Hif inhibitors and use thereof

A method of preventing cell proliferation comprising:

• contacting a cell with a HIF inhibitor, wherein said HIF inhibitor is 3-(2,5-diethoxyphenyl)-1-(2-thienyl)-2-propen-1-one, N2-(4-bromo-3-nitrobenzoyl)leucinamide, 2-bromo-N-(2-methoxyphenyl)propanamide, 6-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl-N-hydroxyhexanamide, 15-deoxy-Δ12,14-prostaglandin J2 (PGJ2),
• wherein:
• R1 and R2 are each independently H, alkyl, alkenyl, alkynyl, or taken together with the N atom to which they are attached form a 5-8 membered heterocyclyl or heteroaryl, each of which can be optionally substituted;
• R3 is H, alkyl, alkenyl, or alkynyl, each of which can be optionally substituted;
• R4 is independently for each occurrence halogen, alkyl, alkenyl, alkynyl, alkoxy, CF3, NO2, N(R5)2, CN, OH, SRS, SO2R5, or two R4 taken together form an optionally substituted 3,4-methylenedioxy, each of which can be optionally substituted;
• R5 is independently for each occurrence H, alkyl, alkenyl, or alkynyl, each of which can be optionally substituted;
• m is 1, 2, 3, 4 or 5;
• n is 0, 1, 2, or 3;
• R11 is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cyclyl or optionally substituted heterocyclyl, or
• R12 is optionally substituted aryl or optionally substituted heteroaryl;
• R21 is halogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cyclyl, heterocyclyl, CF3, NO2, N(R23)2, CN, OH, SR23, SO2R23, or C(O)R24, each of which can be optionally substituted;
• R22 is H, alkoxy, halogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cyclyl, heterocyclyl, CF3, NO2, N(R25)2, CN, OH, SR23, or SO2R23, each of which can be optionally substituted;
• R23 is independently for each occurrence H, alkyl, alkenyl or alkynyl, each of which can be optionally substituted;
• R24 is alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cyclyl heterocyclyl,
• wherein the aryl can be optionally substituted, or
• each of which can be optionally substituted;
• R25 is independently for each occurrence H, alkyl, alkenyl, alkynyl, N(R23)2 or N═R26, each of which can be optionally substituted;
• R26 is independently for each occurrence H, alkyl, alkenyl alkynyl, or
• each of which can be optionally substituted;
• X is absent, S, O, or NH;
• R31 is independently for each occurrence hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, CF3, NO2, N(R34)2, CN, OH, SR34, (O)N(H)R35, or SO2R34, each of which can be optionally substituted;
• R32 is independently for each occurrence halogen, alkyl, alkenyl, alkynyl, alkoxy, CF3, NO2—, N(R34)2, CN, OH, SR34, or SO2R34, each of which can be optionally substituted;
• R33 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, halo, or
• each of which can be optionally substituted;
• R34 is independently for each occurrence H, alkyl, alkenyl, alkynyl, C(O)R36, or C(O)C(Br)CH3 each of which can be optionally substituted;
• R35 is alkylamide, optionally substituted;
• R36 is alkyl, optionally substituted;
• and
• pharmaceutically acceptable salts and combinations thereof.

A method of reducing inflammation or treating an angiogenic disease or disorder in a subject in need thereof, comprising administrating to said host of an effective amount of an HIF inhibitor, wherein said inhibitor is 3-(2,5-diethoxyphenyl)-1-(2-thienyl)-2-propen-1-one, N2-(4-bromo-3-nitrobenzoyl)leucinamide, 2-bromo-N-(2-methoxyphenyl)propanamide, 6-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl-N-hydroxyhexanamide, 15-deoxy-Δ12,14-Prostaglandin J2 (PGJ2),

