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1. WO2000014095 - NOVEL HETEROAROMATIC INHIBITORS OF FRUCTOSE 1,6-BISPHOSPHATASE

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

We claim:

O
A compound of formula (I): R5-X-P-YR' (I)
YR1
wherein R5 is selected from the group consisting of:


wherein:
each G is independently selected from the group consisting of C, N, O, S, and Se, and wherein only one G may be O, S, or Se, and at most one G is N;
each G' is independently selected from the group consisting of C and N and wherein no more than two G' groups are N;
A is selected from the group consisting of -H, -NR42, -CONR42, -CO2R3, halo, -S(O)R\ -SO2R3, alkyl, alkenyl, alkynyl, perhaloalkyl, haloalkyl, aryl, -CH2OH,

-CH2NR42, -CH2CN, -CN, -C(S)NH2, -OR3, -SR3, -N3, -NHC(S)NR42, -NHAc, and null; each B and D are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)Rn, -C(O)SR\ -SO2R", -S(O)R\ -CN, -NR92, -OR3, -SR3, perhaloalkyl, halo, -NO2, and null, all except -H, -CN, perhaloalkyl, -NO2, and halo are optionally substituted;
E is selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, alkoxyalkyl, -C(O)OR\ -CONR42, -CN, -NR92, -NO2, -OR3, -SR3, perhaloalkyl, halo, and null, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;
J is selected from the group consisting of -H and null;

X is an optionally substituted linking group that links R5 to the phosphorus atom via 2-4 atoms, including 0-1 heteroatoms selected from N, O, and S, except that if X is urea or carbamate there is 2 heteroatoms, measured by the shortest path between R5 and the phosphorus atom, and wherein the atom attached to the phosphorus is a carbon atom, and wherein there is no N in the linking group unless it is connected directly to a carbonyl or in the ring of a heterocycle; and wherein X is not a 2 carbon atom -alkyl- or -alkenyl-group; with the proviso that X is not substituted with -COOR2, -SO3R', or -PO3R'2;
Y is independently selected from the group consisting of -O-, and -NR6-;
when Y is -O-, then R1 attached to -O- is independently selected from the group consisting of -H, alkyl, optionally substituted aryl, optionally substituted alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, -C(R2)2OC(O)NR22, -NR2-C(O)-R3, -C(R2)2- OC(O)R\ -C(R2)2-O-C(O)OR\
-C(R2)2OC(O)SR3, -alkyl-S-C(O)R3, -alkyl-S-S-alkylhydroxy, and -alkyl-S-S-S-alkylhydroxy,
when Y is -NR6-, then R1 attached to -NR6- is independently selected from the group consisting of -H, -[C(R2)2]q-COOR3, -C(R4)2COOR\ -[C(R2)2]q-C(O)SR, and -cycloalkylene-COOR3;
or when either Y is independently selected from -O- and -NR6-, then together R1 and R1 are -alkyl-S-S-alkyl- to form a cyclic group, or together R1 and R1 are


wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1 -alkenyl, and 1-alkynyl; or nr Λ .
264
together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy,
alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both Y groups attached to the phosphorus; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the Y attached to the phosphorus;
together V and W are connected via an additional 3 carbon atoms to form an
optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl,
heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R3, -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO2R3, -OR2 , -SR2,
-CHR2N3, -CH2aryl, -CH(aryl)OH, -CH(CH=CR22)OH, -CH(C≡CR2)OH, -R2 , -NR22,
-OCOR3, -OCO2R3, -SCOR3, -SCO2R\ -NHCOR2, -NHCO2R3, -CH2NHaryl, -(CH2)p-OR2, and -(CH2)p-SR2;
p is an integer 2 or 3;
q is an integer 1 or 2;
with the provisos that:
a) V, Z, W, W' are not all -H; and
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic;
R2 is selected from the group consisting of R3 and -H;
R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
each R4 is independently selected from the group consisting of -H, and alkyl, or together R4 and R4 form a cyclic alkyl group;

R6 is selected from the group consisting of -H, lower alkyl, acyloxyalkyl, alkoxycarbonyloxyalkyl, and lower acyl;
each R9 is independently selected from the group consisting of -H, alkyl, aralkyl, and alicyclic, or together R9 and R9 form a cyclic alkyl group;
R" is selected from the group consisting of alkyl, aryl, -NR22, and -OR2; and with the provisos that:
1) when G' is N, then the respective A, B, D, or E is null;
2) at least one of A and B, or A, B, D, and E is not selected from the group
consisting of -H or null;
3) when R5 is a six-membered ring, then X is not any 2 atom linker, an
optionally substituted -alkyl-, an optionally substituted -alkenyl-, an
optionally substituted -alkyloxy-, or an optionally substituted -alkylthio-; 4) when G is N, then the respective A or B is not halogen or a group directly bonded to G via a heteroatom;
5) R1 is not unsubstituted C 1 -C 10 alkyl;
6) when X is not an -aryl- group, then R5 is not substituted with two or more aryl groups;
and pharmaceutically acceptable prodrugs and salts thereof.

2. The compounds of claim 1 wherein R5 is selected from the group consisting of pyrrolyl, imidazolyl, oxazolyl, thiazolyl, isothiazolyl, 1,2,4-thiadiazolyl, pyrazolyl, isoxazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, and 1,3-selenazolyl, all of which contain at least one substituent.

3. The compounds of claim 1 wherein
A is selected from the group consisting of -H, -NR42, -CONR42, -CO2R3, halo, Cl-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perhaloalkyl, C1-C6 haloalkyl, aryl, -CH2OH, -CH2NR42, -CH2CN, -CN, -C(S)NH2, -OR4, -SR4, -N3, -NHC(S)NR42, -NHAc, and null;
each B and D are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)R", -C(O)SR3, -SO2Rn, -S(O)R3, -CN, -NR22, -OR3, -SR3, perhaloalkyl, halo, and null, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;

E is selected from the group consisting of -H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, C4-C6 alicyclic, alkoxyalkyl, -C(O)OR\ -CONR42, -CN, -NR92, -OR3, -SR3, C1-C6 perhaloalkyl, halo, and null, all except -H, -CN, perhaloalkyl, and halo are optionally substituted; and
each R4 is independently selected from the group consisting of -H, and C1-C2 alkyl.

4. The compounds of claim 1 wherein R5 is


5. The compounds of claim 1 wherein R is


6. The compounds of claim 1 wherein R5 is selected from the group consisting of:




268
wherein
A" is selected from the group consisting of -H, -NR42, -CONR 2, -CO2R\ halo, Cl-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perhaloalkyl, C1-C6 haloalkyl, aryl, -CH2OH, -CH2NR42, -CH2CN, -CN, -C(S)NH2, -OR3, -SR3, -N3, -NHC(S)NR42, and -NHAc;
B" and D" are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)R", -C(O)SR\ -SO2R", -S(O)R\ -CN, -NR92, -OR3, -SR3, perhaloalkyl, and halo, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;
E" is selected from the group consisting of -H, C1-C6 alkyl, C2-C6 alkenyl, C2- C6 alkynyl, C4-C6 alicyclic, alkoxyalkyl, -C(O)OR\ -CONR42, -CN, -NR92, -OR3, -SR3, Cl -C6 perhaloalkyl, and halo, all except H, -CN, perhaloalkyl, and halo are optionally substituted; and
each R4 is independently selected from the group consisting of -H and C1-C2 alkyl.

7. The compounds of claim 6 wherein R5 is selected from the group consisting of:




The compounds of claim 6 wherein R5 is selected from the group consisting of:



The compounds of claim 6 wherein R5 is selected from the group consisting of:



10. The compounds of claim 1 wherein X is selected from the group consisting of -alkyl(hydroxy)-, -alkyl-, -alkynyl-, -aryl-, -carbonylalkyl-, -1,1-dihaloalkyl-,
-alkoxyalkyl-, -alkyloxy-, -alkylthioalkyl-, -alkylthio-, -alkylaminocarbonyl-,
-alkylcarbonylamino-, -alicyclic-, -aralkyl-, -alkylaryl-, -alkoxycarbonyl-,
-carbonyloxyalkyl-, -alkoxycarbonylamino-, and -alkylammocarbonylamino-, all optionally substituted.

11. The compounds of claim 4 wherein X is selected from the group consisting of -alkyl(hydroxy)-, -alkyl-, -alkynyl-, -aryl-, -carbonylalkyl-, -1,1-dihaloalkyl-,
-alkoxyalkyl-, -alkyloxy-, -alkylthioalkyl-, -alkylthio-, -alkylaminocarbonyl-,
-alkylcarbonylamino-, -alicyclic-, -aralkyl-, -alkylaryl-, -alkoxycarbonyl-,
-carbonyloxyalkyl-, -alkoxycarbonylamino-, and -alkylaminocarbonylamino-, all optionally substituted.

12. The compounds of claim 5 wherein X is selected from the group consisting of -alkyl(hydroxy)-, -alkyl-, -alkynyl-, -aryl-, -carbonylalkyl-, -1,1-dihaloalkyl-,
-alkoxyalkyl-, -alkyloxy-, -alkylthioalkyl-, -alkylthio-, -alkylaminocarbonyl-,
-alkylcarbonylamino-, -alicyclic-, -aralkyl-, -alkylaryl-, -alkoxycarbonyl-,
-carbonyloxyalkyl-, -alkoxycarbonylamino-, and -alkylaminocarbonylamino-, all optionally substituted.

13. The compounds of claim 3 wherein X is selected from the group consisting of -heteroaryl-, -alkylcarbonylamino-, -alkylaminocarbonyl-, -alkoxycarbonyl-, and -alkoxyalkyl-.

