteroatom, b) a substituted or unsubstituted lower alkylene, c) lower alkylene linked to a heteroatom, wherein said substituent is L, or d) R3 and R4 together with the atoms to which they are attached form a heterocyclic moiety;
• or alternatively,
• (v) R2, R7, R8, Q each independently is as set forth in (i), and n is zero or 1;
• R3 and R4 each independently is as set forth in either of (i) or (iv);
• R5 and R6 each independently is a heteroatom or a substituted or unsubstituted lower alkylene or a lower alkylene linked to a heteroatom, wherein said substituent is L and also wherein R5 and R6 together with the atoms to which they are attached form a heterocyclic moiety;
• or alternatively,
• (vi) Q, R2, R6 and R8 each independently is as set forth in (i),
• R3 and R4 each independently is as set forth in either of (i) or (iv);
• n is zero;
• and
• R5 and R7 each independently is a heteroatom or a substituted or unsubstituted lower alkylene or lower alkylene linked to a heteroatom, wherein said substituent is L and also wherein R5 and R7 together with the atoms to which they are attached form a heterocyclic moiety;
• or alternatively,
• (vii) Q, R2, R5 and R6 each independently is as set forth in (i);
• R3 and R4 each independently is as set forth in either of (i) or (iv);
• n is 0;
• R6 and R7 each independently is a heteroatom or a substituted or unsubstituted lower alkylene or lower alkylene linked to a heteroatom, wherein said substituent is L and also wherein R6 and R7 together with the atoms to which each is attached form a 6-12 membered bicyclic heterocyclic or heteroaryl moiety.