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US 6,294,672 B1Granted
Indole and azaindole inhibitors of Fructose-1,6-biphosphatase
AssigneeMetabasis Therapeutics, Inc.
InventorsK. Raja Reddy, Gerard R. Scarlato, Qun Dang, Mark D. Erion, Srinivas Rao Kasibhatla, M. Rami Reddy
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Abstract
The present invention is directed towards novel azaindole compounds which bind to the AMP site and are potent FBPase inhibitors. The present invention also is directed towards the clinical use of the novel FBPase inhibitors as a method of treatment or prevention of diseases responsive to lowered blood glucose levels.
Claims22
A compound of formula 1:
- wherein:
- A, E, and L are selected from the group consisting of —NR82, —NO2, —H, —OR7, —SR7, —C(O)NR42, halo, —COR11, —SO2R3, guanidine, amidine, —NHSO2R5, —SO2NR42, —CN, sulfoxide, perhaloacyl, perhaloalkyl, perhaloalkoxy, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, and lower alicyclic, or together A and L form a cyclic group, or together L and E form a cyclic group, or together E and J form a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- J is selected from the group consisting of —NR82, —NO2, —H, —OR7, —SR7, —C(O)NR42, halo, —C(O)R11, —CN, sulfonyl, sulfoxide, perhaloalkyl, hydroxyalkyl, perhaloalkoxy, alkyl, haloalkyl, aminoalkyl, alkenyl, alkynyl, alicyclic, aryl, and aralkyl, or together with Y forms a cyclic group including aryl, cyclic alkyl and heterocyclic alkyl;
- X is selected from the group consisting of alkylamino, alkyl(hydroxy), alkyl(carboxyl), alkyl(phosphonate), alkyl, alkenyl, alkynyl, alkyl(sulfonate), aryl, heteroaryl, carbonylalkyl, 1,1-dihaloalkyl, aminocarbonylamino, alkylaminoalkyl, alkoxyalkyl, alkylthioalkyl, alkylthio, alkylaminocarbonyl, alkylcarbonylamino, alicyclic, aralkyl, and alkylaryl, all optionally substituted;
- or together with Y forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- Y is selected from the group consisting of —H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, aryloxyalkyl, alkoxyalkyl, —C(O)R3, —S(O)2R3, —C(O)—OR3, —CONHR3, —NR22, and —OR3, all except H are optionally substituted;
- or together with X forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- R1 is independently selected from the group consisting of —H, alkyl, aryl, alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, —C(R2)2-aryl, alkylaryl, —C(R2)2OC(O)NR22, —NR2—C(O)—R3, —C(R2)2—OC(O)R3, C(R2)2—O—C(O)OR3, —C(R2)2OC(O)SR3, alkyl-S—C(O)R3, alkyl-S—S-alkylhydroxy, and alkyl-S—S—S-alkylhydroxy, or together R1 and R1 are -alkyl-S—S-alkyl to form a cyclic group, or together R1 and R1 are
- wherein
- V and W are independently selected from the group consisting of hydrogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, 1-alkynyl, and —R9;
- or
- together V and Z are connected to form a cyclic group containing 3-5 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarboxy, or aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus;
- or
- together V and W are connected to form a cyclic group containing 3 carbon atoms substituted with hydroxy, acyloxy, alkoxycarboxy, alkylthiocarboxy, hydroxymethyl, and aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus;
- Z is selected from the group consisting of —CH2OH, —CH2OCOR3, —CH2OC(O)SR3, —CH2OCO2R3, —SR3, —S(O)R3, —CH2N3, —CH2NR22, —CH2Ar, —CH(Ar)OH, —CH(CH═CR2R2)OH, —CH(C≡CR2)OH, and —R2;
- with the provisos that:
- a) V, Z, W are not all —H;
- and
- b) when Z is —R2, then at least one of V and W is not —H or —R9;
- R2 is selected from the group consisting of R3 and —H;
- R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
- R4 is independently selected from the group consisting of —H, lower alkyl, lower alicyclic, lower aralkyl, and lower aryl;
- R5 is selected from the group consisting of lower alkyl, lower aryl, lower aralkyl, and lower alicyclic;
- R6 is independently selected from the group consisting of —H, and lower alkyl;
- R7 is independently selected from the group consisting of —H, lower alkyl, lower alicyclic, lower aralkyl, lower aryl, and —C(O)R10;
- R8 is independently selected from the group consisting of —H, lower alkyl, lower aralkyl, lower aryl, lower alicyclic, —C(O)R10, or together said R8 groups form a bidentate alkyl;
- R9 is selected from the group consisting of alkyl, aralkyl, and alicyclic;
- R10 is selected from the group consisting of —H, lower alkyl, —NH2, lower aryl, and lower perhaloalkyl;
- R11 is selected from the group consisting of alkyl, aryl, —OH, —NH2 and —OR3;
- or
- pharmaceutically acceptable prodrugs or salts thereof;
- with the provisos that:
- a) R is not lower alkyl of 1-4 carbon atoms;
- b) X is not alkylamine and alkylaminoalkyl substituted with phosphonic esters or acids;
- c) A, L, E, J, Y, and X together may only form 0-2 cyclic groups;
- and
- d) X is not aryl and alkylaryl linked 1,4 through a 6-membered aromatic ring.