14. The compounds of claim 13 wherein X is selected from the group consisting of -heteroaryl-, and -alkoxycarbonyl-.

15. The compounds of claim 3 wherein said compound is a compound of formulae II, III, or IV



O O

II II
R5-C-NH-CH2-P-YR', (III)
I

YR1 , and

O O

II II
R5-C-OCH2-P-YR' (TV)

YR1

16. The compounds of claim 6 wherein X is selected from the group consisting of -alkyl(hydroxy)-, -alkyl-, -alkynyl-, -aryl-, -carbonylalkyl-, -1,1-dihaloalkyl-,
-alkoxyalkyl-, -alkyloxy-, -alkylthioalkyl-, -alkylthio-, -alkylaminocarbonyl-,
-alkylcarbonylamino-, -alicyclic-, -aralkyl-, -alkylaryl-, -alkoxycarbonyl-,
-carbonyloxyalkyl-, -alkoxycarbonylamino-, and -alkylaminocarbonylamino-, all optionally substituted.

17. The compounds of claim 16 wherein X is selected from the group consisting of -heteroaryl-, -alkylcarbonylamino-, -alkylaminocarbonyl-, -alkoxycarbonyl-, and -alkoxyalkyl- .

18. The compounds of claim 17 wherein said compound is a compound of formulae II or IV:



O O

II II
R5-C-O-CH2-P-YR' (IV)

YR1 .

19. The compounds of claim 17 wherein A" is selected from the group consisting of -NH2, -CONH,, halo, -CH3, -CF3, -CH2-halo, -CN, -OCH3, -SCH3, and -H.

20. The compounds of claim 19 wherein A" is selected from the group consisting of -Cl, -NH2, -Br, and -CH3.

21. The compounds of claim 17 wherein each B" is selected from the group consisting of -H, -C(O)R", -C(O)SR3, alkyl, aryl, alicyclic, halo, -CN, -SR3, -NR9, and -OR3.

22. The compounds of claim 21 wherein each B" is selected from the group consisting of -H, -C(O)OR\ -C(O)SR3, C1-C6 alkyl, alicyclic, halo, heteroaryl, and -SR3.

23. The compounds of claim 17 wherein D" is selected from the group consisting of -H, -C(O)R", -C(O)SR3, alkyl, aryl, alicyclic, halo, -NR92, and -SR3.

24. The compounds of claim 23 wherein D" is selected from the group consisting of -H, -C(O)OR3, lower alkyl, alicyclic, and halo.

25. The compounds of claim 17 wherein E" is selected from the group consisting of -H, C1-C6 alkyl, lower alicyclic, halogen, -CN, -C(O)OR\ -SR3, and -CONR42.

26. The compounds of claim 25 wherein E" is selected from the group consisting of -H, -Br, and -Cl.

27. The compounds of claim 1, where both Y groups are -O-.

28. The compounds of claim 4, where both Y groups are -O-.

29. The compounds of claim 5, where both Y groups are -O-.

30. The compounds of claim 1, where one Y is -NR6-, and one Y is -O-.

31. The compounds of claim 4, where one Y is -NR6-, and one Y is -O-.

32. The compounds of claim 5, where one Y is -NR6-, and one Y is -O-.

33. The compounds of claim 1 wherein when Y is -O-, then R1 attached to -O-is independently selected from the group consisting of -H, optionally substituted aryl, optionally substituted alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, -C(R2)2OC(O)R\ -C(R2)2-O-C(O)OR\ -C(R2)2OC(O)SR3, -alkyl-S-C(O)R3, and -alkyl-S-S-alkylhydroxy;

when Y is -NR6-, then R1 attached to -NR6- is independently selected from the group consisting of -H, -[C(R2)2]q-COOR3, -[C(R2)2]q -C (O)SR3, -C(R4)2COOR\ and -cycloalkylene-COOR3;
or when either Y is independently selected from -O- and -NR6-, then together R1 and R1 are


wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl, or
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R3, -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO2R\ -OR2 , -SR2, -R2 , -NHCOR2, -NHCO2R\ -(CH2)p-OR2, and -(CH2)p-SR2;
p is an integer 2 or 3;

q is an integer 1 or 2;
with the provisos that:
a) V, Z, W, W' are not all -H;
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic; and
c) both Y groups are not -NR6-;
R2 is selected from the group consisting of R3 and -H;
R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
R6 is selected from the group consisting of -H, and lower alkyl.

34. The compounds of claim 33 wherein when both Y groups are -O-, then R1 is independently selected from the group consisting of optionally substituted aryl, optionally substituted benzyl, -C(R2),OC(O)R3, -C(R2)2OC(O)OR\ and -H; and
when Y is -NR6-, then the R1 attached to said -NR6- group is selected from the group consisting of -C(R4)2-COOR3, and -C(R2)2COOR3; and the other Y group is -O- and then R1 attached to said -O- is selected from the group consisting of optionally substituted aryl, -C(R2)2OC(O)R3, and -C(R2),OC(O)OR3.

35. The compounds of claim 34 wherein both Y groups are -O-, and R1 is H.

36. The compounds of claim 17 wherein both Y groups are -O-, and R is aryl, or -C(R2)2-aryl.

37. The compounds of claim 17 wherein both Y groups are O-, and at least one R1 is selected from the group consisting of -C(R2)2-OC(O)R3, and -C(R2)2-OC(O)OR3.

38. The compounds of claim 17 wherein both Y groups are -O- and at least one

R , ι1 i •s -alkyl-S-S-alkylhydroxyl, -alkyl-S-C(O)R\ and -alkyl-S-S-S-alkylhydroxy, or together R1 and R1 are -alkyl-S-S-alkyl- to form a cyclic group.

39. The compounds of claim 17 wherein at least one Y is -O-, and together R1 and R are

wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl, or
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R3, -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO,R3, -OR2 , -SR2, -R2 , -NHCOR2, -NHCO2R3, -(CH2)p-OR2, and -(CH2)p-SR2;
p is an integer 2 or 3;
with the provisos that:
a) V, Z, W, W' are not all -H;
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic; and
c) both Y groups are not -NR6-;
R2 is selected from the group consisting of R3 and -H;

R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
R6 is selected from the group consisting of -H, and lower alkyl.

40. The compounds of claim 34 wherein one Y is -O-, and R1 is optionally substituted aryl; and the other Y is -NR6-, where R' attached to said -NR6- is selected from the group consisting of -C(R4)2COOR3, and -C(R2),C(O)OR3.

41. The compounds of claim 40 wherein R1 attached to -O- is selected from the group consisting of phenyl, and phenyl substituted with 1-2 substituents selected from the group consisting of -NHC(O)CH3, -F, -Cl, -Br, -C(O)OCH2CH3, and -CH3; and wherein R' attached to -NR6- is -C(R2)2COOR3; each R2 is independently selected from the group consisting of -CH3, -CH>CH3, and -H.

42. The compounds of claim 41 wherein the subsituents of said substituted phenyl are selected from the group consisting of 4-NHC(O)CH3, -Cl, -Br, 2- C(O)OCH2CH3, and -CH3.

43. The compounds of claim 6 wherein
A" is selected from the group consisting of -NH2, -CONH2, halo, -CH3, -CF3, -CH2-halo, -CN, -OCH3, -SCH3, and -H;
B" is selected from the group consisting of -H, -C(O)Ru, -C(O)SR\ alkyl, aryl, alicyclic, halo, -CN, -SR3, OR3 and -NR9,;
D" is selected from the group consisting of -H, -C(O)R", -C(O)SR\ -NR9,, alkyl, aryl, alicyclic, halo, and -SR3;
E" is selected from the group consisting of -H, C1-C6 alkyl, lower alicyclic, halo,

-CN, -C(O)OR3, and -SR3.
X is selected from the group consisting of -alkyl(hydroxy)-, -alkyl-, -alkynyl-, -aryl-, -carbonylalkyl-, -1,1-dihaloalkyl-, -alkoxyalkyl-, -alkyloxy-, -alkylthioalkyl-, -alkylthio-, -alkylaminocarbonyl-, -alkylcarbonylamino-, -alicyclic-, -aralkyl-, -alkylaryl-, -alkoxycarbonyl-, -carbonyloxyalkyl-, -alkoxycarbonylamino-, and
-alkylaminocarbonylamino-, all optionally substituted;
when both Y groups are -O-, then R1 is independently selected from the group consisting of optionally substituted aryl, optionally substituted benzyl, -C(R2)2OC(O)R\ -C(R2)2OC(O)OR3, and -H; or when one Y is -O-, then R' attached to -O- is optionally substituted aryl; and the other Y is -NR6-, then R1 attached to -NR6- is selected from the group consisting of -C(R4)2COOR\ and -C(R2),C(O)OR3; or
when Y is -O- or -NR6-, then together R1 and R1 are


wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl, or
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R3, -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO2R\ -OR2, -SR2, -R2 , -NHCOR2, -NHCO2R3, -(CH2)p-OR2, and -(CH2)p-SR2;
p is an integer 2 or 3;
with the provisos that: a) V, Z, W, W' are not all -H;
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic; and
c) both Y groups are not -NR6-;
R2 is selected from the group consisting of R3 and -H;
R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
R6 is selected from the group consisting of -H, and lower alkyl.

44. The compounds of claim 6 wherein R5 is


X is selected from the group consisting of methylenoxycarbonyl, and furan-2,5-diyl; at least one Y group is -O-; and pharmaceutically acceptable salts and prodrugs thereof.

45. The compounds of claim 44 wherein when Y is -O-, then R1 attached to -O-is independently selected from the group consisting of -H, optionally substituted phenyl, -CH,OC(O)-tBu, -CH,OC(O)Et, and -CH2OC(O)-iPr;
when Y is -NR6-, then R1 is attached to -NR6- independently selected from the group consisting of -C(R2)2COOR3, -C(R4)2COOR3, or
when Y is -O- or -NR6-, and at least one Y is -O-, then together R! and R1 are


wherein V is selected from the group consisting of optionally substituted aryl, and optionally substituted heteroaryl; and Z, W', and W are H; and
R6 is selected from the group consisting of -H, and lower alkyl.

