AR107245A1 - HISTONE DEMETILASE INHIBITORS - Google Patents

Abstract

The present description relates generally to compositions and methods for the treatment of cancer and neoplastic disease. Substituted pyridine derivative compounds and pharmaceutical compositions comprising these compounds are provided herein. The present compounds and compositions are useful for the inhibition of at least one histone demethylase. In addition, the present compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer or melanoma and the like. Claim 1: A compound having the structure of the formula (1), wherein a compound of the formula (1) includes isomers and pharmaceutically acceptable salts thereof, and wherein: n is 0, 1 or 2; R⁴ is hydrogen or optionally substituted C₁₋₆ alkyl; R⁶ is hydrogen or XY, where X is a bond, O, S, N (R), C (O), N (R) C (O), C (O) N (R) or optionally C alquilo alkyl substituted, wherein R is hydrogen or optionally substituted alkyl, and Y is optionally substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl; and R⁵, R⁷, and R⁸ are each independently selected from hydrogen, halogen, hydroxyl, cyanyl, N (R¹) (R²), or C₁₋₆ alkyl, C₁₋₆ alkynyl, C₁₋₆ alkenyl, C₁₋₆ alkoxy, C₃₋₇ carbocyclyl, C₃₋₇ carbocyclyloxy, C₄₋₁₂ carbocyclylalkyl, C₄₋₁₂ carbocyclylalkoxy, C₆₋₁₀ aryl, C₆₋₁₀ aryloxy, S-C₆₋₁₀ aryl, C-SO₂ aryl, C₇₋₁₄ aralkoxy, heteroaryl , heteroaryloxy, heterocyclyl, heterocyclyloxy, heterocyclylalkyl, heterocyclylalkoxy or heteroaryl-S, optionally substituted wherein R¹ is hydrogen or optionally substituted alkyl, and R² is alkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkylalkyl, aryl-CO, hetero-CO, hetero optionally substituted cycloalkyl-CO or alkyl-CO. Claim 11: A compound of the formula (2), wherein a compound of formula (2) includes isomers and pharmaceutically acceptable salts thereof, and wherein: n is 0 1 or 2; R⁴ is hydrogen or optionally substituted C₁₋₆ alkyl; and R³ is N (R) (R⁹), N (R) C (O), C (O) N (R), or C₃₋₇ carbocyclyl, C₃₋₇ carbocyclyloxy, C₄₋₁₂ carbocyclylalkyl, C₄₋₁₂ carbocyclylalkoxy, C₆₋₁₀ aryl, C₆₋₁₀ aryloxy, C-S-aryl, C₂-aryl-SO₆₋₁₀, C a aralkoxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, heterocyclylalkyl, heterocyclylalkoxy or heteroaryl-S, optionally substituted where R it is hydrogen or optionally substituted alkyl, and R⁹ is C₃₋₇ carbocyclyl, C₃₋₇ carbocyclyloxy, C₄₋₁₂ carbocyclylalkyl, C₄₋₁₂ carbocyclylalkoxy, C₆₋₁₀ aryl, C₆₋₁₀ aryloxy, C S-aryl-aryl-SO₂ C₆₋₁₀, Cral aralkoxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, heterocyclylalkyl, heterocyclylalkoxy or optionally substituted S-heteroaryl.