34 more elements
A method of treating an animal for diabetes mellitus, comprising
- administering to said animal a therapeutically effective amount of a compound of formula (1):
- wherein:
- A, E, and L are selected from the group consisting of —NR82, —NO2, —H, —OR7, —SR7, —C(O)NR42, halo, —COR11, —SO2R3, guanidine, amidine, —NHSO2R5, —SO2NR42, —CN, sulfoxide, perhaloacyl, perhaloalkyl, perhaloalkoxy, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, and lower alicyclic, or together A and L form a cyclic group, or together L and E form a cyclic group, or together E and J form a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- J is selected from the group consisting of —NR82, —NO2, —H, —OR7, —SR7, —C(O)NR42, halo, —C(O)R11, —CN, sulfonyl, sulfoxide, perhaloalkyl, hydroxyalkyl, perhaloalkoxy, alkyl, haloalkyl, aminoalkyl, alkenyl, alkynyl, alicyclic, aryl, and aralkyl, or together with Y forms a cyclic group including aryl, cyclic alkyl and heterocyclic alkyl;
- X is selected from the group consisting of alkylamino, alkyl(hydroxy), alkyl(carboxyl), alkyl(phosphonate), alkyl, alkenyl, alkynyl, alkyl(sulfonate), aryl, heteroaryl, carbonylalkyl, 1,1-dihaloalkyl, aminocarbonylamino, alkylaminoalkyl, alkoxyalkyl, alkylthioalkyl, alkylthio, alkylaminocarbonyl, alkylcarbonylamino, alicyclic, aralkyl, and alkylaryl, all optionally substituted;
- or together with Y forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- Y is selected from the group consisting of —H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, aryloxyalkyl, alkoxyalkyl, —C(O)R3, —S(O)2R3, —C(O)—OR3, —CONHR3, —NR22, and —OR3, all except H are optionally substituted;
- or together with X forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- R1 is independently selected from the group consisting of —H, alkyl, aryl, alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, —C(R2)2-aryl, alkylaryl, —C(R2)2OC(O)NR22, —NR2—C(O)—R3, —C(R2)2—OC(O)R3, C(R2)2—O—C(O)OR3, —C(R2)2OC(O)SR3, alkyl-S—C(O)R3, alkyl-S—S-alkylhydroxy, and alkyl-S—S—S-alkylhydroxy, or together R1 and R1 are -alkyl-S—S-alkyl to form a cyclic group, or together R1 and R1 are
- wherein
- V and W are independently selected from the group consisting of hydrogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, 1-alkynyl, and —R9;
- or
- together V and Z are connected to form a cyclic group containing 3-5 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarboxy, or aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus;
- or
- together V and W are connected to form a cyclic group containing 3 carbon atoms substituted with hydroxy, acyloxy, alkoxycarboxy, alkylthiocarboxy, hydroxymethyl, and aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus;
- Z is selected from the group consisting of —CH2OH, —CH2OCOR3, —CH2OC(O)SR3, —CH2OCO2R3, —SR3, —S(O)R3, —CH2N3, —CH2NR22, —CH2Ar, —CH(Ar)OH, —CH(CH═CR2R2)OH, —CH(C≡CR2)OH, and —R2;
- with the provisos that:
- a) V, Z, W are not all —H;
- and
- b) when Z is —R2, then at least one of V and W is not —H or —R9;
- R2 is selected from the group consisting of R3 and —H;
- R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
- R4 is independently selected from the group consisting of —H, lower alkyl, lower alicyclic, lower aralkyl, and lower aryl;
- R5 is selected from the group consisting of lower alkyl, lower aryl, lower aralkyl, and lower alicyclic;
- R6 is independently selected from the group consisting of —H, and lower alkyl;
- R7 is independently selected from the group consisting of —H, lower alkyl, lower alicyclic, lower aralkyl, lower aryl, and —C(O)R10;
- R8 is independently selected from the group consisting of —H, lower alkyl, lower aralkyl, lower aryl, lower alicyclic, —C(O)R10, or together said R8 groups form a bidentate alkyl;
- R9 is selected from the group consisting of alkyl, aralkyl, and alicyclic;
- R10 is selected from the group consisting of —H, lower alkyl, —NH2, lower aryl, and lower perhaloalkyl;
- R11 is selected from the group consisting of alkyl, aryl, —OH, —NH2 and —OR3;
- or
- pharmaceutically acceptable prodrugs or salts thereof.