46. The compounds of claim 45 wherein A" is -NH2, X is furan-2,5-diyl, and

B" is -CH2-CH(CH3)2.

47. The compounds of claim 45 wherein A" is -NH2, X is furan-2,5-diyl, and B" is -COOEt.

48. The compounds of claim 45 wherein A" is -NH2, X is furan-2,5-diyl, and B" is -SMe.

49. The compounds of claim 46 wherein A" is -NH,, X is
methyleneoxycarbonyl, and B" is -CH(CH3)2.

50. The compounds of claim 46 wherein both Y groups are -O- and R1 is -H.

51. The compounds of claim 46 wherein both Y groups are -O-, and R1 is -CH2OC(O)OEt.

52. The compounds of claim 46 wherein both Y groups are -O-, and
R1 and R1 together are


and V is phenyl substituted with 1-3 halogens.

53. The compounds of claim 47 wherein both Y groups are -0-, and R' and R1 together are


and V is phenyl substituted with 1-3 halogens.

54. The compounds of claim 48 wherein both Y groups are -O-, and R1 and R1 together are


and V phenyl substituted with 1-3 halogens.

55. The compounds of claim 49 wherein both Y groups are -O-, and R1 and R1 together are


and V is phenyl substituted with 1-3 halogens.

56 The compounds of claim 52 wherein V is selected from the group consisting of 3,5-dichlorophenyl, 3-bromo-4-fluorophenyl, 3-chlorophenyl, and 3-bromophenyl

57 The compounds of claim 46 wherein one Y is -O- and its corresponding R1 is -phenyl while the other Y is -NH- and its corresponding R1 is -CH(Me)CO,Et and -NH-*CH(Me)CO,Et is in the L-configuration

58 The compounds of claim 6 wherein R is


X is furan-2,5-dιyl, and methyleneoxycarbonyl, and A" is -NH2, at least one Y group is -O-, and pharmaceutically acceptable salts and prodrugs thereof

59 The compounds of claim 58 wherein
when Y is -O-, then each R is independently selected from the group
consisting of -H, optionally substituted phenyl, -CH2OC(O)-tBu, -CH,OC(O)Et, and -CH,OC(0)-ιPr,
or when Y is -NR6-, then each R1 is independently selected from the group consisting of -C(R2)2C(O)OR3, and -C(R4)2COOR3,
or when Y is independently selected from -O- and -NR6-, then together R1 and R1 are


wherein
V selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl; and Z, W', and W are H.

60. The compounds of claim 59 wherein B" is -SCH,CH,CH3; and X is furan-2,5-diyl.

61. The compounds of claim 60 wherein both Y groups are -O- and R1 is -H.

62. The compounds of claim 60 wherein one Y is -O- and its corresponding R1 is -phenyl while the other Y is -NH-, and its corresponding R' is -CH(Me)CO2Et, and -NH*CH(Me)CO,Et is in the L-configuration.

63. The compounds of claim 60 wherein both Y groups are -O- and R1 is

-CH2OC(O)OEt.

64. The compounds of claim 60 wherein both Y groups are -O-, R1 and R1 together are


and V is phenyl substituted with 1-3 halogens.

65. The compounds of claim 64 wherein V is selected from the group consisting of 3,5-dichlorophenyl, 3-bromo-4- fluorophenyl, 3-chlorophenyl, and 3-bromophenyl.

66. The compounds of claim 6 wherein R3 is


A" is -NH2, E" and D" are -H, B" is n-propyl and cyclopropyl, X is furan-2,5-diyl and methyleneoxycarbonyl; at least one Y group is -O-; and pharmaceutically acceptable salts and prodrugs thereof.

67. The compounds of claim 66 wherein
when Y is -O-, then each R is independently selected from the group
consisting of -H, optionally substituted phenyl, -CH2OC(O)-tBu, -CH2OC(O)Et, and -CH2OC(O)-iPr;
or when Y is -NR6-, then each R1 is independently selected from the group consisting of -C(R2)2C(O)OR\ and -C(R4)2COOR3;
or when Y is independently selected from -O- and -NR6-, then together R and R are


wherein
V selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl; and Z, W', and W are H.

68. The compounds of claim 6 wherein R3 is


A" is -NH2, D" is -H, B" is n-propyl and cyclopropyl, X is furan-2,5-diyl and methyleneoxycarbonyl; at least one Y group is -O-; and pharmaceutically acceptable salts and prodrugs thereof.

69. The compounds of claim 68 wherein
when Y is -O-, then each R is independently selected from the group
consisting of -H, optionally substituted phenyl, -CH2OC(O)-tBu, -CH,OC(O)Et, and -CH2OC(O)-iPr;
or when Y is -NR6-, then each R1 is independently selected from the group consisting of -C(R2),C(O)OR3, and -C(R4)2COOR3;
or when Y is independently selected from -O- and -NR6-, then together R1 and R1 are


wherein
V selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl; and Z, W', and W are H.

70. A method of treating a fructose- 1,6-bisphosphatase dependent disease or condition in an animal which comprises administering to an animal suffering from a fructose- 1,6-bisphosphatase dependent disease or condition a pharmaceutically effective amount of a compound of formula (I):

O

R5-X-P-YR' (I)
YR1
wherein R5 is selected from the group consisting of:



wherein:
each G is independently selected from the group consisting of C, N, O, S and Se, and wherein only one G may be O, S, or Se;
each G' is independently selected from the group consisting of C and N and wherein no more than two G' groups are N;
A is selected from the group consisting of -H, -NR42, -CONR42, -CO2R3, halo, -S(O)R3, -SO,R3, alkyl, alkenyl, alkynyl, perhaloalkyl, haloalkyl, aryl, -CH2OH, -CH2NR42, -CH2CN, -CN, -C(S)NH2, -OR3, -SR3, -N3, -NHC(S)NR42, -NHAc, and null; each B and D are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)R", -C(O)SR3, -SO2R", -S(O)R3, -CN, -NR92, -OR3, -SR3, perhaloalkyl, halo, -NO2, and null, all except -H, -CN, perhaloalkyl, -NO,, and halo are optionally substituted;
E is selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, alkoxyalkyl, -C(O)OR3, -CONR 2, -CN, -NR92, -NO,, -OR3, -SR3, perhaloalkyl, halo, and null, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;
j is selected from the group consisting of -H and null;

X is an optionally substituted linking group that links R' to the phosphorus atom via 2-4 atoms, including 0-1 heteroatoms selected from N, O, and S, except that if X is urea or carbamate there is 2 heteroatoms, measured by the shortest path between R5 and the phosphorus atom, and wherein the atom attached to the phosphorus is a carbon atom, and wherein there is no N in the linking group unless it is connected directly to a carbonyl or in the ring of a heterocycle; and wherein X is not a 2 carbon atom -alkyl- or -alkenyl-group; with the proviso that X is not substituted with -COOR2, -SO3R', or -PO3R',;
Y is independently selected from the group consisting of -O-, and -NR6-;
when Y is -O-, then R1 attached to -O- is independently selected from the group consisting of -H, alkyl, optionally substituted aryl, optionally substituted alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, -C(R2),OC(O)NR2,, -NR2-C(O)-R3, -C(R2)2- OC(O)R3, -C(R2),-O-C(O)OR3,
-C(R2),OC(O)SR3, -alkyl-S-C(O)R\ -alkyl-S-S-alkylhydroxy, and -alkyl-S-S-S-alkylhydroxy,
when Y is -NR6-, then R1 attached to -NR6- is independently selected from the group consisting of -H, -[C(R2)2]q-COOR3, -C(R4)2COOR3, -[C(R2)2]q-C(O)SR, and -cycloalkylene-COOR3;
or when either Y is independently selected from -O- and -NR6-, then together R1 and R1 are -alkyl-S-S-alkyl- to form a cyclic group, or together R1 and R! are


wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both Y groups attached to the phosphorus; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the Y attached to the phosphorus;
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R3, -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO2R3, -OR2 , -SR2, -CHR N3, -CH,aryl, -CH(aryl)OH, -CH(CH=CR22)OH, -CH(C≡CR2)OH, -R2 , -NR22, -OCOR3, -OCO,R3, -SCOR3, -SCO,R3, -NHCOR2, -NHCO,R3, -CH2NHaryl, -(CH2)p-OR2, and -(CH2)p-SR2;
p is an integer 2 or 3;
q is an integer 1 or 2;
with the provisos that:
a) V, Z, W, W' are not all -H; and
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic;
R2 is selected from the group consisting of R3 and -H;
R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
each R4 is independently selected from the group consisting of -H, and alkyl, or together R4 and R4 form a cyclic alkyl group;

R6 is selected from the group consisting of -H, lower alkyl, acyloxyalkyl, alkoxycarbonyloxyalkyl, and lower acyl;
each R9 is independently selected from the group consisting of -H, alkyl, aralkyl, and alicyclic, or together R9 and R9 form a cyclic alkyl group;
R" is selected from the group consisting of alkyl, aryl, -NR2,, and -OR2; and with the provisos that:
1) when G' is N, then the respective A, B, D, or E is null;
2) at least one of A and B, or A, B, D, and E is not selected from the group
consisting of -H or null;
3) when R5 is a six-membered ring, then X is not any 2 atom linker, an
optionally substituted -alkyl-, an optionally substituted -alkenyl-, an
optionally substituted -alkyloxy-, or an optionally substituted -alkylthio-; 4) when G is N, then the respective A or B is not halogen or a group directly bonded to G via a heteroatom;
5) R1 is not unsubstituted C 1 -C 10 alkyl;
6) when X is not an -aryl- group, then R5 is not substituted with two or more aryl groups;
and pharmaceutically acceptable prodrugs and salts thereof.

