COMPOSITIONS AND METHODS OF MODULATING SHORT-CHAIN DEHYDROGENASE ACTIVITY

1 - 79 . (canceled)

80 : A compound having the formula (V):

or a pharmaceutically acceptable salt thereof;

wherein n=1;

R 1 is

R 3 is H, alkyl, —CO 2 H, —CO 2 alkyl, —CONH 2 , —CONH(alkyl), —CON(alkyl) 2 ,

R 2 is N or CH;

R 4 is H or NH 2 ;

R 5 is a branched or linear alkyl or

wherein n 2 =0-6 and X is CF 3 , CHF 2 , CH 2 F, CCl 3 , CHCl 2 , CH 2 Cl, OH, OAc, OMe, CN, or

wherein n 3 =0-5 and m=1-5;

each R 6 is the same or different and is independently one or more substituent selected from the group consisting of hydrogen, substituted or unsubstituted C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, C 3 -C 20 aryl, heterocycloalkenyl containing from 5-6 ring atoms, heteroaryl or heterocyclyl containing from 5-14 ring atoms, C 6 -C 24 alkaryl, C 6 -C 24 aralkyl, halo, silyl, hydroxyl, sulfhydryl, C 1 -C 24 alkoxy, C 2 -C 24 alkenyloxy, C 2 -C 24 alkynyloxy, C 5 -C 20 aryloxy, acyl, acyloxy, C 2 -C 24 alkoxycarbonyl, C 6 -C 20 aryloxycarbonyl, C 2 -C 24 alkylcarbonato, C 6 -C 20 arylcarbonato, carboxy, carboxylato, carbamoyl, C 1 -C 24 alkyl-carbamoyl, arylcarbamoyl, thiocarbamoyl, carbamido, cyano(—CN), isocyano, cyanato, isocyanato, isothiocyanato, azido, formyl, thioformyl, amino, C 1 -C 24 alkyl amino, C 1 -C 24 alkyl amino substituted with hydroxyl, C 5 -C 20 aryl amino, C 2 -C 24 alkylamido, C 6 -C 20 arylamido, sulfanamido, imino, alkylimino, arylimino, nitro, nitroso, sulfo, sulfonato, C 1 -C 24 alkylsulfanyl, arylsulfanyl, C 1 -C 24 alkylsulfinyl, C 5 -C 20 arylsulfinyl, C 1 -C 24 alkylsulfonyl, C 5 -C 20 arylsulfonyl, sulfonamide, phosphono, phosphonato, phosphinato, phospho, phosphino, polyalkyl ethers, phosphates, phosphate ester, and combinations thereof;

provided that R 3 is not hydrogen if R 1 is an unsubstituted thiophene or an unsubstituted thiazole and R 5 is butyl;

provided that R 3 is not an unsubstituted phenyl if R 1 is

an unsubstituted thiophene, or an unsubstituted thiazole; and R 5 is (CH 2 )n 5 (CH 3 ), wherein n 5 =0-7; and

provided that R 3 is not —CF 3 if R 1 is an unsubstituted thiophene.

81 : The compound of claim 80 , wherein R1 is a heterocyclyl containing 5-6 ring atoms.

82 : The compound of claim 80 , wherein R 1 is a substituted or unsubstituted thiazole, oxazole, imidazole, pyrimidine or pyridine.

83 : The compound of claim 80 , wherein R 2 is CH.

84 : The compound of claim 80 , wherein R 3 is H, substituted or unsubstituted aryl, cycloalkyl, heterocyclyl, alkyl, —CO 2 H, —CO 2 alkyl, —CONH 2 , —CONH(alkyl), and —CON(alkyl) 2 ,

85 : The compound of claim 80 , wherein R 3 is

86 : The compound of claim 80 , wherein R 6 is independently selected from hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, amino, substituted or unsubstituted C 1 -C 24 alkyl amino, or C 1 -C 24 alkyl amino substituted with hydroxyl.

87 : The compound of claim 80 , wherein R 4 is NH 2 .