29 more elements
A method of lowering blood glucose levels in an animal in need thereof, comprising administering to said animal a pharmaceutically acceptable amount of a compound of formula (1):
- wherein:
- A, E, and L are selected from the group consisting of —NR82, —NO2, —H, —OR7, —SR7, —C(O)NR42, halo, —COR11, —SO2R3, guanidine, amidine, —NHSO2R5, —SO2NR42, —CN, sulfoxide perhaloacyl, perhaloalkyl, perhaloalkoxy, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, and lower alicyclic, or together A and L form a cyclic group, or together L and E form a cyclic group, or together E and J form a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- J is selected from the group consisting of —NR82, —NO2, —H, —OR7, —SR7, —C(O)NR42, halo, —C(O)R11, —CN, sulfonyl, sulfoxide, perhaloalkyl, hydroxyalkyl, perhaloalkoxy, alkyl, haloalkyl, aminoalkyl, alkenyl, alkynyl, alicyclic, aryl, and aralkyl, or together with Y forms a cyclic group including aryl, cyclic alkyl and heterocyclic alkyl;
- X is selected from the group consisting of alkylamino, alkyl(hydroxy), alkyl(carboxyl), alkyl(phosphonate), alkyl, alkenyl, alkynyl, alkyl(sulfonate), aryl, heteroaryl, carbonylalkyl, 1,1-dihaloalkyl, aminocarbonylamino, alkylaminoalkyl, alkoxyalkyl, alkylthioalkyl, alkylthio, alkylaminocarbonyl, alkylcarbonylamino, alicyclic, aralkyl, and alkylaryl, all optionally substituted;
- or together with Y forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- Y is selected from the group consisting of —H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, aryloxyalkyl, alkoxyalkyl, —C(O)R3, —S(O)2R3, —C(O)—OR3, —CONHR3, —NR22, and —OR3, all except H are optionally substituted;
- or together with X forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- R1 is independently selected from the group consisting of —H, alkyl, aryl, alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, —C(R2)2-aryl, alkylaryl, —C(R2)2OC(O)NR22, —NR2—C(O)—R3, —C(R2)2—OC(O)R3, C(R2)2—O—C(O)OR3, —C(R2)2OC(O)SR3, alkyl-S—C(O)R3, alkyl-S—S-alkylhydroxy, and alkyl-S—S—S-alkylhydroxy, or together R1 and R1 are -alkyl-S—S-alkyl to form a cyclic group, or together R1 and R1 are
- wherein
- V and W are independently selected from the group consisting of hydrogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, 1-alkynyl, and —R9;
- or
- together V and Z are connected to form a cyclic group containing 3-5 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarboxy, or aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus;
- or
- together V and W are connected to form a cyclic group containing 3 carbon atoms substituted with hydroxy, acyloxy, alkoxycarboxy, alkylthiocarboxy, hydroxymethyl, and aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus;
- Z is selected from the group consisting of —CH2OH, —CH2OCOR3, —CH2OC(O)SR3, —CH2OCO2R3, —SR3, —S(O)R3, —CH2N3, —CH2NR22, —CH2Ar, —CH(Ar)OH, —CH(CH═CR2R2)OH, —CH(C≡CR2)OH, and —R2;
- with the provisos that:
- a) V, Z, W are not all —H;
- and
- b) when Z is —R2, then at least one of V and W is not —H or —R9;
- R2 is selected from the group consisting of R3 and —H;
- R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
- R4 is independently selected from the group consisting of —H, lower alkyl, lower alicyclic, lower aralkyl, and lower aryl;
- R5 is selected from the group consisting of lower alkyl, lower aryl, lower aralkyl, and lower alicyclic;
- R6 is independently selected from the group consisting of —H, and lower alkyl;
- R7 is independently selected from the group consisting of —H, lower alkyl, lower alicyclic, lower aralkyl, lower aryl, and —C(O)R10;
- R8 is independently selected from the group consisting of —H, lower alkyl, lower aralkyl, lower aryl, lower alicyclic, —C(O)R10, or together said R8 groups form a bidentate alkyl;
- R9 is selected from the group consisting of alkyl, aralkyl, and alicyclic;
- R10 is selected from the group consisting of —H, lower alkyl, —NH2, lower aryl, and lower perhaloalkyl;
- R11 is selected from the group consisting of alkyl, aryl, —OH, —NH2 and —OR3;
- or
- pharmaceutically acceptable prodrugs or salts thereof.