71. The method of claim 70 wherein R5 is selected from the group consisting of pyrrolyl, imidazolyl, oxazolyl, thiazolyl, isothiazolyl, 1,2,4-thiadiazolyl, pyrazolyl, isoxazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3,4-tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, and 1,3-selenazolyl, all of which contain at least one substituent.

72. The method of claim 70 wherein R5 is selected from the group consisting of:



wherein
A" is selected from the group consisting of -H, -NR4,, -CONR42, -CO,R\ halo, Cl-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perhaloalkyl, C1-C6 haloalkyl, aryl, -CH,OH, -CH,NR4,, -CH,CN, -CN, -C(S)NH,, -OR3, -SR3, -N3, -NHC(S)NR42, and -NHAc;
B" and D" are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)R", -C(O)SR3, -SO2R", -S(O)R3, -CN, -NR9,, -OR3, -SR3, perhaloalkyl, and halo, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;
E" is selected from the group consisting of -H, C1-C6 alkyl, C2-C6 alkenyl, C2- C6 alkynyl, aryl, C4-C6 alicyclic, alkoxyalkyl, -C(O)OR, -CONR4,, -CN, -NR92, -OR3, -SR3, C1-C6 perhaloalkyl, and halo, all except -H, -CN, perhaloalkyl, and halo are optionally substituted; and
C" is selected from the group consisting of -H, alkyl, alkylalkenyl, alkylalkynyl, aryl, alicyclic, aralkyl, aryloxyalkyl, and alkoxyalkyl, all optionally substituted;
R4 is selected from the group consisting of -H and C1-C2 alkyl; and
R" is selected from the group consisting of alkyl, aryl, -NR22, and -OR2.

73. The method of claim 70 wherein R5 is selected from the group consisting of:




wherein
A" is selected from the group consisting of -H, -NR4,, -CONR42, -CO,R3, halo, Cl-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perhaloalkyl, C1-C6 haloalkyl, aryl, -CH2OH, -CH,NR4,, -CH2CN, -CN, -C(S)NH2, -OR3, -SR3, -N3, -NHC(S)NR42, and -NHAc;
B" and D" are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)Rπ, -C(O)SR3, -SO2R", -S(O)R3, -CN, -NR9,, -OR3, -SR3, perhaloalkyl, and halo, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;
E" is selected from the group consisting of -H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C4-C6 alicyclic, alkoxyalkyl, -C(O)OR3, -CONR42, -CN, -NR92, -OR3, -SR3, C1-C6 perhaloalkyl, and halo, all except H, -CN, perhaloalkyl, and halo are optionally substituted; and
each R4 is independently selected from the group consisting of -H and C1-C2 alkyl.

74. The methods of claim 73 wherein X is selected from the group consisting of -alkyl(hydroxy)-, -alkyl-, -alkynyl-, -aryl-, -carbonylalkyl-, -1,1-dihaloalkyl-,
-alkoxyalkyl-, -alkyloxy-, -alkylthioalkyl-, -alkylthio-, -alkylaminocarbonyl-,
-alkylcarbonylamino-, -alicyclic-, -aralkyl-, -alkylaryl-, -alkoxycarbonyl-,
-carbonyloxyalkyl-, -alkoxycarbonylamino-, -alkylaminocarbonylamino-, -alkylamino-, and -alkenyl-, all optionally substituted.

75. The method of claim 74 wherein X is selected from the group consisting of -heteroaryl-, -alkylcarbonylamino-, -alkylaminocarbonyl-, -alkoxycarbonyl-, and
-alkoxyalkyl-.

76. The method of claim 75 wherein R5 is


X is selected from the group consisting of methylenoxycarbonyl, and furan-2,5-diyl; at least one Y group is -0-; and pharmaceutically acceptable salts and prodrugs thereof.

77. The method of claim 75 wherein R is

X is furan-2,5-diyl, and methyleneoxycarbonyl, and A" is -NH2; at least one Y group is -O-; and pharmaceutically acceptable salts and prodrugs thereof.

78. The method of claim 75 wherein R5 is


A" is -NH2, E" and D" are -H, B" is n-propyl and cyclopropyl, X is furan-2,5-diyl and methyleneoxycarbonyl; at least one Y group is -O-; and pharmaceutically acceptable salts and prodrugs thereof.

79. The method of claim 75 wherein R is


A" is -NH2, D" is -H, B" is n-propyl and cyclopropyl, X is furan-2,5-diyl and methyleneoxycarbonyl; at least one Y group is -O-; and pharmaceutically acceptable salts and prodrugs thereof.

80. A method of treating diabetes, by administering to patient in need thereof a pharmaceutically effective amount of an FBPase inhibitor of Formula I:

O
R5-X-P-YR' (I)
YR1
wherein R5 is selected from the group consisting of:



wherein:
each G is independently selected from the group consisting of C, N, O, S and Se, and wherein only one G may be O, S, or Se;
each G' is independently selected from the group consisting of C and N and wherein no more than two G' groups are N;
A is selected from the group consisting of -H, -NR42, -CONR42, -CO2R3, halo, -S(O)R3, -SO,R3, alkyl, alkenyl, alkynyl, perhaloalkyl, haloalkyl, aryl, -CH,OH, -CH,NR4,, -CH,CN, -CN, -C(S)NH2, -OR3, -SR3, -N3, -NHC(S)NR4,, -NHAc, and null; each B and D are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)R", -C(O)SR3, -SO2Rπ, -S(O)R3, -CN, -NR92, -OR3, -SR3, perhaloalkyl, halo, -NO2, and null, all except -H, -CN, perhaloalkyl, -NO,, and halo are optionally substituted;
E is selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, alkoxyalkyl, -C(O)OR3, -CONR42, -CN, -NR92, -NO2, -OR3, -SR3, perhaloalkyl, halo, and null, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;
j is selected from the group consisting of -H and null;
X is an optionally substituted linking group that links R5 to the phosphorus atom via 2-4 atoms, including 0-1 heteroatoms selected from N, O, and S, except that if X is urea or carbamate there is 2 heteroatoms, measured by the shortest path between R5 and the phosphorus atom, and wherein the atom attached to the phosphorus is a carbon atom, and wherein there is no N in the linking group unless it is connected directly to a carbonyl or in the ring of a heterocycle; and wherein X is not a 2 carbon atom -alkyl- or -alkenyl-group; with the proviso that X is not substituted with -COOR2, -SO3R!, or -PO3R'2;
Y is independently selected from the group consisting of -O-, and -NR6-;
when Y is -O-, then R1 attached to -O- is independently selected from the group consisting of -H, alkyl, optionally substituted aryl, optionally substituted alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, -C(R2),OC(O)NR22, -NR2-C(O)-R3, -C(R2)2- OC(O)R\ -C(R2),-O-C(O)OR3,
-C(R2),OC(O)SR3, -alkyl-S-C(O)R3, -alkyl-S-S-alkylhydroxy, and -alkyl-S-S-S-alkylhydroxy,
when Y is -NR6-, then R1 attached to -NR6- is independently selected from the group consisting of -H, -[C(R2)2]q-COOR3, -C(R4)2COOR3, -[C(R2)2]q-C(O)SR, and -cycloalkylene-COOR3;
or when either Y is independently selected from -O- and -NR6-, then together R1 and R1 are -alkyl-S-S-alkyl- to form a cyclic group, or together R1 and R1 are


wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both Y groups attached to the phosphorus; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the Y attached to the phosphorus;
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of -CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R3, -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO2R3, -OR2 , -SR2, -CHR2N3, -CH2aryl, -CH(aryl)OH, -CH(CH=CR22)OH, -CH(C≡CR2)OH, -R2 , -NR22, -OCOR3, -OCO,R3, -SCOR3, -SCO2R3, -NHCOR2, -NHCO2R3, -CH2NHaryl, -(CH2)p-OR2, and -(CH,)p-SR2;
p is an integer 2 or 3;
q is an integer 1 or 2;
with the provisos that:
a) V, Z, W, W' are not all -H; and
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic;
R2 is selected from the group consisting of R3 and -H;
R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
each R4 is independently selected from the group consisting of -H, and alkyl, or together R4 and R4 form a cyclic alkyl group;
R6 is selected from the group consisting of -H, lower alkyl, acyloxyalkyl, alkoxycarbonyloxyalkyl, and lower acyl;
each R9 is independently selected from the group consisting of -H, alkyl, aralkyl, and alicyclic, or together R9 and R9 form a cyclic alkyl group;
R" is selected from the group consisting of alkyl, aryl, -NR2,, and -OR2; and with the provisos that:
1) when G' is N, then the respective A, B, D, or E is null;
2) at least one of A and B, or A, B, D, and E is not selected from the group
consisting of -H or null;
3) when R' is a six-membered ring, then X is not any 2 atom linker, an
optionally substituted -alkyl-, an optionally substituted -alkenyl-, an
optionally substituted -alkyloxy-, or an optionally substituted -alkylthio-; 4) when G is N, then the respective A or B is not halogen or a group directly bonded to G via a heteroatom;
5) R1 is not unsubstituted C 1 -C 10 alkyl;
6) when X is not an -aryl- group, then R5 is not substituted with two or more aryl groups;
and pharmaceutically acceptable prodrugs and salts thereof.

81. The method of claim 80 wherein R5 is selected from the group consisting of pyrrolyl, imidazolyl, oxazolyl, thiazolyl, isothiazolyl, 1,2,4-thiadiazolyl, pyrazolyl, isoxazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1 ,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3,4-tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, and 1,3-selenazolyl, all of which contain at least one substituent.

