Barbituric acid analogs as therapeutic agents

A method of inhibiting HIF-1 activity in a cell, comprising contacting said cell with an effective amount of a compound having the following formula:

• 125
• wherein:
• Q2 is ═O, ═S, or ═NRN2;
• Q4 is ═O, ═S, or ═NRN4;
• α is a single bond or a double bond;
• β is a single bond or a double bond;
• with the proviso that α and β are not both double bonds, and that if β is a double bond, RN1 is absent;
• and wherein:
• (i) R5B is —H and R5A is RC5;
• or,
• (ii) R5A and R5B together are ═O, α is a single bond, and β is a single bond;
• or,
• (iii) R5A and R5B together are ═CHRC5, wherein RC5 may be cis- or trans-, α is a single bond, and β is a single bond;
• and wherein:
• (iv) R6B is —H and R6A is RC6;
• or,
• (v) R6A and R6B together are ═O, α is a single bond, and β is a single bond;
• or,
• (vi) R6A and R6B together are ═CHRC6, wherein RC6 may be cis- or trans-, α is a single bond, and β is a single bond;
• or wherein:
• R5A and R6A, together form a bidentate structure, R56, which, together with the two carbon atoms to which it is attached, forms a cyclic structure with five or six ring atoms, wherein 1 or 2 of said ring atoms are nitrogen, and the remainder are carbon, and wherein the bonds between said ring atoms of the cyclic structure are single or double bonds, as permitted by the valencies of the ring atoms;
• and,
• R5B and R6B, if present, are both —H;
• and wherein:
• each one of RN1, RN2, RN3, and RN4 is a nitrogen substituent, and is independently hydrogen, optionally substituted C1-7alkyl, optionally substituted C3-20heterocyclyl, or optionally substituted C5-20aryl;
• and wherein:
• each one of RC5 and RC6 is a carbon substituent, and is independently optionally substituted C1-7alkyl, optionally substituted C3-20heterocyclyl, or optionally substituted C5-20aryl;
• or a pharmaceutically acceptable salt, solvate, amide, ester, N-oxide, chemically protected form, or prodrug thereof.