28 more elements
A method of inhibiting FBPase at the AMP site in patients in need thereof, comprising administering to said patients a compound of formula (1):
- wherein:
- A, E, and L are selected from the group consisting of —NR82, —NO2, —H, —OR7, —SR7, —C(O)NR42, halo, —COR10, —SO2R3, guanidine, amidine, —NHSO2R5, —SO2NR42, —CN, sulfoxide, perhaloacyl, perhaloalkyl, perhaloalkoxy, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, and lower alicyclic, or together A and L form a cyclic group, or together L and E form a cyclic group, or together E and J form a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- J is selected from the group consisting of —NR82, —NO2, —H, —OR7, —SR7, —C(O)NR42, halo, —C(O)R10, —CN, sulfonyl, sulfoxide, perhaloalkyl, hydroxyalkyl, perhaloalkoxy, alkyl, haloalkyl, aminoalkyl, alkenyl, alkynyl, alicyclic, aryl, and aralkyl, or together with Y forms a cyclic group including aryl, cyclic alkyl and heterocyclic alkyl;
- X is selected from the group consisting of alkylamino, alkyl(hydroxy), alkyl(carboxyl), alkyl(phosphonate), alkyl, alkenyl, alkynyl, alkyl(sulfonate), aryl, heteroaryl, carbonylalkyl, 1,1-dihaloalkyl, aminocarbonylamino, alkylaminoalkyl, alkoxyalkyl, alkylthioalkyl, alkylthio, alkylaminocarbonyl, alkylcarbonylamino, alicyclic, aralkyl, and alkylaryl, all optionally substituted;
- or together with Y forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- Y is selected from the group consisting of —H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, aryloxyalkyl, alkoxyalkyl, —C(O)R3, —S(O)2R3, —C(O)—OR3, —CONHR3, —NR22, and —OR3, all except H are optionally substituted;
- or together with X forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- R1 is independently selected from the group consisting of —H, alkyl, aryl, alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, —C(R2)2-aryl, alkylaryl, —C(R2)2OC(O)NR22, —NR2—C(O)—R3, —C(R2)2—OC(O)R3, C(R2)2—O—C(O)OR3, —C(R2)2OC(O)SR3, alkyl-S—C(O)R3, alkyl-S—S-alkylhydroxy, and alkyl-S—S—S-alkylhydroxy, or together R1 and R1 are -alkyl-S—S-alkyl to form a cyclic group, or together R1 and R1 are
- wherein
- V and W are independently selected from the group consisting of hydrogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, 1-alkynyl, and —R9;
- or
- together V and Z are connected to form a cyclic group containing 3-5 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarboxy, or aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus;
- or
- together V and W are connected to form a cyclic group containing 3 carbon atoms substituted with hydroxy, acyloxy, alkoxycarboxy, alkylthiocarboxy, hydroxymethyl, and aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus;
- Z is selected from the group consisting of —CH2OH, —CH2OCOR3, —CH2OC(O)SR3, —CH2OCO2R3, —SR3, —S(O)R3, —CH2N3, —CH2NR22, —CH2Ar, —CH(Ar)OH, —CH(CH═CR2R2)OH, —CH(C≡CR2)OH, and —R2;
- with the provisos that:
- a) V, Z, W are not all —H;
- and
- b) when Z is —R2, then at least one of V and W is not —H or —R9;
- R2 is selected from the group consisting of R3 and —H;
- R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
- R4 is independently selected from the group consisting of —H, lower alkyl, lower alicyclic, lower aralkyl, and lower aryl;
- R5 is selected from the group consisting of lower alkyl, lower aryl, lower aralkyl, and lower alicyclic;
- R6 is independently selected from the group consisting of —H, and lower alkyl;
- R7 is independently selected from the group consisting of —H, lower alkyl, lower alicyclic, lower aralkyl, lower aryl, and —C(O)R10;
- R8 is independently selected from the group consisting of —H, lower alkyl, lower aralkyl, lower aryl, lower alicyclic, —C(O)R10, or together said R8 groups form a bidentate alkyl;
- R9 is selected from the group consisting of alkyl, aralkyl, and alicyclic;
- R10 is selected from the group consisting of —H, lower alkyl, —NH2, lower aryl, and lower perhaloalkyl;
- R11 is selected from the group consisting of alkyl, aryl, —OH, —NH2 and —OR3;
- or
- pharmaceutically acceptable prodrugs or salts thereof.