82. The method of claim 80 wherein R5 is selected from the group consisting of:


wherein
A" is selected from the group consisting of -H, -NR4,, -CONR42, -CO,R3, halo, Cl-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perhaloalkyl, C1-C6 haloalkyl, aryl, -CH-OH, -CH,NR42, -CH,CN, -CN, -C(S)NH2, -OR3, -SR3, -N3, -NHC(S)NR4,, and -NHAc;
B" and D" are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)R", -C(O)SR3, -SO,R", -S(O)R3, -CN, -NR9,, -OR3, -SR3, perhaloalkyl, and halo, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;
E" is selected from the group consisting of -H, C1-C6 alkyl, C2-C6 alkenyl, C2- C6 alkynyl, aryl, C4-C6 alicyclic, alkoxyalkyl, -C(O)OR, -CONR42, -CN, -NR92, -OR3, -SR3, C1-C6 perhaloalkyl, and halo, all except -H, -CN, perhaloalkyl, and halo are optionally substituted; and
C" is selected from the group consisting of -H, alkyl, alkylalkenyl, alkylalkynyl, aryl, alicyclic, aralkyl, aryloxyalkyl, and alkoxyalkyl, all optionally substituted;
R4 is selected from the group consisting of -H and C1-C2 alkyl; and
R" is selected from the group consisting of alkyl, aryl, -NR22, and -OR2.

83. The method of claim 80 wherein R5 is selected from the group consisting of:



wherein
A" is selected from the group consisting of -H, -NR4,, -CONR4,, -CO,R3, halo, Cl-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perhaloalkyl, C1-C6 haloalkyl, aryl, -CH,OH, -CH,NR4,, -CH,CN, -CN, -C(S)NH2, -OR3, -SR3, -N3, -NHC(S)NR42, and -NHAc;
B" and D" are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)Rπ, -C(O)SR3, -SO2Ru, -S(O)R3, -CN, -NR9,, -OR3, -SR3, perhaloalkyl, and halo, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;
E" is selected from the group consisting of -H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C4-C6 alicyclic, alkoxyalkyl, -C(O)OR3, -CONR42, -CN, -NR92, -OR3, -SR3, C1-C6 perhaloalkyl, and halo, all except H, -CN, perhaloalkyl, and halo are optionally substituted; and
each R4 is independently selected from the group consisting of -H and C1-C2 alkyl.

84. The methods of claim 83 wherein X is selected from the group consisting of -alkyl(hydroxy)-, -alkyl-, -alkynyl-, -aryl-, -carbonylalkyl-, - 1 ,1 -dihaloalkyl-,
-alkoxyalkyl-, -alkyloxy-, -alkylthioalkyl-, -alkylthio-, -alkylaminocarbonyl-,
-alkylcarbonylamino-, -alicyclic-, -aralkyl-, -alkylaryl-, -alkoxycarbonyl-,
-carbonyloxyalkyl-, -alkoxycarbonylamino-, -alkylaminocarbonylamino-, -alkylamino-, and -alkenyl-, all optionally substituted.

85. The method of claim 84 wherein X is selected from the group consisting of -heteroaryl-, -alkylcarbonylamino-, -alkylaminocarbonyl-, -alkoxycarbonyl-, and
-alkoxyalkyl-.

86. The method of claim 85 wherein R' is


X is selected from the group consisting of methylenoxycarbonyl, and furan-2,5-diyl; at least one Y group is -0-: and pharmaceutically acceptable salts and prodrugs thereof.

87. The method of claim 85 wherein R5 is

X is furan-2,5-diyl, and methyleneoxycarbonyl, and A" is -NH2; at least one Y group is -0-; and pharmaceutically acceptable salts and prodrugs thereof.

The method of claim 85 wherein R is


A" is -NH2, E" and D" are -H, B" is n-propyl and cyclopropyl, X is furan-2,5-diyl and methyleneoxycarbonyl; at least one Y group is -0-; and pharmaceutically acceptable salts and prodrugs thereof.

89. The method of claim 85 wherein R5 is


A" is -NH2, D" is -H, B" is n-propyl and cyclopropyl, X is furan-2,5-diyl and methyleneoxycarbonyl; at least one Y group is -O-; and pharmaceutically acceptable salts and prodrugs thereof.

90. The method of claim 85, where said patient has Type I diabetes.

91. The method of claim 85, where said patient has Type II diabetes.

92. A method of treating glycogen storage diseases, by adminstering to a patient in need thereof a pharmaceutically effective amount of an FBPase inhibitor of formula I:

O

R5-X-P-YR' (I)
YR1
wherein R' is selected from the group consisting of:



wherein:
each G is independently selected from the group consisting of C, N, O, S and Se, and wherein only one G may be O, S, or Se;
each G' is independently selected from the group consisting of C and N and wherein no more than two G' groups are N;
A is selected from the group consisting of -H, -NR4,, -CONR42, -CO,R3, halo,

-S(O)R3, -SO,R3, alkyl, alkenyl, alkynyl, perhaloalkyl, haloalkyl, aryl, -CH2OH, -CH2NR4,, -CH,CN, -CN, -C(S)NH2, -OR3, -SR3, -N3, -NHC(S)NR 2, -NHAc, and null; each B and D are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)Ru, -C(O)SR3, -SO2R", -S(O)R3, -CN, -NR9,, -OR3, -SR3, perhaloalkyl, halo, -NO2, and null, all except -H, -CN, perhaloalkyl, -NO,, and halo are optionally substituted;
E is selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, alkoxyalkyl, -C(O)OR3, -CONR42, -CN, -NR9,, -NO2, -OR3, -SR3, perhaloalkyl, halo, and null, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;
J is selected from the group consisting of -H and null;

X is an optionally substituted linking group that links R' to the phosphorus atom via 2-4 atoms, including 0-1 heteroatoms selected from N, O, and S, except that if X is urea or carbamate there is 2 heteroatoms, measured by the shortest path between R5 and the phosphorus atom, and wherein the atom attached to the phosphorus is a carbon atom, and wherein there is no N in the linking group unless it is connected directly to a carbonyl or in the ring of a heterocycle; and wherein X is not a 2 carbon atom -alkyl- or -alkenyl-group; with the proviso that X is not substituted with -COOR2, -SO3R', or -PO3R'2;
Y is independently selected from the group consisting of -O-, and -NR6-;
when Y is -O-, then R' attached to -O- is independently selected from the group consisting of -H, alkyl, optionally substituted aryl, optionally substituted alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, -C(R2),OC(0)NR2,, -NR2-C(O)-R3, -C(R2)2- OC(O)R3, -C(R2),-O-C(O)OR3,
-C(R2),OC(0)SR3, -alkyl-S-C(O)R\ -alkyl-S-S-alkylhydroxy, and -alkyl-S-S-S-alkylhydroxy,
when Y is -NR6-, then R1 attached to -NR6- is independently selected from the group consisting of -H, -[C(R2)2]q-COOR3, -C(R4)2COOR\ -[C(R2)2]q-C(O)SR, and -cycloalkylene-COOR3;
or when either Y is independently selected from -O- and -NR6-, then together R1 and R1 are -alkyl-S-S-alkyl- to form a cyclic group, or together R' and R1 are


wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both Y groups attached to the phosphorus; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the Y attached to the phosphorus;
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R3, -CHR2OC(S)OR\ -CHR2OC(O)SR3, -CHR2OCO2R3, -OR2 , -SR2, -CHR2N3, -CH,aryl, -CH(aryl)OH, -CH(CH=CR22)OH, -CH(C≡CR2)OH, -R2 , -NR22, -OCOR3, -OCO,R\ -SCOR3, -SCO,R\ -NHCOR2, -NHCO,R3, -CH2NHaryl, -(CH,)p-OR2, and -(CH,)p-SR2;
p is an integer 2 or 3;
q is an integer 1 or 2;
with the provisos that:
a) V, Z, W, W' are not all -H; and
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic;
R2 is selected from the group consisting of R3 and -H;
R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
each R4 is independently selected from the group consisting of -H, and alkyl, or together R4 and R4 form a cyclic alkyl group;

R6 is selected from the group consisting of -H, lower alkyl, acyloxyalkyl, alkoxycarbonyloxyalkyl, and lower acyl;
each R9 is independently selected from the group consisting of -H, alkyl, aralkyl, and alicyclic, or together R9 and R9 form a cyclic alkyl group;
R" is selected from the group consisting of alkyl, aryl, -NR2,, and -OR2; and with the provisos that:
1) when G' is N, then the respective A, B, D, or E is null;
2) at least one of A and B, or A, B, D, and E is not selected from the group
consisting of -H or null;
3) when R5 is a six-membered ring, then X is not any 2 atom linker, an
optionally substituted -alkyl-, an optionally substituted -alkenyl-, an
optionally substituted -alkyloxy-, or an optionally substituted -alkylthio-; 4) when G is N, then the respective A or B is not halogen or a group directly bonded to G via a heteroatom;
5) R1 is not unsubstituted C1-C10 alkyl;
6) when X is not an -aryl- group, then R5 is not substituted with two or more aryl groups;
and pharmaceutically acceptable prodrugs and salts thereof.

93. The method of claim 92 wherein R5 is selected from the group consisting of pyrrolyl, imidazolyl, oxazolyl, thiazolyl, isothiazolyl, 1,2,4-thiadiazolyl, pyrazolyl, isoxazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3,4-tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, and 1,3-selenazolyl, all of which contain at least one substituent.

94. The method of claim 92 wherein R5 is selected from the group consisting of:


wherein
A" is selected from the group consisting of -H, -NR42, -CONR4,, -CO2R\ halo, Cl-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perhaloalkyl, C1-C6 haloalkyl, aryl, -CH,OH, -CH,NR4,, -CH,CN, -CN, -C(S)NH,, -OR3, -SR3, -N3, -NHC(S)NR42, and -NHAc;
B" and D" are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)Rπ, -C(O)SR3, -SO2Ru, -S(O)R3, -CN, -NR9,, -OR3, -SR3, perhaloalkyl, and halo, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;
E" is selected from the group consisting of -H, C1-C6 alkyl, C2-C6 alkenyl, C2- C6 alkynyl, aryl, C4-C6 alicyclic, alkoxyalkyl, -C(O)OR, -CONR4,, -CN, -NR92, -OR3, -SR3, C1-C6 perhaloalkyl, and halo, all except -H, -CN, perhaloalkyl, and halo are optionally substituted; and
C" is selected from the group consisting of -H, alkyl, alkylalkenyl, alkylalkynyl, aryl, alicyclic, aralkyl, aryloxyalkyl, and alkoxyalkyl, all optionally substituted;
R4 is selected from the group consisting of -H and C1-C2 alkyl; and
R" is selected from the group consisting of alkyl, aryl, -NR22, and -OR2.

