Inhibition of VEGF translation

A method for treating a disease associated with elevated levels of VEGF in a subject in need thereof comprising administering a therapeutically effective amount of a compound of Formula (IV):

• or a pharmaceutically acceptable salt, racemate or stereoisomer thereof, wherein,
• X is hydrogen;
• C1 to C6 alkyl optionally substituted with one or more halogens;
• hydroxyl;
• halogen;
• or C1 to C5 alkoxy optionally substituted with phenyl;
• Ro is halogen;
• cyano;
• nitro;
• sulfonyl substituted with C1 to C6 alkyl or morpholinyl;
• amino optionally substituted with C1 to C6 alkyl, —C(O)—Rb, —C(O)O—Rb, alkylsulfonyl, piperidinyl, morpholinyl or tetrahydropyranyl, wherein piperidinyl, morpholinyl or tetrahydropyranyl are optionally further substituted with —C(O)O—Rn;
• C1 to C6 alkyl optionally substituted with one or more substituents independently selected from hydroxl, halogen or amino;
• —C(O)—Rn;
• —ORa;
• Ra is hydrogen;
• C2 to C8 alkenyl;
• —C(O)O—Rb;
• —C(O)—NH—Rb;
• C1 to C8 alkyl optionally substituted with one or more substituents independently selected from hydroxyl, halogen, C1 to C4 alkoxy, C1 to C4 alkoxy-C1 to C4 alkoxy, amino, alkylamino, dialkylamino, acetamide, —C(O)—Rb, —C(O)O—-Rb, aryl, morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl, piperazinyl, 1,3-dioxolan-2-one, oxiranyl, tetrahydrofuranyl, tetrahydropyranyl, 1,2,3-triazole, 1,2,4-triazole, furan, imidazole, isoxazole, isothiazole, oxazole, pyrazole, thiazole, thiophene or tetrazole;
• wherein amino is optionally substituted with C1 to C4 alkoxycarbonyl, imidazole, isothiazole, pyrazole, pyridine, pyrazine, pyrimidine, pyrrole or thiazole, wherein pyridine and thiazole are each optionally substituted with C1 to C4 alkyl;
• wherein alkylamino and dialkylamino are each optionally substituted on alkyl with hydroxyl, C1 to C4 alkoxy, imidazole, pyrazole, pyrrole or tetrazole;
• and
• wherein morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl, piperazinyl and oxiranyl are each optionally substituted with —C(O)—Rn, —C(O)O—Rn or C1 to C4 alkyl, wherein C1 to C4 alkyl is optionally substituted with hydroxyl;
• Rb is hydroxyl;
• amino;
• alkylamino, optionally substituted on alkyl with hydroxyl, amino, alkylamino or C1 to C4 alkoxy;
• C1 to C4 alkoxy;
• C2 to C8 alkenyl;
• C2 to C8 alkynyl;
• aryl optionally substituted with one or more substituents independently selected from halogen and C1 to C4 alkoxy;
• furan;
• or C1 to C8 alkyl optionally substituted with one or more substituents independently selected from C1 to C4 alkoxy, aryl, amino, morpholinyl, piperidinyl or piperazinyl, wherein the amino, morpholinyl, piperidinyl and piperazinyl groups are optionally substituted with at least one independently selected C1 to C8 alkyl, oxo or —C(O)O—Rn substituent;
• Rd is phenyl optionally substituted by one or more substituents independently selected from halogen, nitro, C1 to C6 alkyl, —C(O)O—Re, and —ORe;
• Re is hydrogen;
• C1 to C6 alkyl optionally substituted with one or more substituents independently selected from halogen and alkoxy;
• or phenyl, wherein phenyl is optionally substituted with one or more substituents independently selected from halogen and alkoxy;
• and
• Rn is hydroxyl, C1 to C4 alkoxy, amino or C1 to C6 alkyl;
• wherein the compound reduces VEGF levels as measured by an ELISA assay or a quantitative immunofluorescence assay, or reduces VEGF levels in HT1080 clones stably expressing epitope-tagged VEGF with a 5′-UTR;
• and
• wherein the disease is solid tumor cancer, diabetic retinopathy, rheumatoid arthritis, psoriasis, atherosclerosis, chronic inflammation, a chronic inflammation-related disease or disorder, obesity, or exudative macular degeneration.