28 more elements
A method of inhibiting gluconeogenesis in an animal in need thereof, comprising administering to said animal an FBPase inhibitory amount of a compound of formula (1):
- wherein:
- A, E, and L are selected from the group consisting of —NR2, —NO2, —H, —OR7, —SR7, —C(O)NR42, halo, —COR11, —SO2R3, guanidine, amidine, —NHSO2R5, —SO2NR42, —CN, sulfoxide, perhaloacyl, perhaloalkyl, perhaloalkoxy, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, and lower alicyclic, or together A and L form a cyclic group, or together L and E form a cyclic group, or together E and J form a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- J is selected from the group consisting of —NR82, —NO2, —H, —OR7, —SR7, —C(O)NR42, halo, —C(O)R11, —CN, sulfonyl, sulfoxide, perhaloalkyl, hydroxyalkyl, perhaloalkoxy, alkyl, haloalkyl, aminoalkyl, alkenyl, alkynyl, alicyclic, aryl, and aralkyl, or together with Y forms a cyclic group including aryl, cyclic alkyl and heterocyclic alkyl;
- X is selected from the group consisting of alkylamino, alkyl(hydroxy), alkyl(carboxyl), alkyl(phosphonate), alkyl, alkenyl, alkynyl, alkyl(sulfonate), aryl, heteroaryl, carbonylalkyl, 1,1-dihaloalkyl, aminocarbonylamino, alkylaminoalkyl, alkoxyalkyl, alkylthioalkyl, alkylthio, alkylaminocarbonyl, alkylcarbonylamino, alicyclic, aralkyl, and alkylaryl, all optionally substituted;
- or together with Y forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- Y is selected from the group consisting of —H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, aryloxyalkyl, alkoxyalkyl, —C(O)R3, —S(O)2R3, —C(O)—OR3, —CONHR3, —NR22, and —OR3, all except H are optionally substituted;
- or together with X forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;
- R1 is independently selected from the group consisting of —H, alkyl, aryl, alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, —C(R2)2-aryl, alkylaryl, —C(R2)2OC(O)NR22, —NR2—C(O)—R3, —C(R2)2—OC(O)R3, C(R2)2—O—C(O)OR3, —C(R2)2OC(O)SR3, alkyl-S—C(O)R3, alkyl-S—S-alkylhydroxy, and alkyl-S—S—S-alkylhydroxy, or together R1 and R1 are -alkyl-S—S-alkyl to form a cyclic group, or together R1 and R1 are
- wherein
- V and W are independently selected from the group consisting of hydrogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, 1-alkynyl, and —R9;
- or
- together V and Z are connected to form a cyclic group containing 3-5 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarboxy, or aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus;
- or
- together V and W are connected to form a cyclic group containing 3 carbon atoms substituted with hydroxy, acyloxy, alkoxycarboxy, alkylthiocarboxy, hydroxymethyl, and aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus;
- Z is selected from the group consisting of —CH2OH, —CH2OCOR3, —CH2OC(O)SR3, —CH2OCO2R3, —SR3, —S(O)R3, —CH2N3, —CH2NR22, —CH2Ar, —CH(Ar)OH, —CH(C═CR2R2)OH, —CH(C≡CR2)OH, and —R2;
- with the provisos that:
- a) V, Z, W are not all —H;
- and
- b) when Z is —R2, then at least one of V and W is not —H or —R9;
- R2 is selected from the group consisting of R3 and —H;
- R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;
- R4 is independently selected from the group consisting of —H, lower alkyl, lower alicyclic, lower aralkyl, and lower aryl;
- R5 is selected from the group consisting of lower alkyl, lower aryl, lower aralkyl, and lower alicyclic;
- R6 is independently selected from the group consisting of —H, and lower alkyl;
- R7 is independently selected from the group consisting of —H, lower alkyl, lower alicyclic, lower aralkyl, lower aryl, and —C(O)R10;
- R8 is independently selected from the group consisting of —H, lower alkyl, lower aralkyl, lower aryl, lower alicyclic, —C(O)R10, or together said R8 groups form a bidentate alkyl;
- R9 is selected from the group consisting of alkyl, aralkyl, and alicyclic;
- R10 is selected from the group consisting of —H, lower alkyl, —NH2, lower aryl, and lower perhaloalkyl;
- R11 is selected from the group consisting of alkyl, aryl, —OH, —NH2 and —OR3;
- or
- pharmaceutically acceptable prodrugs or salts thereof.
28 more elements
Dependencies are inferred from the claim text.