95. The method of claim 92 wherein R5 is selected from the group consisting of:




wherein
A" is selected from the group consisting of -H, -NR42, -CONR4,, -CO2R3, halo, Cl-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perhaloalkyl, C1-C6 haloalkyl, aryl, -CH2OH, -CH2NR42, -CH,CN, -CN, -C(S)NH2, -OR3, -SR3, -N3, -NHC(S)NR42, and -NHAc;
B" and D" are independently selected from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, -C(O)R", -C(O)SR3, -SO2R", -S(O)R3, -CN, -NR9,, -OR3, -SR3, perhaloalkyl, and halo, all except -H, -CN, perhaloalkyl, and halo are optionally substituted;
E" is selected from the group consisting of -H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C4-C6 alicyclic, alkoxyalkyl, -C(O)OR3, -CONR42, -CN, -NR92, -OR3, -SR3, C1-C6 perhaloalkyl, and halo, all except H, -CN, perhaloalkyl, and halo are optionally substituted; and
each R4 is independently selected from the group consisting of -H and C1-C2 alkyl.

96. The methods of claim 95 wherein X is selected from the group consisting of -alkyl(hydroxy)-, -alkyl-, -alkynyl-, -aryl-, -carbonylalkyl-, -1,1-dihaloalkyl-,
-alkoxyalkyl-, -alkyloxy-, -alkylthioalkyl-, -alkylthio-, -alkylaminocarbonyl-,
-alkylcarbonylamino-, -alicyclic-, -aralkyl-, -alkylaryl-, -alkoxycarbonyl-,
-carbonyloxyalkyl-, -alkoxycarbonylamino-, -alkylaminocarbonylamino-, -alkylamino-, and -alkenyl-, all optionally substituted.

97. The method of claim 96 wherein X is selected from the group consisting of -heteroaryl-, -alkylcarbonylamino-, -alkylaminocarbonyl-, -alkoxycarbonyl-, and
-alkoxyalkyl-.

98. The method of claim 97 wherein R5 is


X is selected from the group consisting of methylenoxycarbonyl, and furan-2,5-diyl; at least one Y group is -O-; and pharmaceutically acceptable salts and prodrugs thereof.

99. The method of claim 97 wherein R5 is

X is furan-2,5-diyl, and methyleneoxycarbonyl, and A" is -NH2; at least one Y group is -0-; and pharmaceutically acceptable salts and prodrugs thereof.

100. The method of claim 97 wherein R 5 i •s


A" is -NH2, E" and D" are -H, B" is n-propyl and cyclopropyl, X is furan-2,5-diyl and methyleneoxycarbonyl; at least one Y group is -O-; and pharmaceutically acceptable salts and prodrugs thereof.

101. The method of claim 97 wherein R5 is


A" is -NH2, D" is -H, B" is n-propyl and cyclopropyl, X is furan-2,5-diyl and methyleneoxycarbonyl; at least one Y group is -O-; and pharmaceutically acceptable salts and prodrugs thereof.

102. The method of claim 70 wherein said disease or condition is selected from the group consisting of atherosclerosis, hyperinsulinemia, hypercholesterolemia, and hyperlipidemia.

103. The method of claim 70 wherein said FBPase inhibitor is administered to prevent myocardial ischemic injury.

104. The compounds of formula (X):


wherein:
G" is selected from the group consisting of -O- and -S-;
A2, L2, E2, and J2 are selected from the group consisting of
-NR 2, -NO2, -H, -OR2, -SR2, -C(O)NR42, halo, -COR11, -SO2R3, guanidinyl, amidinyl,

aryl, aralkyl, alkyoxyalkyl, -SCN, -NHSO2R9, -SO2NR 2, -CN, -S(O)R3, perhaloacyl, perhaloalkyl, perhaloalkoxy, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, and lower alicyclic, or together L2 and E2 or E2 and J2 form an annulated cyclic group;
X2 is an optionally substituted linking group that links R5 to the phosphorus atom via 1-3 atoms, including 0-1 heteroatoms, selected from N, O, and S, and wherein in the atom attached to the phosphorus is a carbon atom;
with the proviso that X2 is not substituted with -COOR2, -SO3R', or -PO3R'2;
Y is independently selected from the group consisting of -O-, and -NR6-;
when Y is -O-, then R1 attached to -O- is independently selected from the group consisting of -H, alkyl, optionally substituted aryl, optionally substituted alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, -C(R2)2OC(O)NR2,, -NR2-C(O)-R3, -C(R2)2- OC(O)R3, -C(R2)2-O-C(O)OR\
-C(R2)2OC(O)SR3, -alkyl-S-C(O)R3, -alkyl-S-S-alkylhydroxy, and -alkyl-S-S-S-alkylhydroxy,
when Y is -NR6-, then R1 attached to -NR6- is independently selected from the group consisting of -H, -[C(R2)2]q-COOR3, -C(R4)2COOR3, -[C(R )2]q-C(O)SR, and -cycloalkylene-COOR3;

or when either Y is independently selected from -O- and -NR6-, then together R1 and R1 are -alkyl-S-S-alkyl- to form a cyclic group, or together R1 and R1 are


wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both Y groups attached to the phosphorus; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the Y attached to the phosphorus;
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;

Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R3, -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO,R3, -OR2 , -SR2, -CHR2N3, -CH-aryl, -CH(aryl)OH, -CH(CH=CR2,)OH, -CH(C≡CR2)OH, -R2 , -NR22, -OCOR3, -OCO,R3, -SCOR3, -SCO,R3, -NHCOR2, -NHCO,R3, -CH-NHaiyl, -(CH2)p-OR2, and -(CH2)p-SR2:
p is an integer 2 or 3;
q is an integer 1 or 2;
with the provisos that:
a) V, Z, W, W' are not all -H; and
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic;
R2 is selected from the group consisting of R3 and -H;
R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
each R4 is independently selected from the group consisting of -H, alkyl, or together R4 and R4 form a cyclic alkyl;
R6 is selected from the group consisting of -H, lower alkyl, acyloxyalkyl, alkoxycarbonyloxyalkyl, and lower acyl;
each R9 is independently selected from the group consisting of -H, alkyl, aralkyl, and alicyclic, or together R9 and R9 form a cyclic alkyl group;
R" is selected from the group consisting of alkyl, aryl, -NR22, and -OR2; and
pharmaceutically acceptable prodrugs and salts thereof.

105. The compounds of claim 104 wherein G" is -S-.

106. The compounds of claim 104 wherein A2, L2, E2, and J2 are independently selected from the group consisting of -H, -NR42, -S-C≡N, halogen, -OR3, hydroxy, -alkyl(OH), aryl, alkyloxycarbonyl, -SR3, lower perhaloalkyl, and C1-C5 alkyl, or together L2 and E2 form an annulated cyclic group.

107. The compound of claim 106 wherein A2, E2, E2 and J2 are independently selected from the group consisting of -H, -NR4 , -S-C≡N, halogen, lower alkoxy, hydroxy, lower alkyl(hydroxy), lower aryl, and C1-C5 alkyl, or together L: and E2 form an annulated cyclic group.

108. The compounds of claim 107 wherein A2 is -NH,, -H, halo, and C1-C5 alkyl.

109. The compounds of claim 107 wherein L2 and E2 are independently selected from the group consisting of -H, -S-C≡N, lower alkoxy, C1-C5 alkyl, lower
alkyl(hydroxy), lower aryl, and halogen or together L2 and E2 form an annulated cyclic group containing an additional 4 carbon atoms.

110. The compounds of claim 109 wherein J2 is selected from the group consisting of -H, and C1-C5 alkyl.

111. The compounds of claim 104 wherein X2 is selected from the group consisting of -alkyl-, -alkenyl-, -alkynyl-, -alkylene-NR4-, -alkylene-O-, alkylene-S-, -C(O)-alkylene-, and -alkylene-C(O)-.

112. The compounds of claim 111 wherein X2 is selected from the group consisting of -alkylene-O-, alkylene-S-, and -alkyl-.

113. The compounds of claim 112 wherein X2 is -methyleneoxy-.

114. The compounds of claim 104 where both Y groups are -O-.

115. The compounds of claim 104, where one Y is -NR6-, and one Y is -O-.

116. The compounds of claim 104 wherein when Y is -O-, then R1 attached to -O- is independently selected from the group consisting of -H, optionally substituted aryl, optionally substituted alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, -C(R2)2OC(O)R3, -C(R2)2-O-C(O)OR3, -C(R2),OC(O)SR3, -alkyl-S-C(O)R3, and -alkyl-S-S-alkylhydroxy;

when Y is -NR6-, then R1 attached to -NR6- is independently selected from the group consisting of -H, -[C(R2)2]q-COOR3, -[C(R2)2]q -C (O)SR\ -C(R4)2COOR3, and -cycloalkylene-COOR3;
or when either Y is independently selected from -O- and -NR6-, then together R1 and R1 are


wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl, or
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R3, -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO2R3, -OR2 , -SR2, -R2 , -NHCOR2, -NHCO,R3, -(CH2)p-OR2, and -(CH2)p-SR2;
p is an integer 2 or 3;

q is an integer 1 or 2;
with the provisos that:
a) V, Z, W, W' are not all -H;
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic; and
c) both Y groups are not -NR6-;
R2 is selected from the group consisting of R3 and -H;
R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
R6 is selected from the group consisting of -H, and lower alkyl.