88 : The compound of claim 80 , wherein R 5 is branched or linear C 1 -C 6 alkyl;

wherein n 2 =2-6 and X is CF 3 , CHF 2 , CH 2 F, CCl 3 , CHCl 2 , CH 2 Cl, OH, OAc, OMe, or CN; or

wherein n 3 =0-5 and m=1-5.

89 : The compound of claim 80 , wherein R5 is branched or linear C 2 -C 6 alkyl or

wherein n 3 =0 and m=1-5.

90 : The compound of claim 80 , wherein the compound has formula (V 1 )

or a pharmaceutically acceptable salt thereof;

wherein n=1;

R 3 is selected from the group consisting of H, alkyl, —CO 2 H, —CO 2 alkyl, —CONH 2 , —CONH(alkyl), —CON(alkyl) 2 ,

R 2 is N or CH;

R 4 is selected from the group consisting of H and NH 2 ;

R 5 is a branched or linear alkyl or

wherein n 2 =0-6 and X is any of the following: CF y H z (y+z=3), CCl y H z (y+z=3), OH, OAc, OMe, CN, or

(n 3 =0-5, m=1-5);

each R 6 is the same or different and is independently one or more substituent selected from the group consisting of hydrogen, substituted or unsubstituted C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, C 3 -C 20 aryl, heterocycloalkenyl containing from 5-6 ring atoms, heteroaryl or heterocyclyl containing from 5-14 ring atoms, C 6 -C 24 alkaryl, C 6 -C 24 aralkyl, halo, silyl, hydroxyl, sulfhydryl, C 1 -C 24 alkoxy, C 2 -C 24 alkenyloxy, C 2 -C 24 alkynyloxy, C 5 -C 20 aryloxy, acyl, acyloxy, C 2 -C 24 alkoxycarbonyl, C 6 -C 20 aryloxycarbonyl, C 2 -C 24 alkylcarbonato, C 6 -C 20 arylcarbonato, carboxy, carboxylato, carbamoyl, C 1 -C 24 alkyl-carbamoyl, arylcarbamoyl, thiocarbamoyl, carbamido, cyano(—CN), isocyano, cyanato, isocyanato, isothiocyanato, azido, formyl, thioformyl, amino, C 1 -C 24 alkyl amino, C 5 -C 20 aryl amino, C 2 -C 24 alkylamido, C 6 -C 20 arylamido, sulfanamido, imino, alkylimino, arylimino, nitro, nitroso, sulfo, sulfonato, C 1 -C 24 alkylsulfanyl, arylsulfanyl, C 1 -C 24 alkylsulfinyl, C 5 -C 20 arylsulfinyl, C 1 -C 24 alkylsulfonyl, C 5 -C 20 arylsulfonyl, sulfonamide, phosphono, phosphonato, phosphinato, phospho, phosphino, polyalkyl ethers, phosphates, phosphate ester, and combinations thereof;

R 3 is not hydrogen if R 5 is butyl; or R 3 is not an unsubstituted phenyl if R 5 is (CH 2 )n 5 (CH 3 )(n 5 =0-5).

91 : The compound of claim 90 , wherein R3 is selected from the group consisting of H, substituted or unsubstituted aryl, cycloalkyl, heterocyclyl, alkyl, —CO 2 H, —CO 2 alkyl, —CONH 2 , —CONH(alkyl), and —CON(alkyl) 2 .

92 : The compound of claim 80 , the compound inhibiting the activity of a 15-PGDH enzyme.

93 : The compound of claim 80 , wherein the compound inhibits the enzymatic activity of recombinant 15-PGDH at an IC 50 of less than 250 nM.

94 : The compound of claim 80 , wherein the compound inhibits the enzymatic activity of recombinant 15-PGDH at an IC 50 of less than 50 nM.

95 : The compound of claim 80 , wherein the compound inhibits the enzymatic activity of recombinant 15-PGDH at an IC 50 of less than 10 nM.

96 : The compound of claim 80 , wherein the compound inhibits the enzymatic activity of recombinant 15-PGDH at an IC 50 of less than 5 nM.

97 : The compound of claim 80 , wherein the compound inhibits the enzymatic activity of recombinant 15-PGDH at an IC 50 of less than 1 PM.

98 : A compound selected from:

or a pharmaceutically acceptable salt thereof.