Inhibitors of short-chain dehydrogenase activity for treating fibrosis

A method of treating lung fibrosis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor, wherein the 15-PGDH inhibitor includes a compound having formula (VI):

• wherein:
• n=1;
• X6 is N or CRc;
• R1 is selected from the group consisting of branched or linear alkyl and
• wherein n2=0-6 and X is any of the following:
• CFyHz (y+z=3), CClyHz (y+z=3), OH, OAc, OMe, R71, OR72, CN, N(R73)2,
• R5 is selected from the group consisting of H, CI, F, NH2, and N(R76)2,
• R6 and R7 are the same or different and are each independently one of the following:
• and
• each R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44, R45, R46, R47, R48, R49, R50, R51, R52, R53, R54, R55, R56, R57, R58, R59, R60, R61, R62, R63, R64, R65, R66, R67, R68, R69, R70, R71, R72, R73, R74, R76, and Rc are the same or different and are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-C24 alkyl, C2-C24 alkenyl, C2-C24 alkynyl, C6-C20 aryl, heterocycloalkenyl containing from 5-6 ring atoms, (wherein from 1-3 of the ring atoms is independently selected from N, NH, N(C1-C6 alkyl), NC(O)(C1-C6 alkyl), O, and S), heteroaryl or heterocyclyl containing from 5-14 ring atoms, (wherein from 1-6 of the ring atoms is independently selected from N, NH, N(C1-C3 alkyl), 0, and S), C6-C24 alkaryl, C6-C24 aralkyl, halo, silyl, hydroxyl, sulfhydryl, C1-C24 alkoxy that is optionally substituted with at least one hydroxyl, amino, or mono- or di-(C1-C24 alkyl)-amino, C2-C24 alkenyloxy, C2-C24 alkynyloxy, C5-C20 aryloxy, acyl, acyloxy (—O-acyl), C2-C24 alkoxycarbonyl (—(CO)—O-alkyl), C6-C20 aryloxycarbonyl (—(CO)—O-aryl), C2-C24 alkylcarbonato (—O—(CO)—O-alkyl), C6-C20 arylcarbonato (—O—(CO)—O-aryl), carboxy (—COOH), carboxylato (—COO—), carbamoyl (—(CO)—NH2), C1-C24 alkyl-carbamoyl (—(CO)—NH(C1-C24 alkyl)), arylcarbamoyl (—(CO)—NH-aryl), thiocarbamoyl (—(CS)—NH2), carbamido (—NH—(CO)—NH2), cyano (—CN), isocyano (—N+C—), cyanato (—O—CN), isocyanato (—O—N+=C—), isothiocyanato (—S—CN), azido (—N═N+=N—), formyl (—(CO)—H), thioformyl (—(CS)—H), amino (—NH2), mono- or di-(C1-C24 alkyl)-amino that is optionally substituted with at least one hydroxyl, amino, or mono- or di-(C1-C24 alkyl)-amino, C6-C20 aryl amino, C2-C24 alkylamido (—NH—(CO)-alkyl), C6-C20 arylamido (—NH—(CO)-aryl), sulfanamido (—SO2N(R)2 where R is independently H, alkyl, aryl or heteroaryl), imino, alkylimino, arylimino, nitro (—NO2), nitroso (—NO), sulfo (—SO2—OH), sulfonato (—SO2—O—), C1-C24 alkylsulfanyl, arylsulfanyl, C1-C24 alkylsulfinyl (—(SO)-alkyl), C5-C20 arylsulfinyl (—(SO)-aryl), C1-C24 alkylsulfonyl (—SO2-alkyl), C5-C20 arylsulfonyl (—SO2-aryl), sulfonamide (—SO2—NH2, —SO2NY2 (wherein Y is independently H, arlyl or alkyl), phosphono (—P(O)(OH)2), phosphonato (—P(O)(O—)2), phosphinato (—P(O)(O—)), phospho (—PO2), phosphino (—PH2), polyalkyl ethers (—[(CH2)nO]m), phosphates, phosphate esters [—OP(O)(OR)2 where R═H, methyl or other alkyl], and combinations thereof, or pharmaceutically acceptable salts thereof.