117. The compounds of claim 116 wherein when both Y groups are -O-, then R' is independently selected from the group consisting of optionally substituted aryl, optionally substituted benzyl, -C(R2):OC(O)R\ -C(R2),OC(O)OR3, and -H; and
when Y is -NR6-, then the R1 attached to said -NR6- group is selected from the group consisting of -C(R4)2-COOR\ -C(R2)2COOR3, and -H; and the other Y group is -O-and the R' group attached to said -O- group is selected from the group consisting of optionally substituted aryl, -C(R2),OC(O)R3, and -C(R2)2OC(O)OR3.

118. The compounds of claim 116 wherein both Y groups are -O-, and R1 is H.

119. The compounds of claim 116 wherein both Y groups are -O-, and R1 is aryl, or -C(R2),-aryl.

120. The compounds of claim 116 wherein both Y groups are O-, and at least one R , ι i •s selected from the group consisting of -C(R2)2-OC(O)R3, and -C(R2)2-OC(O)OR3.

121. The compounds of claim 116 wherein both Y groups are -O- and at least one R is -alkyl-S-S-alkylhydroxyl, -alkyl-S-C(O)R3, and -alkyl-S-S-S-alkylhydroxy, or together R and R are -alkyl-S-S-alkyl- to form a cyclic group.

122. The compounds of claim 116 wherein at least one Y is -O-, and together R1 and R are

wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl, or
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R3, -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO2R\ -OR2 , -SR2, -R2 , -NHCOR2, -NHCO2R3, -(CH2)p-OR2, and -(CH2)p-SR2;
p is an integer 2 or 3;
with the provisos that:
a) V, Z, W, W' are not all -H;
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic; and
c) both Y groups are not -NR6-;
R2 is selected from the group consisting of R3 and -H;

R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
R6 is selected from the group consisting of -H, and lower alkyl.

123. The methods of claim 112 wherein R1 is alicyclic where the cyclic moiety contains carbonate or thiocarbonate.

124. The compounds of claim 117 wherein one Y is -O-, and R1 is optionally substituted aryl; and the other Y is -NR6-, where R' attached to said -NR6- is selected from the group consisting of -C(R4),COOR3, and -C(R2)2C(O)OR3.

125. The compounds of claim 124 wherein R' attached to -O- is selected from the group consisting of phenyl, and phenyl substituted with 1-2 substituents selected from the group consisting of -NHC(O)CH3, -Cl, -Br, -C(O)OCH,CH3, and -CH3; and wherein R1 attached to -NR6- is -C(R2)2COOR3; each R2 is independently selected from the group consisting of -CH3, and -CH,CH3.

126. The compounds of claim 125 wherein the subsituents of said substituted phenyl are selected from the group consisting of 4-NHC(O)CH3, -Cl, -Br, 2-C(O)OCH,CH3, and -CH3.

127. The compounds of claim 104 wherein A2 is selected from the group consisting of -H, -NH,, -CH3, Cl, and Br;
L2 is -H, lower alkyl, halogen, lower alkyloxy, hydroxy, -alkenylene-OH, or together with E2 forms a cyclic group including aryl, cyclic alkyl, heteroaryls, heterocyclic alkyl;
E2 is selected from the groups consisting of H, lower alkyl, halogen, SCN, lower alkyloxycarbonyl, lower alkyloxy, or together with L2 forms a cyclic group including aryl, cyclic alkyl, heteroaryl, or heterocyclic alkyl;
J2 is selected from the groups consisting of H, halogen, and lower alkyl;
G" is -S-;
X2 is -CH,O-; and
at least one Y group is -O-; and pharmaceutically acceptable salts and prodrugs thereof.

128. The compounds of claim 127 wherein one Y is -O- and its corresponding R1 is optionally substituted phenyl, while the other Y is -NH-, and its corresponding R1 is -C(R2),-COOR3.

129. The compounds of claim 128 wherein when the other Y is -NH-, then the corresponding R1 is -CHR2COOR3, and -NH-*CHR2COOR3 has L stereochemistry.

130. The compounds of claim 127 where A2 is NH,, L2 is -Et, E2 is -SCN, and J2 is -H.

131. The compounds of claim 130 wherein both Y groups are -O-, then R1 is -H.

132. The compounds of claim 130 wherein both Y groups are -O-, and R1 is -CH,OC(O)OEt.

133. The compounds of claim 130 wherein both Y groups are -O-, and
R1 and R1 together are


and V is phenyl substituted with 1-3 halogens.

134. The compounds of claim 133 wherein V is selected from the group consisting of 3,5-dichlorophenyl, 3-bromo-4-fluorophenyl, 3-chlorophenyl, and 3-bromophenyl.

135. The compounds of claim 130 wherein one Y is -O-, and its corresponding R1 is -phenyl, while the other Y is -NH- and its corresponding R1 is -CH(Me)CO2Et, and -NH*CH(Me)CO2Et is in the L-configuration.

136. A method of treating a fructose- 1,6-bisphosphatase dependent disease or condition in an animal which comprises administering to an animal suffering from a fructose- 1,6-bisphosphatase dependent disease or condition a pharmaceutically effective amount of a compound of formula (X):


wherein:
G" is selected from the group consisting of -O- and -S-;
A2, L2, E2, and J2 are selected from the group consisting of
-NR42, -NO2, -H, -OR2, -SR2, -C(O)NR4,, halo, -COR11, -SO2R3, guanidinyl, amidinyl,

aryl, aralkyl, alkyoxyalkyl, -SCN, -NHSO2R9, -SO2NR42, -CN, -S(O)R\ perhaloacyl, perhaloalkyl, perhaloalkoxy, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, and lower alicyclic, or together L2 and E2 or E2 and J2 form an annulated cyclic group;
X2 is an optionally substituted linking group that links R5 to the phosphorus atom via 1-3 atoms, including 0-1 heteroatoms, selected from N, O, and S, and wherein in the atom attached to the phosphorus is a carbon atom;
with the proviso that X2 is not substituted with -COOR2, -SO3R', or -PO3R'2;
Y is independently selected from the group consisting of -O-, and -NR6-;
when Y is -O-, then R1 attached to -O- is independently selected from the group consisting of -H, alkyl, optionally substituted aryl, optionally substituted alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, -C(R2)2OC(O)NR2,, -NR2-C(O)-R3, -C(R2)2- OC(O)R3, -C(R2),-O-C(O)OR3,
-C(R2)2OC(O)SR3, -alkyl-S-C(O)R3, -alkyl-S-S-alkylhydroxy, and -alkyl-S-S-S-alkylhydroxy, when Y is -NR6-, then R1 attached to -NR6- is independently selected from the group consisting of -H, -[C(R2)2]q-COOR\ -C(R4),COOR3, -[C(R2)2]q-C(O)SR, and -cycloalkylene-COOR3;
or when either Y is independently selected from -O- and -NR6-, then together R1 and R1 are -alkyl-S-S-alkyl- to form a cyclic group, or together R' and R1 are


wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both Y groups attached to the phosphorus; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the Y attached to the phosphorus;
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;

together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R\ -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO,R3, -OR2 , -SR2, -CHR2N3, -CH-aryl, -CH(aryl)OH, -CH(CH=CR2,)OH, -CH(C≡CR2)OH, -R2 , -NR22, -OCOR3, -OCO,R3, -SCOR3, -SCO,R3, -NHCOR2, -NHCO,R3, -CH2NHaryl, -(CH2)p-OR2, and -(CH,)p-SR2;
p is an integer 2 or 3;
q is an integer 1 or 2;
with the provisos that:
a) V, Z, W, W' are not all -H; and
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic;
R2 is selected from the group consisting of R3 and -H;
R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
each R4 is independently selected from the group consisting of -H, alkyl, or together R4 and R4 form a cyclic alkyl;
R6 is selected from the group consisting of -H, lower alkyl, acyloxyalkyl, alkoxycarbonyloxyalkyl, and lower acyl;
each R9 is independently selected from the group consisting of -H, alkyl, aralkyl, and alicyclic, or together R9 and R9 form a cyclic alkyl group;
R11 is selected from the group consisting of alkyl, aryl, -NR22, and -OR2; and
pharmaceutically acceptable prodrugs and salts thereof.

137. A method of treating diabetes, by administering to a patient in need thereof a pharmaceutically effective amount of an FBPase inhibitor of formula (X):

wherein:
G" is selected from the group consisting of -O- and -S-.
A2, L2, E2, and J2 are selected from the group consisting of
-NR4,, -NO,, -H, -OR2, -SR2, -C(O)NR4,, halo, -COR1 ', -SO2R3, guanidinyl, amidinyl,

aryl, aralkyl, alkyoxyalkyl, -SCN, -NHSO2R9, -SO2NR42, -CN, -S(O)R3, perhaloacyl, perhaloalkyl, perhaloalkoxy, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, and lower alicyclic, or together L2 and E2 or E2 and J2 form an annulated cyclic group;
X2 is an optionally substituted linking group that links R5 to the phosphorus atom via 1-3 atoms, including 0-1 heteroatoms, selected from N, O, and S, and wherein in the atom attached to the phosphorus is a carbon atom;
with the proviso that X2 is not substituted with -COOR2, -SO3R', or -PO3R'2;
Y is independently selected from the group consisting of -O-, and -NR6-;
when Y is -O-, then R1 attached to -O- is independently selected from the group consisting of -H, alkyl, optionally substituted aryl, optionally substituted alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, -C(R2)2OC(O)NR 2, -NR2-C(O)-R3, -C(R2)2- OC(O)R\ -C(R2)2-O-C(O)OR3,
-C(R2)2OC(O)SR3, -alkyl-S-C(O)R\ -alkyl-S-S-alkylhydroxy, and -alkyl-S-S-S-alkylhydroxy,
when Y is -NR6-, then R1 attached to -NR6- is independently selected from the group consisting of -H, -[C(R2)2]q-COOR3, -C(R4)2COOR3, -[C(R2)2]q-C(O)SR, and -cycloalkylene-COOR3;
or when either Y is independently selected from -O- and -NR6-, then together R and R1 are -alkyl-S-S-alkyl- to form a cyclic group, or together R1 and R1 are