• wherein:
• R1 and R2 are each independently H, alkyl, alkenyl, alkynyl, or taken together with the N atom to which they are attached form a 5-8 membered heterocyclyl or heteroaryl, each of which can be optionally substituted;
• R3 is H, alkyl, alkenyl, or alkynyl, each of which can be optionally substituted;
• R4 is independently for each occurrence halogen, alkyl, alkenyl, alkynyl, alkoxy, CF3, NO2, N(R5)2, CN, OH, SRS, SO2R5, or two R4 taken together form an optionally substituted 3,4-methylenedioxy, each of which can be optionally substituted;
• R5 is independently for each occurrence H, alkyl, alkenyl, or alkynyl, each of which can be optionally substituted;
• m is 1, 2, 3, 4 or 5;
• n is 0, 1, 2, or 3;
• R11 is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cyclyl optionally substituted heterocyclyl, or
• R12 is optionally substituted aryl or optionally substituted heteroaryl;
• R21 is halogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cyclyl, heterocyclyl, CF3, NO2, N(R23)2, CN, OH, SR23, SO2R23, or C(O)R24, each of which can be optionally substituted;
• R22 is H, alkoxy, halogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cyclyl, heterocyclyl, CF3, NO2, N(R25)2, CN, OH, SR23, or SO2R23, each of which can be optionally substituted;
• R23 is independently for each occurrence H, alkyl, alkenyl or alkynyl, each of which can be optionally substituted;
• R24 is alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cyclyl, heterocyclyl,
• wherein the aryl can be optionally substituted, or
• each of which can be optionally substituted;
• R25 is independently for each occurrence H, alkyl, alkenyl, alkynyl, N(R23)2 or N═R26, each of which can be optionally substituted;
• R26 is independently for each occurrence H, alkyl, alkenyl alkynyl, or
• each of which can be optionally substituted;
• X is absent, S, O, or NH;
• R31 is independently for each occurrence hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, CF3, NO2, N(R34)2, CN, OH, SR34, C(O)N(H)R35, or SO2R34, each of which can be optionally substituted;
• R32 is independently for each occurrence halogen, alkyl, alkenyl, alkynyl, alkoxy, CF3, NO2—, N(R34)2, CN, OH, SR34, or SO2R34, each of which can be optionally substituted;
• R33 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, halo, or
• each of which can be optionally substituted;
• R34 is independently for each occurrence H, alkyl, alkenyl, alkynyl, C(O)R36, or C(O)C(Br)CH3 each of which can be optionally substituted;
• R35 is alkylamide, optionally substituted;
• R36 is alkyl, optionally substituted;
• and
• pharmaceutically acceptable salts and combinations thereof.

A pharmaceutical composition for inhibiting angiogenesis comprising a HIF inhibitor and a pharmaceutically acceptable carrier or excipient, wherein said inhibitor is 3-(2,5-diethoxyphenyl)-1-(2-thienyl)-2-propen-1-one, N2-(4-bromo-3-nitrobenzoyl)leucinamide, 2-bromo-N-(2-methoxyphenyl)propanamide, 6-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl-N-hydroxyhexanamide, 15-deoxy-Δ12,14-Prostaglandin J2 (PGJ2),

• wherein:
• R1 and R2 are each independently H, alkyl, alkenyl, alkynyl, or taken together with the N atom to which they are attached form a 5-8 membered heterocyclyl or heteroaryl, each of which can be optionally substituted;
• R3 is H, alkyl, alkenyl, or alkynyl, each of which can be optionally substituted;
• R4 is independently for each occurrence halogen, alkyl, alkenyl, alkynyl, alkoxy, CF3, NO2, N(R5)2, CN, OH, SRS, SO2R5, or two R4 taken together form an optionally substituted 3,4-methylenedioxy, each of which can be optionally substituted;
• R5 is independently for each occurrence H, alkyl, alkenyl, or alkynyl, each of which can be optionally substituted;
• m is 1, 2, 3, 4 or 5;
• n is 0, 1, 2, or 3;
• R11 is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cyclyl optionally substituted heterocyclyl, or
• R12 is optionally substituted aryl or optionally substituted heteroaryl;
• R21 is halogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cyclyl, heterocyclyl, CF3, NO2, N(R23)2, CN, OH, SR23, SO2R23, or C(O)R24, each of which can be optionally substituted;
• R22 is H, alkoxy, halogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cyclyl, heterocyclyl, CF3, NO2, N(R25)2, CN, OH, SR23, or SO2R23, each of which can be optionally substituted;
• R23 is independently for each occurrence H, alkyl, alkenyl or alkynyl, each of which can be optionally substituted;
• R24 is alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, cyclyl heterocyclyl,
• wherein the aryl can be optionally substituted, or
• each of which can be optionally substituted;
• R25 is independently for each occurrence H, alkyl, alkenyl, alkynyl, N(R23)2 or N═R26, each of which can be optionally substituted;
• R26 is independently for each occurrence H, alkyl, alkenyl alkynyl, or
• each of which can be optionally substituted;
• X is absent, S, O, or NH;
• R31 is independently for each occurrence hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, CF3, NO2, N(R34)2, CN, OH, SR34, C(O)N(H)R35, or SO2R34, each of which can be optionally substituted;
• R32 is independently for each occurrence halogen, alkyl, alkenyl, alkynyl, alkoxy, CF3, NO2—, N(R34)2, CN, OH, SR34, or SO2R34, each of which can be optionally substituted;
• R33 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, halo, or each of which can be optionally substituted;
• R34 is independently for each occurrence H, alkyl, alkenyl, alkynyl, C(O)R36, or C(O)C(Br)CH3 each of which can be optionally substituted;
• R35 is alkylamide, optionally substituted;
• R36 is alkyl, optionally substituted;
• and
• pharmaceutically acceptable salts and combinations thereof.