wherein
V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both Y groups attached to the phosphorus; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the Y attached to the phosphorus;
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R\
-CHR2OC(S)R3, -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO,R3, -OR2 , -SR2, -CHR2N3, -CH,aryl, -CH(aryl)OH, -CH(CH=CR\)OH, -CH(C≡CR2)OH, -R2 , -NR2,, -OCOR3, -OCO2R3, -SCOR3, -SCO,R3, -NHCOR2, -NHCO2R3, -CH,NHaryl, -(CH2)p-OR2, and -(CH,)p-SR2;
p is an integer 2 or 3;
q is an integer 1 or 2;
with the provisos that:
a) V, Z, W, W' are not all -H; and
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic;
R2 is selected from the group consisting of R3 and -H;
R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
each R4 is independently selected from the group consisting of -H, alkyl, or together R4 and R4 form a cyclic alkyl;
R6 is selected from the group consisting of -H, lower alkyl, acyloxyalkyl, alkoxycarbonyloxyalkyl, and lower acyl;
each R9 is independently selected from the group consisting of -H, alkyl, aralkyl, and alicyclic, or together R9 and R9 form a cyclic alkyl group;
R" is selected from the group consisting of alkyl, aryl, -NR22, and -OR2; and
pharmaceutically acceptable prodrugs and salts thereof.

138. A method of treating glycogen storage diseases, by adminstering to a patient in need thereof a pharmaceutically effective amount of an FBPase inhibitor of formula (X):


wherein:

G" is selected from the group consisting of -O- and -S-.
A2, L2, E2, and J2 are selected from the group consisting of
-NR4,, -NO,, -H, -OR2, -SR2, -C(O)NR „ halo, -COR11, -SO2R\ guanidinyl, amidinyl,

aryl, aralkyl, alkyoxyalkyl, -SCN, -NHSO,R9, -SO2NR42, -CN, -S(O)R3, perhaloacyl, perhaloalkyl, perhaloalkoxy, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, and lower alicyclic, or together L2 and E2 or E2 and J2 form an annulated cyclic group;
X2 is an optionally substituted linking group that links R5 to the phosphorus atom via 1-3 atoms, including 0-1 heteroatoms, selected from N, O, and S, and wherein in the atom attached to the phosphorus is a carbon atom;
with the proviso that X2 is not substituted with -COOR2, -SO3R\ or -PO3R'2;
Y is independently selected from the group consisting of -O-, and -NR6-;
when Y is -O-, then R1 attached to -O- is independently selected from the group consisting of -H, alkyl, optionally substituted aryl, optionally substituted alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, -C(R2)2OC(O)NR22, -NR2-C(O)-R\ -C(R2)2- OC(O)R3, -C(R2)2-O-C(O)OR\
-C(R2)2OC(O)SR\ -alkyl-S-C(O)R\ -alkyl-S-S-alkylhydroxy, and -alkyl-S-S-S-alkylhydroxy,
when Y is -NR6-, then R1 attached to -NR6- is independently selected from the group consisting of -H, -[C(R2)2]q-COOR3, -C(R4)2COOR3, -[C(R2)2]q-C(O)SR, and -cycloalkylene-COOR3;
or when either Y is independently selected from -O- and -NR6-, then together R1 and R1 are -alkyl-S-S-alkyl- to form a cyclic group, or together R1 and R1 are


wherein V, W, and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both Y groups attached to the phosphorus; or
together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the Y attached to the phosphorus;
together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from a Y attached to the phosphorus;
together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
together W and W' are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
Z is selected from the group consisting of-CHR2OH , -CHR2OC(O)R3,
-CHR2OC(S)R3, -CHR2OC(S)OR3, -CHR2OC(O)SR3, -CHR2OCO,R3, -OR2 , -SR2, -CHR2N3, -CH2aryl, -CH(aryl)OH, -CH(CH=CR22)OH, -CH(C≡CR2)OH, -R2 , -NR22, -OCOR3, -OCO2R3, -SCOR3, -SCO2R3, -NHCOR2, -NHCO2R3, -CH2NHaryl, -(CH2)p-OR2, and -(CH2)p-SR2;
p is an integer 2 or 3;
q is an integer 1 or 2;
with the provisos that:
a) V, Z, W, W' are not all -H; and
b) when Z is -R2, then at least one of V, W, and W' is not -H, alkyl, aralkyl, or alicyclic;
R2 is selected from the group consisting of R3 and -H;
R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;

each R4 is independently selected from the group consisting of -H, alkyl, or together R4 and R4 form a cyclic alkyl;
R6 is selected from the group consisting of -H, lower alkyl, acyloxyalkyl, alkoxycarbonyloxyalkyl, and lower acyl;
each R9 is independently selected from the group consisting of -H, alkyl, aralkyl, and alicyclic, or together R9 and R9 form a cyclic alkyl group;
R" is selected from the group consisting of alkyl, aryl, -NR22, and -OR2; and
pharmaceutically acceptable prodrugs and salts thereof.

139. The compounds of claim 45 wherein A" is -NH2, X is furan-2,5-diyl, and

B" is -SCH2CH,CH3.

140. The compounds of claim 45 wherein one Y is -O- and its corresponding R1 is -phenyl, and the other Y is -NH- and its corresponding R1 is -CH2CO2Et.

141. The compounds of claim 45 wherein one Y is -O- and its corresponding R1 is -phenyl, and the other Y is -NH- and its corresponding R1 is -C(Me)2CO2Et.

142. The compounds of claims 45 wherein one Y is -O- and its corresponding R1 is -<phenyl-4-NHC(O)CH3), and the other Y is -NH- and its corresponding R1 is

-CH,CO2Et.

143. The compounds of claim 45 wherein one Y is -O- and its corresponding R1 is -(phenyl-4-NHC(O)CH3), and the other Y is -NH- and its corresponding R1 is
-C(Me)2CO,Et.

144. The compounds of claim 45 wherein one Y is -O- and its corresponding R1 is -(phenyl-2-CO2Et), and the other Y is -NH- and its corresponding R1 is -CH2CO2Et.

145. The compounds of claim 45 wherein one Y is -O- and its corresponding R1 is -(phenyl-2-CH3), and the other Y is -NH- and its corresponding R1 is -CH2CO2Et.

146. The compounds of claim 46 wherein one Y is -O- and its corresponding R1 is -phenyl, and the other Y is -NH- and its corresponding R1 is -CH2CO2Et.

147. The compounds of claim 46 wherein one Y is -O- and its corresponding R1 is -phenyl, and the other Y is -NH- and its corresponding R1 is -C(Me),CO2Et.

148. The compounds of claim 46 wherein one Y is -O- and its corresponding R1 is -(phenyl-4-NHC(O)CH3), and the other Y is -NH- and its corresponding R1 is
-CH,CO2Et.

149. The compounds of claim 46 wherein one Y is -O- and its corresponding R1 is -(phenyl-4-NHC(O)CH3), and the other Y is -NH- and its corresponding R1 is
-C(Me),CO,Et.

150. The compounds of claim 46 wherein one Y is -O- and its corresponding R1 is -(phenyl-2-CO,Et), and the other Y is -NH- and its corresponding R1 is -CH2CO2Et.

151. The compounds of claim 46 wherein one Y is -O- and its corresponding R1 is -(phenyl-2-CH3), and the other Y is -NH- and its corresponding R is -CH2CO2Et.

152. The compounds of claim 47 wherein both Y groups are -O- and R1 is -H.

153. The compounds of claim 47 wherein both Y groups are -O-, and R1 is -CH2OC(O)OEt.

154. The compounds of claim 48 wherein both Y groups are -O- and R1 is H-.

155. The compounds of claim 48 wherein both Y groups are -O-, and R1 is -CH2OC(O)OEt.

156. The compounds of claim 49 wherein both Y groups are -O- and R1 is H-.

157. The compounds of claim 49 wherein both Y groups are -O-, and R1 is -CH2OC(O)OEt.

158. The compounds of claim 53 wherein V is selected from the group consisting of 3,5-dichlorophenyl, 3-bromo-4-fluorophenyl, 3-chlorophenyl, and 3-bromophenyl.

159. The compounds of claim 47 wherein one Y is -O- and its corresponding R! is -phenyl while the other Y is -NH- and its corresponding R1 is -CH(Me)CO2Et and -NH-*CH(Me)CO,Et is in the L-configuration.

160. The compounds of claim 54 wherein V is selected from the group consisting of 3,5-dichlorophenyl, 3-bromo-4-fluorophenyl, 3-chlorophenyl, and 3-bromophenyl.

161. The compounds of claim 48 wherein one Y is -O- and its corresponding R1 is -phenyl while the other Y is -NH- and its corresponding R1 is -CH(Me)CO2Et and -NH- *CH(Me)CO,Et is in the L-configuration.

162. The compounds of claim 55 wherein V is selected from the group consisting of 3,5-dichlorophenyl, 3-bromo-4-fluorophenyl, 3-chlorophenyl, and 3-bromophenyl.

163. The compounds of claim 49 wherein one Y is -O- and its corresponding R1 is -phenyl while the other Y is -NH- and its corresponding R1 is -CH(Me)CO2Et and -NH-*CH(Me)CO,Et is in the L-configuration.

164. The compounds of claim 60 wherein one Y is -O- and its corresponding R1 is -phenyl, while the other Y is -NH, and its corresponding R1 is -CH2CO2Et.

165. The compounds of claim 130 wherein one Y is -O-, and its corresponding R1 is phenyl, while the other Y is -NH, and its corresponding R1 is -CH2CO2Et.